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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Virus Infection Willing and able to provide written informed consent Treatment-naive or treatment-experienced adult, U.S. Veteran Chronic genotype 2 (GT2) HCV infection Classified as Eligible for treatment with interferon (IFN)-based therapy Ineligible for IFN treatment Intolerant to IFN Cirrhosis determination Laboratory parameters within prespecified ranges at screening A negative serum pregnancy test is required for females of childbearing potential Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Current participation in an interventional clinical trial Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) History of any other clinically significant chronic liver disease (e.g., hemochromatosis; Wilson's disease; α1-antitrypsin deficiency), except nonalcoholic steatohepatitis (NASH) Decompensated liver History of hemoglobinopathies Contraindication or hypersensitivity to RBV History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participation for the full duration of the study, such that it is not in the best interest of the individual to participate Clinically significant ECG abnormality at screening History of solid organ transplantation Presence of hepatocellular carcinoma (HCC) Malignancy within 5 years prior to screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer and prostate cancer in remission). Individuals under evaluation for possible malignancy are not eligible
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 40.0-70.0, Pulmonary Disease, Chronic Obstructive Male or female aged between 40 and 70 years of age inclusive, at the time of signing the informed consent Subjects with a documented history of COPD exacerbation(s) in the 12 months prior to study participation meeting at least one of the following >=2 COPD exacerbations resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center; 1 COPD exacerbation resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center and a plasma fibrinogen concentration at screening >=3.5 milligram/milliliter (mg/mL) Diagnosis of symptomatic chronic obstructive pulmonary disease with mild to moderate airflow obstruction (COPD-GOLD I or II) for at least 2 years based on American Thoracic Society (ATS)/ European Respiratory Society (ERS) current guidelines or symptoms consistent with COPD for at least 2 years Subjects with a post-bronchodilator FEV1/FVC ratio of < 0.7 and FEV1 >=50% of predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equation at Visit 1 A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international units/mL (MIU/mL) and estradiol < 40 picogram (pg)/mL (<147 picomole/Liter [pmol/L]) is confirmatory]. Females on hormone replacement therapy (HRT) will not be enrolled in the study Body weight >=45 kilogram (kg) Current smokers and former smokers with a cigarette smoking history of >=10 pack years (1 pack year =20 cigarettes smoked per day for 1 year or equivalent). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1 Subjects with a history of respiratory symptoms, including chronic cough and/or mucus hypersecretion on most days for at least the previous 3 months prior to Visit 1 Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2x upper limit of normal (ULN); alkaline phosphatase and bilirubin <=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) Able to perform lung function tests reliably Diagnosis of asthma, or other clinically relevant lung disease (other than COPD), e.g. sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung cancer; Subject with alpha-1-antitrypsin deficiency as the underlying cause of COPD Pulse Oximetry levels <88% (at rest on room air) at screening Less than 14 days have elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation Diagnosis of Pneumonia (chest X-Ray or computed tomography [CT] confirmed) within the last 3 months prior to screening History or current evidence of clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension or any other clinically significant cardiovascular, neurological, endocrine, or hematological abnormalities that are uncontrolled on permitted therapy. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subjects at risk through study participation, or which would affect the safety analysis or other analysis if the disease/condition exacerbated during the study A positive pre-study drug/alcohol screen A positive test for human immunodeficiency virus (HIV) antibody A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Provision of written informed consent Male and female patients aged 18 years and above Willing to use two effective methods of contraception during the treatment period and 24 weeks post HBsAg negative Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the investigator is unlikely to demonstrate spontaneous viral clearance Compensated liver disease (Child-Pugh A) Negative pregnancy test at screening and 24 hours prior to first dose of study drugs Medically stable on the basis of physical examination, medical history and vital signs Adequate English to provide reliable responses to the study questionnaires Recent hepatitis C infection, as defined by: A) i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii) Documented anti-HCV Ab negative within the 24 months prior to anti-HCV antibody positive result, OR B) i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii) acute clinical hepatitis (jaundice or ALT> 10 X ULN) within the previous 12 months prior to first positive HCV antibody or HCV RNA, with no other cause of acute hepatitis identifiable If co-infection with HIV is documented, the subject must meet the following Standard exclusions to RBV therapy Pregnancy/lactation or male subjects whose female partners are pregnant Subject has a history of decompensated liver disease: history of ascites, hepatic encephalopathy, or bleeding oesophageal varices, and/or any of the following screening laboratory results: a.INR of ≥1.5; Serum albumin <3.3 g/dL; Serum total bilirubin >1.8 times upper limit of normal, unless isolated in subjects with Gilbert's syndrome
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Fibrosis Hepatitis C Chronic Patients with established advanced liver disease caused by hepatitis C virus (HCV) chronic infection defined by a positive test for anti-HCV antibodies and detectable serum HCV RNA (Amplicor HCV 2.0 polymerase chain reaction (PCR) assay) Sign an informed consent form to allow the collection of liver biopsies before and after treatment No antifibrotic, antiviral or immunosuppressive drugs for at least 6 months before starting pirfenidone therapy No alcohol intake for at least 6 months before nor during Pirfenidone (PFD) treatment Patients with clinical contraindications to hepatic biopsy
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 3.0-17.0, Hepatitis C Virus Infection Key Consent of parent or legal guardian required Chronic HCV infection genotype 2 or 3 Screening laboratory values within defined thresholds PK Lead-in only: all individuals must be treatment naive Key History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus Clinical hepatic decompensation (ie, ascites, encephalopathy or variceal hemorrhage) Pregnant or nursing females Known hypersensitivity to study medication Use of any prohibited concomitant medications as within 28 days of the Day 1 visit Note: Other protocol defined Inclusion/
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 0.0-999.0, Hepatitis C For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Males and Females ≥18 years of age, inclusive Chronic HCV infection Genotype 1 only Non-cirrhotic Treatment naive subjects with no previous exposure to an Interferon formulation (ie, IFNα, pegIFNα), ribavirin (RBV) or HCV Direct Acting Antiviral (DAA) (protease, polymerase inhibitor, etc.) HCV Genotype other than Genotype 1 Documented or suspected hepatocellular carcinoma Evidence of decompensated liver disease Contraindication(s) to Peg/RBV therapy
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Hepatitis C, Chronic Adults from 18 years Male OR female with documented hysterectomy OR menopausal female with last menstrual period at least 12 months prior to screening Written informed consent consistent with International Conference on Harmonization/Good Clinical Practice and local legislation given prior to any study procedures Chronic HCV infection demonstrated by positive HCV immunoglobulin G Antibody HCV genotype 1 which has to be confirmed by central laboratory test before Visit 2 For non-cirrhotic cohorts: Liver biopsy obtained within the last 36 months consistent with HCV infection showing minimal to mild liver fibrosis and without cirrhosis (Ishak or Metavir grade ≤ 2). For cirrhotic cohorts, previous liver biopsy or Fibroscan consistent with liver cirrhosis performed at any time before screening HCV RNA load > 100,000 IU RNA per ml serum at screening All fertile males not willing to use an adequate form of contraception (condom, sterilisation at least 6 months post operation) in case their partner is of childbearing potential and is not using an adequate form of contraception (hormonal contraceptives, oral or injectable/ implantable, intra-uterine device) Patients who have been treated with at least one dose of any HCV-polymerase inhibitor for acute or chronic hepatitis C infection Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis Decompensated liver disease within past 12 months, as indicated by variceal bleeding, ascites, encephalopathy, Prothrombin or International Normalized Ratio (INR) prolonged to >1.7 x upper limit of normal (ULN), serum bilirubin > 2 mg/dl or albumin < 3.5 g/dl (i.e. Child-Pugh grade B, score > 7) For non-cirrhotic cohorts: Any previous liver biopsy consistent with cirrhosis. For cirrhotic cohorts: Any liver biopsy or fibroscan result from last 2 years excluding liver cirrhosis Positive test for human immunodeficiency virus (HIV) or hepatitis B antigen at screening Current alcohol or drug abuse, or history of the same, within the past six (6) months. Exception: Occasional use of cannabis is not an criterion. The investigator must however instruct the patient that consumption of cannabis is not allowed during the treatment period Any concurrent disease (cardiovascular, pulmonary, renal, haematological, neurological, psychiatric, immunologic, metabolic or endocrine dysfunction) if clinically significant based on the investigator's medical assessment at screening. A clinically significant disease is defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study. is also necessary for any pre-existing cardiac abnormality by history Clinically significant abnormalities at screening ECG, including but not limited to a QTc longer than 435 msec, Pulse Rate > 240 msec at baseline and any bundle branch block pattern, but not necessarily non-specific T wave abnormalities History of malignancy (except for previously cured squamous cell or basal cell carcinoma)
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, HIV Infections Hepatitis C Men and women age greater than or equal to 18 to less than or equal to 70 years at study entry Body mass index (BMI) from greater than or equal to 18 to less than 38 kg/m^2 within 42 days of study entry. BMI was calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m) HIV-1 infection CD4+ cell count greater than or equal to 200 cells/uL and CD4+ cell percentage greater than or equal to 14% within 42 days of study entry On a stable, qualifying ART regimen for at least 8 weeks prior to entry HIV-1 RNA less than 50 copies/mL for at least 6 months prior to study entry Presence of chronic HCV infection defined as positive for anti-HCV antibody or HCV RNA at least 6 months before screening, and positive for HCV RNA at the time of screening; OR positive for HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection any time prior to study entry HCV treatment-naïve or unsuccessful treatment with pegylated or standard IFN alfa with or without RBV. NOTE: No prior exposure to HCV NS3/4A PI (including but not limited to TVR, BOC, simeprevir), NS5A inhibitors (including but not limited to daclatasvir or ledipasvir), NS5B NNI or NI inhibitors (including but not limited to sofosbuvir) was allowed HCV genotype 1a or 1b infection Serum HCV RNA greater than 10,000 IU/mL obtained within 42 days prior to study entry Breastfeeding Pregnant sexual partner for male participants with HCV genotype 1a infection who would receive RBV. This criterion did not apply to male participants with HCV genotype 1b infection who would not receive RBV Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation Acute or serious illness requiring systemic treatment and/or hospitalization within 42 days prior to study entry Active hepatitis B infection (positive hepatitis B surface antigen [HBsAg]) within 42 days prior to study entry History of decompensated liver disease (including but not limited to encephalopathy, variceal bleeding, or ascites) prior to study entry Any cause of liver disease other than chronic HCV infection, including but not limited to the following: hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, autoimmune hepatitis, alcoholic liver disease, or drug-related liver disease Uncontrolled or active depression or other psychiatric disorder within 24 weeks prior to study entry that in the opinion of the site investigator might preclude adherence to study requirements Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements Serious illness including uncontrolled seizure disorders, active coronary artery disease within 24 weeks prior to study entry, or other chronic medical conditions that in the opinion of the site investigator might preclude completion of the protocol
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV) Coinfected Subjects ≥ 18 years old Chronic HIV-1 infection, as diagnosed on the basis of the presence of serum HIV antibodies detected by EIA and western-blot Chronic HCV infection as proven by detecting HCV antibodies in plasma, as well as detectable plasma HCV-RNA by PCR To start a new ART regimen during the study period Subjects with hepatotoxic events in the 2 months previous to Eviplera® treatment Acute infections or uncontrolled chronic infection in the two months previous to Eviplera® treatment Concomitant use of any drug with potential drug-drug interaction with Eviplera® Documented resistance to study drugs Concomitant therapy including anti-HCV agents, cytotoxic chemotherapy or immunosuppressors during Eviplera® treatment Subjects taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied have stopped for more than 12 weeks before Eviplera® treatment
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Hepatitis C Key Willing and able to provide written informed consent Chronic HCV infection Cirrhosis determination (liver biopsy may be required) Screening laboratory values within specified limits Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Specific genotype, prior medical history, or concurrent disease as required by the specific study group Key History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol Pregnant or nursing female, or male with pregnant female partner Clinical hepatic decompensation (ie, ascites, encephalopathy or variceal hemorrhage) Use of any prohibited concomitant medications Note: Other protocol defined Inclusion/
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, HIV Fatty Liver Nonalcoholic Steatohepatitis 18 years or older 2. Confirmed positive serology for HIV mono-infection 3. Valid Fibroscan/CAP results 4. Able to provide informed consent (available in French or English) 5. Receiving any approved antiretroviral regimen that does not contain integrase-inhibitor 6. Evidence of fatty liver (CAP>237.8dB/m) AND/OR evidence of significant liver fibrosis (Fibroscan > 8KPa) 7. HIV viral suppression (<50 copies/mL) for at least 6 months 8. No prior evidence of resistance to raltegravir or co-administered nucleoside backbone Clinical evidence of decompensated liver disease at entry (e.g. ascites, bleeding esophageal varices, hepatic encephalopathy, or hepatoma/ hepatocellular carcinoma). 2. Co-infection with hepatitis C virus (HCV) or hepatitis C virus (HBV) (presence of serum HCV-Ab or HBsAg); 3. Alpha-fetoprotein (AFP) greater than or equal to 200 ng/mL at screening. 4. Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease or other cause of chronic liver disease. 5. Chronic renal insufficiency (eGFR < 20 mL/min) at screening. 6. Pregnancy and planned pregnancy (not using adequate contraception). 7. Women who are breastfeeding. 8. Active opportunistic infection (except oral thrush) or neoplasm (except Kaposi's sarcoma, skin cancer, or cancer of the cervix or anus, unless known or suspected liver metastasis)
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 3.0-17.0, Hepatitis C Virus Infection Key Consent of parent or legal guardian required Chronic HCV infection Screening laboratory values within defined thresholds Key History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage) Pregnant or nursing females Known hypersensitivity to study medication Use of any prohibited concomitant medications as within 28 days of the Day 1 visit Note: Other protocol defined Inclusion/
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Chronic Hepatitis B Male or female subject between 18 and 65 years of age at the time of randomization Must be HBeAg negative and anti-HBe Abs positive for at least 1 year prior to screening and at screening Has HBV DNA < 40 IU/mL for at least 1 year prior to screening and at screening Has both ALT and AST levels ≤ ULN for at least 1 year prior to screening and at screening Must be HBsAg positive at screening Has been treated with NUCs for at least 2 years prior to screening Has not been treated with PEG-IFN or IFN for at least 1 year prior to screening For all females, must have a negative serum pregnancy test at screening. For female of childbearing potential, must have been using adequate contraception and must agree to continue to use it during all study period and for 6 months after completion of the study product administration Has provided written informed consent Has elevated blood levels of alpha-fetoprotein (AFP) (> 500 ng/mL) Has cirrhosis, defined as platelet count < 150,000/mm3, with esophageal varices on imaging and spleen size > 12, or liver stiffness of 11 kilopascal [kPa] as measured by elastography using FibroScan® or .an AST to Platelet Ratio Index (APRI) > 2) Has hepatocellular carcinoma (HCC) (diagnosed by ultrasonography) Has liver decompensation (albumin < 3.5 g/dL and bilirubin ≥1.3 mg/dL) Is Hepatitis C virus (HCV) Ab positive at screening Is Hepatitis delta virus (HDV) Ab positive at screening Is Human Immunodeficiency Virus (HIV) Ab positive at screening Has an immune suppressive disorder or treatment with immunosuppressive drugs
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Hepatitis C HCV genotype 4 infection HCV RNA >10,000 IU/mL at screening Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) Any liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A, drug or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the investigator Infection/co-infection with HCV non-genotype 4 Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen [HBsAg] positive) Presence of significant co-morbidities or conditions that would compromise the subject's safety and could interfere with the subject's participation for the full duration of the study in the opinion of the investigator Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-75.0, Hepatitis C Lichen Planus Vasculitis Autoimmune Diseases Patients with evidence of HCV infection and mucocutaneous complaint and contraindicated to have standard antiviral therapy Hypersensitivity to Ribavirin Pregnant & Lactating women Male partners of pregnant women
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 16.0-999.0, Cystic Fibrosis Cystic Fibrosis (CF) diagnosed ( established by genotype or sweat sodium>70 mmol/l or sweat chloride of>60 mmol/l) Clinically stable at time of study entry (defined as no requirement for antibiotics or change in respiratory medication in the preceding 4 wk) Chronic sputum production, at least ≥ 15 ml /24h Familiar and trained in the use of autogenic drainage technique (at least 6 months) and resistive inspiratory manoeuvre (at least three previous sessions) To be able to provide written, informed consent Lung function: Forced expiratory volume in 1 second < 30 % pred . ; Forced vital capacity < 40 % pred Active haemoptysis during the previous month Supplemental oxygen or non-invasive ventilation (NIV)
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C, Chronic Documented chronic Hepatitis C virus (HCV) infection: diagnosis of HCV more than (>) 6 months before the Screening visit, either by detectable HCV ribonucleic acid (RNA), a HCV positive antibody or the presence of histological changes consistent with chronic hepatitis HCV genotype 1 or 4 infection and HCV RNA plasma level >10,000 international unit per milliliter (IU/mL) (both determined at screening) Presence of cirrhosis, which is defined as a FibroScan with a result of >14.5 kilopascals (kPa) at Screening HCV treatment-naive participants: participant has not received treatment with any approved or investigational drug for the treatment of HCV infection and HCV treatment-experienced participants: participant has had at least 1 documented previous course of a non-direct-acting antiviral agent (DAA), interferon (IFN)-based HCV therapy (with or without Ribavirin [RBV]). Last dose in this previous course should have occurred at least 2 months prior to Screening Decompensated liver disease: Panel 1: Child Pugh A (mild hepatic impairment) with evidence of portal hypertension [confirmed by the presence of esophageal varices on gastroscopy or hepatic venous pressure gradient (HVPG) greater than or equal to (>=) 10 millimeter of mercury (mm Hg)], Panel 2: Child-Pugh B (moderate hepatic impairment) 7 to 9 (extremes included) Co-infection with any HCV genotype Co-infection with human immunodeficiency virus (HIV)-1 or -2 (positive HIV-1 or HIV-2 antibodies test at Screening) Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, drug or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the Investigator Use of any disallowed therapies before the planned first dose of study drugs
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Virus For Arms A, B and C Participants must meet one of the following Treatment-naive: Participant has never received antiviral treatment for hepatitis C infection OR Treatment Experienced (Prior null responders, Partial responders or Relapsers to IFN/RBV); For Arm D Participant must have prior treatment experience with SOF/pegIFN/RBV or SOF/RBV and meet one of the following categories Prior SOF breakthrough/non-responder: HCV RNA detectable at the end of treatment with SOF/pegIFN/RBV or SOF/RBV Prior SOF relapser: achieved HCV RNA undetectable at end of a prior treatment course SOF/pegIFN/RBV or SOF/RBV, but HCV RNA was detectable within 52 weeks following completion of therapy. For Arms A, B, C and D Chronic HCV genotype 4 infection with cirrhosis Participant has plasma HCV RNA level > 1,000 IU/mL at Screening Positive test result at Screening for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) Current enrollment in another interventional clinical study, previous enrollment in this study, or previous use of any protease inhibitor, non-nucleoside polymerase inhibitor, or Nonstructural viral protein (NS) 5A inhibitor, either investigational or commercially available (including previous exposure to paritaprevir or ombitasvir), or receipt of any investigational product within 6 weeks prior to study drug administration. Prior use of any direct-acting antiviral will not be allowed, except for Arm D where prior experience with the nucleoside polymerase inhibitor, sofosbuvir with pegIFN/RBV or SOF with RBV is required Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites, variceal bleeding, or hepatic encephalopathy Confirmed presence of hepatocellular carcinoma Any cause of liver disease other than chronic HCV infection Abnormal laboratory tests
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Hepatitis C Infection older than 18 years initiation of therapy including a direct-acting antiviral against HCV HIV-infection unable to provide written informed consent
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Participants have voluntarily signed the informed consent form. 2. 18 years of age or older. 3. Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater than 6 months. 4. HCV RNA plasma ≥ 1000 IU/ml at Screening. 5. HCV genotypes 1-6. 6. Recent injecting drug use (previous 6 months). 7. Compensated liver disease. 8. Participants with Fibroscan >12 KPa or AFP >50 ng/mL must have an abdominal ultrasound or CT scan without evidence of hepatocellular carcinoma within 2 months prior to screening. 9. Negative pregnancy test at baseline (females of childbearing potential only). 10. All fertile males and females must be using effective contraception during treatment and during the 30 days after treatment end History of any of the following: 1. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded. 2. Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal haemorrhage) 3. Solid organ transplant 4. Malignancy within 5 years prior to screening, with exception of specific cancers that may have been cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are also excluded. 5. Significant drug allergy (such as anaphylaxis or hepatotoxicity). 2. Screening ECG with clinically significant abnormalities 3. Any of the following lab parameters at screening: 1. ALT > 10 x ULN 2. AST > 10 x ULN 3. Direct bilirubin > 1.5 x ULN 4. Platelets < 50,0000/μL 5. HbA1c > 8.5% 6. Creatinine clearance (CLcr) < 60 mL/min 7. Haemoglobin < 11 g/dL for females ; < 12 g/dL for males 8. Albumin < 30g/L 9. INR > 1.5 ULN unless subject has known haemophilia or is stable on an anticoagulant regimen affecting INR 4. Pregnant or nursing female. 5. HIV infection or HBV infection (HBcAb and HBsAg positive) 6. Use of prohibited concomitant medications as described in section 5.2 7. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day) 8. Known hypersensitivity to GS-5816, sofosbuvir (SOF) or formulation excipients. 9. Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug. 10. Any investigational drug ≤6 weeks prior to the first dose of study drug. 11. Previous therapy with sofosbuvir (SOF) or an NS5A inhibitor prior to the first dose of study drug. 12. Ongoing severe psychiatric disease as judged by the treating physician. 13. Frequent injecting drug use that is judged by the treating physician to compromise treatment safety. 14. Inability or unwillingness to provide informed consent or abide by the requirements of the study
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Hepatitis C, Chronic Willing and able to provide written informed consent. 2. East Asian subjects, male or female, and age between 18 (or legal adult age) and 70 years, inclusive, at Baseline/Day 1. 3. Body mass index (BMI) in the range of 18.0 to 35.0 kg/m2 (inclusive) and body weight ≥ 40 kg. 4. Presence of chronic hepatitis C (CHC) as documented below: (1) A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit or (2) A liver biopsy or FibroTest performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection, such as the presence of fibrosis and/or inflammation. 5. Positive for anti-HCV antibody at Screening. 6. Presence of an HCV RNA level ≥ 1 x 10000 IU/mL at Screening as determined by the Central Laboratory. 7. Presence of genotype 1b HCV-infection at Screening as determined by the Central Laboratory. Any non-definitive results will the subject from study participation. 8. HCV treatment naïve defined as no prior therapy with any interferon (IFN), ribavirin (RBV), or other approved or investigational HCV-specific agent. 9. Absence of cirrhosis Cirrhosis as defined as any one of the following: 1. Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥ 5). 2. FibroScan showing cirrhosis or results > 12.5 kPa. 3. FibroTest fibrosis score of > 0.58 and APRI (AST: platelet ratio index) of > 2 during Screening. If no definitive diagnosis of cirrhosis by the above a liver biopsy is required; liver biopsy results will supersede non-invasive testing results and be considered definitive. 10. Screening ECG without clinically significant abnormalities. 11. Subjects must have the following laboratory parameters at Screening: 1. ALT ≤ 10 × the upper limit of normal (ULN) 2. AST ≤ 10 × ULN 3. Total bilirubin ≤ 1.5 × ULN except history of Gilbert's syndrome. If Gilbert's syndrome is the proposed etiology, the total bilirubin must ≤ 2 × ULN. 4. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 5. Platelet count ≥ 90,000 cells/mm3 6. HbA1c ≤ 8.5% 7. Thyroid stimulating hormone (TSH) and free T4 ≤ ULN 8. Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault equation 9. Serum creatinine ≤ 1.5 × ULN 10. Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects 11. Albumin ≥ 3.5 g/dL 12. INR (International Normalized Ratio for Prothrombin Time) ≤ 1.5 x ULN unless subject is stable on an anticoagulant regimen affecting INR 13. Anti-nuclear antibodies (ANA) ≤ 1:320. 12. Subject must be of generally good health, with the exception of chronic HCV infection, as determined by Investigator. 13. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments, including all required Post-Treatment visits. 14. A female subject is eligible to enter the study if it is confirmed that she is: (1) Not pregnant or nursing. (2) Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 50 years of age with cessation (for ≥12 months) of previously occurring menses), or (3) Of childbearing potential (i.e., women who have not had a hysterectomy, have not had both ovaries removed, and have not had medically documented ovarian failure). Women ≤ 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at the Baseline/Day 1 visit prior to randomization. They must also agree to one of the following from Screening until 6 months after the last dose of study drug(s) Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not permitted. Or Consistent and correct use of 1 of the following methods of birth control listed below, in addition to a male partner who correctly uses a condom, from Screening until 6 months after the last dose of study drug(s): 1. intrauterine device (IUD) with a failure rate of < 1% per year 2. female barrier method: cervical cap or diaphragm with spermicidal agent 3. tubal sterilization 4. vasectomy in male partner 5. hormone-containing contraceptive: i. implants of levonorgestrel ii. injectable progesterone iii. oral contraceptives (either combined or progesterone only) iv. contraceptive vaginal ring v. transdermal contraceptive patch. 15. Male subjects must agree to consistently and correctly use a condom, while their female partner agrees to use 1 of the methods of birth control listed above, from Screening until 6 months after the last dose of study drug(s). 16. Male subjects must agree to refrain from sperm donation from Screening until at least 6 months after the last dose of study drug(s) Presence of cirrhosis. 2. Positive serological test for IgM anti-HAV (hepatitis A virus) antibody or HBsAg at Screening. 3. Positive ELISA test for HIV-1 or HIV-2 at Screening. 4. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson disease, alfa-1 antitrypsin deficiency, cholangitis). 5. Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1. 6. Clinically-relevant drug abuse within 12 months of Screening. A positive drug screen will subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by Investigator. 7. Alcohol misuse as defined by an AUDIT score of ≥ 8. 8. Contraindications to RBV or IFN therapy, including hemoglobinopathies (e.g., thalassemia major or sickle-cell anemia), autoimmune thyroiditis or other autoimmune disorders including autoimmune hepatitis. 9. Pregnant or nursing female or male with pregnant female partner. 10. Use of any prohibited medications within 30 days of the Baseline/Day 1 visit: (1) Hematologic stimulating agents (e.g., erythropoiesis-stimulating agents [ESAs], granulocyte colony stimulating factor [G-CSF], and thrombopoietin [TPO] mimetics) (2) Chronic use of systemic immunosuppressants including, but not limited to, corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks), azathioprine, or monoclonal antibodies (eg, infliximab) (3) Investigational agents or devices for any indication (4) Drugs disallowed per prescribing information of RBV or IFN (5) Any prohibited medications listed in Table 6-2. 11. Known hypersensitivity to RBV, IFN, TG-2349, sulfa drugs, or formulation excipients. 12. Current or prior history of any of the following: 1. Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded. 2. Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drugs. 3. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. 4. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage). 5. Central nervous system (CNS) trauma, seizure disorder, stroke or transient ischemic attack. 6. Solid organ transplantation. 7. Significant cardiac disease (including but not limited to the myocardial infarction based on ECG and/or clinical history). 8. Significant pulmonary disease or porphyria. 9. Clinically significant retinal disease 10. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 12 months prior to Baseline/Day 1 or has not required medication in the last 12 months may be included. 11. Malignancy within 5 years prior to Screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible. 12. Significant drug allergy (such as anaphylaxis or hepatotoxicity)
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 0.0-999.0, Chronic Hepatitis B patients who had chronic hepatitis B and achieved HBsAg level≤100 IU/ml with undetectable HBV DNA level by interferon treatment Active consumption of alcohol and/or drugs Co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus History of autoimmune hepatitis Psychiatric disease Evidence of neoplastic diseases of the liver
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Hepatitis C Virus HCV genotype 1 infection and HCV RNA plasma level greater than (>) 10,000 international units per milliliter (IU/mL), both determined at Screening Participants of Arm A should have evidence of early stages of liver fibrosis, defined by a FibroSURE score less than or equal to (<=) 0.48 and aspartate aminotransferase to platelet ratio index (APRI) score <=1 Participants of Arm B should have evidence of cirrhosis, defined by a FibroSURE score >0.75 and APRI score >2, OR a previous (historical) biopsy documenting a score F4. In addition, participants should have absence of esophageal varices or presence of small (grade 1) esophageal varices determined by upper gastrointestinal endoscopy, and absence of findings indicative of hepatocellular carcinoma in an ultrasonography HCV treatment-naive, defined as not having received treatment with any approved or investigational drug for chronic HCV infection Pegylated interferon (PegIFN) and ribavirin (RBV) eligible, defined as not having any contraindication to the use of PegIFN and RBV, in line with the prescribing information for each compound A. Main Study Co-infection with HCV of another genotype than genotype 1 and/or human immunodeficiency virus (HIV) type 1 or 2 (positive HIV-1 or HIV 2 antibody test at Screening) Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, hepatitis B infection (hepatitis B surface antigen positive), drug or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the Investigator Evidence of clinical hepatic decompensation or presence of grade 2/3 esophageal varices Any of the protocol defined laboratory abnormalities B. Sub-study Presence of coagulopathy (hemophilia) or hemoglobinopathy (including sickle cell disease, thalassemia) Use of any anti-coagulant (for example, warfarin, heparin) or anti-platelet medications within 1 week of the Screening visit Any of the protocol defined laboratory abnormalities
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-80.0, Biliary Cirrhosis, Primary Major Diagnosis of PBC or PBC-Autoimmune hepatitis overlap as established according to American Association for the Study of Liver Diseases/European Association for the Study of Liver (AASLD/EASL) definitions. Definite or probable PBC diagnosis, as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors History of elevated alkaline phosphatase (ALP) levels (>1.67 ULN) for at least 6 months prior to Day 1 Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex) Liver biopsy consistent with PBC Ursodeoxycholic acid (UDCA) non-responders defined as >6 months of UDCA and at the time of enrolment a serum ALP >1.67 ULN Laboratory markers of cholestasis identified within 3 months of Visit 1 Treatment with cholestyramine at a dose >4g BID or colestipol > 5mg for at least 3 months The patient has a VAS-Itch of at least 30 mm during the day before baseline (Visit 2) The patient is a male or non-pregnant female ≥18 years of age and ≤80 years of age with body mass index (BMI) ≥18.5 but <35 kg/m2; Major Any condition that, in the opinion of the Investigator constitutes a risk for the patient or a contraindication for participation and completion of the study, or could interfere with study objectives, conduct, or evaluations Jaundice of extrahepatic origin The patient has a structural abnormality of the GI tract The patient has a known, active, clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti infectives within 4 weeks of treatment start (study day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of screening period The patient has unexplained and clinically significant GI alarm signals (e.g., lower GI bleeding or heme-positive stool, iron-deficiency anaemia, unexplained weight loss) or systemic signs of infection or colitis
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-80.0, Chronic Hepatitis B HBeAg positive group 1. Age >18 years and older, male or female. 2. Known serum HBsAg and HBeAg positivity at the time of screening. 3. Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry. 4. HBV DNA levels <100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study. 5. ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening 6. Written informed consent HBeAg negative group 1. Age >18 years and older, male or female. 2. Known serum HBsAg positivity and HBeAg negativity at the time of screening. 3. Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry. 4. HBV DNA levels <100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study 5. ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening 6. Written informed consent (for both eAg positive and negative patients) 1. Co-infection with HDV as defined by the presence of anti-HDV in serum and/or HDV antigen in the liver. 2. Co-infection with HCV as defined by the presence of HCV RNA in serum. 3. Co-infection with HIV as defined by the presence of anti-HIV in serum. 4. Decompensated liver disease as defined by serum bilirubin >2.5 mg/dL (with direct bilirubin > 0.5 mg/dL), prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3 g/dL, or a history of ascites, variceal bleeding or hepatic encephalopathy. 5. Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, severe nonalcoholic steatohepatitis defined as the presence of marked ballooning injury on liver biopsy, alpha-1-anti-trypsin deficiency). 6. A history of organ transplantation or in the absence of organ transplantation, any immunosuppressive therapy requiring the use of more than 5 mg of prednisone (or its equivalent) daily. 7. Significant systemic illness other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis and diabetes mellitus with poor control, that in the opinion of the investigator may interfere with therapy. 8. Pregnancy or inability to practice contraception in patients capable of bearing or fathering children 9. Lactating women. 10. Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the liver that is suggestive of HCC, or an alpha-fetoprotein level of greater than 500 ng/mL. 11. eGFR < 50 ml/min, serum creatinine > 1.3 mg/dl or urine protein >1 gram/24-hours 12. History of hypersensitivity to pegylated interferon-alpha 13. Platelet count <70 mm(3)/dL 14. Hgb <12 g/dL for males and <11 g/dL for females 15. Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study. 16. History of malignancy or treatment for a malignancy within the past 3 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin). 17. Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study. 18. History of immune-mediated disease, or cerebrovascular, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician. 19. Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study for at 1 year. 20. For subjects who interrupt therapy, documentation of a viral load >1,000 IU/ml while off therapy
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Chronic Hepatitis C Males or females, ≥ 18 years & ≤ 65 years of age. 2. HCV antibody positive, with serum HCV RNA ≥ 10,000 IU/mL, with clinical history compatible with chronic hepatitis C. 3. HCV genotype-4 infection, confirmed at the central study laboratory 4. Body mass index (BMI) between 18 and 35 kg/m2, inclusive. 5. Both male and female patients who have childbearing potential must agree to practice an acceptable method of birth control during the study and for at least 6 months after the cessation of treatment; such contraceptive methods must at least one barrier method. 6. Patients for Group 1 must be treatment-naïve i.e., they have never received any antiviral treatment for their HCV infection, including interferon, pegylated interferon, ribavirin, or other regulatory-approved or investigational HCV antiviral therapies. 7. Patients for Groups 2 and 3 must have previously failed treatment with an interferon-based therapy i.e., interferon or pegylated interferon, with or without ribavirin, with no other previous HCV antiviral therapies. Patients for Group 2 must be non-cirrhotic diagnosed on screening visit by both Fibroscan™ liver stiffness measurement < 12.5 kPa and FIB-4 score < 3.25 if the results of Fibroscan and FIB-4 score are not matching; liver biopsy will be used for detection of cirrhosis. In case that the liver biopsy is not applicable, hepatic imaging or ultrasound reports could be used for determination of cirrhosis. Patients for Group 3 must have underlying cirrhosis diagnosed on screening visit by both Fibroscan liver stiffness measurement > 12.5 kPa and FIB-4 score > 3.25, if the results of Fibroscan and FIB-4 score are not matching liver biopsy will be used for detection of cirrhosis. In case that the liver biopsy is not applicable, hepatic imaging or ultrasound reports could be used for determination of cirrhosis. 8. Willing and able to give informed consent 9. Willing and able to complete all study visits and procedures, including compliance with the requirements and restrictions listed in the consent form Mixed genotype or non-typable HCV genotype infection, 2. Positive test for HBsAg or HIV antibody, or IgM antibody to HAV or HEV 3. History of schistosomiasis or positive test for schistosoma surface antigen at Screen. 4. Serum alpha-fetoprotein (AFP) >100ng/ml. Patients with an AFP between 50 and 100ng/ml may be included as long as a liver ultrasound within 3 months of Screening, or at Screening, shows no evidence of potential hepatocellular cancer. 5. History of treatment with any investigational or regulatory-approved direct-acting antiviral (DAA) agent for HCV infection nucleos(t)ide or non-nucleosidic HCV polymerase inhibitor, HCV protease inhibitor, NS5A inhibitor, or other antiviral agent for HCV infection other than pegylated -interferon and/or ribavirin Previous pegylated interferon and/or ribavirin treatment is allowed for Groups 2 and 3 but prohibited for group 1, as noted above in criterion 6) 6. Evidence of a medical condition other than HCV that is contributing to liver disease 7. History of, or clinical signs of, hepatic decompensation or portal hypertension: Variceal bleeding, or documented esophageal or GI varices (at investigator discretion, patients suspected of having esophageal varices should be evaluated by endoscopy, and varices excluded) Ascites by history or on physical examination Documented or suspected hepatic encephalopathy Physical signs of portal hypertension: Clinically significant splenomegaly Spider angiomata History of porto-systemic shunt procedure(s) 8. Uncontrolled diabetes mellitus as evidenced by HgbA1C ≥ 8.5% at Screening. 9. Hemoglobin < 11g/dL for females and < 12 g/dL for males 10. WBC count < 3,500/mm3 OR absolute neutrophil count (ANC) < 1800/mm 11. Platelet count < 75,000/mm3 12. Serum creatinine > 1.3 x ULN OR creatinine clearance (GFR) < 50 mL/minute 13. Serum ALT or AST >10x ULN 14. Serum albumin ≤ 3.2 g/dl 15. Direct serum bilirubin > 2xULN 16. INR > 1.7. 17. History of poorly controlled asthma, with one or more hospitalizations or emergency room visits in the previous 6 months 18. History of any malignancy within the last 5 years (except prostate cancer still within Glisson's capsule or basal cell carcinoma of the skin). 19. History of alcohol abuse as assessed by the investigator within the past 2 years, or an alcohol use pattern that may interfere with the patient's study compliance. Patients must have abstained from alcohol for at least 6 months prior to study start. 20. History of drug abuse as assessed by the investigator within the last 2 years. 21. Pregnancy, including current lactation in female patients, male patients with partners who are pregnant, or female patients intending to become pregnant. 22. Major surgery requiring overnight hospitalization within 3 months prior to Screening 23. Participation in another clinical trial of an investigational drug or device within 6 months prior to Screening 24. Current use or history of use within the preceding 6 months of immunosuppressive or immune-modulating agents, including: azathioprine, systemic corticosteroids (prednisone or prednisone equivalent of more than 10mg/day for more than 10 days), or other immunosuppressive agents. Use of inhaled steroids for mild/moderate asthma and topical steroids for minor skin conditions is allowed. 25. History of solid organ or bone marrow transplantation. 26. History of use of medications associated with QT prolongation concurrently or within the 30 days prior to Screening Visit, including: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, and tricyclic anti-depressants. 27. correction, or a personal or family history of Torsades de Pointe. 28. Cardiac ischemia with history of recurrent angina, clinically symptomatic cardiac abnormalities, or requirement for cardiac pacemaker 29. History of a known allergy to ribavirin (RBV), or any excipient in the investigational product, or history of drug or other allergy that, in the opinion of the investigator, mitigates against study participation
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-80.0, Hepatitis C All patients admitted to the one day clinic for surgery and gastroenterology none
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Cirrhosis All age greater than 18 male or female 2. Capacity to provide written informed consent 3. Evidence of HCV RNA in 2 serum samples at least 6 months apart. 4. All HCV genotypes 5. Liver biopsy in the last 2 years prior to enrollment showing Ishak fibrosis score of either 0-1 or 5-6. An alternative to liver biopsy will be a Fibroscan study performed in the 6 months prior to study enrollment showing a score of either kPa <7 or above 13. 6. Child-Pugh score less than or equal to 6 7. Prior to each liver biopsy and portal vein cannulation procedure, blood will be drawn for CBC, PT/INR & acute care panel Pregnant women or females at child bearing age not taking measures to prevent pregnancy during the period of study 2. Patients currently on treatment for hepatitis C 3. Clinical, serologic or histopathologic evidence supporting other etiologies of chronic liver disease besides HCV 4. Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy etc.) 5. Cross sectional liver imaging study from the past 6 months showing a focal lesion suspicious of hepatocellular carcinoma and/or alpha-fetoprotein level greater than 200 ng/mL. 6. Patients with active bacterial, viral or fungal, systemic or localized infection. 7. Antibiotic treatment 30 days prior to study enrollment 8. History of chronic inflammatory diseases of the bowel (Crohn s disease, Ulcerative colitis and celiac disease) 9. History of congestive heart failure of moderate to severe degree. 10. History of non-cirrhotic portal hypertension or portal vein thrombosis 11. Patients with severe allergic reactions to iodine contrast, which cannot be controlled by premedication with antihistamines and steroids. 12 FOR MRI: 12.1 Subjects with contraindication to MRI scanning. These contraindications but are not limited to the following devices or conditions: <TAB>a. Implanted cardiac pacemaker or defibrillator <TAB>b. Cochlear Implants <TAB>c. Ocular foreign body (e.g. metal shavings) <TAB>d. Embedded shrapnel fragments <TAB>e. Central nervous system aneurysm clips <TAB>f. Implanted neural stimulator <TAB>g. Medical infusion pumps <TAB>h. Any implanted device that is incompatible with MRI. 12.2 Unsatisfactory performance status as judged by the referring physician such that the subject could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would unstable angina and dyspnea at rest. 12.3 Subjects requiring sedation for MRI studies. 12.4 Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.). 12.5 Pregnant or lactating women. 12.6 Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination. 12.7 For Gadolinium based and SPIO MRI Use: <TAB>a. History of severe allergic reaction to these contrast agents despite the use of premeditation with an anti-histaminic and cortisone. <TAB>b. eGFR < 60 ml/min/1.73m^2 13. Absolute neutrophil count below 1000/mm^3, Hemoglobin level below 10.0 g/dl or platelet count lower than 70,000/mm^3. 14. INR greater than or equal to 1.5, PTT greater than or equal to 1.3 times control and/or any known history of disease associated with increased bleeding diathesis. 15. Serum creatinine greater than or equal to 2.0 mg/dl unless the measured creatinine clearance is greater than 60 mL/min
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-60.0, Chronic Hepatitis B patients who achieved HBeAg seroconversion by interferon treatment Active consumption of alcohol and/or drugs Co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus History of autoimmune hepatitis Psychiatric disease Evidence of neoplastic diseases of the liver
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Diabetes Mellitus Hyperglycemia Hereditary Diseases Glucose Intolerance African descent aged 18 years or older not pregnant currently residing in Durban (eThekwini Municipality) non African descent pregnant not currently residing in Durban (eThekwini Municipality)
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Chronic Hepatitis D Infection Males or females, 18 to 65 years of age who are diagnosed with HDV by PCR Chronic hepatitis D infection, genotype 1, documented by a positive anti-HDV Ab test at least of 6 months duration and detectable HDV RNA by PCR within 3 months to study entry Liver biopsy within the last two years Positive viral load by quantitative PCR Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality and a QT/QTc interval <450 milliseconds using Bazett's correction Females of childbearing potential (intact uterus and within 1 year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, these subjects should agree to use one of the following acceptable birth control methods throughout the study: 1. abstinence 2. surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six months minimum 3. IUD in place for at least six months 4. barrier methods (condom or diaphragm) with spermicide 5. surgical sterilization of the partner (vasectomy for six months) 6. hormonal contraceptives for at least three months prior to the first dose of study drug Willing and able to comply with study procedures and provide written informed consent Participation in a clinical trial with or use of any investigational agent within 30 days of Study Visit 1 Patients co-infected with HIV Patients with screening tests positive for HCV, or anti-HIV Ab History of decompensated cirrhosis within the past year Active jaundice defined by total bilirubin > 2.0 excluding Gilbert's disease INR ≥ 1.5 Eating disorder or alcohol abuse within the past 2 years, excessive alcohol intake (> 20 g per day for females (1.5 standard alcohol drinks) or > 30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) (1.0 fluid oz (US) = 29.57 mL) Drug abuse within the last six months with the exception of cannabinoids and their derivatives Patients with absolute neutrophil count (ANC) < 1500 cells/mm3; platelet count < 100,000 cells/mm3; hemoglobin < 12 g/dL for women and < 13 g/dL for men; abnormal TSH,T4, or T3 or thyroid function not adequately controlled; or serum creatinine concentration ≥ 1.5 times upper limit of normal (ULN) History or clinical evidence of any of the following: 1. variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6, decompensated liver disease or any other form of non-viral hepatitis 2. immunologically mediated disease (e.g., rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) requiring more than intermittent nonsteroidal anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids (inhaled asthma medications are allowed) 3. any malignancy within 3 years except for basal cell skin cancer 4. significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia) 5. chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment 6. severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization 2
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Adult (18 years of age or older) Positive test for HCV RNA Planning to initiate treatment for HCV in the near future Not diagnosed with any additional liver diseases, such as autoimmune hepatitis, hepatitis B, alcoholic liver disease, or HIV Able to travel to Mount Sinai Must understand and speak English Willing to sign informed consent and participate Pregnancy Incarcerated Person
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Hepatitis C Cirrhosis Hepatitis C Virus US military veteran currently receiving healthcare through the Veterans Health Administration Screening laboratory result indicating hepatitis C virus (HCV), genotype 1-infection Positive for hepatitis C antibodies or HCV RNA at least 6 months before Screening, and HCV RNA > 1,000 IU/mL at the time of Screening or HCV RNA > 1,000 IU/mL at the time of Screening with a liver biopsy consistent with chronic HCV-infection (or a liver biopsy performed prior to enrollment with evidence of chronic hepatitis C disease) Women who are pregnant or breastfeeding Positive test result for hepatitis B surface antigen (HbsAg) or anti-HIV antibodies (HIV Ab) Prior or current use of any investigational or commercially available anti-HCV agents other than IFN, pegIFN, RBV or sofosbuvir Any current or past clinical evidence of Child-Pugh B or C classification Confirmed presence of hepatocellular carcinoma indicated on imaging techniques within 3 months prior to Screening or on an ultrasound performed at Screening for participants with cirrhosis
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Hepatitis C Virus An offender at the PEI Provincial Correction Centre during the enrollment time Male, 18 -70 years of age, inclusive, at time of screening Chronic HCV genotype 1 infection HCV infection, as demonstrated by positive HCV immunosorbant assay and detectable HCV viral load No evidence of decompensated liver disease (refractory ascites, variceal bleed within 1 year, active hepatic encephalopathy or Child-Pugh score greater than 6) HIV negative Males must be abstinent from sexual intercourse, surgically sterile or agree to practice two effective forms of birth control from those listed below, throughout the course of the study, starting with Study Day 1 and for 7 months after the last dose of study drug (or per local RBV label) Partner(s) using an IUD (intrauterine device) Partner(s) using oral, injected, or implanted methods of hormonal contraceptives Subject and/or partner(s) using condoms, contraceptive sponge, or diaphragm with spermicidal jellies or creams History of severe, life-threatening or other significant sensitivity to any drug Positive test result at screening for Hepatitis B surface antigen Prior therapy with direct acting antivirals for the treatment of HCV Evidence of decompensated liver disease (current or past refractory ascites, variceal bleed within 1 year, active hepatic encephalopathy) HIV positive screening test Unwilling to follow up for 48 weeks after treatment completion Use of any herbal supplements (including milk thistle) within 2 weeks or 10 half-lives of the respective supplement, whichever is longer, prior to the first dose of study drug HCV genotype performed during screening indicating unable to genotype or co-infection with any other HCV genotype Use of any medications contraindicated for use with the study regimen Clinically significant abnormalities, other than HCV-infection, based upon the results of a medical history, physical examination, vital signs, and laboratory profile that make the subject an unsuitable candidate for this study in the opinion of the investigator
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 25.0-75.0, Chronic Hepatitis B Antiviral Treatment all participants should have finished the clinical trial <Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients with High Viral Load but Slight Aminotransferase Elevation> without drop-out willingness to adhere to treatment and follow-up plans co-infection with HIV, HCV, or HDV presence of cirrhosis on histopathology hepatic decompensation defined as serum bilirubin > 2mg/dl and prolonged prothrombin time > 3 seconds concurrent malignant diseases including hepatocellular carcinoma severe co-morbidity with life expectancy < 1year pregnant or lactating women organ transplantation except cornea or hair transplant suspected or confirmed chronic liver diseases from etiologies other than HBV (e.g. alcoholic hepatitis, Wilson disease, Hemochromatosis…etc) serum creatinine >1.5mg/dL refusal to undergo liver biopsy
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Autoimmune Hepatitis Diagnosis of autoimmune hepatitis according to Autoimmune Hepatitis International Group with indication for treatment No evidence of decompensated liver cirrhosis Non-pregnant women and women with no intention to become pregnant Willing to participate in the study Discrete biochemical changes and histological inflammatory activity absent / minimal (periportal / peri-septal: 0/1 +) or decompensated cirrhosis Cases of loss of follow up
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-80.0, Chronic Hepatitis C Subjects must meet all of the following to be eligible for participation in this study Willing and able to provide written informed consent Male or female, age greater than or equal to18 years Body mass index (BMI) greater than or equal to 18 kg/m^2 HCV RNA greater than or equal to10^4 IU/mL at Screening HCV genotypes 1a, 1b, 2, 3 or 4 at screening Confirmation of chronic HCV infection documented by either A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or A liver biopsy performed within 12 weeks prior to the Baseline/Day 1 visit with evidence of chronic HCV infection. A prior biopsy would be acceptable if performed with 12 weeks AND liver tissue stored in RNALater was available Screening ECG without clinically significant abnormalities Subjects who meet any of the following will not to be enrolled in this study Current or prior history of any of the following Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage) Solid organ transplantation Significant pulmonary disease, significant cardiac disease or porphyria Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 12 months prior to randomization or has not required medication in the last 12 months may be included
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-75.0, Hepatitis C, Chronic Patients with chronic hepatitis C and indication for interferon-free antiviral therapy Written informed consent to study participation, especially to long-term follow-up monitoring of quality of life, emotional state, fatigue, and neurocognitive performance after antiviral treatment Age of study participants: between 18 and 75 years At study entry, all participating patients need to have documented antibodies to HCV and circulating HCV-RNA as measured by reverse-transcription polymerase chain reaction (Cobas Amplicor HCV MonitorTM test, Roche Diagnostics) Insufficient knowledge of the German language or cognitive impairment (due* to the indispensable application of questionnaires and the TAP, test battery of attentional performance) Age under 18 years or over 75 years Coinfections such as hepatitis B virus or human immunodeficiency virus Severe internal diseases (e.g., cancer, ischemic heart disease, autoimmune disease) Major depressive disorder (according to DSM-IV criteria), psychosis, active intravenous drug use or alcohol abuse
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Alcoholic Hepatitis Alcoholic hepatitis Jaundice < 3 months Bilirubin > 5 mg/dl PTI (INR) Increased: >1.4 Leucocytosis >> 11,000/micro L. AST< 300 IU/l ; AST/ALT >2 2. Hepatic Encephalopathy 3. Men and women age > 18 years and above 4. DF>32 5. MELD≥21 6. Actively consuming alcohol within 6 weeks of entry into the study 7. Patient with controlled upper GI bleed, resolved sepsis and acute kidney injury can be enrolled 8. Voluntary informed consent Failure to obtain informed consent 2. Jaundice more than 3 months 3. AST>500 IU/L, ALT>300 IU/L 4. Other concomitant causes of liver disease: viral hepatitis, autoimmune liver disease, metabolic liver disease, vascular liver disease 5. HIV positive 6. Cow milk allergy or severe lactose intolerance 7. Active Gastrointestinal bleeding 8. Acute kidney injury at time of randomization with Creatinine> 1.5 mg/dL 9. Evidence of acute pancreatitis or biliary obstruction 10. Subjects who are pregnant or lactating 11. Significant systemic cardio-pulmonary illness (what if on ventilator for HE or respiratory failure) These are terminally ill patients, hence be excluded 12. Patients requiring the use of vasopressors or inotropic support in 12 hours prior to randomization 13. Treatment for alcoholic hepatitis within 1 month of study entry with corticosteroids use>1 week. 14. Any patient who has received any investigational drug or device within 30 days entering into the study. 15. Patient who withdraw consent
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-100.0, Chronic Hepatitis C Hepatitis C (HCV) Hepatitis C Genotype 1a Screening laboratory result indicating hepatitis C viral (HCV) genotype (GT) 1a infection. 2. Chronic HCV infection. 3. Participants must be non-cirrhotic. 4. Participants must be treatment-naïve or have documentation that they were adherent to prior pegIFN/RBV combination therapy and meet the of prior pegylated-interferon (pegIFN)/ribavirin (RBV) treatment failure. 5. Participants must meet specific human leukocyte antigen (HLA) allele requirements Women who are pregnant or breastfeeding. 2. Positive test result for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) positive immunoassay. 3. Clinically significant abnormalities or co-morbidities, other than HCV infection, that make the subject unsuitable for this study or treatment. 4. Current enrollment in another interventional clinical study, previous enrollment in this study, prior or current use of any investigational or commercially available anti-HCV agents other than pegIFN or RBV (including previous exposure to paritaprevir, ombitasvir, or dasabuvir), or receipt of any investigational product within 6 weeks prior to study drug administration. 5. History of solid organ transplant. 6. Screening laboratory analysis that shows abnormal results
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis c for Part A Subjects must meet all of the following to be eligible for participation in this study. 1. Willing and able to provide written informed consent. 2. Male or female, age ≥ 18 years. 3. HCV RNA ≥ 104 IU/mL at screening. 4. Confirmed chronic HCV infection as documented by either: a. a positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or 5. HCV genotype 4 at screening as determined by the Central Laboratory. Any non-definitive results will the subject from study participation. 6. The subject's medical records must be sufficient to categorize prior treatment history as one of the following: i) IFN-intolerant: subject had documented intolerance to IFN during prior IFN therapy of up to 12 weeks duration ii) Non-response: subject did not achieve undetectable HCV RNA levels on treatment iii) Relapse/Breakthrough: subject achieved undetectable HCV RNA levels during treatment or within 4 weeks after treatment and later showed detectable HCV RNA An Absence of cirrhosis is defined as any one of the following Liver biopsy within 2 years of Screening showing absence of cirrhosis Fibroscan with a result of ≤ 12.5 kPa within 6 months of Baseline/Day1 FibroTest score of ≤ 0.48 AND APRI of ≤ 1 performed during Screening In the absence of a definitive diagnosis of the presence or absence of cirrhosis by the above a liver biopsy is required. Liver biopsy results supersede the results obtained by Fibroscan or Fibro Test. 7. Body mass index (BMI) ≥ 18 kg/m2. 8. Screening ECG without clinically significant abnormalities. 9. Subjects must have the following laboratory parameters at screening ALT ≤ 10 x the upper limit of normal (ULN) AST ≤ 10 x ULN Hemoglobin ≥ 12 g/dL for male, ≥ 11 g/dL for female subjects Platelets > 50,000 cells/mm3 INR ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR Albumin ≥ 3 g/dL for Part A Subjects who meet any of the following are not to be enrolled in this study. 1. for treatment naïve subjects only: Prior exposure to IFN, RBV, or other approved or experimental direct-acting antiviral targeting the HCV. 2. for treatment-experienced subjects: prior exposure to a NS5a inhibitor, NS5b nucleotide inhibitor, or NS5b non-nucleotide inhibitor targeting the HCV 3. Pregnant or nursing female or male with pregnant female partner. 4. Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis). 5. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV). 6. Contraindication to RBV therapy e.g., history of clinically significant hemoglobinopathy (sickle cell disease, thalassemia). 7. History of malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screening); subjects under evaluation for malignancy are not eligible. 8. Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent > 10 mg/day). 9. Clinically-relevant drug or alcohol abuse within 12 months of screening. A positive drug screen will subjects unless it can be explained by a prescribed medication; the diagnosis and prescription should be approved by the investigator. 10. History of solid organ transplantation. 11. Current or prior history of clinical hepatic decompensation (eg, ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome). 12. History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol. 13. History of a gastrointestinal disorder (or post-operative condition) that could interfere with the absorption of the study drug. 14. History of significant pulmonary disease, significant cardiac disease or porphyria. 15. Excessive alcohol ingestion, defined as 3 glasses/day (1 glass is equivalent to 284 mL beer, 125 mL wine, or 25 mL distilled spirits) for females and 4 glasses/day for males. 16. History of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. 17. Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1. 18. Known hypersensitivity to RBV, the study investigational medicinal product, the metabolites, or formulation excipients for Part B Subjects who meet any of the following are not to be enrolled in this study. 1. For treatment naïve subjects only (Cohort 1): Prior exposure to IFN, RBV, or other approved or experimental direct-acting antiviral targeting the HCV. 2. Current or prior history of any of the following: A Clinical hepatic decompensation (ie, ascites, encephalopathy or variceal hemorrhage) B Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol, or, current evaluation for a potentially clinically significant illness (other than HCV) C Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug D Solid organ transplantation E Significant pulmonary disease, significant cardiac disease or porphyria F Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 6 months prior to Baseline/Day 1 or that has not required medication in the last 12 months may be enrolled. G Any malignancy within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.), or current evaluation for possible malignancy H Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy I Significant drug allergy (such as anaphylaxis or hepatotoxicity) 3. Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis) 4. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) 5. Use of any prohibited concomitant medications 6. Contraindication to RBV therapy, including significant history of clinically significant hemoglobinopathy (eg, sickle cell disease, thalassemia) 7. In the judgment of the investigatory, any clinically-relevant drug or alcohol abuse within 12 months of screening that may interfere with subject treatment, assessment of compliance with the protocol 8. Pregnant or nursing females or male with pregnant female partner 9. Known hypersensitivity to RBV, SOF, or formulation excipients
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-85.0, Portal Hypertension Cirrhosis Age 18-85 HCV infection (HCV-RNA positive) Compensated cirrhosis will be defined histologically and/or clinically (presence of compatible lab findings (platelet count ≤ 150,000, total bilirubin ≥ 2, serum albumin ≤ 3.5, INR ≥ 1.2) PLUS compatible physical exam features (cutaneous stigmata, gynecomastia in men, or splenomegaly) OR compatible radiological findings (nodular liver surface, splenomegaly, and/or collaterals). (The ultimate confirmation of the diagnosis of cirrhosis will be a baseline HVPG > 5 mmHg) Planned anti-HCV therapy in the next 3 months Any clinically-evident complication of cirrhosis that defines decompensation : jaundice, ascites, variceal hemorrhage, overt hepatic encephalopathy) Hepatocellular carcinoma Co-infection with HBV or HIV Ongoing alcohol abuse Occlusive portal thrombosis Presence of comorbid conditions conferring a life expectancy<1 year, history of allergy to iodides, pregnancy
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Chronic Hepatitis C Virus (HCV) Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean, and Taiwanese parentage. 2. Chronic HCV-infection prior to study enrollment. 3. Screening laboratory result indicating HCV genotype 1b-infection. 4. Compensated cirrhosis defined as a Child-Pugh Score of less than or equal to 6 at Screening. 5. Per local standard practice, documentation of cirrhosis by one of the following methods Diagnosis on previous liver biopsy or liver biopsy conducted during screening e.g., Metavir Score of > 3 (including 3/4 or 3 , Ishak score of > 4 or FibroScan score ≥ 14.6 kiloPascals (kPa) within 6 months of Screening or during the Screening Period HCV genotype performed during screening indicating unable to genotype or infection with any other HCV genotype. 2. Positive test result at Screening for Hepatitis B surface antigen (HBsAg), or hepatitis B virus (HBV) DNA > Lower Limit of Quantification (LLOQ) if HBsAg negative, or anti-Human Immunodeficiency virus antibody (HIV Ab). 3. Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inhibitors of CYP2C8 within 2 weeks or within 10 half-lives, whichever is longer, of the respective medication/supplement prior to study drug administration. 4. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding, or hepatic encephalopathy. 5. Serum Alpha-Fetoprotein (sAFP) > 100 ng/mL at Screening. 6. Confirmed presence of hepatocellular carcinoma (HCC) indicated on imaging techniques such as computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to Screening or on an ultrasound performed at Screening (a positive ultrasound result should be confirmed with CT scan or MRI.) 7. Any primary cause of liver disease other than chronic HCV-infection, including but not limited to the following Hemochromatosis Alpha-1 antitrypsin deficiency Wilson's disease Autoimmune hepatitis Alcoholic liver disease Drug-related liver disease Steatosis and steatohepatitis on a liver biopsy coincident with HCV-related changes would not be considered exclusionary unless the steatohepatitis is considered to be the primary cause of the liver disease. 8. Screening laboratory analyses showing abnormal kidney, hepatic, or hematologic function
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Chronic Delta Hepatitis Key 1. Male or female, 18 to 65 years of age, inclusive 2. Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV RNA by qPCR at study entry 3. Liver biopsy demonstrating evidence of chronic hepatitis 4. Willingness to practice appropriate contraception Key Previous use of lonafarnib 2. Co-infected with HIV or HCV 3. Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilbert's disease 4. Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy 5. Serum creatinine concentration ≥1.5 times upper limit of normal (ULN) 6. Evidence of another form of viral hepatitis or another form of liver disease 7. Evidence of hepatocellular carcinoma 8. Use of alpha interferon, either interferon alfa-2a or interferon alfa-2b, or pegylated interferon alfa-2a within 2 months before the start of screening 9. Concomitant use of any of the following: 1. Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19 2. Drugs known to prolong the PR or QT interval 3. Receipt of systemic immunosuppressive therapy within the 3 months before start of screening 4. Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation 5. Medications contraindicated in the prescribing information for ritonavir
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Chronic Hepatitis C Infection HBV Coinfection Hepatitis B Reactivation HCV RNA positive HBsAg positive with detectable or undetectable HBV DNA Receiving pan oral direct-acting anti-HCV regimen Pregnant or nursing female or male with pregnant female partner HIV infection Hematologic or biochemical parameters at Screening outside the protocol specified requirements Active or recent history (≤ 1 year) of drug or alcohol abuse History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Virus (HCV) Chronic hepatitis C virus (HCV) infection Non-cirrhotic subjects Screening laboratory results showing HCV Genotype 1a (HCV GT1a) infection HCV treatment-naïve or if treated previously, only with interferon (IFN) or pegylated interferon (pegINF) with or without ribavirin (RBV) Pregnant or breastfeeding women Positive for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) HCV genotype of any subtype other than GT1a or unable to subtype Prior or current use of any investigational or commercially available anti-HCV agents other than IFN, pegIFN or RBV. Subjects with previous participation in trials of investigational direct-acting antiviral agents (DAAs) may be enrolled if they can produce documentation that they received only placebo Current enrollment in another interventional clinical study or receipt of any investigational product within 6 weeks prior to study drug administration
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 20.0-65.0, Chronic Hepatitis C for Part A: To be eligible to participate in this study, subjects must meet all of the following at screening: 1. Male or female between 20 to 55 years of age inclusive 2. For females, not breast-feeding, not pregnant, post-menopausal for at least 2 years, surgically sterile, or willing to use a double barrier method [intrauterine device (IUD) plus condom, spermicidal gel plus condom] of contraception, or other effective contraceptive methods from screening until 30 days after the last dose of study drug 3. For males, willing to use a reliable form of contraception (use of a male condom with spermicide or a partner fulfilling the above criteria), or abstinence from screening until 30 days after the last dose of study drug 4. Body weight ≥ 50 kg inclusive and body mass index (BMI) in the range of 19.0 to 30.0 kg/m2, extremes included 5. Good physical and mental health conditions on the basis of medical history and vital signs performed at screening 6. Healthy on the basis of clinical laboratory tests performed at screening. If the results are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal not to be clinically significant. This determination must be recorded in the subject's source document and initialed by the investigator. This is not applicable to the laboratory abnormalities listed in the [using the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity criteria-see Section 13.3]. 7. Non-smoking for at least 3 months prior to screening, to be confirmed by a urine cotinine dipstick test 8. 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function Heart rate (HR) between 50 and 100 bpm QTcF interval ≤ 430 ms (male) or ≤ 450 ms (female) QRS interval lower than 120 ms PR interval ≤ 200 ms Willing to abstain from caffeine or xanthine-containing beverages and food, including coffee and tea, alcohol, grapefruit juice, and bitter oranges during the study period 10. Willing to sign an Informed Consent Form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study for Part A: Subjects must be excluded if they meet any of the following 1. Breast-feeding or pregnant female 2. History of heart arrhythmias (any clinically relevant) or having baseline prolongation of QTcF interval > 430 ms (male) or > 450 ms (female), history of risk factors for Torsade de Pointes syndrome (hypokalemia, family history of long QT syndrome), or a HR (supine pulse as obtained from vital signs) < 50 bpm or > 100 bpm 3. History or suspicion of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise subject's safety and/or compliance with the study procedures 4. Hepatitis A, B, or C infection (confirmed by hepatitis A antibody IgM, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) or HIV-1 or HIV-2 infection (confirmed by CLIA test) at study screening 5. Clinically relevant, currently active or underlying gastrointestinal, cardiovascular-, nervous system, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease 6. History of drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy witnessed in previous trials with investigational drugs 7. Any condition that, in the opinion of the investigator, would compromise the study or the well-being of the subject or prevent the subject from meeting or performing study requirements 8. Use of concomitant medication, including over-the-counter product, herbal medication and dietary supplement in a period of 14 days before the study 9. Donation of blood or plasma over 250 mL within 60 days preceding the study 10. Subjects with one or more of the following laboratory abnormalities at screening as defined by DMID Adult Toxicity Table Hemoglobin grade 1 or greater (≤ 10.5 gm/dL) Platelet count grade 1 or greater (< 100,000/mm3)
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C HIV Male and females ≥18 years Documented HIV infection Evidence of infection with hepatitis C virus (all genotypes): Positive anti-HCV antibody and HCV RNA Absence of advanced liver disease or clinical signs of extra-hepatic disease F0-F2 (< 9,5 kPa) established by transient elastography, and No clinical signs of extra-hepatic disease Not on HCV antiviral treatment Currently on/or history of hepatitis C treatment Patients with initial fibrosis stage ≥ F3 (≥ 9,5 kPA on transient elastography) Patients not able/willing to adhere to the consultation, laboratory and liver stiffness measurement testing schedule as proposed in this study
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Hepatitis C, Chronic Male and female patients with chronic hepatitis C and genotype 1 (1a or 1b) or genotype 4 Age between 18 and 70 years Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test Present with at least one elevated serum alanine-aminotransferase (ALT) level higher than normal in the last 6 months before therapy start including the screening period Positive HCV-RNA level in serum Laboratory parameters (within 35 days prior to study start): -Hepatitis A anti IgM negativity, HIV-Ab negativity, HBsAg negativity, Hemoglobin values > 12 g/dl in women or > 13 g/dl in men, Leukocyte count (WBC) > 3 000 /mcl, Platelets count > 100 000/mcl, Creatinine not 1.5 times higher than normal, normal TSH, normal uric acid with a maximum tolerance of 15 % in patients without history of gout Liver biopsy findings within 6 months prior to study therapy consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis. Biopsies older than 1 year are eligible only after direct communication with the principal investigator Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug. If there is no laboratory report existing, the physician should make an entry in the medical history that the pregnancy test was negative All fertile females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end. All fertile men with female partners must be using two forms of effective contraception during treatment and during the 7 months after treatment end Any IFN and / or Pegylated IFN and ribavirin therapy at any previous time Class B or C cirrhosis as coded by Child Pugh classification Women with ongoing pregnancy or breast feeding Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) 6 months prior to the first dose of study drug Any investigational drug 6 weeks prior to the first dose of study drug Drug addiction within 1 year prior to study start (patients participating in an official methadone program are eligible) Diabetes mellitus in patients receiving an insulin therapy Hemophiliac patients (due to the increased risk of requested liver biopsy) History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Virus Infection Chronic Hepatitis C Compensated Cirrhosis Screening laboratory result indicating hepatitis C virus (HCV) Genotype 1, 2, 4, 5 or 6 (GT1,2,4,5,6) infection Chronic HCV infection Subject must be HCV treatment-naïve or have failed prior HCV treatment Subject must have documented compensated cirrhosis and no current or past clinical evidence of decompensated liver disease Positive test result at screening for Hepatitis B surface antigen or anti-human immunodeficiency virus (anti-HIV) antibody HCV genotype performed during screening indicating co-infection with more than 1 HCV genotype Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-493/ABT-530
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 19.0-999.0, Chronic Liver Disease Acute Derangement of Liver Function Chronic liver disease: Chronic hepatitis B, Chronic hepatitis C, Alcoholic liver disease, Biopsy proven or clinically diagnosed liver cirrhosis, Other chronic liver diseases including non-alcoholic fatty liver disease, primary biliary cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, a-1 antitrypsin deficiency, and cryptogenic causes Acute deterioration of liver function: more than one of the below 1. development of new ascites within 4 weeks or re-emergence of ascites who have previous well controlled ascites (greater than or equal to grade 2 or 3; International ascites club criteria) 2. development of hepatic encephalopathy 3. development of gastrointestinal hemorrhage 4. development of jaundice (serum bilirubin greater than or equal to 3mg/dl) 5. development of bacterial infection spontaneous bacteremia: positive blood cultures without a source of infection spontaneous bacterial peritonitis: ascitic fluid polymorphonuclear cells >250/µL lower respiratory tract infections: new pulmonary infiltrate in the presence of: i) at least one respiratory symptom (cough, sputum production, dyspnea, pleuritic pain) with ii) at least one finding on auscultation (rales or crepitation) or one sign of infection (core body temperature >38_C or less than 36_C, shivering, or leukocyte count >10,000/mm3 or <4,000/mm3) in the absence of antibiotics Clostridium difficile Infection: diarrhea with a positive C. difficile assay bacterial entero-colitis: diarrhea or dysentery with a positive stool culture for Salmonella, Shigella, Yersinia, Campylobacter, or pathogenic E. coli soft-tissue/skin Infection: fever with cellulitis urinary tract infection (UTI): urine white blood cell >15/high-power field with either positive urine gram stain or culture intra-abdominal infections: diverticulitis, appendicitis, cholangitis, etc Patients who do not have chronic liver disease Patients who have hepatocellular carcinoma Patients who admitted for extrahepatic manifestations Patients who have HIV infection Patients who admitted for symptomatic control of chronic liver disease, other than acute deterioration of liver function
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-75.0, Hepatocellular Carcinoma Underwent open hepatic resection Diagnosis of HCC was confirmed by imageological examination with or without AFP HBsAg (+) Child-Pugh A liver function Anti-HCV(+) Diagnosis of HCC was not confirmed by histopathological examination of surgical samples after surgery
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-80.0, ESRD Hepatitis C Donor The donor candidate must be anti-HCV positive by ELISA and HCV RNA negative by PCR, with both tests repeated for confirmation, as per standard protocol The donor must be evaluated and cleared by Hepatology, which is currently the standard of care for HCV seropositive individuals The donor must meet for living kidney donation and be approved by the UF Health Shands Kidney Transplant Medical Review Board. Recipient The recipient may be HCV antibody negative or anti-HCV antibody positive but HCV RNA negative by PCR The recipient must meet the for kidney transplantation and be approved by the UF Health Kidney Transplant Program Medical Review Board
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hernia, Inguinal Hernia, Inguinal, Direct Hernia, Inguinal, Indirect all patients who have undergone inguinal hernia repair using either an open technique or a robotic-assisted (da Vinci®) approach Eligible subjects must have had their inguinal hernia repair completed according to the following timeframes for 1. Robotic-assisted (da Vinci®) hernia repair all consecutive robotic cases from the initiation of robotic -assisted inguinal hernia repair at each institution until 30 days prior to the date of study initiation (IRB approval and fully executed contract). 2. Open hernia repair all consecutive open hernia repair cases from the day prior to the 1st da Vinci® inguinal hernia repair until the number of open repair cases collected is equivalent to the number of da Vinci® cases entered, or the date 5 years pre-robotic initiation is reached Subjects who have undergone robotic-assisted or open inguinal hernia repair outside of required timeframe
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Cold Agglutinin Disease Autoimmune Hemolytic Anemia CAD diagnosis defined by the combination of - 1. Chronic hemolysis 2. Cold agglutinin titer 64 or higher 3. Positive direct antiglobulin test when performed with polyspecific antiserum, negative (or only weakly positive) with anti-IgG, and strongly positive with anti-C3d 2. The presence of a clonal B-cell lymphoproliferative disorder defined by - 1. Monoclonal band by serum electrophoresis with immunofixation, and/or 2. CD20 positive lymphocyte population with cellular kappa/lamda-ratio higher than 3.5 or less than 0.9, using flowcytometric immunophenotyping of bone marrow aspirates 3. Indication for therapy, i.e. significant anemia and/or considerable cold-induced circulatory symptoms 4. Written informed consent An aggressive lymphoma 2. Non-lymphatic malignant disease other than basal cell carcinoma of the skin. A history of probably cured cancer is not an criterion. 3. Known HIV infection 4. Acute or chronic hepatitis B or C 5. Liver failure or active parenchymal liver disease. Bilirubin levels higher than 51 mol/L (3.0 mg/dL) when due to hepatic impairment. Elevated serum bilirubin level due to hemolysis is not an criterion. 6. Pregnancy or breast-feeding 7. Patients of childbearing age who are not willing to use safe contraception during the entire study period and 6 months following its cessation 8. All contraindications to the study drugs will be regarded as 9. Age below 18 years 10. Inability to cooperate
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-85.0, Postoperative Pain ASA I-III BMI<40 non-anemic High risk grade hypertension, chronic renal failure, known allergy to local anesthetic or NSAIDs, chronic treatment with steroids, drugs dependency, history of diabetes mellitus, ulcer or chronic gastritis, infection on the puncture site, chronic obstructive pulmonary disease, neuropathy at the surgical level
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 10.0-70.0, Autoimmune Diseases Written informed consent 2. Autoimmune hepatitis(according to the defined by the international autoimmune hepatitis Group ,Hepatology, 2008;48:169-176) 3. Negative pregnancy test 4. Moderately active disease under standard treatment Hepatocellular carcinoma or other Malignancies 2. Pregnant or lactating women 3. Vital organs failure (Cardiac, Renal or Respiratory, et al) 4. Sepsis 5. Active thrombosis in the portal or hepatic veins 6. Concomitant psychiatric disease or any other chronic illness or drug-abuse that could interfere with the ability to comply with the protocol or to give informed consent 7. Surgery during the last 2 months or surgery planned during the study, 8. Participation in other biomedical research in the last 3 months or planned during the study
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, HIV-1 Infection HCV Infection Key Chronic genotype (GT) 1, HCV infected, male and non-pregnant/ non-lactating female individuals, without cirrhosis, treatment-naive or treatment-experienced with interferon (IFN) +/ ribavirin (RBV) +/ HCV protease inhibitor (PI) Compensated cirrhotic individuals must be HCV treatment-naive No prior treatments with NS5A and NS5B or any HCV direct acting antivirals, except boceprevir, telaprevir and simeprevir, in combination with IFN and RBV Currently on an ARV regimen (2 NRTI + a third agent) without change for 6 months prior to screening Documented plasma HIV-1 RNA levels < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 6 months preceding the screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values ("blips") of HIV-1 RNA ≥ 50 copies/mL followed by resuppression is allowed For individuals with 3 or more prior ARV regimens, a regimen history should be provided for approval by the Sponsor Note: Individuals that changed from TDF to TAF less than 6 months ago will be eligible as long as the TDF/ TAF change was the only change to the regimen
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Hepatitis C Virus Hepatitis C Virus Females were postmenopausal for at least 2 years; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Screening and agreed to practice 1 effective method of birth control from Screening through 30 days after stopping study drug. Sexually active males were surgically sterile or, if sexually active with a female partner of childbearing potential, agreed to practice 1 effective form of birth control from Screening through 30 days after stopping study drug Screening central laboratory result indicated HCV single genotype infection for the appropriate treatment arm, without co-infection of any other genotype Chronic HCV infection is defined as one of the following Positive for anti-HCV antibody (Ab) and/or HCV RNA at least 6 months before Screening A liver biopsy consistent with chronic HCV infection Agreed to voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study specific procedures Participants who were able to understand and adhere to the study visit schedule and all other protocol requirements Absence of hepatocellular carcinoma (HCC) as indicated by an ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI) Females who were pregnant or planned to become pregnant, or breastfeeding or males whose partner was pregnant or planning to become pregnant during the study Participants co-infected with hepatitis B virus or human immunodeficiency virus Use of contraindicated medications or supplements within 2 weeks or 10 half-lives (if known), whichever was longer, prior to the first dose of any study drug Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator Any cause of liver disease other than chronic HCV infection Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of decompensated liver disease Consideration by the investigator, for any reason, that the participant is an unsuitable candidate to receive ABT-493/ABT-530
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Hepatitis C, Chronic Caucasians, male or female aged between 18 and 70 years Indication: serological proof of a chronic hepatitis C infection with positive result of anti-Hepatitis C virus (HCV) test and detectable HCV Ribo Nucleic Acid (RNA) in serum Proven HCV genotype 1 by means of the reverse hybridization assays Proven histological infection activity within the liver with or without proven compensated cirrhosis within the last 24 months prior to start of the study (Child-Pugh degree A) Participants without previous anti-HCV therapy Known hypersensitivity to interferon or ribavirin or any of the other component parts Pregnant or nursing women, women with child bearing potential and without using a high effective method of contraception. The urine and serum pregnancy test at visit 0 in fertile participants or cohabitants of participants must show a negative result Male partners of pregnant women Infection with HCV genotype 2, 3, 4, 5, or 6 Pretreatment with interferon and/or ribavirin Immunocompromised participants Treatment of systemic anti-neoplastic or immunomodulatoric medication (including supraphysiological doses of steroids or radiation therapy) within the last 6 months prior to the start of treatment and during the complete time interval of study treatment Chronic hepatitis due to hepatitis C virus (e.g. haemochromatosis, autoimmunohepatitis, metabolic or alcohol-related liver disease) Decompensated liver cirrhosis or liver disease Child-Pugh degree B or C or condition after decompensation Signs of a hepatocellular carcinoma within 2 months prior to randomization in case of a cirrhosis or a transition to cirrhosis
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C HCV RNA evidence of HCV infection Documented history of chronic HCV RNA infection with Genotype 1 Able to provide informed consent Available for ongoing follow-up if required <18 years old Evidence of decompensated liver disease HOMA IR< 2.0 HIV seropositivity Chronic HBV/HIV infection Use of immune suppressing medications Active malignancy
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-70.0, Hepatitis B Hepatitis, Viral Documented evidence of chronic HBV infection (eg, HBsAg positive for at least 6 months or HBV DNA positive for at least 6 months). In the absence of documented evidence of HBsAg or HBV DNA, the subject must be HBsAg positive, and anti-HBc (IgM) negative at Screening. 2. Not on any antiviral medications for at least 6 months. If a subject is HBeAg negative, they will be eligible if they have not received antiviral medications for at least 3 months. Antiviral medications lamivudine, telbivudine, adefovir, tenofovir, entecavir, IFN therapies of any type, and all other medications with potential antiviral activity. 3. HBV DNA > 2000 IU/mL for HBeAg-negative subjects and > 20000 IU/mL for HBeAg-positive subjects at Screening 4. ALT > ULN, but < 5 x the ULN and ≤ 200 U/L 5. Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma 6. Must be willing and able to comply with all study requirements 7. Negative urine or serum pregnancy test (for women of childbearing potential [WOCBP]) documented within the 24-hour period prior to the first dose of test drug. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion. All fertile males must also refrain from sperm donation while on IP and for 3 months after completion of IP. 8. Must have the ability to understand and sign a written ICF; consent must be obtained prior to initiation of study procedures for Extension Period: Subjects who meet all of the following may be eligible to be enrolled into the Extension Period: 1. Signed informed consent form 2. Subject was randomized in Part A or Part B Subjects who meet any of the following are not to be enrolled in this study: 1. Any prior liver biopsy evidence of metavir F3 or F4 disease 2. Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices 3. Evidence of cirrhosis as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals (kPa) or both a Fibrotest ≥ 0.65 and AST:platelet ratio index (APRI) ≥ 1.0 (subjects will not be excluded if only 1 of the Fibrotest or APRI result is higher than allowed) or have had evidence of Metavir F3-F4 on liver biopsy at any time. 4. Laboratory parameters not within defined thresholds: white blood cells (WBC) < 4000 cells/µL, (SI unit < 4.0 × 109/L), hemoglobin (HgB) < 12 g/dL (SI unit < 120 g/L) for females, < 13 g/dL (SI unit < 130 g/L) for males, platelets < 130,000 per µL, (SI unit < 130 × 109/L), albumin < 3.5 g/dL,(SI unit < 35 g/L), international normalized ratio (INR) > 1.5, total bilirubin > 1.2 mg/dL, (SI unit > 20.52 µmol/L), or alpha-fetoprotein (AFP) > 50 ng/mL (SI unit > 180.25 nmol/L). Subjects with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. Subjects with an AFP > 50 ng/mL but ˂ 500 ng/mL can be included if computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months shows no evidence of hepatocellular carcinoma 5. Creatinine > 1.2 mg/dL, (SI unit > 106.08 µmol/L), creatinine clearance < 50 mL/min, (SI unit < 0.83 L/s/m2) 6. Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus 7. Evidence or history of hepatocellular carcinoma 8. Malignancy within 5 years prior to Screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible. 9. Significant cardiovascular, pulmonary, or neurological disease 10. Received solid organ or bone marrow transplant 11. Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN) 12. Subjects currently taking medication(s) that are transported through organic anion transporting polypeptide 1 (OATP1) including, but not limited to, atazanavir, rifampin, cyclosporine, eltrombopag, gemfibrozil, lopinavir/ritonavir, and saquinavir 13. Use of another investigational agent within 3 months of Screening 14. Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance 15. Females who are pregnant or may wish to become pregnant during the study 16. If the Investigator believes the prospective subject will not be able to comply with the requirements of the protocol and complete the study 17. Any medical condition, in the opinion of the Investigator, that could interfere with evaluation of the study objectives or safety of the subjects for Extension Period Subjects who meet any of the following are not to be enrolled into the Extension Period: 1. Any condition, comorbidity, or laboratory abnormality that, based on the package insert of tenofovir or in the opinion of the Investigator, excludes the subject 2. Subjects who were withdrawn from Part A or Part B due to an AE or serious adverse event (SAE) related to the use of tenofovir 3. Participation in any other interventional study 4. Subject fully terminated from Part A or Part B
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Chronic hepatitis C defined as detectable HCV RNA for more than 6 months Age > 18 years old No current HCV antiviral treatment No medications for dyslipidemia in the preceding 2 months Listed in the national waiting list for liver transplant with an estimated time to transplantation of 3 months or less, either for complications of cirrhosis or for hepatocellular carcinoma No abdominal surgery that could alter biliary or intestinal anatomy HCV RNA level > 10.000 IU/mL No evidence of sitosterolemia Negative pregnancy test in urine (for females) Signed informed consent document Hepatitis B or HIV co-infection
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Hepatitis Hepatitis C Infection PRE-REGISTRATION Presence of active, chronic HCV infection confirmed by positive HCV RNA Willingness to use adequate contraception to avoid pregnancy or impregnation for the duration of study participation; Note The effects of INO-8000 with or without INO-9012 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation For men and women who are not postmenopausal (i.e., >= 12 months of non-therapy-induced amenorrhea, confirmed by follicle stimulating hormone [FSH], if not on hormone replacement) or surgically sterile (vasectomy in males or absence of ovaries and/or uterus in females), agreement to remain abstinent or use highly effective or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and at least through week 12 after last dose Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception Examples of contraceptive methods with an expected failure rate of < 1% per year male sterilization and hormonal implants; alternatively, proper use of combined oral or injected hormonal contraceptives and certain intrauterine devices or two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year (barrier methods must always be supplemented with the use of a spermicide) Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately Should a female partner of a male study participant become pregnant while the male participant is on study, the male participant should inform his study physician immediately Willingness to avoid excessive use of alcohol during the study; note: excessive use is defined as drinking >= 8 alcoholic drinks per week on average PRE-REGISTRATION Failure of previous HCV therapies Human immunodeficiency virus (HIV) infection Any previous treatment for HCV =< 6 months prior to registration Other uncontrolled immune-compromising illness Autoimmune disorders, transplant recipients, other immunosuppression including any concurrent condition requiring the use of immunosuppressive/ immunomodulating agents; Exception: eye drop-containing and infrequent inhaled corticosteroids are permissible; topical corticosteroids are permissible at locations other than the administration site (upper arm); Note: All systemic corticosteroids must be discontinued at least 4 weeks prior to randomization; inhaled corticosteroids must be discontinued >= 48 hours prior to randomization and courses of more than 2 weeks are not permissible within 4 weeks of randomization Ongoing hepatitis B virus (HBV) infection Documented evidence of fibrosis or cirrhosis (Metavir 2, 3, and 4) and subjects with significant extrahepatic manifestations of hepatitis C (such as cryoglobulinemia with symptoms or evidence of end-organ manifestations, renal disease, type 2 diabetes, or porphyria cutanea tarda Other known causes of significant liver disease including chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency Active malignancy; exception: non-melanoma skin cancers cancer(s) for which diagnosis and treatment was completed >= 3 years prior to pre-registration
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Virus Infection Key History of chronic HCV infection (≥ 6 months) HCV genotype 1, 2, 3, 4, 5, 6, or indeterminate Liver transplant ≥ 3 months prior to screening Male and nonpregnant/ non-lactating female individuals without cirrhosis or with compensated cirrhosis Key History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol Co-infection with HIV or hepatitis B virus Known hypersensitivity to study medication Use of any prohibited concomitant medications as within with window before the Day 1 visit De novo or recurrent hepatocellular carcinoma posttransplant NOTE: Other protocol defined Inclusion/
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-100.0, Hepatitis B Hepatitis C Patients attending The Royal London Hospital with cirrhosis (defined as fibroscan score >11.5 OR aspartate aminotransferase (AST) to platelet ratio index (APRI) score >2 OR liver biopsy or imaging report of cirrhosis) who are planning to commence antiviral therapy for either chronic hepatitis B or chronic hepatitis C Patients attending The Royal London Hospital with cirrhosis (defined as above) due to chronic hepatitis C infection who have undergone successful antiviral therapy in the past Patients attending The Royal London Hospital with cirrhosis (defined as above) due to chronic hepatitis B infection who are taking antiviral medication Age 18 or above Willing and able to provide Informed consent Any not met Pregnancy or breast feeding Known allergy to ICG
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Hernia, Inguinal Unilateral inguinal hernia Contralateral hernia repair history Recurrent inguinal hernia Incarceration or strangulation Bilateral inguinal hernia Severe congestive heart failure Severe hypertension Rheumatoid arthritis Systemic or neurologic diseases altering lower extremity functions
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 21.0-999.0, Hernia, Inguinal 21 years or older 2. No prior open abdominal surgery at or below the umbilicus 3. Primary or recurrent unilateral inguinal hernia repair 4. No previous preperitoneal mesh placement 5. BMI less than or equal to 40kg/m2 Need for an open inguinal hernia repair 2. Patients presenting for evaluation of bilateral inguinal hernias 3. Patients requiring surgical repair of a strangulated inguinal hernia 4. Patients with liver disease defined by the presence of ascites 5. Patients with end-stage renal disease requiring dialysis 6. Patients who are unable to give informed consent
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 20.0-999.0, Hepatitis C Virus Infection Key Genotype 1 or 2 HCV infection Chronic HCV infection (≥ 6 months prior to screening) documented by prior medical history or liver biopsy Previously treated with a DAA-containing regimen of at least 4 week duration Note: Other protocol defined Inclusion/
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Hepatitis C Cryoglobulinemia Subjects must meet all of the following to be eligible for participation in this study. 1. Willing and able to provide written informed consent 2. Male or female, age ≥18 years 3. HCV RNA ≥ 15 IU/mL at Screening 4. HCV genotype 1 5. Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy 6. Classification as treatment naïve or treatment experienced: 1. Treatment naïve is defined as having never been exposed to approved or experimental HCV-specific direct-acting antiviral agents or prior treatment of HCV with interferon or ribavirin or DAAs (except for SOF-containing regimens). 2. Treatment experienced is defined as prior treatment failure or relapse to a regimen containing interferon either with or without RBV or DAAs (except for SOF-containing regimens) that was completed at least 8 weeks prior to Baseline/Day 1. The subject's medical records must sufficient detail of prior virologic failure to allow for categorization of prior response, as either: 1. Non-Responder: Subject did not achieve undetectable HCV RNA levels while on treatment, or 2. Relapse/Breakthrough: Subject achieved undetectable HCV RNA levels during treatment or within 4 weeks of the end of treatment but did not achieve SVR. 7. Cirrhosis determination (approximately 20% of subjects may have cirrhosis) a. Cirrhosis is defined as any one of the following: i) Any previous liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥5) ii) FibroMeter® score >0.442 or an AST:platelet ratio index (APRI) >2 during Screening iii) Fibroscan with a result of >12.5 kPa at any time prior to or during screening. b. Absence of cirrhosis is defined as any one of the following: i) Liver biopsy within 2 years of Screening showing absence of cirrhosis ii) FibroMeter® score <0.442 or APRI ≤ 1 performed during Screening iii) Fibroscan with a result of ≤12.5 kPa within 6 months of Baseline/Day 1 Fibroscan results will supersede FibroMeter® /APRI; liver biopsy results will supersede Fibrotest® /APRI or Fibroscan results and be considered definitive. 8. Liver imaging (ultrasound, CT scan or MRI) within 6 months of screening is required in patients with cirrhosis to hepatocellular carcinoma (HCC) 9. Presence of MC vasculitis (please see on the note below). 10. Null or partial response to previous therapies for MC, including corticosteroids, cytotoxic agents (cyclophosphamide, azathioprine), hydroxychloroquine, methotrexate, mono or combination therapy with IFNα/PEG-IFN and ribavirin, and/or CD20 depletion with Rituximab. a. Patients can be on ongoing treatment with one of the drugs described above at unless there is significant DDI. 11. Subjects has the following laboratory parameters at screening: 1. ALT <10 x the upper limit of normal (ULN) 2. AST <10 x ULN 3. Adequate bone marrow function as indicated hematologic parameters listed below and/or bone marrow cellularity >60-70% average for age. i. WBC >1500 /uL ii.Platelets > 50,000/uL d) Direct bilirubin >2 x ULN e) INR >1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR 12. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Baseline/Day 1 prior to treatment. 13. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. 14. Lactating females must agree to discontinue nursing before the study drug is administered. 15. Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator. 16. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments. Note: Definition of Mixed Cryoglobulinemia (patients must meet one of the five overlapping syndromes listed below and the presence of cold-precipitable immune complexes in blood on two different occasions Clinical evidence of cryoglobulinemia, overlapping syndromes: 1. Cutaneous vasculitis (Raynaud's phenomenon, purpura, skin ulcers, livedo, acrocyanosis) 2. Glomerulonephritis (hypertension, hematuria, nephrotic syndrome) 3. Arthropathy (arthralgias, arthritis) 4. Neuropathy (peripheral and/or central nervous system, distal sensorimotor, mononeuritis multiplex) 5. Sicca syndrome (xerostomia, xerophthalmia) Other factors that will be assessed / recorded in patients with MC will be: 1. Associated laboratory abnormalities including Positive HCV serology (recombinant immunoblot assay), viral nucleic acid quantitation diagnostic for HCV infection, and reflex genotyping Evidence of glomerulonephritis, including an active urinary sediment, hypoalbuminemia (albumin <3gm/dL) and/or significant proteinuria (>300mg/day) Abnormal nerve conduction testing. 2. Pathologic evidence of cryoglobulinemia including Leukocytoclastic vasculitis Membranoproliferative glomerulonephritis Vasculopathy and/or mononuclear cell infiltrates on sural nerve biopsy Lip biopsy suggestive for Sjogren's syndrome. 3. Laboratory evidence of cryoglobulinemia including
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2
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 0.0-999.0, Spinal Muscular Atrophy For affected subjects: genetic diagnosis of SMA For unaffected family members: parent or sibling of any age (without genetic diagnosis of SMA) of affected subject enrolled in study None
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 20.0-70.0, Hepatitis Viruses Ages of 20 to 70 yeas Male or female Body mass index (BMI) 18.5-35.0 kg/m2 Chronic HCV infection, defined as patients who meet as least one of the two following 1. Anti-HCV antibody (Abbott HCV enzyme-linked immunosorbent assay [EIA] 2.0, Abbott Laboratories, Abbott Park, Illinois, USA) or HCV RNA > 1,000 IU/mL for at least 6 months before screening 2. Positive HCV RNA > 1,0000 IU/mL (Cobas TaqMan HCV Test v2.0, Roche Diagnostics Gesellschaft mit beschränkter Haftung [GmbH], Mannheim, Germany, low limit of quantification (LLOQ): 25 IU/mL) at the time of screening with a liver biopsy consistent with chronic HCV infection HCV GT-1b infection (Abbott RealTime HCV genotyping II, Abbott Molecular Inc. Illinois, USA) Treatment-naïve or treatment-experienced (including patients who relapsed, who had virological breakthrough, or who were null-responsive to IFN-based therapies) HCV RNA > 10,000 IU/mL at screening Absence of cirrhosis with documented results of one of the following 1. Liver biopsy within 24 months prior to or during screening demonstration the absence of cirrhosis, e.g. score ≤ 3 or Ishak score ≤ 4. 2. A screening transient elastography (Fibroscan) result of < 12.5 kilopascal (kPa) 3. A screening Fibrosis Index Based on 4 markers (FIB-4) of ≤ 1.45 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) of ≤ 2 4. Subjects with non-qualifying FIB-4/APRI or Fibroscan result may only be enrolled if they have a qualifying liver biopsy within 24 months prior to or during screening Estimated glomerular filtration (eGFR) rate < 15 mL/min/1.73m2 as assessed by modified of diet in renal disease (MDRD) equation, and receiving regular hemodialysis HCV infection other than HCV GT-1b Hepatitis B virus (HBV) or HIV co-infection Presence of cirrhosis (Child-Puge class A, B or C) Any primary cause of liver disease other than chronic HCV infection, including but not limited to the following 1. Hemochromatosis 2. Alfa-1 antitrypsin deficiency 3. Wilson's disease 4. Autoimmune hepatitis 5. Alcoholic liver disease 6. Drug-induced hepatitis Screening laboratory analyses showing any of the following results 1. Hemoglobin (Hb) level < 10 g/dL 2. Absolute neutrophil count (ANC) < 1,500 cells/μL 3. Platelet count < 60,000 cells/mm3 4. International normalized ratio (INR) > 2.0 5. Albumin (Alb) < 2.8 g/dL 6. Bilirubin (Bil) > 3.0 mg/dL 7. Alanine aminotransferase (ALT) > 5X upper limit of normal (ULN) 8. Aspartate aminotransferase (AST) > 5X upper limit of normal (ULN) 9. Serum alfa-fetoprotein (AFP) > 100 ng/mL Presence of hepatocellular carcinoma (HCC) on imaging studies such as computed tomography (CT) scan or magnetic resonance imaging (MRI) History of malignancy (except cutaneous melanoma) within 5 years at the screening Organ transplantation other than cornea and hair (prior renal transplantation with graft failure not included) Prior exposure to investigational agents for HCV (direct acting antiviral agents, host-targeting agents, or therapeutic vaccines) Pregnancy
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 20.0-70.0, Hepatitis, Autoimmune Patients aged 20-70 years Diagnosed with AIH or primary biliary cirrhosis-autoimmune hepatitis overlap syndrome based on liver biopsy results and without indication of immunosuppressive therapy High levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST)(1-3 X ULN) High levels of IgG(1-1.5 X ULN) Liver biopsy showed mild lymphocytic piecemeal necrosis (interface hepatitis) Agreed to participate in the trial, and assigned informed consent The presence of hepatitis A, B, C, D, or E virus infection Patients with presence of liver cirrhosis or portal hypertension Patients with presence of fulminant liver failure Primary sclerosing cholangitis, non-alcoholic steatohepatitis, drug induced liver disease or Wilson disease confirmed by liver biopsy Pregnant and breeding women Severe disorders of other vital organs, such as severe heart failure, cancer Parenteral administration of blood or blood products within 6 months before screening Recent treatment with drugs having known liver toxicity Taken part in other clinic trials within 6 months before screening
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 1.0-31.0, B Acute Lymphoblastic Leukemia Central Nervous System Leukemia Ph-Like Acute Lymphoblastic Leukemia Testicular Leukemia Patients must be enrolled on APEC14B1 and consented to Screening on the Part A consent form prior to enrollment on AALL1131 White Blood Cell Count (WBC) Age 1-9.99 years: WBC >= 50 000/uL Age 10-30.99 years: Any WBC Age 1-30.99 years: Any WBC with Testicular leukemia CNS leukemia (CNS3) Steroid pretreatment Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131 With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131 Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction DS HR B-ALL patients with Induction failure or BCR-ABL1 Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs Lactating females are not eligible unless they have agreed not to breastfeed their infant Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Chronic Viral Hepatitis B With Delta-agent Signed Informed Consent form. 2. Males and females 18 to 65 years of age (inclusively). 3. Patients with chronic hepatitis B (HBeAg-positive or negative) and HBsAg-positive for at least 6 months prior to Screening. 4. Positive for anti-HDV antibodies for at least 6 months prior to Screening. 5. HDV RNA-positive at Screening. 6. ALT ≥ 1 x ULN and < 10 x ULN. 7. The patient agreed to use adequate method of contraception during the study, starting from the time of Informed Consent signing and until completion of the Follow-up Period Intolerance or hypersensitivity to the active ingredient or other components of the study drug Myrcludex B. 2. Intolerance or hypersensitivity to interferons alfa, genetically engineered E.coli medications, polyethylene glycol or other components of peginterferon alfa-2a. 3. Previous treatment with Myrcludex B (patients with previous exposure to interferon are eligible). 4. Therapy with antiviral drugs for chronic viral hepatitis B with delta-agent over the previous 6 months. 5. Therapy with anti-tumour agents (including radiotherapy) or immunomodulatory medications (including systemic glucocorticoids) over the previous 6 months. 6. The following laboratory test results at Screening: 1. Hemoglobin < 100 g/L 2. Leucocytes < 3000/µL 3. Neutrophils < 1500/µL 4. Platelets < 90000/µL 5. Serum creatinine >1.5 x ULN. 7. Total bilirubin > 34.2 µM/L. Patients with higher total bilirubin may be enrolled upon consultation with the study Medical Monitor, if there is clear evidence that the elevated bilirubin is caused by Gilbert's syndrome. 8. Current or previous decompensated liver disease, including coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminaemia, ascites, and oesophageal varices haemorrhage; Child-Pugh score of B/C or ≥6 points. 9. HCV or HIV coinfection (patients with anti-HCV antibodies and no HCV RNA at Screening are eligible). 10. Hepatocellular carcinoma. 11. Signs of drug or alcohol-induced liver disease or any other medical conditions associated with chronic liver disease (e.g. autoimmune hepatitis, hemochromatosis, thalassaemia, alcoholic hepatitis, toxic liver disease). 12. Contraindications for liver biopsy. 13. Concurrent malignancy (current diagnosed or suspected malignancy; risk of a previous malignancy recurrence). 14. Severe decompensated cardiovascular diseases, including unstable and poorly controlled conditions, over 6 months before Screening. 15. History of poorly controlled thyroid conditions or clinically significant signs of thyroid dysfunction at Screening. 16. Previous or current severe renal failure or significant renal dysfunction at Screening. 17. Previous or current chronic pulmonary disease with respiratory distortion at Screening. 18. Previous or current severe retinopathy, significant ophthalmology disorders associated with diabetes mellitus or hypertension. 19. Previous or current severe psychiatric disorders at Screening (e.g. severe depressions, suicidal attempts, severe neuroses or cognitive disorders). 20. Previous or current endocrine disorders (hypoglycaemia, hyperglycaemia, diabetes mellitus) that are not adequately controlled at Screening. 21. History of visceral organ transplantation. 22. Signs of drug and/or alcohol dependence (80 g of alcohol/day for men and 40 g of alcohol/day for women) within 1 year before Screening. 23. History of immune disorders (e.g. idiopathic thrombocytopenic purpura, lupus erythematosus, sclerodermia, severe psoriasis, rheumatoid arthritis). 24. Need for concomitant use of glucocorticoids or myelotoxic agents. 25. Participation in another clinical study within 30 days prior to enrollment into this study. 26. Pregnant or breast-feeding females. 27. Any other condition that, in the opinion of Investigator, precludes the patient from taking part in this study
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C HIV ≥18 years of age Patients with early chronic hepatitis C (Genotype 1 or 4) which is defined as chronic hepatitis C with known episode of AHC within the last 4 years including those who failed to PEG/RBV or those who never received therapy for AHC. AHC infection is diagnosed on the basis of documented HCV-RNA positivity (> 10.000 IU/mL) and anti-HCV seroconversion No history of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs/symptoms of advanced liver disease Have liver disease staging assessment as follows: Fibroscan performed within 3 previous months of Day 1 of this study showing result <8 kPa Be HIV-1 infected, documented by any licensed rapid HIV test and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load Be on stable HIV Antiretroviral Therapy (ART) for at least 8 weeks prior to study entry using a dual NRTI backbone of tenofovir or abacavir < 18 years of age Patients with chronic hepatitis C genotypes other than 1 or 4 History of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs/symptoms of advanced liver disease Have liver disease staging assessment as follows: Fibroscan performed within 3 previous months of Day 1 of this study showing result > 8kPa Not be HIV-1 infected, documented by any licensed rapid HIV test and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load Due to known or suspected drug-drug interactions, for the purpose of this study, the use of Non Nucleoside Reverse Transcriptase Inhibitors, Inhibitors or Protease Inhibitors against HIV will be not allow
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 22.0-60.0, Hepatitis B Vaccines for HCV group were as follows: (1) aged ≥ 22 years and Han nationality; (2) no history of hepatitis B vaccination; (3) not-in-treatment patients with anti-HCV and HCV RNA positive; (4) diagnosis of chronic hepatitis C on the basis of self-reported history of HCV infection (more than 6 months) and screening tests for inclusion; (5) negative for HBsAg, anti-HBs, hepatitis B e antigen (HBeAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc). for healthy control group were as follows: (1) aged ≥ 22 years and Han nationality; (2) no history of hepatitis B vaccination; (3) negative for anti-HCV and HCV RNA; (4) negative for HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc; (5) no self-reported acute and chronic diseases (1) allergy to any vaccine component; (2) pregnancy or lactation; (3) axillary temperature ≥38℃ in the past three days, acute disease in the past seven days or vaccination history of any vaccine in the past four weeks; (4) suffering from diseases that may influence immune function, such as severe cirrhosis with Child-Pugh score >5, renal failure, bleeding diathesis, malignant tumor and HIV infection; (5) have received or being taking antiviral treatment; (6) chronic liver diseases except causing by HCV
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Chronic HIV Infections Documented HIV-1 infection Currently receiving cART and having received cART for a minimum of 24 months, HIV-1 plasma RNA <20 copies/mL for at least 1.5 year (excluding viral load blips) CD4 T cell count >350 cells/mm3 Able, willing to give written informed consent and to adhere to therapy and to comply with time requirements for study visits and evaluations Adequate vascular access for leukapheresis Acute HIV-1 infection Received blood transfusions or hematopoetic growth factors within 3 months receipt of compounds with HDAC inhibitor-like activity, such as valproic acid within the last 1 month. Potential participants may enroll after a 30-day washout period Any significant acute medical illness in the past 8 weeks Any evidence of an active AIDS-defining opportunistic infection Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood Patient has the following laboratory values within 3 weeks before starting the investigational drug 1. Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN) 2. Serum total bilirubin ≥1.5 ULN 3. Serum creatinine levels ≥1.5 x ULN, or calculated creatinine clearance ≤60 ml/min 4. Platelet count ≤100 x109/L 5. Absolute neutrophil count ≤1.5x109/L 6. Serum potassium, magnesium, phosphorus outside normal limits 7. Total calcium (corrected for serum albumin) or ionized calcium ≤lower normal limits A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure) History of malignancy or transplantation, including skin cancers or Kaposi sarcoma History of diabetes mellitus Known hypersensitivity to the components of chidamide or its analogues
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-80.0, Autoimmune Hepatitis Between ages 18-80 years Diagnosis of Autoimmune Hepatitis Type I Medical Hospitalization in the last 30 days New immunosuppression agent started <6 weeks prior to study Patients with concurrent viral hepatitis and/or alcoholic liver disease Patients with decompensated cirrhosis (defined as ascites, encephalopathy, variceal hemorrhage) Patients with hepatocellular carcinoma Patients post-liver transplantation Psychological Any psychotic disorder or current psychiatric symptoms Attitudinal Inability to commit to program schedule and attendance of classes Physical Inability to physically attend classes; disability or physical impairment not included as an
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-60.0, Hepatitis B, Chronic Part 1 Healthy Volunteers only Absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead Electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis A Body Mass Index (BMI) between 18 to 30 kilograms per square meter (kg/m^2) inclusive Female participants must be either surgically sterile or post-menopausal for at least one year For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm Part 2 Chronic HBV-infected participants only A BMI between 18 to 30 kg/m^2 inclusive Chronic Hepatitis B infection, defined as positive test for Hepatitis B surface antigen (HBsAg) for more than 6 months prior to randomization HBV DNA at screening greater than or equal to (>/=) 2 × 10^4 international units per milliliter (IU/mL) for Hepatitis B e antigen (HBeAg) positive participants, or >/=2 × 10^3 IU/mL for HBeAg-negative participants Part 1 Healthy Volunteers only History or symptoms of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis History of Gilbert's syndrome Participants who have had significant acute infection, e.g., influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks of dose administration Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies Any clinically significant concomitant diseases or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study Positive test at screening of any of the following: Hepatitis A (HAV IgM Ab), Hepatitis B (HBsAg), Hepatitis C (HCV RNA or HCV Ab) or human immunodeficiency virus (HIV Ab) Acute narrow-angle glaucoma (for MAD-midazolam cohorts) Part 2 Chronic HBV-infected participants only
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 20.0-999.0, Hepatocellular Carcinoma Anti-HCV positive and HBsAg-negative HCV genotype 1 or 2 infection, mixed infection GT 1 & 2 is allowed HCV RNA ≥ 10,000 IU/ml at the time of screening Age > 20 y/o BCLC stage 0 or A HCC confirmed by pathology and receiving the first time of curative treatment No recurrence of HCC confirmed by contrast-enhanced image studies (CT or MRI) within 3 months post the curative treatment Performance status Eastern Cooperative Oncology Group (ECOG) 0-1 Child-Pugh score ≤7 HBV, or HIV coinfection Co-existing other malignancy Intolerance to ribavirin Marked decompensated liver cirrhosis (CTP score>7) Uremia or renal impaired patients (eGFR<30)
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Chronic Delta Hepatitis Willing and able to comply with study procedures and provide written consent 2. 18 years old 3. Body mass index (BMI) of ≥ 18 kg/m2 and weighs ≥ 45 kg 4. CHD infection of at least 6 months' duration documented by a positive HDV antibody (Ab) test and HDV RNA ≥ 3 log10/mL by qPCR at study entry 5. Serum ALT > upper limit of the normal range (ULN) and < 10 × ULN 6. Liver biopsy within 12 months of Day 1 demonstrating evidence of chronic hepatitis. If no liver biopsy is available, the patient must be willing to consent to and have no contraindication to liver biopsy 7. ECGs demonstrating no acute ischemia or clinically significant abnormality and a QT interval corrected for heart rate (QTcF) < 450 ms for male patients and < 460 ms for female patients 8. Dilated retinal examination ≤ 1 year before screening: For patients with diabetes, hypertension, or other risk factors for retinal disease, performed by a licensed ocular specialist; for all other patients, a normal retinal examination as assessed by the investigator or a licensed ocular specialist 9. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and for 90 days after the last dose of study drug. Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal. For females: 2 of the following contraceptive methods, with at least 1 being a barrier method Hormonal contraceptives for ≥ 3 months before screening Intrauterine device (IUD) in place ≥ 3 months before screening Double-barrier methods (use of condom [male partner] with either diaphragm with spermicide or cervical cap with spermicide) from screening Surgical sterilization of the partner (vasectomy ≥ 1 month before screening) For males Surgical sterilization (vasectomy ≥ 1 month before screening) or Both of the following contraceptive methods from screening Consistently and correctly use a condom Partner must agree to use a hormonal contraceptive or a nonhormonal barrier method (IUD or diaphragm with spermicide or cervical cap with spermicide) General Exclusions 1. Participation in a clinical trial with, or use of, any investigational agent within 30 days before screening 2. Previous use of LNF. 3. Female patients who are pregnant or breastfeeding. Male patients must confirm that their female sexual partners are not pregnant. Female patients must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of any investigational agent). Exclusions Based on Disease 4. Current or previous history of decompensated liver disease (Child-Pugh Class B or C) 5. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). 6. Positive results for HIV or HCV Ab at screening. Patients with a positive HCV Ab at screening are allowed if they have completed a curative antiviral regimen and have documented undetectable HCV RNA for at least 3 months before screening and at screening. 7. Past history or current evidence of decompensated liver disease, defined as any of the following at screening Bilirubin level ≥ 2.5 mg/dL unless due to Gilbert's disease Serum albumin level < 3.0 g/dL International normalized ratio (INR) ≥ 1.5 8. Evidence of significant portal hypertension such as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg; current presence or history of esophageal or abdominal varices, variceal bleeding, or splenomegaly > 12 cm length on imaging 9. Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy 10. Current evidence or history of hepatic encephalopathy 11. Any of the following abnormal laboratory test results at screening Platelet count < 90,000 cells/mm3 White blood cell (WBC) count < 3,000 cells/mm3 Absolute neutrophil count (ANC) < 1,500 cells/mm3 Hemoglobin < 11 g/dL for women < 12 g/dL for men
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic HCV Infection Willing and able to provide written informed consent Male or female, age ≥ 18 years Body Mass Index (BMI) ≥ 18 kg/m2 HCV RNA ≥ 100 000 IU/mL at Screening Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy, only genotype 1b virus. (Positive for anti HCV antibody, HCV RNA, or an HCV genotype) Treatment-naïve with no prior exposure to any IFN, RBV, or approved or experimental HCV-specific DAA Non severe fibrosis (F<2) according to combination of this two tests : Fibroscan lower than 9.5kPa and Fibrotest lower than 0.59 Females of childbearing potential (as defined in protocol Appendix 4) must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to enrollment Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use 2 effective method(s) of contraception from at least two weeks prior to Day 1 through 14 days after the last dose of study drugs If acceptable by local regulatory agencies, methods of birth control allowed in the study are: intrauterine device (IUD), diaphragm with spermicide, hormonal contraceptives (e.g., birth control pills, transdermal patch, or injectables), contraceptive sponge, female condom, male condom with spermicide or vasectomy Is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures Current or prior history of any of the following Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy History of decompensation (e.g., clinical ascites, encephalopathy, and/or variceal hemorrhage) Solid organ transplantation (including hematopoietic stem cell transplants) other than kidney, cornea and hair Significant cardiac disease Unstable psychiatric condition including hospitalization, suicidal attempt, and/or a period of disability as a result of their psychiatric illness within 2 years prior to Screening Malignancy within the 5 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are not eligible
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Indolent B-cell Lymphomas Chronic Hepatitis B Lymphoma, Small Lymphocytic Mantle-Cell Lymphoma Waldenstrom's Macroglobulinaemia Follicular Lymphoma Adult patients between age of 18 years 2. Patients with indolent B-cell lymphoproliferative neoplasms that have relapsed or are refractory after at least one standard line of therapy that contains rituximab 3. Pathologically proven B-cell lymphoproliferative neoplasms including chronic lymphocytic leukaemia/small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone B-cell lymphoma, and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma). 4. Pathologically proven follicular lymphoma, with relapse or disease progression > 12 months after previous rituximab therapy. 5. Chronic HBV carriers (HBsAg+) 6. Occult HBV carriers (HBsAg-, anti-HBc+ and HBV DNA-) 7. Haematology values within the following limits: 1. Absolute neutrophil count (ANC)1000/mm3 independent of growth factor support 2. Platelets 100,000/mm3, or 50,000/mm3 if bone marrow is involved, and independent of transfusion support in either situation 8. Biochemical values within the following limits: 1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN) 2. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin 3. Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockcroft Gault) ≥ 40 mL/min/1.73m2 9. Competent to give an informed consent Concomitant chronic liver diseases not related to HBV 2. Known history of drug-induced liver injury, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver and portal hypertension 3. Known history of drug induced pneumonitis 4. Known history of inflammatory bowel disease 5. Woman who are pregnant or breast-feeding 6. Patients who do not consent to the use of effective contraception during the study 7. Active infections. 8. Evidence of ongoing active HBV hepatitis (ALT and/or AST > 2x upper limit of normal, and detectable HBV DNA) 9. Patients known to have histological transformation of CLL to an aggressive lymphoma 10. Vaccinated with live, attenuated vaccines within 4 weeks of enrolment
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 20.0-75.0, Hepatitis C, Chronic Chronic hepatitis C virus (HCV) infection All participants must have HCV genotype 1 or 2 infection, determined at screening HCV ribonucleic acid (RNA) plasma levels greater than or equal to (>=)10,000 international units per Milliliter (IU/mL), determined at screening Direct-acting antiviral (DAA)-naive participants, defined as not having received treatment with any approved or investigational DAA drug for chronic HCV infection; prior HCV therapy consisting of interferon (IFN, pegylated or nonpegylated) with or without ribavirin (RBV) is allowed Participants without cirrhosis or with compensated cirrhosis Infection with HCV genotype 4, 5, or 6 Co-infection with human immunodeficiency virus (HIV 1 or HIV 2 antibody positive) or hepatitis B virus (HBV) (hepatitis B surface antigen [HBsAg] positive) Prior treatment with any investigational or approved HCV DAA, either in combination with PegIFN or IFN free Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection (immunoglobulin M), drug or alcohol related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha 1 antitrypsin deficiency, primary biliary cirrhosis, or any other non-HCV liver disease that is considered clinically significant by the investigator Evidence of hepatic decompensation as assessed with Child-Pugh Class B or C or any of the following: history or current clinical evidence of ascites, bleeding varices, or hepatic encephalopathy
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 0.0-999.0, Hepatitis C HSCT recipients (allogeneic and autologous) with HCV infection Transplanted from anytime until May 2017, followed from December 2015 to November 2017
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Hepatitis B， Chronic =age at treatment<=65 years old Was diagnosed as chronic hepatitis B (ICD10:K73.901) and one of the following Chinese syndromes: hypochondriac pain (TCD:BNG010), jaundice(TCD:BNG020) or abdominal mass (TCD:BNG040) Combined with other virus hepatitis or alcoholic hepatitis Combined with autoimmune disease Combined with liver cancer or cirrhosis Combined with severe hepatitis with or without complications Combined with unstable cardio-cerebrovascular disease Combined with severe lung, kidney, endocrine system, nervous system and hematological system diseases Combined with Tuberculosis Chronic hepatitis patients with ongoing INF treatment Woman with pregnancy or breasting feeding Mental disorder and can not express self clearly
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic Hepatitis C Willing and able to provide written informed consent Chronic HCV infection (≥ 6 months) Positive HCV antibody Serum HCV RNA of ≥ 1 × 104 IU/mL Hepatitis C virus GT1 Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or host-targeting antivirals for HCV The liver biopsy methods in the protocol (non-cirrhosis is defined as: Metavir score ˂ 4), or as determined by Fibroscan defined as: ˂ 14.6 kPa. Patients who have not obtained a liver biopsy or Fibroscan in the last 1 years will have a study related Fibroscan performed in order to confirm the diagnosis Others as specified in the detailed protocol Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy Patients with a history of liver cell cancer, screening before or screening suspected hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules, or AFP > 50 ng/mL Positive hepatitis A antibody，positive hepatitis B surface antigen，syphilis antibody or HIV antibody at screening Others as specified in the detailed protocol
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-60.0, Hepatitis B Chronic Hepatitis B Viral Hepatitis B Main for All Subjects: 1. Subject has provided written consent. 2. In the investigator's opinion, the subject is able to understand and comply with protocol requirements, instructions, and study restrictions and is likely to complete the study as planned. 3. Subject is in good health as deemed by the investigator, based on the totality of findings following a medical evaluation, including medical history, physical examination, laboratory tests and ECG. 4. Male or female, 18-60 years of age. 5. Body mass index 18-30 kg/m2, inclusive. The minimum weight is 50 kg. 6. A female subject is eligible to participate in this study if she is of non-childbearing potential (defined as females with a documented tubal ligation, bilateral oophorectomy or hysterectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone level within the laboratory's reference range for postmenopausal females). A post-menopausal female receiving hormone replacement therapy who is willing to discontinue hormone therapy 28 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation. 7. If male, subject is surgically sterile or practicing required forms of birth control until 6 months after the last dose of the study drug(s). Males must agree to refrain from sperm donation from check-in through 6 months after the last dose of the study drug(s). 8. Subject has been a nonsmoker and has not used nicotine or nicotine-containing products for at least 6 months. 9. Subjects who participated in Part 1 and/or Part 2 may participate in subsequent Part(s) upon satisfactory completion of a posttreatment visit, 7 days (+2 days) following the subject's last dose, and provided they continue to meet all of the and none of the Main Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 to 10 years. 2. Subject has a history of any illness that, in the opinion of the investigator, would confound the objectives or results of the study or poses an additional risk to the subject by their participation in the study. 3. Subject has an estimated creatinine clearance of ≤80 mL/min based on the Cockcroft-Gault equation; An actual creatinine clearance, as determined by a 24-hour urine collection, may be used in place of, or in conjunction with, the Cockcroft-Gault equation; subjects who have an actual or estimated creatinine clearance within 10% of 80 mL/min may be enrolled in the study at the discretion of the investigator. 4. Pregnant or nursing (lactating) females, confirmed by a positive human chorionic gonadotropin laboratory test or females contemplating pregnancy. Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 6 months after their last dose of study drugs. 5. Clinically significant cardiovascular, respiratory, skeletal, renal, gastrointestinal, hematologic, hepatic, immunological, neurologic, endocrine, genitourinary abnormalities or disease or any other medical illness as determined by the investigator or Sponsor's Medical Monitor. 6. Subject has a history of malignancy except completely excised basal cell carcinoma or squamous cell carcinoma of the skin. 7. Subject lacks or has poor peripheral venous access. 8. Positive screening result for hepatitis B, hepatitis C and/or HIV serology. 9. Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the subject or prevent the subject from meeting the study requirements. 10. Clinically significant abnormal ECG findings. Particularly, a history or family history of prolonged QT syndrome (eg, torsade de pointes) or sudden cardiac death. 11. ECG with PR >200 ms, QRS >120 ms, QTcF >450 ms, as assessed by triplicate 12-lead ECG at the screening visit. 12. Subject has had major surgery, or clinically significant blood loss or elective blood donation of significant volume (ie, >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7 days of first dose of study drug. 13. Abnormal heart rate, respiratory rate, temperature or blood pressure values outside of the normal range (evaluated in a semi-recumbent or recumbent position after 5 minutes of rest). One repeat measurement after an additional 5 minutes of rest is permitted. 14. Evidence of active infection. 15. Unwilling to abstain from alcohol for at least 48 hours prior to the start of dosing through the study completion visit. 16. History of regular alcohol intake >7 units per week of alcohol for females and >14 units per week for males (one unit is defined as 10 g alcohol) within 3 months of the screening visit. 17. The subject has a positive screening or Day -1 drugs of abuse screen. 18. The use of concomitant medications, including prescription, over the counter medications, and herbal medications (such as St. John's Wort [Hypericum perforatum]) within 30 days prior to the first dose of study medication is excluded, unless approved by the Sponsor's Medical Monitor. Occasional use of ibuprofen/paracetamol/ acetaminophen is permitted. 19. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 90 days before the planned study drug. 20. Subject has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food. 21. Hypersensitivity to the active substances or to any of the excipients of AL-3778, entecavir or tenofovir disoproxil fumarate. 22. Subject has known allergy to heparin or history of heparin-induced thrombocytopenia. 23. Abnormal biochemistry or hematology laboratory results obtained at screening determined to be clinically significant by the Investigator. Screening ALT, AST, GGT, albumin, and total bilirubin must be within normal ranges. Creatine kinase >1.5 x ULN is exlusionary 24. Unwillingness or inability to comply with the study protocol for any other reason
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Chronic HIV Infection HIV-infected and receiving antiretroviral therapy (ART) Receiving care at Prince Cyril Zulu Clinic in Durban Stable on Current ART Regimen and due the 6 month follow-up visit post ART initiation Willing/able to provide written informed consent to participate in the stud Have significant signs/symptoms of illness that requires active medical care by a clinic doctor Does not plan to receive HIV care at the Prince Cyril Zulu Communicable Diseases Clinic for the following 12 months Currently pregnant
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Virus (HCV) Male or female (of non-childbearing potential or using allowed contraceptive methods) at least 18 years of age time of Screening Participant had a positive anti-hepatitis C virus (HCV) antibody (Ab) and plasma HCV ribonucleic acid (RNA) greater than or equal to 1000 IU/mL at the Screening Visit Participant had an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease (MDRD) method at Screening according to the following formula: eGFR (mL/min/1.73 m^2 ) = 175 × (Serum Creatinine) ^-1.154 × Age^-0.203 × (0.742 if female) × (1.212 if black), or were dialysis dependent. Subjects requiring dialysis had to have been receiving dialysis for at least 1 month prior to enrollment, and may have been on hemodialysis or peritoneal dialysis Cirrhotic participants only: absence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months prior to Screening or a negative ultrasound at Screening. Participants who had an ultrasound with results suspicious of HCC followed by a subsequent negative CT or MRI of the liver were eligible for the study Female participants who were pregnant, breastfeeding, or were considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug Current hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection on screening tests, defined as Positive test result at Screening for hepatitis B surface antigen (HBsAg), or HBV deoxyribonucleic acid (DNA) greater than lower limit of quantification (LLOQ) in participants with isolated positive hepatitis B core antibody (HBcAb), (i.e., negative HBsAg and Anti-HBsAg), or Positive anti-HIV antibody (Ab) Any current or historical clinical evidence of decompensated cirrhosis, including any current or past evidence of Child-Pugh B or C classification, hepatic encephalopathy or variceal bleeding; radiographic evidence of small ascites; or prior or current empiric use of lactulose/rifaximin for neurologic indications. Prophylactic use of beta blockers was not exclusionary Clinical history of acute renal failure in the 3 months prior to Screening History of severe, life-threatening, or other significant sensitivity to any excipients of the study drugs Clinically significant abnormalities or co-morbidities, or recent (within 6 months prior to study drug administration) alcohol or drug abuse that could preclude adherence to the protocol in the opinion of the investigator Receipt of any investigational or commercially available direct acting anti-HCV agents other than sofosbuvir
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Awaiting Organ Transplant Men and women who are age ≥ 18 years Active on either the cardiac or lung transplant waiting list Willing and able to provide written informed consent to receive organs from an increased risk donor with a known transmissible infection HIV antibody or HIV NAT positive Hepatitis B surface antigen or Hepatitis B NAT or viral load positive Evidence of cirrhosis or clinically significant liver disease
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 20.0-80.0, Hepatitis C Hepatitis C Relapse patients with diagnosis of chronic hepatitis C genotype 2 or 3 Patients with hepatitis genotype I and IV
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 0.0-999.0, Hepatitis B， Chronic Patients with chronic HBV infection (defined as HBsAg positive for at least 6 months) Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and/or hepatitis D virus (HDV) History of liver transplantation History of hepatocellular carcinoma (HCC)
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-999.0, Hepatitis C Virus (HCV) Infection Be a current resident of France Have HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening Have documented chronic HCV GT4 (with no evidence of non-typeable or mixed genotype) infection Have liver biopsy performed within 24 months of Day 1 of this study (if participant has cirrhosis, there is no time restriction on biopsy), or have FibroScan® performed within 12 months of Day 1 of this study with interpretable result in kilopascals (kPa) as follows: Fibrosis score of F0-F2, Fibrosis score of F3, or Cirrhosis (F4) Have a prior treatment history of either HCV TN or HCV TE with interferon (IFN) +/- ribavirin (RBV) +/ Sofosbuvir (SOF) (on-treatment failure, relapser, or other/intolerant) Females who are of reproductive potential must agree to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence from heterosexual activity OR (2) use (or have her partner use) acceptable contraception during heterosexual activity If Human Immunodeficiency Virus (HIV) co-infected, then have HIV-1 infection documented prior to screening Had prior treatment (defined as 1 dose or more) with direct-acting antiviral (DAA) therapy Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of active advanced liver disease Classified as Child-Pugh B or C or has a Child Pugh-Turcotte score (CPT) > 6 Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC Hepatitis B virus surface antigen (HBsAg) positive at screening. Participants who are HBsAg negative and hepatitis B core antibody (anti-HBc) positive at screening may be included Under evaluation for active or suspected malignancy, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study
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1
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 40.0-90.0, Osteoarthritis Patients undergoing primary total shoulder arthroplasty at Rush University Medical Center Patients with prior shoulder surgery of any kind Patients with a known infection or history of infection with clinical signs such as elevated erythrocyte sedimentation rate, C-reactive protein, positive culture aspiration Patients with a known allergy to doxycycline Patients with a known allergy to cefazolin or penicillin
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-65.0, Hepatitis B HBeAg negative Chronic HBV infection who are having HBV DNA-undetectable. ALT <40 IU/ml No Advanced fibrosis[LSM <14 KPa] TDF/ETV >1 year Clinical Relapse after stopping NA will be defined as HBV DNA>2000IU/ml and ALT > 80IU HBeAg+ CHB Pregnancy Cirrhosis on biopsy or LSM >14 Co-infection HIV/HCV/HDV Immunosuppressive therapy Renal failure S.Bilirubin>2mg/dl Patient having neutropenia
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-100.0, Ulcers, Leg Male or female over 18 years old who has provided his/her written informed consent 2. Patient who can be monitored by the same investigation team throughout the whole duration of the study 3. Patient who agrees to wear an effective venous compression system every day, associated with the trial dressing 4. Leg ulcer with an Ankle Brachial Pressure Index (ABPI) not less than 0.7 and not more than 1.3 5. Ulcer area between 3 and 20 cm2 6. Ulcer duration between 3 and 18 months, 7. Ulcer presenting a surface wound bed covered with 50% or more by granulation tissue 8. Moderately or heavily exudative ulcers A. Clinical infection on the wound bed
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-120.0, Hepatocellular Carcinoma (HCC) patients diagnosed with HCC Minors under the age of 18 Pregnant women People without primary liver cancer
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0
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A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.
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eligible ages (years): 18.0-99.0, HBV Fibrosis, Liver Cirrhosis, Liver Alcoholic Hepatitis Hepatocellular Carcinoma Hepatitis, Delta Age 18 years or older HBV-infected, defined as any single positive HBsAg assay Unable or unwilling to provide informed consent HIV-positive
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0
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