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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 Infection To be eligible for this trial, patients must have documentation of the following Male or female > 18 years old HCV genotype-1 infection Liver biopsy consistent with Chronic Hepatitis C (CHC) within the last 3 years No previous treatment with any anti-HCV therapy (approved or investigational) For women of childbearing potential, a negative urine pregnancy test result documented within 24 hours prior to the first dose of any study drug (BOC, PEG-INF alfa-2b, or ribavirin). Additionally, all female patients of childbearing potential and all males with female partners of childbearing potential must use two forms of effective contraception (combined) during study treatment and for 6 months after treatment Willingness to give written informed consent and to participate in and comply with requirements of the study Patients with any of the following will not be eligible for participation Infection with HCV other than genotype 1 History or other evidence of a medical condition associated with chronic liver disease other than CHC (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) History or other evidence of decompensated liver disease (e.g., coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, bleeding from esophageal varices) or a Child-Pugh score > 6 (see Appendix 1) Infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or HIV as demonstrated by a positive test at screening for anti-HAV immunoglobulin M (IgM) antibodies (Ab), hepatitis B surface antigen, anti-hepatitis B core protein IgM Ab, or anti-HIV antibodies History of having received IFN, PEG-IFN, ribavirin, viramidine, levovirin, or investigational HCV protease or polymerase inhibitors at any previous time, or any other systemic antiviral therapy with established or perceived activity against HCV within 3 months prior to enrollment Pregnant or breastfeeding Male partners of females who are pregnant or breastfeeding Hemoglobin concentration < 12 g/dL in females or < 13 g/dL in males or any patient with an increased risk for anemia (e.g., thalassemia, sickle cell anemia, spherocytosis, history of gastrointestinal bleeding) or for whom anemia would be medically problematic Absolute neutrophil count (ANC) < 1000 cells/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): 18.0-65.0, Hepatitis C Male and female participants between the ages of 18 and 65 years History of orthotopic liver transplantation less than 10 years before the Screening visit but no sooner than 6 months before Day 1 Taking a stable immunosuppressant regimen based on either tacrolimus or cyclosporine without substantial dose changes over the past 3 months Naive to pegylated interferon/ribavirin treatment or experienced with pegylated interferon/ribavirin prior to transplantation with relapse, partial, or null response Documented cirrhosis after liver transplantation Ascites or hepatic encephalopathy within 6 months before Screening Retransplantation for recurrent hepatitis C Treatment for hepatitis C post liver transplantation History within the past 3 months of: rejection within 3 months or greater than (>) 1 rejection within 12 months Current treatment with sirolimus or methylprednisolone. Low dose prednisone use (<5 milligram per day) is permitted History within 3 months of any bacterial infection requiring >1 week of intravenous antibiotics, cytomegalovirus viremia or cytomegalovirus infection with end-organ involvement, fungal disease (except cutaneous and mild oral thrush) History of post transplant lymphoproliferative disease Acceptable laboratory values at Screening as specified in the protocol Positive for human immunodeficiency virus 1/2 (HIV1/2) enzyme immunoassay (EIA) antibody screen or Hepatitis B deoxyribonucleic acid (DNA) or Hepatitis B surface antigen
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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 All adult patients (age 18 or older) being treated with antiviral HCV treatment regimens that contain telaprevir or boceprevir Inability to provide written informed consent Currently participating in another clinical trial of hepatitis C therapeutics. Studies comparing HCV RNA assays are not considered exclusionary
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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 Infections Hepatitis C (Groups A and B) Men and women 18 years of age or older Presence of chronic HCV infection, defined by presence of plasma or serum HCV RNA in a participant with HCV antibody for at least 180 days, two documented HCV RNA positive results greater than 180 days apart, or positive HCV RNA with biopsy demonstrating chronic hepatitis. More information on this criterion can be found in the protocol Serum or plasma HCV RNA level 10,000 IU/mL or greater obtained within 42 days prior to study entry Screening HCV genotype 1 performed within 6 months prior to study entry Liver biopsy or HCV FibroSURE™ test within 104 weeks prior to study entry with interpretation consistent with chronic HCV infection. If a liver biopsy HCV FibroSURE™ test had not been performed within 104 weeks prior to study entry, then either a biopsy or HCV FibroSURE™ test must have been obtained prior to enrollment. The cut-off value for the FibroSURE™ test was 0.74, where greater than 0.74 was interpreted as cirrhosis. More information on this criterion can be found in the protocol Alpha feto protein (AFP) levels less than 50. If 50 or greater, they must have had a liver imaging study (e.g., ultrasound, computed tomography [CT] scan, magnetic resonance imaging [MRI] showing no evidence of hepatocellular carcinoma HIV-1 infection. More information on this criterion can be found in the protocol Currently not on any antiretroviral therapy (ART) for at least 4 weeks immediately prior to entry or on stable ART for at least 8 weeks prior to study entry using a dual NRTI backbone PLUS one of the following: EFV, RAL, LPV/RTV 400/100 mg twice daily, ATV/RTV, DRV/RTV 600/100 mg twice daily. Breaks in therapy for a maximum of 14 days were allowed. Dose modifications or changes in drugs during the 8 weeks prior to study entry were permitted unless the change in drug was due to treatment failure. More information on this criterion can be found in the protocol CD4+ T-cell count greater than 200 cells/mm^3 obtained within 42 days prior to study entry (Groups A and B) Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation Evidence of decompensated liver disease manifested by the presence of or history of ascites, variceal bleeding, or hepatic encephalopathy. If hepatic cirrhosis was determined by liver biopsy (Stage 4 Metavir or Stage 5, 6 Ishak) or by imaging, then participants had to be no more than Child-Pugh Class A and have a Child-Pugh-Turcotte (CPT) score of 6 or less. More information on this criterion can be found in the protocol Other known causes of significant liver disease including chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency Infection with any HCV genotype other than genotype 1, or mixed genotype infection Uncontrolled or active depression or other psychiatric disorder such as untreated. Grade 3 psychiatric disorder or Grade 3 disorder not amenable to medical intervention that in the opinion of the site investigator might have precluded tolerability or safety of study requirements. Individuals with suicidal ideation or history of a suicidal attempt in the last 5 years prior to enrollment were excluded History of uncontrolled seizure disorders Serious illness including malignancy, active coronary artery disease within 24 weeks prior to study entry, or other chronic medical conditions that in the opinion of the site investigator may have precluded completion of the protocol Presence of active or acute AIDS-defining opportunistic infections within 12 weeks prior to study entry. More information on this criterion can be found in the protocol History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to hemolysis
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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, Genotype 1 Chronic Hepatitis C Participant has genotype 1 chronic hepatitis C with HCV RNA level >1000 IU/mL Participant is either treatment-naïve and did not receive any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C, or participant is treatment-experienced who did not achieve sustained virologic response (SVR) 24 weeks after at least 1 prior course of Peg-IFN/RBV therapy (null-responder, partial-responder or viral relapse) Participant must have documentation of liver biopsy or fibroscan within 2 years before the screening visit or agree to have a biopsy or fibroscan within the screening period unless histological cirrhosis was demonstrated by a biopsy or fibroscan > 2 years ago prior to screening A female participant of childbearing potential and a nonvasectomized male participant who has a female partner of childbearing potential must agree to the use of 2 effective methods of birth control from screening until 6 months (female participant ) or 7 months (male participant) after the last dose of RBV Prior non-responder that is classified as a viral breakthrough participant Participant is infected or co-infected with HCV of another genotype than genotype 1 Participant has history of decompensated liver disease or shows evidence of significant liver disease in addition to hepatitis C Participant has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection Participant has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma or hepatocellular carcinoma
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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 Have diagnosis of HIV-1 or HIV-2 infection, or HIV-1 and HIV-2 coinfection for more than 6 months before the screening visit Should have been on a stable permissible HAART regimen for more than 8 weeks before Day 1 without switches. OR Not on a HAART regimen and not expected to start HIV treatment during the study, ie, have CD4 count of ≥500 cells/mm3 and a HIV-1 and/or HIV-2 viral load ≤50,000 copies/mL at screening If on stable permissible HAART regimen, have CD4 count ≥200 cells/mm3 or ≥15% and HIV-1 and/or HIV-2 viral load <50 copies/mL for at least 6 months before starting treatment is recommended Have evidence of HCV infection genotype 1 (molecular assay) - Have a quantifiable plasma HCV RNA Is eligible for enrollment into an ongoing clinical study of telaprevir Is infected or coinfected with HCV of another genotype than genotype 1 Has a contraindication to the administration of Peg-IFN-alfa or RBV, or medical history or laboratory values that preclude treatment with Peg-IFN-alfa or RBV according to the respective local prescribing information Have any contraindication to the currently prescribed HAART regimen at screening. Note: Patients who have a contraindication to a nonprescribed permissible HAART medication are not excluded. - Positive human leukocyte antigen (HLA)-B5701 genotyping result at screening (or documented result prior to screening) if abacavir is a component of HAART
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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, Alcoholic Liver Disease Alcoholic Hepatitis Cancer Viral Hepatitis, other Hepatitis
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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 patients who need the of French Early Access Program for boceprevir and telaprevir or after the marketing authorization approval patients aged of 18 years or more with chronic hepatitis C relapsers or partial-responders or null-responders to treatment with PEG'IFN α2a or 2b associated or not with RBV chronic infection with genotype 1 HCV fibrosis Metavir score of 4 (cirrhosis) without decompensated liver disease naïve of direct anti-viral treatment without HIV or HBV co-infection signature of participation to the cohort
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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 C All chronically HCV-infected patients who fail peg-IFN and RBV therapy and are eligible for combined treatment with PI therapy will be enrolled. Briefly, this includes: 1. Male or female 2. Age 18 to 65 3. Chronic HCV infection evidenced by liver biopsy or persistent HCV viremia for >6 months 4. Treatment experienced and classified as non-responder or relapser to prior interferon-based therapy Treatment naïve chronically HCV-infected patients. 2. Patients with a history of inflammatory bowel diseases (IBD) or suspected IBD, autoimmune diseases, including rheumatoid arthritis, and any patients on systemic immunomodulators. 3. Pregnancy 4. HIV
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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 C, Chronic Chronic hepatitis C, diagnosed by positive anti-hepatitis C virus(HCV) antibodies and detected HCV ribonucleic acid(RNA) at screening in addition to: 1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or, 2. liver biopsy consistent with chronic HCV infection HCV infection of genotype 1 confirmed by genotypic testing at screening Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection Plasma HCV RNA = 100,000 IU/mL at screening Hepatitis C infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening Human immunodeficiency virus (HIV) co-infection Decompensated liver disease, or history of decompensated liver disease Body weight < 40 or > 125 kg at screening Hemoglobin <12.0g/dL for women and <13.0g/dL for men at screening White blood cell count <3000 cells/mm3 at screening Absolute neutrophil count < 1,500 cells/mm3 at screening Platelet count < 90,000 /mm3 at screening Serum creatinine > 1.5xUpper Limit of Normal range(ULN) or creatinine clearance =50 mL/min at screening
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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, HCV Coinfection HIV Infection HIV infection. 2. Infection with HCV genotype 4. 3. No prior treatment with any interferon or no response to a previous treatment with Peg-IFN plus RBV. The lack of response will both nonresponders, and those who showed relapse. 4. Stable antiretroviral therapy 24 weeks before starting the study drugs, with undetectable plasma HIV RNA during that period of time. 5. Commitment to use two non-hormonal contraception during the study and up to 24 weeks after treatment. 6. Acceptance to give written informed consent to participate in the trial Antiretroviral therapy including didanosine, stavudine, zidovudine and abacavir. 2. Decompensated cirrhosis. 3. Presence of other significant liver diseases, including chronic hepatitis or acute hepatitis B, acute hepatitis hepatitis A, hemochromatosis or deficiency of alpha-1 antitrypsin. 4. Pregnancy and lactation. 5. Men planning pregnancy with their partners during the study and up to 24 weeks after treatment. 6. Active or uncontrolled depression, other psychiatric illness, or disease during the previous year which may, in the investigator's opinion, prevent participation in the study. 7. Previous suicide attempt. 8. Active thyroid disease or poorly controlled with treatment. 9. Previous autoimmune diseases such as inflammatory bowel disease, psoriasis serious, or rheumatoid arthritis, which may be exacerbated by interferon. 10. Chemotherapy or immunomodulatory 24 weeks before starting the study. 11. Serious illness, including cancer or unstable coronary disease, 24 weeks before starting the study. 12. Any chronic disease which, in the opinion of the investigator, may prevent complete the study. 13. Presence of acute or active opportunistic infections 48 weeks before starting the study. 14. Evidence of hepatocellular carcinoma or alpha-fetoprotein levels ≥ 50 ng / ml, unless an imaging technique shows no evidence of liver tumor, all obtained 24 weeks before starting the study. 15. Hemoglobinopathy or other conditions that may facilitate hemolysis. 16. Solid organ or bone marrow transplant. 17. Known hypersensitivity to any of the drugs under study. 18. Active consumption of drugs or alcohol in the opinion of the investigator would interfere with participation in the study. The use of methadone or other opiate replacement therapy is not considered an criterion. 19. Serious side effects from treatment with Peg-IFN plus RBV in patients with prior failure of such treatment
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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, Knee Pain Knee Chondroplasty Diagnosed knee pain requiring chondroplasty knee arthroscopic surgery Men and non-pregnant, non-lactating women over the age of 18 and under the age of 75, able to read, understand and sign English-language informed consent If using psychoactive medication which might have analgesic effects, (i.e. anti-depressants or anti-consultants), treatment must be stable for at least three (3) months prior to study For men and women of child-bearing potential, must be willing to use adequate contraception and not be pregnant or impregnate their partner during the entire time of study Must be willing to commit to all clinical visits during study-related procedures Require use of narcotics for pain relief Patients with significant neurologic impairment, as diagnosed on screening physical examination Patients not fluent in English Patients currently involved in a Workman's Compensation case related to this procedure Receipt of an oral intramuscular or soft-tissue injection of corticosteroid within one (1) month prior to screening History of substance abuse History of malignancy, other than basal or squamous cell of the skin within the last 5 years Tibial plateau fracture within 6 months prior to 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): 18.0-65.0, Hepatitis C has a Body Mass Index (BMI) ≥18.5 kg/m² and ≤36.0 kg/m² has chronic compensated, genotype 1 HCV infection has no cirrhosis of the liver as confirmed by FibroSure®/Fibro Test® and/or local country procedure (e.g. transient elastography/Fibroscan) does not require anticoagulants, nonsteroidal anti-inflammatory agents, and aspirin for at least fourteen (14) days preceding the initial liver biopsy and continuing throughout the entire study if is a female participant of reproductive potential, is willing to use 2 medically acceptable forms of contraception for 2 weeks prior to start of treatment through 2 weeks after last study treatment if is a male participant with a partner(s) of reproductive potential, is willing to use 2 medically acceptable forms of contraception from first dose to 90 days after last dose has a history of stroke, chronic seizures, or major neurological disorder has received previous treatment with a direct-acting antiviral (DAA) has evidence of high grade bridging fibrosis from prior liver biopsy within 3 years of study entry has evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis has clinical or laboratory evidence of cirrhosis or other advanced liver disease has decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices has been diagnosed with, or suspected of having, hepatocellular carcinoma (HCC) has clinically significant abnormality on an electrocardiogram (ECG) is co-infected with human immunodeficiency virus (HIV) is positive for Hepatitis B surface antigen (HBsAg) or other evidence of active Hepatitis B 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, Hepatitis C, Chronic Is ≥ 40 kg and ≤ 125 kg Documented CHC genotype 1 with HCV RNA ≥10,000 International Units (IU)/mL Has IL-28B CC allele gene Has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma (non-invasive fibroscan and Fibrotest can also be used for staging of liver disease) Co-infection with the human immunodeficiency virus (HIV) or hepatitis B virus (Hepatitis B surface antigen [HBsAg] or HIV positive) Previously treated with an interferon and ribavirin regimen or HCV direct acting antiviral regimen Treatment for hepatitis C with any investigational medication, or prior treatments with herbal remedies with known hepatotoxicity Receiving any medication(s) within 2 weeks prior to the Day 1 visit that are highly dependent on Cytochrome P450 3A4 (CYP3A4/5) for clearance, and for which elevated plasma concentrations could be associated with serious and/or life-threatening events Participation in any other clinical trial within 30 days of the screening visit in this trial or intention to participate in another clinical trial during participation in this trial Evidence of decompensated liver disease or hepatocellular carcinoma (HCC) Is diabetic and/or hypertensive with significant retinopathy Has any known medical condition that could interfere with the participation in and completion of the trial including immunologically-mediated disease, chronic pulmonary disease, or current or history of any clinically significant cardiac abnormalities/dysfunction Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years Hemoglobin <12 g/dL for females and <13 g/dL for males
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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, Acute Liver Failure Acute Liver Injury Men and women, ages 18-65 (have not reached their 66th birthday). 2. Acute liver failure, defined as the development of coagulopathy (International normalized ratio [INR] ≥1.5) with encephalopathy in a patient with no prior history of liver disease, with onset of symptoms within 28 days of the inciting event. Patients may have either a history of acetaminophen overdose (defined as >4 g/day within 7 days of presentation) and/or detectable acetaminophen levels in the serum, with a pattern of liver function tests typical for acetaminophen toxicity (bilirubin < 10 mg/dL and alanine aminotransferase (ALT) ≥1000 IU/L), or a diagnosis of hepatitis A, hepatitis B, drug-induced liver injury, autoimmune hepatitis or indeterminate cause based on standard criteria. 3. ALI patients may also be enrolled (those meeting the above plus coagulopathy (INR ≥ 2.0) and no evidence of encephalopathy) 4. Written informed consent from the patient (ALI) or patient's legally authorized representative or family member if he/she is considered encephalopathic (ALF). 5. Ammonia level ≥60 μmol/L at baseline (within 8h prior to T0/initiation of infusion). 6. Serum creatinine levels as follows: 1. Cohort 1: Creatinine ≤1.5 mg/dL; and 2. Cohort 2: Creatinine >1.5 mg/dL and <10mg/dL. 7. Mean arterial pressure of >65 mmHg History of chronic liver disease. 2. Signs of overt cerebral herniation, or uncontrolled intracranial hypertension by intracranial pressure (ICP) monitoring (if applicable). 3. Evidence of Wilson's disease, alcoholic hepatitis, biliary obstruction, ischemic hepatitis, severe acute renal tubular necrosis (ATN) due to shock, or any patient with ongoing hypotension. 4. Significant gastrointestinal bleeding (coffee grounds per nasogastric tube and/or melena). 5. Hemodynamic instability, defined by a mean arterial pressure of <65 mmHg. 6. Cardiopulmonary complications such as pulmonary edema, aspiration pneumonia, heart failure. 7. QT interval of >500msec at baseline EKG. 8. Pregnancy. 9. History of malignancy that has not been cured or any cancer in remission for less than 1 within the past 5 year. Non-melanoma skin cancers do not preclude participation in the trial. 10. Concomitant administration of drugs known to interfere with renal excretion of phenylacetylglutamine or those medications that may induce hyperammonemia such as haloperidol, valproic acid and systemic corticosteroids (prohibited during the study). Alternative ammonia modifying agents such as lactulose and rifaximin are not considered standard of care and are prohibited during the study period. 11. Any other health condition that would preclude participation in the study in the judgment of the principal investigator
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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 Male or female between the age of 18 and 70 years, inclusive, at time of enrollment Subject has never received antiviral treatment for hepatitis C virus (HCV) infection Body mass index (BMI) is ≥ 18 to < 38 kg/m^2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m) Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment Subject has plasma HCV RNA level > 10,000 IU/mL at screening History of severe, life-threatening or other significant sensitivity to any drug Females who are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant Recent history of drug or alcohol abuse that could preclude adherence to the protocol Positive test result for hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) antibodies Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/aspartate aminotransferase to platelet ratio (APRI) or FibroScan® showing cirrhosis or extensive bridging fibrosis
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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): 21.0-999.0, Hepatitis C HIV Healthy according to medical history and physical examination with exception of HCV and HIV diagnoses Confirmation of Chronic HCV infection Confirmation of Chronic HIV-1 infection On a stable protocol approved HIV antiretroviral (ARV) regimen with undetectable HIV-RNA Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication Subjects must be naive to treatment for chronic HCV infection Known or suspected cirrhosis History of any other clinically significant chronic liver disease A history consistent with decompensated liver disease Use of any prohibited medications as defined by the protocol Pregnant or nursing female or male with pregnant female partner Contraindication to PEG or RBV therapy (for Part B) Clinically relevant drug 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): 18.0-60.0, Hepatitis C genotype 1a or 1b HCV infection with HCV RNA level > 100,000 IU/mL A documented prior relapser patient to previous treatment regimens or treatment-naïve Patient must have documentation of a liver biopsy within 3 years before the screening visit or must agree to have a fibroscan/elastography examination within the screening period Patient is judged to be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening Evidence of liver cirrhosis Evidence of decompensated liver disease Evidence of any other cause of significant liver disease in addition to hepatitis C receiving or having received any treatment for HCV during the 6 months before screening History or evidence of current abuse 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
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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, Chronic Adults ≥18 years of age (≥ 20 years for subjects enrolled in Taiwan); subjects who are over 70 years of age must be in generally good health Confirmed diagnosis of chronic hepatitis C (CHC) virus genotype 1 infection: (1) Positive for anti-HCV antibody or HCV RNA at least 6 months before screening, and positive for HCV RNA genotype 1 or anti-HCV antibody at the time of screening; or (2) Positive for anti-HCV antibody or HCV RNA genotype 1 at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis) Compensated liver disease: with normal or elevated alanine aminotransaminase (ALT)/ aspartate aminotranferase (AST) (≤ 5 times the upper limit of normal), normal bilirubin level (< 2 mg/dL, except for Gilbert's syndrome), normal albumin, normal prothrombin time (PT) (INR< 1.3), no clinical symptoms or signs of cirrhosis or liver decompensation, and no evidence of cirrhosis as identified by ultrasound or any other procedures within 6 months before study entry Treatment naïve: never received interferon, ribavirin or any other HCV treatment No other form of chronic liver disease apart from chronic hepatitis C infection Hemoglobin ≥ 13 g/dL in men or ≥ 12 g/dL in women, white blood cell (WBC) count ≥ 3,500/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelet count ≥ 90,000/mm3; renal biochemistry estimated glomerular filtration rate (eGFR) > 60 mL/min Be able to attend all scheduled visits and to comply with all study procedures Be able to provide written informed consent Clinically significant illness or surgery within 4 weeks prior to dosing Any clinically significant abnormality or abnormal laboratory test results found during medical screening besides serum ALT/AST (≤ 5 times the upper limit of normal) Any reason which, in the opinion of the investigator, would prevent the subject from participating in the study Positive test for hepatitis B surface antigen (HBsAg) or human immunodeficiency virus (HIV) at screening Clinically significant vital sign abnormalities at screening Significant or major fundoscopic findings including but not limited to retinal exudates, hemorrhage, detachment, neovascularization, papilloedema, optic atrophy, microaneurysms and macular changes History of significant alcohol or drug abuse within one year prior to the screening visit (alcohol consumption of more than fourteen units of alcohol per week [1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]) or refusal to abstain from alcohol or illicit drugs throughout the study Pregnancy or, in women of child-bearing potential or in spouses of such women, unwillingness or inability to practice adequate contraception, defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicides, or birth control pills, or intrauterine devices throughout the study History of severe allergic or hypersensitivity reactions (like angioedema), specifically asthma, any known reaction to the study medication, allergic skin rash or other allergic reactions (like anaphylaxis), including severe drug allergies Therapy with any systemic anti-viral, anti-neoplastic, and immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to the first dose of study drug
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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 Virus For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Chronic hepatitis C genotype 1. GT-1b Capped at 50 % of naïve subjects Naives to prior anti-HCV therapy [Interferon (IFN) and direct antiviral agent (DAA) based] Relapsers (defined as subjects who had undetectable HCV ribonucleic acid (RNA) on prior treatment regimen of alfa-2a/RBV and Hepatitis C Virus (HCV) RNA > 25IU/mL after discontinuation of treatment). Capped at 20% HCV RNA ≥ 100,000 IU/mL Subjects with compensated cirrhosis can be enrolled and will be capped at approximately 10% Seronegative for human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) Men or women, 18-70 years of age Chronic liver disease due to causes other than chronic HCV Current or past evidence of decompensation Conditions that preclude the use of Alfa/RBV/TVR per respective labels Diagnosed or suspected hepatocellular 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): 18.0-65.0, Hepatic Impairment For Group 1 Moderate liver function impairment (Child Pugh score of 7 to 9) History of hepatic disease, such as hepatitis B, previous hepatitis C, alcoholic liver disease, autoimmune hepatitis, non-alcoholic fatty liver disease, hereditary/metabolic, cryptogenic, other Consistent with the disease process of hepatic impairment and associated symptoms For Group 2 Matched to a patient with moderate hepatic impairment with regards to sex, age (± 5 years), and BMI (± 15%) and healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality For Group 3 Severe liver function impairment (limited to Child Pugh score of 10 to 12) Hepatic impairment due to different etiologies such as hepatitis B, previous hepatitis C, alcoholic liver disease, autoimmune hepatitis, non-alcoholic fatty liver disease, hereditary/metabolic, cryptogenic, other Consistent with the disease process of hepatic impairment and associated symptoms For Group 1 and 3 Has acute infectious hepatitis Has grade 3 or 4 encephalopathy Has grade 3 or 4 creatinine elevation Is an active candidate for liver transplantation Has had variceal bleeding or spontaneous bacterial peritonitis For Group 1 only Has a porta-caval shunt or transjugular intrahepatic porto-systemic shunts For Group 2: Has acute hepatitis A or hepatitis B or hepatitis C infection
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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): 20.0-65.0, Hepatitis C Virus enrolled voluntarily, can understand and sign informed consent; 2. More than 18 years and less than 65 years; 3. body mass index (BMI) is at 18 4. anti-HCV antibodies and / or HCV RNA positive, and / or other evidence of chronic hepatitis C; 5. HCV RNA level ≥ 2000IU/ml (or equal to this viral load); 6. Women's urine pregnancy test was negative, and the subjects (male subjects) is willing to have no pregnancy plans at next 18 months. (7) ALT is within 6 times of the upper limit of normal pregnant women, lactating women or plan to pregnant the next 18 months. 2. mental disorder, including history of mental illness (especially the history of depression or depressive tendencies, epilepsy, etc.); 3. The patient who received interferon therapy within the past six months or had no response at previous interferon therapy. 4. The patient who used a strong immune regulator over two weeks with three months before screening, such as adrenocorticotropic hormone, thymosin of α1, thymus 5 peptide. 5. The patient who used hepatotoxic drugs with 6 months before screening, such as dapsone, erythromycin, fluconazole, ketoconazole, rifampin. 6. co-infection with other viruses (HAV, HBV, HEV, the HIV, EBV, CMV) . 7. patients with a history of hepatocellular carcinoma (HCC), or may had hepatocellular carcinoma evidence, such as imaging of suspicious nodules, or AFP abnormal (AFP> 200ng/mL). FibroScan value greater than or equal to F3 at Screening 8. other causes of liver disease: a chronic alcoholic hepatitis, drug-induced hepatitis, autoimmune liver disease, nonalcoholic steatohepatitis. 9. autoimmune diseases, including psoriasis, systemic lupus erythematosus, thrombocytopenic purpura, and so on. 10. heart and vascular system diseases, a history of myocarditis, hypertension, coronary heart disease, pathological arrhythmia, stroke. 11. endocrine system diseases, including thyroid disease, diabetes, etc. 12. pulmonary diseases, including invasive pulmonary disease, pneumonia, shortness of breath. 13. Eye diseases, including retinopathy, retinopathy. 14. chronic infectious disease history (history of tuberculosis). 15. chronic kidney disease, serum creatinine level> 1.5 times upper limit of normal at screening, renal insufficiency, renal anemia history. 16. anemia (including thalassemia, sickle hemoglobin, anemia), and hemophilia. 17. peptic ulcer not controlled, colitis, pancreatitis and others. 18. malignancies. 19. peripheral blood checking: white blood cell count <3 × 109 / L; neutrophil count <1.5 x 109 / L; platelet count <90 × 109 / L; hemoglobin was less than the normal reference limit. 20. serum total bilirubin> 2 times normal maximum reference value (ULN); serum albumin <35g / L; a history of decompensated cirrhosis evidence. 21. evidence of drug addiction (including excessive alcohol intake, average alcohol consumption: men> 40g / day; women> 20g / day, equivalent to 50 degrees white wine 100ml / day and 50ml / day) within one year before screening. 22. a serious history of drug and food allergy, especially towards the test drug (interferon, ribavirin). 23. plans to accept an organ transplant or have organ transplant. 24. participated other clinical trials before 3 months at screening 25. The researchers judged the patients have other factors which may influence the experiment. ribavirin women Hgb <12g/dl or men Hgb <13gdl at screening. 2. anemia patients (eg, thalassemia, spherocytosis hyperlipidemia, gastrointestinal bleeding history) or suspected anemia patients. 3. patients have a history of coronary artery disease or patients with cerebrovascular disease should not join this study, hemoglobin decline up to 4g/dl (it may be observed in the ribavirin treatment)
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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 with HCV Must have participated in a prior Gilead HCV study Use of highly effective contraception methods if female of childbearing potential or sexually active male Eligible patients those in the following received placebo or Peg-IFN+RBV in a control arm previously participated in a Gilead-sponsored HCV study and did not attain sustained virologic response 24 weeks after discontinuation of therapy (SVR24) on a regimen containing Sofosbuvir+RBV Peg-IFN and/or RBV in combination with one or more Gilead investigational direct-acting agents Pregnant or nursing female or male with pregnant female partner Current or prior history of clinical hepatic decompensation Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Chronic use of systemically administered immunosuppressive agents Active drug abuse Use of any prohibited concomitant medications
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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): 0.083-999.0, Non-Alcoholic Steato-Hepatitis Liver Cirrhosis Non-Alcoholic Fatty Liver Disease Although a liver biopsy is necessary to make the diagnosis of NASH, patients with radiologic evidence of fatty liver and/or cirrhosis in which other causes have been ruled out are eligible to participate. 2. Patients who have already undergone liver transplantation for a confirmed diagnosis of NAFLD or cryptogenic cirrhosis are also eligible to participate. 3. Depending on their willingness to participate, subjects may enroll in DNA laboratory-only or clinical-only. However, to conserve resources and meet study objectives, subjects with known pathogenic mutations will be given priority in selection for extensive clinical studies. 4. Direct blood relatives (typically parents and siblings) of affected individuals with NAFLD and associated conditions are also eligible to participate Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent. 2. Pregnant women. Although fatty liver and cirrhosis are sometimes diagnosed during pregnancy, it is unclear if they were present before and just not diagnosed or if they develop as a complication of pregnancy. Additionally energy metabolism changes during pregnancy and lactation which may confound our analysis. If the condition persists after pregnancy and the diagnosis of NAFLD is clearly established, patients can be referred to the study. 3. We will review a clinical description from the referring physician about a potential research subject to determine that the subject is appropriate to enter into the study. We reserve the right to cases that are clearly not NAFLD or related to our direct research interests (e.g. fatty liver induced by chronic alcohol use, infectious causes, drug-related, or toxin-related). This almost never happens. However, as some of these environmental factors may contribute to a multifactorial etiology of hepatic changes, we may not all such cases
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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 Chronic (diagnosis of hepatitis C more than or 6 months before the screening period) HCV infection. Geno and subtype should be determined or confirmed at screening, and should be 1a or 1b Never received (Peg) IFN, RBV or any other approved or investigational antiviral treatment for chronic HCV infection HCV RNA level of >100,000 IU/mL at screening (as assessed by standard quantitative in vitro nucleic acid amplification assay) Patients having good accessible veins Evidence of liver cirrhosis or decompensated liver disease Patient coinfected with HIV-1 or HIV-2, or hepatitis A or B virus infection, or active tuberculosis at study screening Patient infected/coinfected with non-genotype-1 HCV at study screening Patient with any cardiac disease at screening, or any active clinically significant disease, or medical history or physical examination findings during screening Patient having uncontrolled/unstable disease such as diabetes, epilepsy, a manifest psychiatric disease, thyroid disease or disorders
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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): 20.0-70.0, Autoimmune Hepatitis Cirrhosis Autoimmune hepatitis (Non cirrhotic) Diagnose of Autoimmune hepatitis Presence of antinuclear antibody (ANA, SMA) Biochemical evidence, based on elevation of transaminases Biopsy compatible with Autoimmune hepatitis Ambulatory patients Autoimmune hepatitis (Cirrhotic) Presence of antinuclear antibody (ANA, SMA) Biochemical evidence, based on elevation of transaminases Biopsy compatible with autoimmune cirrhosis Hepatic cirrhosis by USD Hospitalized patients Overlapping syndrome with predominant primary biliary cirrhosis Chronic renal failure Hepatocellular carcinoma Neuropsychiatric disorders
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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 Diagnosis of chronic hepatitis C infection Co-infection with human immunodeficiency virus (HIV) and/or hepatitis B Participants previously treated with pegylated interferon alfa-2a/ribavirin Participation in another clinical study within 30 days prior to study start of ML25544
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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, Autoimmune Hepatitis 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 (female patients in fertile age) Hepatocellular carcinoma or other Malignancies 2. Pregnant or lactating women 3. Viral Hepatitis ( HAV,HBV,HCV, et al ) 4. Vital organs failure (Cardiac, Renal or Respiratory, et al) 5. Sepsis 6. Active thrombosis in the portal or hepatic veins
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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): 3.0-999.0, Hepatitis C Previously participated in a HCV treatment protocol that included grazoprevir in the treatment regimen Must enroll in the present study within three months of the last study visit of their previous protocol in which they received a grazoprevir-containing regimen For Amendment 03: Adult participants must have received a grazoprevir-containing regimen in a prior trial and have been identified as having failed therapy in that study For Amendment 04: Pediatric participants must have received at least 1 dose of a grazoprevir-containing regimen and experienced virologic failure with 1 or more associated treatment-emergent RASs at Follow-up Week 12 in MK-5172-079 (NCT03379506) Has received HCV therapy after completion of the protocol-defined grazoprevir treatment trial regimen and before or after entry into this follow-up study For Amendment 03: Has failed therapy due to re-infection, defined as an HCV RNA sample with a different genotype than the baseline genotype in the prior treatment study, or an HCV RNA sample determined to be reinfection by phylogenetic analysis with comparison to the baseline sequence in the prior treatment study For Amendment 03: Has failed therapy and received retreatment with HCV therapy, except in the case where they were re-treated in a Merck-sponsored 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): 18.0-70.0, Chronic Hepatitis C Infection Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than or equal to 10,000 IU/mL at screening) Subject's hepatitis C virus genotype is subgenotype 1b at Screening without co infection with any other genotype/subgenotype Significant liver disease with any cause other than HCV as the primary cause Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody Positive screen for drugs or alcohol Use of contraindicated medications within 2 weeks of dosing
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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): 20.0-999.0, Hepatitis C Infection Aged 20y/o or older 2. Positive for the HCV antibody and HCV RNA detected with abnormal ALT (≧ 1X) before initiating PegIFN plus RBV treatment 3. HCV Genotype 1 4. Have failed to achieve RVR at week 4 but achieve undetectable HCV RNA at week 8 (< 50 IU/ml) with PegIFN plus RBV treatment 5. Have received PegIFN plus RBV treatment for 12weeks with good compliance (who have received >80% of expected PegIFN and RBV doses and completed at least 80% of the expected duration (80/80/80 adherence) and achieve EVR before entering this study Subjects with decompensated liver disease or overt cirrhosis by ultrasound. 2. With prior exposures to interferon (standard or pegylated) treatment before baseline. 3. With human immunodeficiency virus 4. With hepatitis B infection 5. With neutrophil count < 1500 mm3, 6. With platelet count < 90000 mm3, 7. With hemoglobin level < 12g/dL for men or < 11 g/dL for women 8. With serum creatinine level > 1.5 mg/dL 9. With clinically significant cardiac or cardiovascular abnormalities, organ grafts, systemic infections, clinically significant bleeding disorders, evidence of malignant neoplastic diseases 10. Female patients with pregnancy or lactation. Pregnancy in partners of male patients. 11. Hypersensitive to study drugs cases
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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 Cirrhosis Portal Hypertension With or Without Liver Decompensation Chronic infection with Hepatitis C with HCV RNA > 1000 IU/mL Individuals with cirrhosis with Child-Pugh score < 10 Esophageal or gastric varices on endoscopy within 6 months prior to or at screening Hepatic Venous Pressure Gradient (HVPG) > 6 mmHg Body mass index (BMI) ≥ 18 kg/m^2 Naïve to all nucleotides/nucleoside treatments for chronic HCV infection Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance HIV or chronic hepatitis B virus (HBV) infection (HBsAg positive) Alpha-fetoprotein (AFP) > 50 unless negative imaging for hepatic masses within the last 6 months or during screening Refractory ascites as defined by requiring paracentesis > twice within 1 month prior to screening Active variceal bleeding within 6 months of screening Expected survival of < 1 year History of hepatorenal, or hepatopulmonary syndrome Evidence of renal impairment (CrCl < 50 mL/min) History of major organ transplantation, including liver transplant
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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, Liver Fibrosis Hepatitis C HIV HIV/HCV Co-infection Key HIV-infected individuals must have positive serologies with viral load suppressed below 400 copies/mL HCV-infected individuals must have Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following Been null responder to previous pegylated interferon and ribavirin therapy OR Failed to achieve sustained virologic response (SVR) on a regimen containing a direct-acting antiviral (DAA) in addition to pegylated interferon and ribavirin OR Are unwilling to receive or have contraindications to interferon therapy for HCV HIV/HCV co-infected individuals must have Positive HIV serologies with viral load suppressed below 400 copies/mL Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following Cause of liver fibrosis other than HCV or long-term antiretroviral therapy (ART) treatment for HIV Currently being treated for HCV Evidence of active Hepatitis A, B or D infections History or evidence of hepatocellular carcinoma Unwillingness to undergo a liver biopsy pre-treatment and post-treatment, or to undergo all other protocol required tests/procedures or return to the site for required visits Presence of contraindications to magnetic resonance imaging (e.g., presence of any metal in the body, cardiac or neural pacemaker, aneurysm clip, cochlear implant, claustrophobia)
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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 (CHC) Treatment naive Chronic, compensated HCV GT1 infection Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis No evidence of cirrhosis or hepatocellular carcinoma by biopsy or noninvasive testing (e.g. FibroScan and/or FibroTest) Must agree to use two acceptable methods of birth control from at least 2 weeks prior to first dose and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations Non-GT1 HCV infection, including a mixed GT infection (with a non-GT1) or a non-typeable genotype Documented to be Human Immunodeficiency Virus (HIV) positive or co-infected with hepatitis B virus Hepatocellular carcinoma (HCC) or under evaluation for HCC Participating in or has participated in a study with an investigational compound or device within 30 days of signing informed consent Diabetic and/or hypertensive with clinically significant ocular examination findings Current or history of central nervous system trauma, seizure disorder, stroke or transient ischemic attack Chronic pulmonary disease Current or history of any clinically significant cardiac abnormalities/dysfunction Active clinical gout within the last year History of gastric surgery or history of malabsorption disorders
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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, Chronic Hepatitis C Infection Females must be post-menopausal for at least 2 years or surgically sterile or practicing specific forms of birth control Chronic hepatitis C, genotype 1 infection and HCV RNA level greater than 10,000 IU/mL at screening Previous treatment failure of peg-interferon and ribavirin (pegIFN and RBV) No evidence of liver cirrhosis Positive screen for drugs or alcohol Significant sensitivity to any drug Use of contraindicated medications within 2 weeks of dosing Certain predefined abnormal laboratory tests Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody
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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 All participants CHC genotype 1 (GT1) virus infection (Parts A, B, and C) or GT3 virus infection (Part D) Female participants of childbearing potential or male participant with female partners of childbearing potential, must use two acceptable methods of birth control from ≥2 weeks prior to Day 1 until ≥6 months after last dose of study drug, or longer if dictated by local regulations Part A Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis No evidence of advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by biopsy or noninvasive testing (FibroScan and/or FibroTest) Parts B, C, and D Treatment naïve with or without cirrhosis, or Prior treatment failure to Peg-IFN/Ribavirin with or without cirrhosis, or Co-infected with human immunodeficiency virus (HIV) without cirrhosis Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease Liver disease staging assessment by liver biopsy or noninvasive testing (FibroScan and/or FibroTest) All participants Non-GT1 HCV infection (Part A, Part B, and Part C) or a non-GT3 HCV infection (Part D) including a mixed GT infection (with a non-GT1 [Part A, Part B, and Part C] or non-GT3 [Part D]) or a non-typeable genotype Evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC Currently participating or 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 study Diabetic and/or hypertensive with clinically significant ocular examination findings History of depression associated with hospitalization for depression, electroconvulsive therapy, or resulting in prolonged absence from work and/or significant disruption of daily functions Suicidal or homicidal ideations and/or attempt, or history of severe psychiatric disorders Clinical diagnosis of substance abuse Current history of seizure disorder, stroke, or transient ischemic attack Immunologically mediated 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): 18.0-65.0, Hepatitis C Read and signed the written informed consent form (ICF) after the nature of the study has been fully explained Have participated in an Idenix-sponsored study of an Idenix DAA Received at least 3 consecutive days of DAA treatment in an Idenix-sponsored study Agreed to comply with the visit schedule and laboratory tests Treatment with placebo only, in an Idenix sponsored study Antiviral treatment for HCV after participation in an Idenix sponsored study of an Idenix DAA
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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 Documented chronic genotype 1a or genotype 1b hepatitis C virus (HCV) infection with HCV ribonucleic acid (RNA) level >100,000 IU/mL at screening Treatment-naive or documented prior relapser to previous treatment regimens and has stopped treatment at least 3 months before screening Liver biopsy within 3 years before the screening visit or elastography results available prior to first study drug dosing Medically stable based on physical examination, medical history, vital signs, and electrocardiogram performed at screening Body mass index of 18.0 to 32.0 kg/m2 and body weight more than 50 kg Evidence of liver cirrhosis by liver biopsy or the presence of esophageal varices or a transient elastography result of >14.6 kPa within 2 years prior to first dosing Evidence of decompensated liver disease defined as prior history or current evidence of ascites, hepatic encephalopathy, bleeding oesophageal or gastric varices Evidence of any significant liver disease in addition to hepatitis C (including but not limited to hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis, or primary biliary cirrhosis) Receiving or has received any HCV-specific direct antiviral agent (HCV protease inhibitors, HCV nucleoside polymerase inhibitors, HCV non-nucleoside polymerase inhibitors, HCV NS5a inhibitors or any other HCV inhibitor targeting an HCV protein or a target involved in the HCV replication cycle Co-infected with human immunovirus (HIV)-1 or HIV-2, with non-genotype 1a/1b HCV, or hepatitis A or B virus 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): 18.0-70.0, Hepatitis C, Chronic A liver biopsy within 3 years prior to the screening visit (or between screening and day of randomization) with histology consistent with chronic Hepatitis C virus (HCV) infection Presence of contraindications for a liver biopsy in patients who are otherwise deemed eligible for participation does not the patient from participation Genotype 1 HCV infection (confirmed at screening) Plasma HCV RNA of > 10,000 IU/mL at screening Prior treatment with any approved or investigational drug for the treatment of hepatitis C Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
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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, Ischemic Reperfusion Injury Insufficiency; Hepatic, Postoperative Liver Tumour Any sex, any race, any ethnicity Age > 18 Primary and secondary liver tumors Normal renal function Anticipated Pringle's length > 30 minutes Renal failure of any grade ASA 4 Associate major surgery Intraoperative bleeding > 1500 ml Allergy to N-acetylcysteine or Methylprednisolone
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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, Hepatitis C, Chronic Chronic hepatitis C infection, diagnosed by positive HCV Ab or detectable HCV RNA at screening in addition to at least one of the following: 1. positive HCV RNA or HCV antibodies at least 6 months prior to screening, or 2. liver biopsy typical of chronic hepatitis C , or 3. history of elevated ALT at least 6 months prior to screening HCV infection of sub-GT1b confirmed by genotypic testing at screening Treatment naïve defined as: 1. no prior treatment with any interferon, pegylated interferon, and /or ribavirin and 2. no prior treatment with at least one dose of any other licensed or investigational antiviral agent for acute or chronic hepatitis C infection Plasma HCV RNA > or = 1,000 IU/mL at screening Liver biopsy within three years or fibroscan within six months prior to randomization. Patients with compensated liver cirrhosis (score Child-Pugh A) could also be included Age 18 to 75 years Female patients with a negative urine pregnancy test (dipstick) at Visit 2 prior to randomization 1. with documented hysterectomy, or 2. who have had both ovaries removed, or 3. with documented tubal ligation, or 4. who are post-menopausal with last menstrual period at least 12 months prior to screening, or 5. of childbearing potential with a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 (Visit 2), that agree to use two non-hormonal methods of birth control from the date of screening until months after the last dose of ribavirin. They must not breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin. Medically accepted methods of contraception for females in this trial are diaphragm with spermicide substance, intrauterine devices, cervical caps and condoms. OR: Male patients 1. who are documented to be sterile, or 2. who consistently and correctly use a condom while their female partners (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin, and 3. without pregnant female partners. It is in the responsibility of the male patient to ensure that his partner (or partners) is not pregnant prior to enrolment into the study or becomes pregnant during the treatment and follow-up phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor) HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening HCV subtype 1a, mixed 1a/1b or GT1 undefined Evidence of liver disease mainly due to causes other than chronic HCV infection such as autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis or Wilson's disease HIV-1 or HIV-2 infection Hepatitis B virus (HBV) infection based on presence of HBs-Ag Evidence of decompensated liver disease, or history of decompensated liver disease, defined as history of ascites, hepatic encephalopathy, or bleeding esophageal varices International Normalized Ratio (INR) > or =1.7 Serum albumin < 3.3 g/dL Serum total bilirubin >2.0 times the upper limit of normal (ULN) with direct/indirect ratio >1, unless history of Gilbert's disease Active or suspected malignancy or history of malignancy within the last 5 years (with the exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix)
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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 Liver Disease Non-Alcoholic Fatty Liver Disease Hepatitis C Virus (HCV) Coinfection Hepatitis B Virus (HBV) Drug-Induced Liver Injury Adult patients (age 18 or older) Men or women Suspected diffuse liver disease Consent to participate in the study Pregnancy Acute illness/cognitive impairment resulting in inability to cooperate with ultrasound Patients that do not consent to ultrasound or sonoelastography
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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 (HCV) Acupuncture Adult patients with a confirmed HCV infection Under 18 years Can not receive standard Peg interferon+ ribavirin treatment for any reason Psychiatric diagnosis Anaemia of hematologic origin Diabetic patient with uncontrolled diabetes Congestive heart failure, arrhythmia Hepatocellular carcinoma HIV infection Hepatitis B infection Auto immune liver disease or alcoholic liver disease
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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 B Hepatitis C Willing and able to provide written informed consent Male or female, age >= 18 Willing and able to comply with the visit procedure Prior diagnosis of chronic HCV infection or chronic HBV infection History of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy History of bleeding disorder Blood loss requiring transfusion or > 3 g/dL decrease in hemoglobin within 4 days of the visit Knowingly co-infected with HCV/HBV or with HIV Currently undergoing therapy for chronic hepatitis C or chronic hepatitis B Currently receiving treatment with any other investigational agent or device -- Enrolled in another clinical study evaluating a treatment or procedure
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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 Infection Male or female, at least 18 years of age at the time of screening Currently taking an immunosuppressant regimen based on either tacrolimus or cyclosporine. Corticosteroids such as prednisone or prednisolone are permitted as components of the immunosuppressant regimen providing the dose is not more than 10 mg/day Hepatitis C virus (HCV) interferon (IFN) therapy treatment-naïve or -experienced, either pre or post-liver or renal transplant Screening HCV genotype testing indicating infection with genotype 1 or 4 (GT1 or GT4) only Use of everolimus or sirolimus as part of the immunosuppressive regimen within 2 months of Screening Visit Use of any medications contraindicated for use with the study regimen as well as those that are contraindicated for use with either ritonavir or ribavirin within 2 weeks prior to study drugs administration or 10 half-lives (if known), whichever is longer Positive test result for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) Documented history of post-transplant complications directly involving the hepatic or renal vasculature as appropriate to the organ transplanted, e.g., thrombosis of the portal vein, the hepatic artery and/or hepatic vein Clinically significant abnormalities, other than HCV infection, in a subject post-transplant based upon the medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG) 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): 18.0-999.0, Alcoholism Liver Disease Liver Fibrosis Patients more than 18 years old; hospitalised for alcoholic weaning; with an alcoholic liver disease; with at risk alcoholic consumption; with an indication of liver biopsy; with a signed consentment patients with a cirrhosis; with other causes of liver disease; with a contraindication of liver biopsy; having had a liver biopsy in the last 3 years; pregnancy; major benefiting from a legal protective measure; no coverage care
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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 Eighteen years of age or older at screening. 2. Female study participants with childbearing potential (as defined below) and all males must be willing to practice either Abstinence from sexual intercourse or One or more forms of effective barrier contraception throughout dosing and for 30 days following the last dose. This cannot hormonal contraception for female subjects. Effective forms of barrier contraception a male condom with spermicide use by female sexual partner of a female condom with spermicide Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) includes any female who Has had a hysterectomy or Has had a bilateral oophorectomy (ovariectomy) or Is post-menopausal (a demonstration of a total cessation of menses for greater than or equal to1 year) Has had a bilateral tubal ligation or fallopian tube inserts 3. Chronic HCV GT-1 or GT-4 infection as documented by greater than or equal to 1 measurement of serum HCV RNA greater than or equal to 2,000 international units per milliliter during screening and at least one of the following A positive anti-HCV antibody, HCV RNA, or HCV genotype test result greater than or equal to 12 months prior to the baseline (day 0) visit together with current positive HCV RNA and anti-HCV antibody test results or 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 Poor venous access interfering with required study blood collection Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage) Solid organ transplantation Significant pulmonary disease, significant cardiac disease or porphyria Unstable psychiatric disease (Subjects with psychiatric illness that is well-controlled on a stable treatment regimen or currently not requiring medication may be included) Any malignancy or its treatment that in the opinion of the PI may cause ongoing interference with host immunity; subjects under evaluation for malignancy are not eligible 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): 18.0-999.0, HIV Hepatitis C Age greater or equal 18 years HIV-HCV co-infection HCV Genotype 1 infection At least one liver biopsy since diagnosis of HCV-infection Fibrosis score = 2 documented by biopsy OR a stiffness greater or equal 7.0 kPa documented by fibroscan during the previous 12 months Documented previous null-response or partial-response to SOC Contraindications to the study drug under study, e.g. known hypersensitivity or allergy to any ingredient of the study drug Patients in need of ART with HIV virological failure (= 400 copies/ml) in the last 3 months
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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, Chronic Hepatitis C Chronic Hepatitis B Age 18-70 Chronic liver disease due to CHC or CHB Starting of disease-specific treatment no earlier than January of 2010. Treatment could consist of combination therapy with peginterferon and ribavirin, with or without a direct-acting viral agent in CHC single or combination therapy containing peginterferon, entecavir, or tenofovir in CHB Established cirrhosis on liver biopsy (METAVIR F4) obtained before starting disease-specific treatment In patients without liver biopsy, any of the following will be used as a surrogate to define cirrhosis History of spleen >13 cm, bilirubin >2, albumin <3.5, INR >1.5 (2 of 3 criteria) History of APRI ([AST/ULN]/platelets x 100) >2, and esophageal varices or ascites History of Fibrotest/Fibrosure >0.74, and TE >12.5 kPa (M-probe) or >10 kPa (XL-probe) Known diagnosis of hepatocellular carcinoma or portal vein thrombosis Conditions limiting Fibrotest/Fibrosure read: hemolysis, Gilbert's syndrome, autoimmune disease Conditions limiting TE read: ascites, heart failure with retrograde vascular congestion, extrahepatic cholestasis Pregnancy or implantable active medical device (such as pacemaker or defibrillator)
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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 Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile Chronic hepatitis C, genotype 1a-infection (HCV RNA level greater than or equal to 10,000 IU/mL at screening) Subject has never received antiviral treatment for hepatitis C infection No evidence of liver cirrhosis Significant liver disease with any cause other than HCV as the primary cause Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody Positive screen for drugs or alcohol Significant sensitivity to any drug Use of contraindicated medications within 2 weeks of dosing 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, Hepatitis C, Chronic Patients with chronic hepatitis C eligible to receive antiviral treatment Patients who had undergone previous antiviral treatment, those with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection, and individuals included in other treatment protocols
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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 C Infection Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile Chronic hepatitis C infection (positive for anti-HCV antibody or HCV RNA at least 6 months before screening and at the time of screening; or positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection) Screening laboratory result indicating HCV genotype 1 infection (HCV GT1) Participant must have documentation of adherence to a prior pegIFN/RBV combination therapy and meet one of the protocol definitions for treatment failure: null responder, partial responder, relapser No evidence of liver cirrhosis Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody Positive screen for drugs or alcohol Significant sensitivity to any drug Use of contraindicated medications within 2 weeks of dosing Abnormal laboratory tests
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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): 1.0-14.0, Japanese Encephalitis Children aged between 1 and 14 years who had clinically diagnosed encephalitis on the basis of history of fever that lasted less than 14 days, altered consciousness with or without a history of new onset seizures with CSF finding of white cell count less than 1000 cells/mm3 with no organisms on Gram stain and a CSF: plasma glucose ratio > 40% admitted in Kanti Children's Hospital and BP Koirala Institute of Health Sciences, Nepal Asexual Plasmodium falciparum parasites in blood Coma appears secondary to other systemic condition, eg hepatic failure, cardiac failure, toxins Patients who have documented antibiotic treatment before admission and in whom partially treated bacterial meningitis appears more likely than encephalitis Children with simple febrile convulsions, defined as a single seizure lasting less than 15 minutes followed by full recovery of consciousness within 60 minutes Pregnant or breastfeeding females Children with a GCS of 3/15, who were receiving artificial ventilation without signs of spontaneous respiration, and with absent oculocephalic reflex
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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 C Subjects must have chronic genotype-1 hepatitis C virus infection and plasma HCV-RNA ≥ 105 IU/mL at the time of screening Subjects must have chronic HCV infection as determined by any of the following be anti-HCV (+) for at least 6 months per subject history or medical records an anti-HCV test, viral load, or genotype > 6 months ago In the setting of a recent positive anti-HCV test (< 6 months), liver biopsy demonstrating chronicity Subjects must have IL-28b genotype "CC" Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 kg/m2. BMI = Body weight (kg) / [Height (m)]2 Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days (for small molecules) whichever is longer; or longer if required by local regulations Previous treatment, including the use of any investigational agents, for the treatment of HCV infection Women of child bearing potential Subjects with IL-28b genotype "CT or TT" ALT γ-GT, and AST must be below 5 x the upper limit of normal (ULN) Serum bilirubin must not exceed ULN The PT (INR) must be within normal limits If necessary, laboratory testing may be repeated on one occasion (as soon as possible) prior to randomization, to rule out any laboratory error Use of drugs that inhibit or induce CYP3A4
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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, Hip Osteoarthritis Consecutive single surgeon series of patients who have undergone primary uncemented hip replacement at our institution through either a posterior approach or direct anterior approach on a fracture table. Posterior approach patient most recent patient prior to March, 2010, compared with consecutive recent anterior approach patients with minimum of 6 month follow-up. 2. Diagnosis of osteoarthritis, inflammatory arthritis, or avascular necrosis. 3. No previous surgery on affected hip. 4. Age 40-90 at time of surgery Patient not permitted to bear full weight after the procedure, per post operative instructions 2. Hip replacement performed for acute fracture. 3. Previous hip 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): 18.0-70.0, Hepatitis C, Chronic Chronic HCV, diagnosed by HCV RNA = 1,000 IU/mL at screening in addition to at least one of the following: 1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening, OR 2. liver biopsy indicating chronic HCV infection, OR 3. history of elevated ALT levels at least 6 months prior to screening. 2. HCV infection of sub-GT1b confirmed by genotypic testing at screening. 3. Treatment naïve defined as: 1. no prior treatment with any interferon, pegylated interferon, and /or ribavirin and 2. no prior treatment with at least one dose of any other licensed or investigational antiviral agent for acute or chronic hepatitis C infection. 4. Availability of a liver biopsy within three years or fibroscan within 6 months prior to randomisation. Note: patients who do not have a liver biopsy (nor fibroscan) due to contraindication of the procedure should not be excluded for this reason. The decision on the of these patients should be discussed with the CML. Patients with a liver biopsy performed 3 or more years (or fibroscan performed 6 months or more) prior to randomisation, demonstrating cirrhosis do not need to repeat a liver biopsy or fibroscan. 5. Age 18 years (inclusive). 6. Female patients 1. with documented hysterectomy, or 2. who have had both ovaries removed, or 3. with documented tubal ligation, or 4. who are post-menopausal with last menstrual period at least 12 months prior to screening, or 5. of childbearing potential with a negative serum pregnancy test at screening and on Day 1 (Visit 2), who agree to use two non-hormonal methods of birth control from the date of screening until 7 months after the last dose of ribavirin. They must not breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin. Accepted methods of contraception for females in this trial are diaphragm with spermicide substances, intrauterine devices, cervical caps and condoms. Note: Systemic hormonal contraceptives may not be as effective in women taking BI 207127/FDV combination therapy and are not accepted methods of contraception in the study. OR: Male patients 1. who are documented to be sterile, or 2. who consistently and correctly use a condom while their female partners (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin, and 3. without pregnant female partners. It is in the responsibility of the male patient to ensure that his partner (or partners) is not pregnant prior to enrolment into the study or becomes pregnant during the treatment and follow-up phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the Sponsor). 7. Signed informed consent form prior to trial participation HCV infection of mixed genotype (1/2, 1/3, and 1/4), HCV sub-GT1a or GT1 undefined, diagnosed at screening by genotypic testing. 2. Liver disease due to causes other than chronic HCV infection which may but is not limited to hemochromatosis, Wilson's disease, or autoimmune liver disease. 3. HIV infection. 4. Hepatitis B virus (HBV) infection based on presence of Hepatitis B surface antigen. 5. Evidence of decompensated liver disease or history of decompensated liver disease, defined as history of ascites, hepatic encephalopathy, bleeding esophageal varices or any other evidence of previous decompensation and/or any laboratory results (International Normalised Ratio, albumin, bilirubin) indicating a Child-Pugh-Turcotte score > 6 points (i.e. CPT-B or -C) 6. Confirmed or suspected active malignancy or history of malignancy within the last 5 years (with the exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix). 7. Patients with ongoing or historical photosensitivity or recurrent rash. 8. History of illicit drug use (other than cannabis) or chronic alcohol abuse within 12 months prior to randomization, in the opinion of the Investigator. 9. Body mass index <18 or >35 kg/m2. 10. Usage of any investigational drugs within 28 days prior to randomisation, or the planned usage of an investigational drug during the course of the current study. 11. Known hypersensitivity to any ingredient of the study drugs. 12. A condition that is insufficiently diagnosed, treated or clinically unstable which in the opinion of Investigator may put the patient at risk because of participation in this study, influence the results of this study, or limit the patient's ability to participate in this study. 13. Alpha fetoprotein value >100ng/mL at screening; if > 20ng/mL and = 100ng/mL, patients can be included if there is no evidence of liver cancer in an appropriate imaging study within 6 months prior to randomisation. 14. A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease (e.g. congestive heart failure, myocardial infarction, unstable angina and arrhythmic disorders) current or within the previous 12 months before randomisation. Clinically significant Electrocardiogram (ECG) abnormalities. A history of congenital QT prolongation, or a family history of congenital QT prolongation or sudden death. 15. Received silymarin (milk thistle) or glycyrrhizin or Sho-saiko-to (SST) within 28 days prior to randomisation or any medication listed in a restricted medication list provided in ISF within 28 days prior to randomisation, with the exception of parenteral analgesics used during liver biopsy procedure. 16. Pre-existing psychiatric conditions that could interfere with the subject's participation in and completion of the study including but not limited to severe depression or hospitalization for depression, suicidal ideation and attempted suicide, schizophrenia, bipolar illness, severe anxiety or personality disorder, history of craniocerebral trauma or active seizure disorders requiring medication, a period of disability or impairment due to a psychiatric disease current or within the previous 3 years before randomisation. 17. Abnormal thyroid function that cannot be controlled effectively by medication. 18. Active autoimmune-mediated disease (e.g., Crohn's disease, ulcerative colitis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis). 19. Requirement for chronic systemic corticosteroids (inhaled or nasally administered or pulmonary steroids will be allowed). 20. History or other evidence of severe retinopathy or clinically significant ophthalmological disorder due to diabetes mellitus or hypertension (but not limited to these conditions). Plus other relating to Peg interferon, ribavirin and Telaprevir
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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 Eighteen years of age or older at screening. 2. HCV treatment-naive, as defined as no prior exposure to any IFN, RBV, or other approved or experimental HCV-specific direct-acting antiviral agent. 3. Participants must be willing to practice either: 1. Abstinence from sexual intercourse or 2. At least 2 forms of contraception including one barrier method from 2 weeks prior to Day 0 through 30 days after the last dose is received. i. Female partners of male study subjects may rely upon hormonal contraception as one of the 2 methods; however female study subjects may not. 4. Chronic hepatitis C infection defined as one of the following: 1. Positive for anti-HCV antibody, HCV RNA, or an HCV genotype at least 6 months before screening, and positive for HCV RNA and anti-HCV antibody at the time of screening or 2. Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of chronic hepatitis C disease, such as the presence of fibrosis). 5. HIV treatment status: 1. Documented HIV infection, ARV untreated for > 8 weeks preceding dosing and having either: 1. a CD4 T-cell count greater than or equal to 500 cells/mm3 within 8 weeks of Day 0 or 2. an HIV viral load less than 500 copies/mL with a stable CD4 count for at least 3 months. 2. Documented HIV infection on a stable, protocol-approved, ARV regimen for greater than or equal to 8 weeks prior to dosing and is expected to continue the current ARV regimen through the end of study with all of the following: 1. a CD4 T-cell count > 100 cells/mm3 2. a documented plasma HIV-1 RNA level less than the level of detection for at least 8 weeks preceding dosing. If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL (e.g.,< 20 copies/mL), the Screening plasma HIV-1 RNA level cannot exceed 50 copies/mL. 3. HIV ARV agents including only combination regimens consisting of medications from the following list: tenofovir (TDF), emtricitabine (FTC), efavirenz, raltegravir, and rilpivirine administered according to their manufacturer s prescribing information. (reference Section 10.3 for additional information) 6. Documentation of hepatitis C genotype 1a, 1b or mixed 1a/1b 7. Absence of cirrhosis, defined as one of the following: 1. A liver biopsy performed within 36 calendar months of screening showing absence of cirrhosis. 2. FibroTest score of < 0.48 AND APRI of < 1 performed during the 8 weeks preceding dosing (In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above a liver biopsy is required). 8. Able to effectively communicate with the Investigator and other center personnel. 9. Willing to give written informed consent and comply with the study restrictions and requirements. 10. If opioid-dependent, subjects must be participating in a supervised treatment. 11. Participants must have a primary medical provider outside of OP8 and the NIH for medical management Subjects who meet any of the following are not to be enrolled in this study: 1. 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 drug. 3. Poor venous access interfering with required study blood collection. 4. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage). 5. Solid organ transplantation. 6. Significant pulmonary disease, significant cardiac disease or porphyria. 7. Unstable psychiatric disease (Subjects with psychiatric illness that is well-controlled on a stable treatment regimen or currently not requiring medication may be included). 8. Any malignancy or its treatment that in the opinion of the PI may cause ongoing interference with host immunity; subjects under evaluation for malignancy are not eligible. 9. Significant drug allergy (such as anaphylaxis or hepatotoxicity). 10. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis). 11. Patients with renal impairment or uncontrolled medical problems that could place them at high risk for developing renal impairment. 2. Positive test at screening for either HBsAg or quantifiable HBV DNA (completed only if necessary to rule out chronic HBV) 3. Current use of non-protocol approved ARVs. 4. A new AIDS-defining condition diagnosed within 30 days prior to screening or active, serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to Day 0. 5. Cirrhosis of the liver 6. Screening or baseline ECG with clinically significant ECG findings. 7. Abnormal hematological and biochemical parameters, including: 1. Neutrophil count < 750 cells/mm(3) 2. Hemoglobin < 9 g/dL. If Hgb is < 11g/dL in women or < 12 g/dL in men. Other causes of anemia should be excluded as medically indicated. 3. Platelet count less than or equal to 50,000 cells/mm(3) 4. Estimated GFR (calculated by the CKD-EP(I) equation) < 50 mL/min/per 1.73 m(2) if not on ARV or < 60 mL/min if on ARVs 5. ALT or AST greater than or equal to 10 times ULN 6. Serum lipase greater than or equal to 1.5 times ULN (at screening or during the screening period) 7. Direct bilirubin greater than or equal to 1.50 times ULN 8. Albumin less than or equal to 3.0 g/dL 9. INR greater than or equal to 1.5 times ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR. 8. Donation or loss of more than 400 mL blood within 8 weeks prior to first dose administration. 9. Poorly controlled diabetes mellitus indicated by hemoglobin A1C > 10% at screening for known diabetics. 10. Known hypersensitivity to, GS-5885, GS-7977, or formulation excipients. 11. Pregnant/Breastfeeding women. 12. Co-enrollment in other clinical trials is restricted, and requires approval of the Investigator. Study staff should be notified of co-enrollment status. 13. Need for use of the following medications from 21 days prior to the start of study drugs through the end of treatment: 1. Hematologic stimulating agents (e.g. erythropoiesis-stimulating agents (ESAs); granulocyte colony stimulating factor (GCSF); thrombopoietin (TPO) mimetics) 2. Chronic systemic immunosuppressants including, but not limited to, corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks), azathioprine, or monoclonal antibodies (e.g., infliximab) 3. Investigational agents or devices for any indication 4. Medications for disease conditions excluded from the protocol (e.g., active cancer, transplantation) are not listed under this Concomitant Medication section and are disallowed in the study. 5. Concomitant use of certain medications or herbal/natural supplements per PI discretion expected to result in pharmacokinetic interactions resulting in increases or decreases in exposure of study drug(s) as listed in Table of this 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): 18.0-999.0, Cirrhosis Chronic Hepatitis C Hepatitis C Hepatitis C, Chronic FOR BOTH 1a and 1b: 1. Adults, ages 18 and above 2. Chronic hepatitis C (HCV RNA in serum for more than 6 months) 3. HCV Genotype 1 4. HCV RNA in serum above 10,000 IU/mL 5. Non-response to previous therapy with peginterferon and ribavirin categorized as null-response as defined by a less than 1 log IU/mL decline in HCV RNA at treatment week 4 or a less than 2 log IU/mL decline in HCV RNA at treatment week 12; and partial response as defined by a greater than or equal to 2 log decrease in HCV RNA at treatment week 12 but continued detection of HCV RNA at treatment week 24 6. No contraindications to agents being used (asunaprevir, daclatasvir, peginterferon and ribavirin). 7. No evidence or history of hepatic decompensation. 8. Females of childbearing potential must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug. 9. Women of childbearing potential (WOCBP) and men must use highly effective methods of birth control to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of P/R. Birth control requirements are or WOCBP and men who are sexually active with WOCBP 10. Women must not be breastfeeding 11. Fully informed, written consent to the study including repeat liver biopsy. FOR 1a 1) Liver biopsy showing Ishak stages 0-2 or 5-6 within 12 weeks of initiating therapy OR a prior biopsy performed within 96 weeks of screening visit WITH saved tissue. Up to 10 subjects who do not fulfill the entry histologic will be allowed to participate in the trial at the discretion of the investigator. FOR 1b 1. Baseline sequence analysis of the NS5A region to presence of mutations known to confer resistance to daclatasvir. FOR GT 1b WHO AT THE OF THE (THESE MUST BE PRIOR TO PEG INFa/RBV Important: In addition to the listed above, the following apply to all Rescue Subjects: a) Subject met a definition of virologic breakthrough or treatment futility, defined as: i) Any confirmed > 1 log10 increase in HCV RNA from nadir, OR; ii) Any confirmed HCV RNA greater than or equal to Lower Limit of quantification (LLOQ) after confirmed HCV RNA <LLOQ Target Not Detected while on treatment, OR; iii) Any confirmed HCV RNA greater than or equal to LLOQ at Week 8. Measurements should be confirmed within 2 weeks of the Week 8 result; b) HCV RNA < 400,000 IU/mL at the last assessment; This cut-off was chosen because it is felt that peginterferon and ribavirin would be ineffective at higher viral loads in prior non-responders to peginterferon and ribavirin with viral breakthrough. c) Women of childbearing potential (WOCBP)1 and men must use highly effective methods of birth control to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of P/R. Birth control requirements are or WOCBP (see Section C.5 for the definition of WOCBP) and men who are sexually active with WOCBP; i) Two (2) forms of birth control are required from time of screening throughout the duration of the on-treatment study period and for at least 24 weeks after the last dose of RBV (or the duration specified by the country-specific RBV label, whichever is longer), in such a manner that the risk of pregnancy is minimized. Examples of highly effective birth control -condom with spermicide; -diaphragm and spermacide; -cervical cap and spermacide female condom intrauterine devices (IUDs); Oral contraceptive pills (OCPs) may be used in this study but cannot be considered as an effective form of contraception for WOCBP subjects. ii) Exceptions 1. WOCBP who are not heterosexually active or who have male partners who have been vasectomized for a minimum of 6 months with a history of confirmed azoospermia; 2. Sexually active men who are vasectomized for a minimum of 6 months with a history of confirmed azoospermia. d) WOCBP 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 P/R. Female subjects must agree to the pregnancy testing requirements of this protocol; e) Women must not be breastfeeding; f) Male Subjects: Requirements (based on RBV label): i) Male subjects (unless vasectomized for at least 6 months with a history of confirmed azoospermia) with female partners who are WOCBP must agree to inform their female partners of the protocol-specified effective birth control methods requirement and pregnancy testing recommendations during treatment and post-treatment (i.e., two forms of effective methods of birth control and monthly pregnancy testing while the subject is enrolled in the study and 6 months following discontinuation of RBV [or for the post-treatment duration specified in the country-specific RBV label]), and agree to adhere to these recommendations both on-treatment and during the post-treatment follow-up period; ii) Male subjects must confirm that their female sexual partners are not pregnant at the time of screening for Genotypes 1b: 1. Medical History and Concurrent Diseases 1. Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair; 2. Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment 3. Documented or suspected HCC, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed) 4. Evidence of decompensated liver disease including, but not limited to, radiologic a history or presence of ascites, bleeding varices, or hepatic encephalopathy 5. Evidence of a medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) 6. History of chronic hepatitis B virus (HBV) as documented by HBV serologies (eg, HBsAg-seropositive). Subjects with resolved HBV infection may participate (eg, HBsAb-seropositive with concurrent HBsAg-seronegative) 7. Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug. (Subjects who have had cholecystectomy are permitted to enter the study) 8. History of HIV infection 9. Hemophilia 10. Uncontrolled diabetes (any subject with a confirmed screening HgA1c greater than or equal to 8.5 must be excluded) 11. Confirmed, uncontrolled hypertension (any screening systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 100 mmHg should be excluded unless discussed with the central medical monitor) 12. Any other medical and/or social reason, including active substance abuse as defined by DSM-IV, Diagnostic for Drug and Alcohol Abuse, which in the opinion of the investigator would make the candidate inappropriate for participation in this study 13. History of severe psychiatric disorders including but not limited to, schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder, mania, etc. 14. Inability to tolerate oral medication; 15. Poor venous access 2. Physical and Laboratory Test Findings Note: Growth factors must not be used to achieve criteria. 1. ALT greater than or equal to 10 times ULN 2. Total bilirubin greater than or equal to 34 micromoles per liter (greater than or equal to 2 mg/dL) unless the subject has documented history of Gilbert s disease 3. Albumin < 3.5 g/dL (35 g/L) 4. Creatinine clearance (CrCl) less than or equal to 50 ml/min (as estimated by Cockcroft and Gault) 5. Platelets < 50 times 10(9) cells/L 6. ANC < 0.5 times 10(9) cells/L 7. Hemoglobin < 8.5 g/dL 8. INR greater than or equal to 1.7 9. Alpha-fetoprotein (AFP): i) AFP > 100 ng/mL OR ii) AFP greater than or equal to 50 ng/mL and less than or equal 100 ng/mL requires a liver ultrasound and subjects with findings suspicious for HCC are excluded j) QTcF or QTcB > 500 msec 3. Allergies and Adverse Drug Reaction a) History of hypersensitivity to drugs with a similar biochemical structure to asunaprevir or daclatasvir. 4. Prohibited Treatments and /or Therapies 1. Exposure to any investigational drug or placebo within 4 weeks of study drug administration; 2. Prior exposure to any HCV DAA; 3. Prior exposure to pegIFN or RBV within 12 weeks prior to screening; 4. Subjects receiving all tricyclic anti-depressants (TCAs) including amitriptyline, clomipramine, desiprmine, dosepin, imipramine, nortriptyline, protriptyline; OR selective serotonin reuptake inhibitors (SSRIs) including fluoxetine, fluvoxamine, paroxetine and sertraline; OR additional agents including venlafaxine, duloxetine, aripiprazole and mirtazapine within 2 weeks prior to Day 1; (subjects may switch to non-prohibited antidepressant therapies (eg citalopram, escitalopram and bupropion) within 2 weeks prior to Day 1). The study of subjects on any anti-depressant not listed above, may be considered after a consultation with the central medical monitor, prior to Day 1; 5. Sex and Reproductive Status 1. Sexually active men whose partners are pregnant at screening are excluded from this study 6. OTHER a) Prisoners or subjects who are involuntarily incarcerated b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness C.5 for Gt 1a subjects and 1b subjects who receive rescue therapy at discretion of the investigator (Prior to initiation of PegIFN /ribavirin therapy): Important: In addition to the listed above WITH THE OF THE TESTS IN C.4.2 A-H, the following apply to all Gt 1a and rescue subjects: a) Severe psychiatric disease that would prohibit use of peg-IFN -2a as judged by the investigator including but not limited to: i) Moderate or severe depression; Beck Depression Score greater than or equal to 15 during screening ii) History of depression associated with hospitalized for depression, electroconvulsive therapy, or depression resulting in a prolonged absence from work and/or significant disruptions from daily functions; iii) Suicidal or homicidal ideation and/or attempt; iv) History of severe psychiatric disorders including but not limited to, schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder, mania, etc.; b) History of hemoglobinopathies (e.g., thalassemia major or sickle cell anemia), diagnoses associated with an increased baseline risk for anemia (e.g., spherocytosis), hemolytic anemia, or diseases in which anemia would be medically problematic, or hemophilia; c) Pre-existing ophthalmologic disorders considered clinically significant on eye exam, including retinal, examination. Note: all subjects with a history of diabetes or hypertension must have a documented eye exam within 12 months prior to initiation of P/R; d) Thyroid-stimulating hormone (TSH) < 0.8 times LLN or > 1.2 times ULN of the laboratory reference range, unless i) The subject is clinically euthyroid as determined by the investigator, AND ii) Free T4 is greater than or equal to 0.8 times LLN and less than or equal to 1.2 times ULN e) History of chronic pulmonary disease associated with functional limitation such as clinically significant chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidois, etc; f) History of cardiomyopathy, coronary artery disease (including angina), interventional procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia, congestive heart failure, pulmonary hypertension, cardiomyopathy, or other clinically significant cardiac disease; g) Historical or current ECG findings indicative of cardiovascular instability, including but not limited to evidence of significant myocardial ischemia, unstable re-entry phenomena, other significant dysarrhythmias and/or uncontrolled hypertension; h) Immunologically-mediated disease (eg, inflammatory bowel disease [Crohn s disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected treatment, or symptomatic thyroid disorder). i) Any known contraindication to peg-IFN -2a or ribavirin, not otherwise specified. j) Alanine aminotransferase (ALT) greater than 10 times ULN; k) Total Bilirubin greater than or equal to 34 mol/L (greater than or equal to 2 mg/dL), unless subject has a documented history of Gilbert s disease; l) INR greater than or equal to 1.7; m) Albumin < 3.5 g/dL (35 g/L); n) Platelets < 70 times 10(9) cells/L; o) ANC < 1,500 cells/mm3 (confirmed ANC < 1,200 cells/mm3 for Black/African-Americans); p) Hemoglobin < 12 g/dL (120 g/L) for women and < 13 g/dL (130 g/L) for men; q) Creatinine Clearance (CrCl) less than or equal to 50 mL/min (as estimated by Cockcroft and Gault); r) History of hypersensitivity to drugs with similar biochemical structure to pegIFN alpha or ribavirin s) QTcF or QTcB > 500 msec
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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): 18.0-35.0, Chronic Viral Hepatitis C No history of chronic diseases Preserved oral health No history of acute illness in the last 30 days Absence of significant clinical symptoms and signs on physical examination laboratory tests within normal limits imaging tests within normal limits Seronegative tests for HIV and B and C Hepatitis; Signing the consent form Male Age between 18 and 35 years Body mass index between 19 and 26 (weight in kg / height in meters squared) Patients with hypersensitivity to Interferon alpha, Escherichia coli-derived products, polyethylene glycol (macrogol), or any constituent salts of these preparations Individuals treated with some type of interferon at any time, prior to the present research History of chronic diseases such as autoimmune diseases, liver failure, decompensated cirrhosis, heart disease, renal failure, diabetes mellitus, thyroid diseases, hemoglobinopathies, cytopenias, history of psychiatric disease, retinopathy, optic neuritis History of acute viral disease in the last 30 days Current use of medications that alter immunity: corticosteroids, immunosuppressants History of known allergy to drugs, including interferon or to any component of the product (at the discretion of the investigator) Having undergone surgery during the 6 months prior to study entry; Had donated blood three months prior to study entry History of alcoholism or current use of alcohol Use of other illicit drugs in the past 6 months Participation in a clinical study with previous therapeutic intervention in the year prior to 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): 20.0-65.0, Chronic Hepatitis C Adult subjects who are 20 to 65 years old (inclusive), of either gender and in any ethnical group in Asia Chronic hepatitis C, positive with both antibody to hepatitis C virus (anti HCV) and HCV RNA assays Confirmed HCV genotype 1 Subjects who are indicated to have combination treatment of PegIFNα 2a and RBV at the discretion of the investigator All fertile males and females receiving RBV must be using two forms of effective contraception during treatment with study drugs and 6 months post treatment completion Subjects must voluntarily give written informed consent indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Subjects must be able to comply with the assessments during the study Subjects must be able to understand study QoL questionnaires Prior treatment with any IFN α or any medicines that contain Cordyceps Prior treatment of hepatitis C with any other antiviral or immune modulators Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study Subjects diagnosed with hepatocellular carcinoma (HCC) by biopsy or α fetoprotein (AFP) serology and radiology (helical computed tomography [CT] and/or magnetic resonance imaging [MRI]) within 5 years of signing the informed consent form Evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) History or evidence of other liver diseases other than chronic HCV infection Subjects with known allergy or hypersensitivity to any ingredient of the study drug or placebo Pregnant, planning on becoming pregnant, or breastfeeding female subject or male subject whose partner is pregnant or planning on becoming pregnant Subject with any of the following laboratory abnormalities: 1. Platelet count <90,000/mm3; 2. Absolute neutrophil count <1500 cells/mm3; 3. Hemoglobin <12 g/dL for women and <13 g/dL for men; 4. Creatinine >1.5 mg/dL; 5. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN); 6. Total serum bilirubin >1.5 x ULN; 7. Subjects without cirrhosis and AFP >50 ng/mL must have an ultrasound between the screening and baseline visit with no findings suspicious for HCC Medical conditions which are contraindications for PegIFNα 2a or RBV therapy: 1. Psychiatric disorders; 2. Organ transplant (other than cornea or hair transplant or skin graft); 3. Severe concurrent medical disease such as severe hypertension, significant coronary heart disease, poorly controlled diabetes mellitus (glycated hemoglobin A1c [HbA1c] >8.5%), not adequately controlled thyroid dysfunction, chronic obstructive pulmonary disease, severe infections (bacterial, viral, fungal, including acute tuberculosis), or hemoglobinopathies (thalassemia major or sickle cell anemia); 4. Autoimmune hepatitis or other autoimmune conditions known to be exacerbated by PegIFNα 2a and RBV
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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, Hepatocellular Carcinoma Male or female patients from 18 to 75 years of age with a diagnosis of HCC. A diagnosis of HCC based on the diagnostic for HCC used by the European Association for the Study of the Liver (EASL). The patient has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation, or any other treatment with chemotherapeutic agents or sorafenib. The patient has not been previously treated with any anti-viral agents, including interferon or nucleosides analogs (NAs). Adults patients with a diagnosis of HCC which is not amenable to surgical resection ,local ablative therapy or any other radically cured treatment. The MDT group of HCC agree to administer TACE in this patient. Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria. No serious concurrent medical illness. Unresectable TNM stage Ⅲ or Ⅳ disease. Zubrod-ECOG-WHO performance status: 0 or 1. and the estimated survival more than 4 months. Not pregnant or breast-feeding patients No significant renal impairment (creatinine clearance < 30 mL/minute) or patients on dialysis No current infections requiring antibiotic therapy Not on anticoagulation or suffering from a known bleeding disorder No unstable coronary artery disease or recent MI Ability to understand the protocol and to agree to and sign a written informed consent document The following laboratory parameters at baseline: Platelet count ≥ 70,000/µL Hemoglobin ≥ 8.5 g/dL Absolute neutrophil count (ANC) >1,500/mm3 Total bilirubin ≤ 1.5 mg/dL Serum albumin ≥ 35 g/L Serum creatinine ≤ 1.5 x upper limit of normal PT prolong time less than 3 seconds Cirrhotic status of Child-Pugh class A only ALT<2×upper limit of normal Hepatitis B surface antigen positive If hepatitis B e antigen positive, HBV DNA level <2000IU/mL; If hepatitis B e antigen negative, HBV-DNA<200IU/mL History of HIV or HCV infection. History of organ allograft Known or suspected allergy to the investigational agents or any agent given in association with this trial. Evidence of bleeding diathesis. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of study entry. Serious non-healing wound, ulcer, or bone fracture Known central nervous system tumors including metastatic brain disease Any event > grade 2 National Cancer Institute [NCI]-Common Terminology for Adverse Events [CTCAE] version 3.0 Severe complication after TACE. History of hepatotoxic medication within 8 wk prior to the current treatment. History of corticosteroid administration
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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 Age 18 years Body Mass Index (BMI) 18-30 Chronic hepatitis C , diagnosed according to Chinese guideline of Hepatitis C (year 2004) Detectable serum HCV-RNA by quantitative polymerase chain reaction assay and positive anti-HCV antibody Female subjects of childbearing age with no history of menopause and negative pregnancy test, both female and male( including their partners ) subjects were required to conduct adequate contraception since screening until the 6 months after treatment Volunteered to participate in this study, understood and signed an informed consent Previous IFN treated patients Hepatotoxic drugs was systematically used more than two weeks within past 6 months Systemic therapy with potent immunomodulatory agents such as adrenocorticotropic hormone, thymosin α1, etc more than two weeks within past 6 months, not including corticosteroid nasal sprays, inhaled steroids and / or topical steroids Co-infection with HAV, HBV, HEV, EBV, CMV and HIV Evidences of hepatic decompensation, including but not limited to serum total bilirubin> 2 times the upper limit of normal (ULN); serum albumin <35g/L; prothrombin activity (PTA) <60%; ascites, upper gastrointestinal bleeding and hepatic encephalopathy; Child-Pugh score B/C grade Diagnosed with primary hepatocellular carcinoma or supported by evidences including but not limited to AFP> l00ng/ml, suspicious liver nodules by imaging examinations Liver diseases from causes other than HCV infection, including alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced hepatitis, autoimmune hepatitis (antinuclear antibody titer higher than 1:100), hepatolenticular degeneration (Wilson's disease) and hemochromatosis, etc White blood cell count <3×109/L; Neutrophil count<1.5×109/L; platelet count<90×109/L; hemoglobin below the lower limit of normal Serum creatinine above the ULN Serum creatine kinase> 3 ULN
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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, Liver Cirrhosis Confirmed diagnosis of AIH based on the diagnostic revised by the International Autoimmune Hepatitis Group 2008 (20): 1. liver related autoantibodies, 2. hypergammaglobulinaemia, 3. typical histological findings and 4. absence of viral markers morbid obesity (BMI > 40) ascites, ileus or subileus peritonitis pregnancy extrahepatic cholestasis and a severe inflammatory flare of AIH
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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 Age 18 years Body Mass Index (BMI) 18-30 Chronic hepatitis C , diagnosed according to Chinese guideline of Hepatitis C (year 2004) Detectable serum HCV-RNA by quantitative polymerase chain reaction assay and positive anti-HCV antibody Female subjects of childbearing age with no history of menopause and negative pregnancy test, both female and male( including their partners ) subjects were required to conduct adequate contraception since screening until the 6 months after treatment Volunteered to participate in this study, understood and signed an informed consent Previous IFN treated patients Co-infection with HAV, HBV, HEV, EBV, CMV and HIV Evidences of hepatic decompensation, including but not limited to serum total bilirubin> 2 times the upper limit of normal (ULN); serum albumin <35g/L; prothrombin activity (PTA) <60%; ascites, upper gastrointestinal bleeding and hepatic encephalopathy; Child-Pugh score B/C grade Hepatotoxic drugs was used for a long time within past 6 months Diagnosed with primary hepatocellular carcinoma or supported by evidences including but not limited to AFP> l00ng/ml, suspicious liver nodules by imaging examinations Liver diseases from causes other than HCV infection, including alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced hepatitis, autoimmune hepatitis (antinuclear antibody titer higher than 1:100), hepatolenticular degeneration (Wilson's disease) and hemochromatosis, etc White blood cell count <3×109/L; Neutrophil count<1.5×109/L; platelet count<90×109/L; hemoglobin below the lower limit of normal Serum creatinine not within the normal range Serum creatine kinase> 3 ULN Positive thyroid antibodies (A-TPO, A-TG)
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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 Heptitis B Age 18 or above Positive hepatitis B surface antigen for at least 6 months On ETV monotherapy as anti-viral treatment for at least 52 weeks HBV DNA (>20 IU/ml) at week 52 or more of ETV treatment Written informed consent obtained Concurrent use of other antiviral treatment (including oral nucleos(t)ide analogs, interferon or pegylated interferon) for chronic hepatitis B Concurrent use of steroids or immunosuppressive agents more than two week consecutively Co-infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) Features suggestive of concomitant chronic liver diseases: positive anti-nuclear antibody (ANA) titer above 1/160, positive anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), abnormal serum ceruloplasmin or iron profile, or histological features of alternative chronic liver disease Pregnancy or breast feeding Inability or unwillingness to give informed consent or abide by the requirements of the study History of other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study Patients with baseline significant impaired renal function with creatinine clearance <30 ml/min or receiving dialysis for end stage renal disease
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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): 15.0-65.0, Schistosomiasis Mansoni Portal Hypertension Upper Gastrointestinal Bleeding age between 15 and 65 years an established diagnosis of hepatosplenic schistosomiasis as the cause of portal hypertension a history of UGIB secondary to rupture of esophageal varices, with at least 20 days having elapsed since the most recent episode of bleeding Chronic alcoholism, defined as an alcohol intake of ≥60 g/EtOH/day in men and ≥40 g/EtOH/day in women evidence of decompensated liver disease of mixed etiology or of any chronic disease that contraindicated surgery were considered absolute the relative for were altered hemostasis (platelet count < 50×109/L or INR > 1.5) presence of fundal varices on endoscopy
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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 Male and female patients *18 years of age Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test Detectable serum HCV-RNA and HCV viral genotype 1 Liver biopsy findings consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis (Exception: hemophiliacs in whom biopsy is medically contra-indicated do not require biopsy.) Compensated liver disease (Child-Pugh Grade A clinical classification) 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 All fertile males and females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end 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 Co-infection with active hepatitis A, hepatitis B and/or human immunodeficiency virus (HIV) 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) Signs or symptoms of hepatocellular carcinoma History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease Neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening
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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, Liver Fibrosis Ages from 18 to 65 years old; 2. Male or female; 3. Treatment-naive patients with chronic HBV-induced fibrosis S2/S3 (similar to F2/F3, Ishak 2/3/4), who consent to undergo liver biopsy before and after treatment; 4. Patients with HBeAg-positive, IU/ml or with HBeAg-negative, IU/ml; 5. Agree to be follow-up regularly; 6. signature of written inform consent Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or hepatocelluar carcinoma; 2. Patients who are allergic to entecavir, interferon, or their components, and those considered not suitable for medications used in this study; 3. Patients coinfection with HCV or HIV, alcoholic liver disease, autoimmune liver disease, genetic liver disease, drug-induced liver injury, severe non-alcoholic fatty liver disease or other chronic liver diseases; 4. Patients with baseline AFP level higher than 100 ng/ml and possible malignant lesion on image, or AFP level higher than 100 ng/ml for continuous three months; 5. Creatinine >1.5×ULN; 6. Patients with other uncured malignant tumors; 7. Patients with severe diseases of heart, lung, kidney, brain, blood system or other organs; 8. Patients with severe neurological or psychological disease (e.g. epilepsy, depression, mania and schizophrenia); 9. Patients with poorly controlled diabetes, hypertension or thyroid disease; 10. Patients with any other reasons not suitable for 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): 18.0-65.0, Liver Cirrhosis Patients from age 18 to 65 years old; 2. Male or female; 3. Treatment-naive patients with chronic hepatitis B histologically confirmed of early cirrhosis S4 (similar to metavir F4, Ishak 5/6) who consent to undergo liver biopsy before and after treatment; 4. Patients with HBeAg-positive, or patients with HBeAg-negative, IU/ml； 5. Agree to be followed up regularly; 6. Signature of written informed consent Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or hepatocelluar carcinoma; 2. Patients who are allergic to entecavir, thymosin or their components, and those considered not suitable for drugs used in this study; 3. Patients with HCV or HIV infection, alcoholic liver disease, autoimmune liver disease, genetic liver disease, drug-induced liver injury, severe non-alcoholic fatty liver disease or other chronic liver diseases; 4. Patients with baseline AFP level higher than 100 ng/ml and possible malignant lesion on image, or AFP level higher than 100 ng/ml for more than three months; 5. Creatinine >1.5×ULN; 6. Patients with other uncured malignant tumors; 7. Patients with severe diseases of heart, lung, kidney, brain, blood or other organs; 8. Patients with any other reasons not suitable for 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): 18.0-65.0, Liver Cirrhosis Patients from age 18 to 65 years ; 2. Male or female; 3. Treatment-naive patients of clinically diagnosed as HBV-induced compensated cirrhosis(meet one of the following two criterions); 1. endoscopy: esophageal varices , of noncirrhotic portal hypertension 2. if no endoscopy,should meet two of the four Criterias Imaging (US, CT or MRI, et al) showing Surface nodularity: Echogenecity Platelet (PLT) < 100×10 < 9 >/L , no other interpretation Albumin (ALB) < 35.0 g/L, or International Standard Value (INR) > 1.3 (Prothrombin Time (PT) prolonged > 3s), or Cholinesterase (CHE) decrease Liver stiffness measurement value > 12.4 kpa (ALT<5×ULN) 4. HBeAg-positive, > 2×10<3> IU/ml or with HBeAg-negative patients, > 2×10<2> IU/ml; 5. Agree to be followed up regularly; 6. Signature of written inform consent Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or hepatocelluar carcinoma; 2. Patients who are allergic to entecavir, thymosin or their components, and those considered not suitable for medicine in this study; 3. Patients with HCV or HIV infection, alcoholic liver disease, autoimmune liver disease, genetic liver disease, drug-induced liver injury, severe non-alcoholic fatty liver disease or other chronic liver diseases; 4. Patients with baseline AFP level higher than 100ng/ml and possible malignant lesion on image, or AFP level higher than 100ng/ml for more than three months; 5. Creatinine > 1.5×ULN; 6. Patients with other uncured malignant tumors; 7. Patients with severe diseases of heart, lung, kidney, brain, blood system or other organs; 8. Patients with any other reasons not suitable for 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, Hepatitis C, Chronic All HCV infected patients who will consecutively come to the participating clinical centers in a given time span (enrollment periods) Younger than 18 years Patients treated at the moment of the enrollment
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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, Chronic Hepatitis C Male or female, at least 18 years of age Asian background HCV treatment-naïve Chronic HCV infection is defined as one of the following Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before Screening, and positive for HCV RNA and anti-HCVAb at the time of Screening; or Positive for anti-HCV Ab and HCV RNA 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) Screening laboratory result indicating HCV genotype 6-infection (HCV-6) Plasma HCV RNA level > 10,000 IU/mL at Screening IL28B C/C genotype (rs12979860) Per local standard practice, documented results of one of the following Non-genotype 6 HCV infection, or evidence of mixed genotype HCV infection IL28B C/T or T/T polymorphism (rs12979860) Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4 Exceed defined thresholds for key laboratory parameters at Screening Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human immunodeficiency virus antibody (HIV Ab) Diagnosis of autoimmune disease, decompensated liver, disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment, as defined by the product label
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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, Hemochromatosis, Type 4 Ferroportin Disease Dysmetabolic Hepatosiderosis Diagnosis for patients Man or woman older than 18 years Subject having a liver iron overload greater than or equal to 100 umol /g dry liver weight, confirmed by MRI (done performed with body antenna and complete deactivation of the surface antenna) and / or by biochemical assay on liver biopsy, and related to dysmetabolic hepatosiderosis or ferroportin disease The ferroportin disease will be retained when patients will present an hyperferritinemia without elevated transferrin saturation and a heterozygote mutation in the gene encoding ferroportin A dysmetabolic hepatosiderosis will be retained following the usual diagnostic investigation including sequencing of the gene for ferroportin (mutation proven negative), if patients do not show any other cause of iron overload and hyperferritinemia is not related to excessive alcohol intake, non-metabolic liver cytolysis (hepatitis C virus, wilson, autoimmune hepatitis, ...), hemolysis, or inflammatory syndrome Status towards the iron-depletive treatment : either no venesection performed (Dysmetabolic HepatoSiderosis and Ferroportin disease groups) or attack iron depletive treatment completed (Treated Dysmetabolic Hepatosiderosis and Treated Ferroportin Disease groups) with ferritin level less than 100 ng / ml, without anemia and with no venesection in the two last months Having given a free and informed consent in writing Affiliate to the social security system for patients Alcohol consumption greater than 30g/d Chronic inflammatory disease HIV, HCV or HBV Infection Blood donation in the last three months Infection during the previous seven days before testing Staying in altitude (>1500 m) dating less than 2 months Night occupation or shift work Pregnancy period in the national register of persons suitable for biomedical research
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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, Viral Hepatitis B Viral Hepatitis C HBV-positive patients Chronic hepatitis B defined by a positive HBsAg ( surface antigen of the hepatitis B virus) for at least 6 months Acute hepatitis B defined as a recent appearance (<6 months) of detectable HBs Ag Chronic hepatitis B with serological remission HbsAg-negative , HB DNA-negative With or without association with acute or chronic hepatitis D HCV-positive patients Chronic hepatitis C defined by the positivity for anti-HCV antibodies for at least 6 months and positive HCV-RNA Acute hepatitis C defined by the recent appearance of HCV RNA (less than 6 months) in patients with risk factors (with or without positive antibodies) Patients with cured hepatitis C defined by long-term eradication, either spontaneous, a positive anti-HCV antibodies associated to a negative RNA at two collection months interval time; either treatment defined by negative viremia 3 month after end of treatment HIV co-infected patients are not eligible to the cohort So-called vulnerable populations (minors, people under guardianship or protection, or a private individual under protection from making legal or administrative decisions) Treatment ongoing hepatitis C during or stopped since less than 3 months Patients end of life Woman whose pregnancy is known
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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): 40.0-65.0, Work Ability Depression HCV infection cancer severe jaundice pulmonary and renal chronic diseases prostatic diseases autoimmune diseases diabetes mellitus decompensated cirrhosis pregnancy hemoglobinopathies hemocromatosis
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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): 20.0-999.0, Hepatitis B Virus-Related Hepatocellular Carcinoma for treatment group: 1. Age older than 20 years old. 2. HBsAg (+) > 6 months 3. Baseline serum HBV DNA ≧ 2000 IU/mL (10,000 copies/mL) 4. Liver cirrhosis (Child A) before or at enrollment, diagnosed by 1). Liver biopsy（Metavir F4 or Ishak > F5） or 2). Ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices) 5. Receiving long-term anti-HBV therapy for control group: 1. Age older than 20 years old. 2. HBsAg (+) > 6 months 3. Baseline serum HBV DNA ≧ 2000 IU/mL (10,000 copies/mL) 4. Liver cirrhosis (Child A) before or at enrollment, diagnosed by 1). Liver biopsy（Metavir F4 or Ishak > F5） or 2). Ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices) 5. without receiving treatment . Co-infection of HCV (anti-HCV (+)) or HIV 2. . Alcoholism (alcohol consumption > 20 gm/day) 3. . Serological evidence suggestive of autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hemochromatosis 4. . Liver decompensation (Child-Pugh classification of B or C) 5. . Evidence of HCC at study entry 6. . 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): 18.0-999.0, HCV Infection Key Cohorts 1 and 2: chronic genotype 1 or 3 HCV infection Cohort 3: chronic genotype 1 or 4 HCV infection HCV RNA ≥ 10^4 IU/mL at screening Screening labs within defined thresholds Cirrhosis determination at screening Key Females who are pregnant or nursing or males who have a pregnant partner Prior null response to pegylated interferon (Peg-IFN)+RBV therapy (Cohorts 1 and 2) or for individuals with cirrhosis, prior treatment failure with IFN-based therapy not resulting from treatment intolerance (Cohort 3) Current of prior history of hepatic decompensation Infection with hepatitis B virus (HBV) or HIV History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with individual's treatment and/or adherence to the protocol 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): 18.0-999.0, HIV-HCV Co-infected Patients Adult ≥ 18 years Patients co-infected HIV-HCV (HCV serology and HCV positive CV before starting HCV treatment) Patients who have been treated with combination therapy Peg-IFN/RBV for at least 12 weeks and having at least a given plasma RBV available in the patient record Free Consent, informed and signed Adult <18 Mono-infection with HCV or HIV Co-infection with HBV (HBsAg +) Pregnant or lactating woman Not obtaining free and informed consent signed
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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, Autoimmune diagnosis of autoimmune hepatitis according to Autoimmune Hepatitis International Group histological remission during treatment with immunosuppressive drugs (Liver biopsy with periportal inflammatory activity less than 2) No evidence of decompensated liver cirrhosis Non-pregnant women and women with no intention to become pregnant Willing to participate in the study patients who needed to suspend the drug under six months of the medication because of side effects or the patient's desire 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): 40.0-65.0, Adult Lymphoblastic Lymphoma Disease ALL in complete remission (CR) at the time of transplant. Remission is defined as "less than 5.0% bone marrow lymphoblasts by morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration Philadelphia chromosome positive ALL is allowed Lymphoid blastic crisis of CML will be included (provided that patients achieve CR) Age Equal or above age 40 and up to 65 years. If younger than 40, there must be comorbidities which preclude the patient to undergo CyTBI conditioning regimen Organ Function All organ function testing should be done within 28 days of study registration Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) ≥ 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) ≥ 50% of predicted Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula: CrCl = (140-age) x weight (kg) x 0.85 (if female)/72 x serum creatinine (mg/dL) Hepatic Non-compliant to medications No appropriate caregivers identified HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive Active life-threatening cancer requiring treatment other than ALL Uncontrolled medical or psychiatric disorders Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration Active central nervous system (CNS) leukemia Preceding allogeneic HSCT Receiving intensive chemotherapy within 21 days of registration. Maintenance type of chemotherapy will be allowed
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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, Breast Cancer Nos Metastatic Recurrent Women Aged 18 years and over With an invasive breast cancer diagnosed by cytology or histology Tumors cT0 to cT3, CN0-3 No clinical evidence of metastasis at the time of Untreated including scored for breast cancer surgery in progress Patient receiving a social security system Patient mastering the French language Free and informed consent for additional biological samples, different questionnaires and collecting information on resource usage Metastatic breast cancer Local recurrence of breast cancer History of cancer within 5 years prior to entry into the trial other than basal cell skin or carcinoma in situ of the cervix Already received treatment for breast cancer ongoing Blood transfusion performed for less than six months Persons deprived of liberty or under supervision (including guardianship)
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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, Thyroid Cancer Newly diagnosed with a first occurrence of thyroid cancer <2-4 weeks of diagnosis (i.e., histologically confirmed thyroid cancer (papillary, follicular, or medullary type; TNM classification system) Willing to participate in the EG meetings >18 years Alert and capable of giving free and informed consent Able to speak and read English or French Anaplastic thyroid cancer Karnofsky Performance Status (KPS) score <60 (rated by the Research Coordinator (RC) or referring physician) or expected survival <6 months according to clinical judgment
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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 Pain Women Clinical diagnosis of chronic pelvic pain More than eighteen years Non-menstrual or noncyclic pelvic pain Duration of pain of at least 6 months Duration of pain less than 6 months Women who were pregnant in the last 12 months
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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 Hepatitis C Virus Compensated Cirrhosis Chronic HCV infection prior to study enrollment Screening laboratory result indicating HCV genotype 1-infection Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening Per local standard, subject is considered to be non-cirrhotic or to have compensated cirrhosis History of severe, life-threatening or other significant sensitivity to any drug Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency Virus antibody (HIV Ab) Prior therapy for the treatment of HCV Any current or past clinical evidence of Child Pugh B or C classification of clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy Any cause of liver disease other than 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): 18.0-999.0, Hepatitis C For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Males and females, ≥ 18 years of age Subjects chronically infected with HCV Genotype (GT)-1b only as documented by positive HCV RNA and anti-HCV antibody at screening and either: 1. Positive anti-HCV antibody, HCV RNA or positive HCV genotype test at least 6 months prior to screening or 2. Liver biopsy consistent with chronic HCV infection (evidence of fibrosis and/or inflammation) Subjects who are intolerant to previous therapy with Interferon Alfa (IFNα) either with or without Ribavirin (RBV) (I±R)(independent of previous response to therapy) or ineligible for I±R and who meet one of the below: 1. Anemia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in hemoglobin to < 8.5 g/dL during therapy (documented); the I±R ineligibles are subjects who have a screening hemoglobin < 10.0 g/dL and ≥ 8.5 g/dL OR 2. Neutropenia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in absolute neutrophil count (ANC) to < 0.5 x 10(9) during therapy (documented); the I±R ineligibles are subjects who have a screening ANC < 1.5 x 10(9) cells/L and ≥ 0.5 x 10(9) cells/L OR 3. Thrombocytopenia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in platelet counts < 25,000 cells/mm3 during therapy (documented); the I±R ineligibles are subjects who have a screening platelet count of < 90 x 10(9) cells/L and ≥ 50 x 10(9) cells/L HCV RNA ≥ 10,000 IU/mL Seronegative for Human Immunodeficiency Virus (HIV) and hepatitis B surface antigen (HBsAg) Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI = weight (kg)/ [height(m)]2 at screening Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 40%). If a subject does not have cirrhosis, a liver biopsy within three years prior to enrollment is required to demonstrate the absence of cirrhosis. If cirrhosis is present, any prior liver biopsy is sufficient. For countries where liver biopsy is not required prior to treatment and where noninvasive imaging tests (Fibroscan® ultrasound) are approved for staging of liver disease, non-invasive imaging test results may be used to assess the extent of liver disease Prior treatment with HCV direct acting antiviral (DAA) Evidence of a medical condition contributing to chronic liver disease other than HCV Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy Diagnosed or suspected hepatocellular carcinoma or other malignancies Uncontrolled diabetes or hypertension History of moderate to severe depression. Well-controlled mild depression is allowed Total bilirubin ≥ 34 µmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease Confirmed alanine aminotransferase (ALT) ≥ 5 x upper limit of normal (ULN) Confirmed albumin < 3.5 g/dL (35 g/L) Alpha-fetoprotein (AFP) > 100 ng/mL OR ≥ 50 and ≤ 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of hepatocellular carcinoma (HCC) are excluded
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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, Coronary Artery Stenosis Age ≥ 18 years Patient with an indication for PCI including angina (stable or unstable), silent ischemia (in absence of symptoms a visually estimated target lesion diameter stenosis of ≥70%, a positive non-invasive stress test, or FFR ≤0.80 must be present), or recent STEMI. For STEMI the time of presentation to the first treating hospital, whether a transfer facility or the study hospital, must be >24 hours prior to randomization and enzyme levels (CK-MB or Troponin) demonstrating that either or both enzyme levels have peaked Non-target vessel PCI are allowed prior to randomization depending on the time interval and conditions as follows: a. During Baseline Procedure: i. PCI of non-target vessels performed during the baseline procedure itself immediately prior to randomization if successful and uncomplicated defined as: <50% visually estimated residual diameter stenosis, TIMI Grade 3 flow, no dissection ≥ NHLBI type C, no perforation, no persistent ST segment changes, no prolonged chest pain, no TIMI major or BARC type 3 bleeding. b. Less than 24 hours prior to Baseline Procedure: i. Not allowed (see #3). c. 24 hours-30 days prior to Baseline Procedure: i. PCI of non-target vessels 24 hours to 30 days prior to randomization if successful and uncomplicated as defined above. ii. In addition, in cases where non-target lesion PCI has occurred 24-72 hours prior to the baseline procedure, at least 2 sets of cardiac biomarkers must be drawn at least 6 and 12 hours after the non-target vessel PCI. If cardiac biomarkers are initially elevated above the local laboratory upper limit of normal, serial measurements must demonstrate that the biomarkers are falling. d. Over 30 days prior to Baseline Procedure: iii. PCI of non-target vessels performed greater than 30 days prior to procedure whether or not successful and uncomplicated Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule. Angiographic (visual estimate) Treatment of up to three de novo target lesions, maximum of one de novo target lesion per vessel Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥2.5 mm to ≤4.25 mm and diameter stenosis ≥50% to <100% Lesion must be ≤28 mm long and can be covered by a single study stent with maximum length of 33 mm (note: multiple focal stenoses may be considered as a single lesion and be enrolled if they can be completely covered with one stent) TIMI flow 2 or 3 If more than one target lesion will be treated, the RVD and lesion length of each must meet the above criteria Planned procedures after the baseline procedure in either the target or non-target vessels STEMI within 24 hours of initial time of presentation to the first treating hospital, whether at a transfer facility or the study hospital or in whom enzyme levels (either CK-MB or Troponin)have not peaked PCI within the 24 hours preceding the baseline procedure and randomization Non-target lesion PCI in the target vessel within 12 months of the baseline procedure History of stent thrombosis Cardiogenic shock (defined as persistent hypotension (systolic blood pressure <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support, including IABP Known LVEF <30% Subject is intubated Relative or absolute contraindication to DAPT for 12 months (including planned surgeries that cannot be delayed, or subject is indicated for chronic oral anticoagulant treatment) Hemoglobin <10 g/dL
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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, Hepacivirus HIV Infections HIV/HCV coinfected patients to 65 years old currently receiving HAART non-pregnant women HIV infection controlled as: undetectable viral load (<40 copies/mL) for at least 8 months and T helper cells count of 200 cells/μL or above no contraindications to IFN alpha2a, RBV or PTX treatment sign informed consent form laboratory parameters within acceptable ranges Women that present a positive pregnancy test during the study Patients that for any reason no longer wish to receive IFN alpha2a, RBV or PTX treatment Serious adverse events that prevent to continue IFN alpha2a, RBV or PTX treatment; such as severe neutropenia, severe thrombocytopenia or severe anemia Presence of an opportunistic infection or malignancy that requires treatment with drugs interacting with IFN alpha2a, RBV or PTX Patients that fail to adhere to 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 HCV Infection Key Willing and able to provide written informed consent HCV RNA ≥ 10^4 IU/mL at screening HCV treatment-naive (HCV genotype 1, 2, 3 or 6), defined as no prior exposure to any interferon (IFN), RBV, or other approved or experimental HCV-specific direct-acting antiviral agent, or HCV treatment-experienced (HCV genotype 1, 2, 3, or 6 only) with medical records that sufficient detail of prior treatment with IFN to allow for categorization of prior response as either IFN Intolerant, non-responder, or experiences viral breakthrough or relapse HCV infection documented by anti-HCV antibody test, genotyping test, or liver biopsy Key Current or prior history of any clinically-significant illness (other than HCV) Pregnant or nursing female or male with pregnant female partner Chronic liver disease of a non-HCV etiology Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) 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): 18.0-999.0, Hepatitis C Hepatitis B Nonalcoholic Fatty Liver Disease (NAFLD) Nonalcoholic Steatohepatitis (NASH) are adults must undergo a liver biopsy as part of their clinical standard of care for suspected or known chronic liver disease caused by HBV, HCV or NASH understand French or English instruction Autoimmune Hepatitis have any contra-indication to MRI (such as claustrophobia, pacemaker, metallic clips for a neurosurgical procedure) are pregnant or trying to become pregnant have a weight or girth preventing them from entering the MR magnet bore are unable to understand or unwilling to provide written informed consent for 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, Chronic Human Immunodeficiency Virus Older than 18 years HIV infection determined by enzymeimmunoassay and confirmed by Western Blot Naïve to treatment including a DAA Initiation of triple therapy including a DAA Written informed consent to participate in the study and to undergo genetic determinations Pregnancy Any contraindication for the administration of peg-IFN, RBV or the respective DAA Patients who are not able to provide informed consent to participate in 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): 20.0-80.0, Hepatitis C, Chronic Patient must be 20 years or older Patient must have HCV GT1 infection combined with HBV infection Patients must be serum HCV RNA detectable, anti-HCV positive, HBsAg positive and HBeAg negative Patient has previously failed treatment with PEG-IFN-α 2a or 2b/RBV for minimum of 12 weeks of treatment Patient must have compensated liver disease consistent with CHC and/or CHB, and no other etiology. Note: patients with cirrhosis should have a liver imaging study (e.g. ultrasound, CT scan or MRI) within the preceding 6 months showing no evidence of hepatocellular carcinoma Patient meets all of the requirements and none of the contra-indications for treatment with PEG-IFN alpha-2b/RBV or boceprevir defined in the labels for the PEG-IFN/RBV to be used in combination with boceprevir Patient is able and willing to provide signed informed consent (prepared by and administered by the physician) as required by local country requirements Mixed genotypes including HCV genotype other than genotype 1 Patient has received boceprevir, narlaprevir, telaprevir, or any other HCV protease inhibitor treatment Patient has evidence of decompensated liver disease including but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy Patient meets any of the following exclusionary hematologic and biochemical (documentation required) Hemoglobin <12 gm/dL for females and <13 gm/dL for males Neutrophils <1500/mm3 Platelets <100,000/mm3 Patient has an organ transplant other than cornea or hair Patient is co-infected with human immunodeficiency virus (HIV) Patient requires or is anticipated to require any of the following prohibited medications: midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives Patient with clinical diagnosis or evidence of substance abuse involving alcohol, intravenous drugs, inhalational psychotropics, narcotics, cocaine prescription or over-the-counter drugs Patient previously demonstrated clinically significant hypersensitivity or other contraindication to any component of the boceprevir formulation. This drug contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine Serious illness, including malignancy, active coronary artery disease or cardiac dysfunction within 24 weeks prior to study entry, that in the opinion of the site investigator may preclude completion of the treatment 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): 18.0-65.0, Chronic Hepatitis B HBeAg-negative patients on entecavir monotherapy for at least 24 months 2. Undetectable HBV DNA by PCR-based assay on 3 separate occasions 6 months apart (as per Asian Pacific guideline in 2008). 3. Normal ALT levels according to the local laboratory reference value on 2 separate occasions 6 months apart Patients previously or currently on interferon therapy 2. Patients who have experienced another antiviral agent besides entecavir 3. Patients with hepatitis C virus infection as indicated by a positive anti-HCV serology test 4. Patients with Child's B liver cirrhosis, cirrhotic complications or hepatocellular carcinoma 5. Patients with organ transplantation 6. Serious medical illnesses or malignancy 7. Age < 18 years or > 65 years 8. No patient 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): 18.0-999.0, Chronic Liver Disease All subjects that aere enrolled in the previous Exalenz trial HIS-EX-408 or PLT-BID-1108 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): 20.0-35.0, Treatment of Iron Deficiency Anemia in Pregnancy Maternal age 20-35 years old Singleton pregnancy between 16 weeks Iron deficiency anemia with average hemoglobin ranging from 7-9 g % at the onset of the study Extremes of reproductive age (less than 20 years old or more than 35 years old) Patients with multiple pregnancies Anemia not linked to iron deficiency Allergy to iron derivatives Any medical disorder like diabetes or tuberculosis (TB), viral hepatitis cirrhosis, cardiovascular disease, renal disease, autoimmune disease, suspected acute infection, cancer Those who had received parenteral iron treatment earlier within 3 months before the start of the study Any obstetric complicating factors like pregnancy induced hypertension Patients with history of chronic blood loss
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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, Chronic Hepatitis C Common with National Program for Viral Hepatitis Age: 18 years to 60 years Positive HCV antibodies using a third generation test Detectable HCV RNA by PCR Liver biopsy showing chronic hepatitis with either a score F1 with elevated liver enzymes or scores F2/F3 Naïve to treatment with PEG-IFN and RBV HBs antigen negative Prothrombin time ≥60 %, normal bilirubin, alpha-foeto protein < 3*normal range of the laboratory, anti-nuclear antibodies<1/160 Effective contraception during the treatment period; no breast-feeding Specific to the trial Prior approval from the Ministry of Health to be treated as part of the National Program with allocation to Peg-IFN α2b treatment Living <100 km from Cairo and able to come to the centre every week for the treatment Common with National program for Viral Hepatitis Serious co-morbid conditions such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes (HbA1C>8%) , chronic obstructive pulmonary disease Major uncontrolled depressive illness Solid transplant organ (renal, heart, or lung) Untreated thyroid disease History of previous anti-HCV therapy Body mass index (BMI) greater than 30 kg/m² Known human immunodeficiency virus (HIV) coinfection: although HIV testing will not be proposed or done, patients with known HIV coinfection will not be included in the trial Anti-HCV therapy contraindications hypersensitivity to one of the two drugs (PEG-IFN, RBV)
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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 C Age < 18 years and > 60 years Positive HCV antibodies using a third generation test Detectable HCV RNA by PCR Liver biopsy showing chronic hepatitis with either a score F1 with elevated liver enzymes or scores F2/F3 Naïve to treatment with PEG-IFN and RBV HBs antigen negative Prothrombin time ≥60 %, normal bilirubin, alpha-foeto protein < 3*normal range of the laboratory, anti-nuclear antibodies<1/160 Effective contraception during the treatment period; no breast-feeding Signed informed consent and willingness to participate in the study Serious co-morbid conditions such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes (HbA1C>8%) , chronic obstructive pulmonary disease Major uncontrolled depressive illness Solid transplant organ (renal, heart, or lung) Untreated thyroid disease History of previous anti-HCV therapy Body mass index (BMI) greater than 30 kg/m² Known human immunodeficiency virus (HIV) coinfection: although HIV testing will not be proposed or done, patients with known HIV coinfection will not be included in the trial hypersensitivity to one of the two drugs (PEG-IFN, RBV) pregnancy or unwilling to comply with adequate contraception breast-feeding
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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): 10.0-25.0, Hepatitis A Viral Hepatitis Vaccines Written informed consent for the 2012 was obtained according to local regulations from the subject/ from the parent(s)/ legally acceptable representative (LAR) of the subject A male or female between and including 10 and 25 years of age, who previously participated in the 2012 in Mexico Information required for the study is not available or incomplete Inadequate or insufficient serum sample to perform the laboratory tests for this study Serum sample is wrongly identified
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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, HIV-HCV Subjects who meet the following are eligible to enter the study: 1. Eighteen years of age or older at screening 2. Naive to treatment for hepatitis C or treatment experienced on previous IFN-containing treatment for chronic HCV infection. Patients who have been re-infected with HCV are excluded. 3. Women are allowed to participate if they agree to always use at least two forms of birth control. One form must be barrier protection (i.e., condom or female condom) and the other is to meet one of the below: 1. Non-childbearing potential status (i.e., physiologically incapable of becoming pregnant) Has had a hysterectomy or Has had a bilateral oophorectomy or Is post-menopausal (age greater than or equal to 50 and a demonstration of a total cessation of menses for greater than or equal to 1 year) or Has had a bilateral tubal ligation or fallopian tube inserts 2. Childbearing potential status women must have a negative serum pregnancy test at screening and agree to use an acceptable form of birth control, such as any of the following Complete abstinence from sexual intercourse 2 weeks prior to administration of the study drug until completion of the follow-up procedures and at least 5 weeks (women) after the last dose of the study drugs Vasectomized partner in reliably monogamous relationship An intrauterine device (IUD) 2 weeks prior to administration of the study drugs continuously until completion of the follow-up procedures and at least 5 weeks after the last dose of the study drugs Double contraceptive method (condom or occlusive cap [diaphragm or cervical/vault caps]; spermicidal foam/gel/film/cream/suppository) Oral, implantable, transdermal, or injectable or any other form of hormonal contraceptives are NOT an acceptable form of contraception for females on this study. 4. Men are allowed to participate if they agree to use at least 2 forms of birth control. One form must be barrier protection (i.e., condom or female condom) and the other is to meet one of the below: 1. Are sterile or 2. Agree to use at least one of the following approved methods of contraception 2 weeks prior to administration of the study drug until the completion of the followup procedures and at least 14 weeks after the last dose of the study drugs Patients with Child Pugh B or C cirrhotics are excluded 9. Ability to communicate effectively with the study investigator and other key personnel. 10. Willingness to comply with the study restrictions and requirements. 11. Opioid-dependent individuals must be participating in a supervised treatment program. 12. Subjects must have an external primary care doctor (outside of the Clinical Center and the NIH) for their medical management. 13. Willingness to have blood or tissue samples stored for future use to study liver disease and immune function. 14. Willingness to undergo HLA typing. 15. Otherwise healthy status as determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements performed at screening. Contraception The effects of ASV and DCV on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception as outlined in the and prior to study entry and until 5 weeks (women ) and 14 weeks (men) after last dose of study medication. Hormonal contraception is NOT considered an effective form of birth control for female subjects on this study. Oral contraceptives are not as effective in women taking ASV and DCV so women cannot rely on this form of birth control to prevent pregnancy. Females of childbearing-age must have a negative pregnancy test result prior to receiving ASV and DCV. If a woman becomes pregnant or suspects of being pregnant during the course of the study, she should inform the study staff and her primary care physician immediately 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 the subject treatment, assessment of compliance with the protocol; subjects currently under evaluation for a clinically-significant illness (other than HCV) are also excluded 2. Gastrointestinal disorder with post-operative condition that could interfere with the absorption of the study drug 3. Poor venous access interfering with required study blood collection 4. Clinical hepatic decompensation (i.e.,-ascites, encephalopathy or variceal hemorrhage) 5. Hepatic impairment (e.g., Child-Pugh class B [moderate] or Child-Pugh class C [severe]) 6. Solid organ transplantation 7. Significant pulmonary disease, significant cardiac disease or porphyria. 8. Unstable psychiatric disease (subjects with psychiatric illness that is well controlled on a stable treatment regimen or currently not requiring medication may be included) 9. Any malignancy or its treatment that in the opinion of the PI may cause ongoing interference with host immunity; subjects under evaluation for malignancy are not eligible 10. Significant drug allergy (such as anaphylaxis or hepatotoxicity) 11. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis) 2. Positive nucleotide sequence analyses of the NS5A gene for Y93H or L31M/V polymorphisms for the 2DAA arm only. 3. Positive test results at screening for hepatitis B virus (HBV) surface antigen (HBsAg) or HBV RNA (completed only if necessary to rule out chronic HBV) 4. Current use of non-protocol approved ARVs 5. A new AIDS-defining condition diagnosed within 30 days prior to date screening consent is signed or active serious infection (other than HIV and HCV), requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to Day 0 6. Abnormal hematological and biochemical parameters at screening, unless the test has been repeated and at least one subsequent result is within the acceptable range prior to study drug administration, including: 1. Neutrophil count <750 cells/mm3 2. Hemoglobin level <9 g/dL 3. Platelet count less than or equal to 50,000 cells/mm3 4. Estimated glomerular filtration rate, calculated by the chronic kidney disease epidemiology collaboration formula: <50 mL/min/1.73 m^2 5. ALT or AST level greater than or equal to10 times upper limit of normal (ULN) 6. Serum lipase level greater than or equal to 1.5 times ULN at screening or during the screening period in a patient with symptoms of pancreatitis 7. Total bilirubin level greater than or equal to 2.0 times ULN, except in subjects with Gilbert s syndrome 8. Albumin level less than or equal to 3.0 g/dL 7. Donation or loss of blood of >400 mL within 8 weeks prior to the first dose of the study drugs 8. Poorly controlled diabetes as indicated by a screening glycosylated hemoglobin (HbA1c) >10 9. Known hypersensitivity to ASV, DCV or formulation excipients 10. Pregnant or breastfeeding 11. Screening or baseline with clinically significant ECG findings, or personal/first degree relative history of Torsade de pointes 12. Need for the use of the following medications from 21 days prior to the start of study drugs through the end of treatment: 1. Hematologic stimulating agents, erythropoiesis stimulating agents (ESAs), granulocyte colony stimulating factor (GCSF), thrombopoeitin (TPO) mimetics 2. Chronic systemic antineoplastic or immunomodulatory treatment including supraphysiologic doses of immunosuppressants such as corticosteroids (e.g., prednisone equivalent >10 mg/day for >2 weeks), azathioprine or monoclonal antibodies (e.g., infliximab) 3. Investigational agents or devices for any indication 13. Previous treatment with an HCV protease inhibitor or any DAA 14. Medications for disease conditions excluded from the protocol (e.g active cancer, transplantation) are not listed under the Concomitant medication section, and are disallowed from the study 15. Use of certain medications and herbal/natural supplements per PI discretion, expected to result in increases or decreases in exposure to study or non-study medications as listed in Section 5.5 while receving study medications and within five half-lives or 14 days [whichever is longer] of the first dose of study medications. 16. Co-enrollment Guidelines: Co-enrollment in other clinical trials is restricted, other than enrollment in observational studies or those evaluating the use of a licensed medication. Study staff should be notified of co-enrollment status, as it may require prior approval of the investigator
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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 Chronic hepatitis C defined as detectable HCV RNA for more than 6 months Age > 18 years old Compensated liver disease (bilirubin < 3mg/dL, unless having Gilbert´s syndrome, albumin > 3 g/dL, INR < 2, no hepatic encephalopathy, no ascites or recent -1 month- history of variceal bleeding) HCV RNA level > 10.000 IU/mL Signed informed consent document History of cholecystectomy or known gallstones Current HCV antiviral treatment Medications for dyslipidemia in the preceding 2 months Abdominal surgery that could alter biliary or intestinal anatomy Evidence of sitosterolemia Negative pregnancy test in urine (for females)
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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 Hepatitis A5327 (Cohort 1 and Cohort 2) Step 1 for both cohorts (Cohort 1 and Cohort 2) HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry 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. [NOTE: The term "licensed" refers to a FDA-approved kit, which is required for all IND studies.] WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load A documented confirmation of acute HCV infection within 6 months prior to A5327 entry or HCV reinfection as described below: 1. Acute HCV infection was defined as meeting one of the following and of other causes of acute hepatitis New (<24 weeks prior to initial A5327 entry) ALT elevation to ≥5X upper limit of normal (ULN) OR >250 U/L in patients with documented normal ALT in the preceding 12 months or ≥10X ULN OR >500 U/L in patients with abnormal or no measured ALT baseline in the preceding 12 months with detectable HCV RNA excluding those with any prior positive anti-HCV. OR Detectable HCV RNA with prior negative anti-HCV Ab or undetectable HCV RNA within the preceding 6 months. 2. Acute HCV reinfection was defined by documentation of clearance of prior infection (as evidenced by positive anti-HCV Ab) either spontaneously or after treatment with two negative HCV RNA a minimum of 6 months apart AND meeting one of the following in addition to of other causes of acute hepatitis New (<24 weeks prior to initial A5327 entry) ALT elevation to ≥5X ULN OR >250 U/L in patients with documented normal ALT in the preceding 12 months or ≥10X ULN OR >500 U/L in patients with abnormal or no measured ALT baseline in the preceding 12 months with detectable HCV RNA. OR Positive HCV RNA with prior negative HCV RNA within the preceding 6 months HCV RNA confirmed to be detectable >12 weeks after first laboratory evidence of acute HCV and still within the <24 week from first laboratory evidence of acute HCV infection window. First laboratory evidence of infection was defined as date of first elevated liver enzymes or date of first serologic evidence of HCV seroconversion and/or viremia (whichever occurs first). [NOTE: If the screening visit occurred less than 12 weeks from the first laboratory evidence of infection, then the participant was required a pre-entry study visit to confirm detectable HCV RNA at least 12 weeks from the first laboratory evidence of infection had passed. It was optimal for this pre-entry visit to occur as close as possible to 12 weeks from first laboratory evidence to ensure timely treatment. Potential participants who entered screening but who had an undetectable HCV RNA (<LLOQ TND) at the pre-entry visit (when required) exhibited evidence of possible spontaneous clearance and will not meet the entry criteria.] Body mass index (BMI) ≥ 18 kg/m^2 Screening electrocardiogram (ECG) without clinically significant abnormalities as determined by the investigator for both cohorts (Cohort 1 and Cohort 2) Received investigational drug or device within 60 days prior to study entry Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, primary sclerosing cholangitis) Presence of active or acute AIDS-defining opportunistic infections within 30 days prior to study entry. [NOTE: A list of AIDS-defining opportunistic infections as defined by the CDC, can be found in Appendix B of the following document: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm] Active, serious infection (other than HIV-1 or HCV) requiring parenteral antibiotics, antivirals, or antifungals within 30 days prior to study entry Infection with hepatitis B virus (HBV) defined as HBsAg positive Evidence of acute hepatitis A infection defined as HAV IGM positive Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent > 10 mg/day) History of solid organ transplantation Current or prior history of clinical hepatic decompensation (eg, ascites, encephalopathy or variceal hemorrhage)
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