Efficacy and Safety of SOF/VEL + RBV and SOF/VEL/VOX for 12 Weeks in HCV Subjects With GT3b and Compensated Cirrhosis

This is an interventional treatment trial for Hepatitis C Read More

Inclusion Criteria:

1. Willing and able to provide written informed consent
2. Male or female, age ≥18 years
3. Body mass index (BMI) between 18.0-35.0kg/m2 and bodyweight ≥ 40 kg
4. Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy
5. Anti-HCV positive at screening
6. HCV RNA 104 IU/mL at screening by the Central Laboratory
7. HCV genotype 3b assessed at screening by the Central Laboratory
8. DAA treatment naïve defined as having never been exposed to approved or experimental HCV-specific direct-acting antiviral agents. Pegylated interferon/interferon based prior treatment is allowed.

9. Cirrhosis Determination: cirrhosis is defined as any one of the following:

   1. Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥5) in 24 months before screening, or
   2. Fibroscan® with a result of >12.5 kPa in 6 months before screening
10. The lab test at screening should meet all the criterion below: a) ALT ≤ 10 the upper limit of normal (ULN); b) AST ≤ 10 ULN; c) Total bilirubin ≤ 2 ULN; d) Platelets ≥ 60,000/L; e) Neutrophile ≥ 1,500/L; f) HbA1c ≤ 8.5%; g) Creatinine clearance (CLcr) ≥ 60 mL /min as calculated by the Cockcroft-Gault equation; h) Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects; i) Albumin ≥ 3 g/dL; j) INR ≤ 1.7 x ULN; k) AFP <100ng/mL；if 20ng/mL≤AFP≤100ng/mL，HCC should be exclude by liver ultrasound
11. Females of childbearing potential must have a negative serum pregnancy test at screening
12. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
13. Male subjects must agree to avoid donating sperm in 6 months after the last dose of drug
14. Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator
15. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments

Exclusion Criteria:

1. Decompensated cirrhosis, including but not limited to: prior or current ascites, variceal hemorrhage and/or hepatic encephalopathy; prior or current Child-Pugh B or C
2. HBsAg posititve at screening
3. Anti-HIV positive at screening
4. Alcohol abuse
5. Contraindication of ribavirin, including but not limited to hemoglobinapathy
6. Pregnant or nursing female or male with pregnant female partner
7. Use of any prohibited concomitant medications as described in Section before screening
8. Known hypersensitivity to SOF, VEL, RBV or formulation excipients
9. Subjects who has any of the following history: a) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis); b) Solid organ transplantation; c) Significant pulmonary disease, significant cardiac disease or porphyria; d) Pancreatitis; e) Autoimmune diseases (e.g., systemic lupus erythematosus, sarcoidosis, psoriasis); f) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years; g) Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible; h) Significant drug allergy (such as anaphylaxis or hepatotoxicity).
10. Assessed as ineligible by investigators