SOF (Sovaldi®) +RBV for 16 or 24 Weeks and SOF+RBV+Peg-IFN for 12 Weeks in Adults With Genotype 2 or 3 Chronic HCV Infection

Phase 3

Completed

Brief Summary: This study will assess the efficacy, safety, and tolerability of 16 or 24 weeks of sofosbuvir (Sovaldi®; SOF) + ribavirin (RBV), and 12 weeks of SOF+RBV+ pegylated interferon (Peg-IFN) in treatment-naive and treatment-experienced adults with chronic genotype 3 hepatitis C virus (HCV) infection, and treatment-experienced adults with cirrhosis and chronic genotype 2 HCV infection.

Recruitment & Eligibility

Inclusion Criteria

Male or female, age greater than or equal to 18 years.
Confirmed chronic HCV infection.
Subjects will have cirrhosis status assessment; liver biopsy may be required.
Genotype 2 subjects must have cirrhosis of the liver to be eligible.
Treatment-naive or prior treatment failure to ≥12 weeks of an interferon- based regimen that was not discontinued prematurely due to an adverse event
Infection with HCV genotype 2 or 3 as determined at Screening
Body mass index (BMI) greater than or equal to 18 kg/m^2
Screening laboratory values within predefined thresholds.
Liver imaging (e.g., ultrasound) within 6 months of Baseline/Day 1 is required in cirrhotic patients to exclude hepatocellular carcinoma (HCC). In the event of intrahepatic lesions, triple phase CT scan or MRI should be performed to exclude HCC.
Subject must be of generally good health as determined by the Investigator.

Key

Exclusion Criteria

Prior use of any other inhibitor of the HCV nonstructural protein (NS)5B polymerase
Pregnant or nursing female or male with pregnant female partner
History of any other clinically significant chronic liver disease.
HIV or chronic hepatitis B virus (HBV) infection.
Malignancy with the exception of certain resolved skin cancers.
Chronic use of systemically administered immunosuppressive agents.
Clinically-relevant drug or alcohol abuse.
History of solid organ transplantation.
Current or prior history of clinical hepatic decompensation.
History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol.
Known hypersensitivity to interferon, RBV, the study investigational medicinal product, the metabolites, or formulation excipients.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Arm && Interventions

Group	Intervention	Description
SOF+RBV 16 weeks	SOF	SOF+RBV for 16 weeks
SOF+RBV 16 weeks	RBV	SOF+RBV for 16 weeks
SOF+RBV 24 weeks	SOF	SOF+RBV for 24 weeks
Retreatment Substudy	Peg-IFN	Participants from the SOF+RBV arms (16 weeks or 24 weeks) who experienced virologic failure on treatment, or during the posttreatment period at or before Posttreatment Week 24 may be eligible to enroll into the Retreatment Substudy to receive SOF+RBV+Peg-IFN for 12 weeks.
SOF+RBV+Peg-IFN 12 weeks	RBV	SOF+RBV+Peg-IFN for 12 weeks
SOF+RBV+Peg-IFN 12 weeks	Peg-IFN	SOF+RBV+Peg-IFN for 12 weeks
Retreatment Substudy	SOF	Participants from the SOF+RBV arms (16 weeks or 24 weeks) who experienced virologic failure on treatment, or during the posttreatment period at or before Posttreatment Week 24 may be eligible to enroll into the Retreatment Substudy to receive SOF+RBV+Peg-IFN for 12 weeks.
Retreatment Substudy	RBV	Participants from the SOF+RBV arms (16 weeks or 24 weeks) who experienced virologic failure on treatment, or during the posttreatment period at or before Posttreatment Week 24 may be eligible to enroll into the Retreatment Substudy to receive SOF+RBV+Peg-IFN for 12 weeks.
SOF+RBV+Peg-IFN 12 weeks	SOF	SOF+RBV+Peg-IFN for 12 weeks
SOF+RBV 24 weeks	RBV	SOF+RBV for 24 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	Up to 24 weeks
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
HCV RNA at Weeks 1, 2, 4, 8, and 12	Weeks 1, 2, 4, 8, and 12
Percentage of Participants Experiencing On-Treatment Virologic Failure	Up to 24 weeks	On-treatment virologic failure was defined as: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24	Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12	Baseline; Weeks 1, 2, 4, 8, and 12
Percentage of Participants Experiencing Viral Relapse	Up to Posttreatment Week 24	Viral relapse is defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement.