Sofosbuvir + Ribavirin for 12 Weeks in Subjects With Chronic Genotype 2 or 3 Hepatitis C Infection Who Are Interferon Intolerant, Interferon Ineligible or Unwilling to Take Interferon

Study Overview
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Brief Summary
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This multicenter study was to evaluate subjects with chronic genotype 2 or 3 HCV infection who were interferon (IFN) ineligible, IFN intolerant or unwilling to take IFN. Participants were randomized in a 3:1 ratio to receive sofosbuvir (SOF)+ribavirin (RBV), or placebo to match SOF+placebo to match RBV. Randomization was stratified by presence/absence of cirrhosis. Approximately 20% of participants may have had evidence of cirrhosis at screening.

Detailed Description
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Participants who were randomized to the placebo arm and completed all scheduled study procedures were eligible to receive active SOF+RBV in open-label Study GS-US-334-0109. Participants who do not achieve sustained virologic response (SVR) were eligible for enrollment in the Sequence Registry Study GS-US-248-0123. The purpose of the Sequence Registry Study is to monitor the persistence of resistant mutations for up to 3 years. Participants who achieved SVR were eligible for enrollment in the SVR Registry Study GS-US-248-0122. The purpose of the SVR Registry Study is to evaluate durability of SVR for up to 3 years after treatment.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GS-7977 + Ribavirin for 12 Weeks in Subjects With Chronic Genotype 2 or 3 HCV Infection Who Are Interferon Intolerant, Interferon Ineligible or Unwilling to Take Interferon

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: SOF
* Drug: RBV
* Drug: Placebo to match SOF
* Drug: Placebo to match RBV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infection with HCV genotype 2 or 3 Cirrhosis determination Subject meets one of the following classifications: IFN unwilling IFN ineligible IFN intolerant Screening laboratory values within defined thresholds Subject has not been treated with any investigational drug or device within 30 days of the Screening visit Use of highly effective contraception methods if female of childbearing potential or sexually active male Exclusion Criteria: Prior exposure to an direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase Pregnant or nursing female or male with pregnant female partner 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 Excessive alcohol ingestion or significant drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF+RBV<br>Participants were randomized to receive SOF+RBV for 12 weeks. | Drug: SOF<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* Ribavirin (RBV) was administered as a tablet orally according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).<br>|
| Placebo Comparator: Placebo<br>Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. | Drug: Placebo to match SOF<br>* Placebo to match SOF was administered orally once daily.<br>Drug: Placebo to match RBV<br>* Placebo to match RBV was administered orally twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR12 | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks after cessation of therapy | Post-treatment Week 12 | 
| Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | The number of subjects experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR4 | SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy | Post-treatment Week 4 | 
| Percentage of Participants Achieving SVR24 | SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy | Post-treatment Week 24 | 
| Percentage of Participants Experiencing Viral Breakthrough | Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values | Baseline to Week 12 | 
| Percentage of Participants Experiencing Viral Relapse | Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement | End of treatment to post-treatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV genotype 2 (GT-2), HCV genotype 3 (GT-3), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Interferon intolerant, Interferon ineligible, GS-7977, Ribavirin