Sofosbuvir + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection (FUSION)

Study Overview
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Brief Summary
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This study was to assess the safety and efficacy of sofosbuvir in combination with ribavirin (RBV) administered for 12 or 16 weeks in participants with genotypes 2 or 3 hepatitis C virus (HCV) infection as assessed by the proportion of participants with sustained virologic response (SVR) 12 weeks after discontinuation of therapy (SVR12).

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Study to Investigate the Efficacy and Safety of GS-7977 + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection

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 Had cirrhosis determination Prior treatment failure Screening laboratory values within defined thresholds Subject had 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 have interfered 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+placebo<br>Participants were randomized to receive SOF+RBV for 12 weeks followed by placebo to match SOF plus placebo to match RBV for 4 weeks. | Drug: SOF<br>* Sofosbuvir (SOF) 400 mg tablet was administered orally once daily.<br>* Other names: PSI-7977;Drug: RBV<br>* Ribavirin (RBV) tablets was administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).<br>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>|
| Experimental: SOF+RBV<br>Participants were randomized to receive SOF+RBV for 16 weeks. | Drug: SOF<br>* Sofosbuvir (SOF) 400 mg tablet was administered orally once daily.<br>* Other names: PSI-7977;Drug: RBV<br>* Ribavirin (RBV) tablets was administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).<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. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm). | Posttreatment Week 12 | 
| Adverse Events Leading to Permanent Discontinuation of Study Drug | Adverse events which led to permanent discontinuation of study drug may or may not have been related to study treatment. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With 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. For the purposes of this efficacy analysis, assessments were made during active treatment (up to Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm). | Up to 16 weeks | 
| Percentage of Participants With 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. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm). | End of treatment to posttreatment Week 24 | 
| Percentage of Participants Achieving SVR4 | SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm). | Posttreatment Week 4 | 
| Percentage of Participants Achieving SVR24 | SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm). | Posttreatment Week 24 | 

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