Sofosbuvir With Peginterferon Alfa 2a and Ribavirin for 12 Weeks in Treatment-Naive Subjects With Chronic Genotype 1, 4, 5, or 6 HCV Infection

Study Overview
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Brief Summary
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This study was to assess whether sofosbuvir in combination with ribavirin (RBV) and pegylated interferon alfa 2a (PEG) administered for 12 weeks is safe and effective in patients with hepatitis C virus (HCV) genotypes 1, 4, 5 , or 6 as assessed by the rate of sustained viral response (SVR) 12 weeks after discontinuation of therapy (SVR12).

Official Title
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A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 With Peginterferon Alfa 2a and Ribavirin for 12 Weeks in Treatment-Naive Subjects With Chronic Genotype 1, 4, 5, or 6 HCV Infection

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Sofosbuvir
* Drug: RBV
* Drug: PEG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infection with HCV genotype 1, 4, 5, or 6 Cirrhosis determination Subject met the following classifications: Treatment-naive Screening laboratory values within defined thresholds Not treated with any investigational drug or device within 30 days of screening 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sofosbuvir+PEG+RBV<br> | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>* Other names: Ribasphere®;Drug: PEG<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>* Other names: PEGASYS®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virologic Response (SVR)12 | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after cessation of therapy. | Posttreatment Week 12 | 
| Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | The number of participants experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment. Participants discontinuing study drug were permitted to remain on the study for further assessments. | 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 | Posttreatment Week 4 | 
| Percentage of Participants Achieving SVR24 | SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy | Posttreatment Week 24 | 
| 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. | Baseline to Week 12 | 
| 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. | 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 1 (GT-1), HCV genotype 4 (GT-4), HCV genotype 5 (GT-5), HCV genotype 6 (GT-6), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Treatment-Naïve, GS-7977, Ribavirin, RBV, Peginterferon Alfa 2a, PEG