Sofosbuvir (GS-7977) in Combination With PEG and Ribavirin for 12 Weeks in Treatment Experienced Subjects With Chronic HCV Infection Genotype 2 or 3

Study Overview
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Brief Summary
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This study is to evaluate the safety, tolerability, and antiviral efficacy of sofosbuvir (SOF) in combination with peginterferon alfa 2a (PEG) and ribavirin (RBV) administered for 12 weeks in participants with chronic genotype 2 or 3 hepatitis C virus (HCV) infection who have previously failed prior treatment with an interferon-based regimen.

Official Title
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A Phase 2, Open-Label Study of Sofosbuvir in Combination With PEG and Ribavirin for 12 Weeks in Treatment Experienced Subjects With Chronic HCV Infection Genotype 2 or 3

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infection with genotype 2 or 3 HCV infection Cirrhosis determination Individual is treatment-experienced Screening laboratory values within defined thresholds Individual 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 a direct-acting antiviral drug targeting the HCV NS5B 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 treatment, assessment, or compliance with the study 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: SOF+PEG+RBV<br>Participants will receive SOF+PEG+RBV for 12 weeks. | Drug: SOF<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: PEG<br>* Peginterferon alfa 2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 15 IU/mL) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | The percentage of participants discontinuing any study drug due to an adverse event was summarized. | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants Experiencing On-treatment Virologic Failure | On-treatment virologic failure was defined as: Viral breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment | Up to 12 weeks | 
| Percentage of Participants Experiencing Viral Relapse | Viral relapse was defined as having HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at the end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement. | Up to Posttreatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antimetabolites, HCV genotype 2 (GT-2), HCV genotype 3 (GT-3), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Treatment-Naïve, GS-7977, Ribavirin, RBV, Peginterferon Alfa 2a, PEG, Additional relevant MeSH terms:, Hepatitis, Hepatitis A, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections, Flaviviridae Infections, Peginterferon alfa-2a, Interferon-alpha, Antiviral Agents, Anti-Infective Agents, Therapeutic Uses, Pharmacologic Actions, Molecular Mechanisms of Pharmacological Action, Immunologic Factors, Physiological Effects of Drugs