Efficacy and Safety of Sofosbuvir Plus Ribavirin in Adults With Chronic HCV Infection

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the efficacy, safety and tolerability of treatment with sofosbuvir (SOF)+ ribavirin (RBV), with or without Pegylated interferon alfa (Peg-IFNα-2a/ PEG)) in participants with chronic genotype (GT)-1, 2, 3, and 6 Hepatitis C virus (HCV) infection.

Official Title
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A Phase 3b, Multicenter, Open-Label, Randomized Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin (± Pegylated Interferon) in Subjects With Chronic Genotype 1, 2, 3 and 6 HCV Infection

Conditions
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Chronic HCV Infection

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing and able to provide written informed consent HCV RNA ≥ 10^4 IU/mL at screening HCV treatment-naive (HCV genotype 1, 2, 3 or 6), defined as no prior exposure to any interferon (IFN), RBV, or other approved or experimental HCV-specific direct-acting antiviral agent, or HCV treatment-experienced (HCV genotype 1, 2, 3, or 6 only) with medical records that include sufficient detail of prior treatment with IFN to allow for categorization of prior response as either IFN Intolerant, non-responder, or experiences viral breakthrough or relapse HCV infection documented by anti-HCV antibody test, genotyping test, or liver biopsy Key Exclusion Criteria: Current or prior history of any clinically-significant illness (other than HCV) Pregnant or nursing female or male with pregnant female partner Chronic liver disease of a non-HCV etiology Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sofosbuvir+RBV+PEG 12 weeks<br>Participants with genotype 1 or 6 will receive sofosbuvir+RBV+Peg-IFNα-2a for 12 weeks. | 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-IFNα-2a) 180 µg/0.5 mL pre-filled syringe administered subcutaneously once a week<br>* Other names: Pegasys®;|
| Experimental: Sofosbuvir+RBV 12 weeks<br>Participants with genotype 1, 2 or 6 will receive sofosbuvir+RBV for 12 weeks. | 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®;|
| Experimental: Sofosbuvir+RBV 16 weeks<br>Participants with genotype 1, 6 will receive sofosbuvir+RBV for 16 weeks. | 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®;|
| Experimental: Sofosbuvir+RBV 24 Weeks<br>Participants with genotype 1, 3, or 6 will receive sofosbuvir+RBV for 24 weeks. | 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®;|

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 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 is defined as HCV RNA < the lower limit of quantification (LLOQ; ie, < 25 IU/mL) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR24 are 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 With On-Treatment Virologic Failure | Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment. | Up to 24 weeks | 
| Percentage of Participants With Viral Relapse | Viral relapse was 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. | Up to Posttreatment Week 24 | 
| Change From Baseline in HCV RNA (log10 IU/mL) |  | Up to 24 weeks |