Sofosbuvir and Ribavirin in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, and antiviral efficacy of GS-7977 with ribavirin (RBV) in participants with genotype 2 or 3 hepatitis C virus (HCV) infection.

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 Treatment Naive and Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection.

Conditions
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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: Age > 18 with chronic genotype 2 or 3 HCV infection HCV RNA > 10,000 IU/mL at screening Subjects must be treatment naive or treatment experienced Presence or absence of cirrhosis; a liver biopsy may be required Healthy according to medical history and physical examination with the exception of HCV diagnosis Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication Exclusion Criteria: Prior use of any other inhibitor of the HCV NS5B Polymerase History of any other clinically significant chronic liver disease Evidence of or history of decompensated liver disease HIV or chronic hepatitis B virus (HBV) infection Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) Chronic use of immunosuppressive agents or immunomodulatory agents History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study or not be in the best interest of the subject in the opinion of the investigator

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo 12 Weeks (GT2/3)<br>Placebo to match SOF + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection. | Drug: Placebo to match SOF<br>* Placebo to match SOF administered orally once daily<br>Drug: Placebo to match RBV<br>* Placebo to match RBV administered orally in a divided daily dose<br>|
| Experimental: SOF 12 Weeks (GT2/3)<br>Placebo to match SOF + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection. | Drug: SOF<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>|
| Experimental: SOF 24 Weeks (GT3)<br>SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection. | Drug: SOF<br>* Sofosbuvir (SOF) 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 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 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks following the last dose of study drug. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group. | Posttreatment Week 12 | 
| Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | The percentage of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was analyzed. | Up to 24 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 was defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA > LLOQ) after having previously had undetectable HCV RNA levels (HCV RNA < LLOQ) while on treatment. Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group. | Up to Posttreatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, Genotype 2, Genotype 3