Safety and Efficacy of Sofosbuvir Plus Ribavirin in Treatment-Naive Adults With Chronic Genotype 1 or 3 HCV Infection

Study Overview
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Brief Summary
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This study will evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) + ribavirin (RBV) in treatment-naive adults with chronic genotype 1 or 3 hepatitis C virus (HCV) infection.

Official Title
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A Phase 3b, Multi-Center, Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Sofosbuvir Plus Ribavirin in Treatment-Naïve Adults With Chronic Genotype 1 or 3 Hepatitis C Virus Infection

Conditions
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Chronic HCV Infection

Intervention / Treatment
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* Drug: Sofosbuvir
* Drug: RBV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV RNA ≥10^4 IU/mL at screening Confirmed chronic HCV genotype 1 or 3 infection HCV treatment naive Approximately 30% of individuals may have compensated cirrhosis at screening Exclusion Criteria: Any other chronic liver disease Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Current or prior history of clinical hepatic de-compensation Contraindication to RBV therapy, e.g., history of clinically significant hemoglobinopathy (sickle cell disease, thalassemia). Chronic use of systemically administered immunosuppressive agents History of solid organ transplantation

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 16 weeks<br>Participants with HCV genotypes 1 and 3 will receive sofosbuvir plus ribavirin for 16 weeks. | Drug: Sofosbuvir<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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: Sofosbuvir+RBV 24 weeks<br>Participants with HCV genotypes 1 and 3 will receive sofosbuvir plus ribavirin for 24 weeks. | Drug: Sofosbuvir<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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, 15 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 (SVR) 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 after stopping study treatment, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With Virologic Failure and Viral Relapse | Virologic failure was defined as: On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit. | Up to Posttreatment Week 24 |