Phase 3 Study of Sofosbuvir and Ribavirin

Study Overview
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Brief Summary
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This study was to assess the safety and efficacy of sofosbuvir (GS-7977; PSI-7977) in combination with ribavirin (RBV) administered for 12 weeks compared with pegylated interferon (PEG)/RBV administered for 24 weeks in treatment-naive patients with Hepatitis C (HCV) genotype 2 or 3. Efficacy was assessed by the rate of sustained viral response (SVR) 12 weeks after the discontinuation of therapy (SVR12). This was a non-inferiority study, and if non-inferiority was demonstrated, the study was then allowed to test for superiority.

Official Title
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A Phase 3, Multicenter, Randomized, Active-Controlled Study to Investigate the Safety and Efficacy of PSI-7977 and Ribavirin for 12 Weeks Compared to Pegylated Interferon and Ribavirin for 24 Weeks in Treatment-Naïve Patients With Chronic Genotype 2 or 3 HCV Infection

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic Genotype 2 or 3 HCV-infection Naive to all HCV antiviral treatment(s) Exclusion Criteria: Positive test at Screening for HBsAg, anti-hepatitis B core immunoglobulin M antibody (anti-HBc IgM Ab), or anti-HIV Ab History of any other clinically significant chronic liver disease A history consistent with decompensated liver disease History or current evidence of psychiatric illness, immunologic disorder, hemoglobinopathy, pulmonary or cardiac disease, seizure disorder or anticonvulsant use, poorly controlled diabetes, cancer, or a history of malignancy, that makes the subject unsuitable for the study. Participation in a clinical study within 3 months prior to first dose

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<br>Participants were randomized to receive sofosbuvir+RBV for 12 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* Ribavirin (RBV) administered as 200 mg tablets up to 1200 mg in a divided daily dose Dose of sofosbuvir+RBV group based on baseline weight: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg Dose of PEG+RBV group: 800 mg<br>|
| Active Comparator: PEG+RBV<br>Participants were randomized to receive PEG+RBV for 24 weeks. | Drug: PEG<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>* Other names: Pegasys®;Drug: RBV<br>* Ribavirin (RBV) administered as 200 mg tablets up to 1200 mg in a divided daily dose Dose of sofosbuvir+RBV group based on baseline weight: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg Dose of PEG+RBV group: 800 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 Stopping All Study Drugs (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; < 25 IU/mL) 12 weeks after study drug cessation. | Post-treatment Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities |  | Up to 24 weeks plus 30 days following the last dose of study drug | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Stopping All Study Drugs (SVR24) | SVR24 was defined as HCV RNA < LLOQ 24 weeks after study drug cessation. | Post-treatment Week 24 | 
| Percentage of Participants With HCV RNA < LLOQ on Treatment |  | Up to 12 Weeks | 
| Change From Baseline in HCV RNA |  | Baseline to Week 12 | 
| Percentage of Participants With Virologic Failure During Treatment | Virologic failure was defined as either Viral breakthrough: HCV RNA ≥ 25 IU/mL after having previously had HCV RNA < 25 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement Non-response: HCV RNA persistently ≥ 25 IU/ml while on treatment (through Week 12) | Baseline up to Week 24 | 
| Percentage of Participants With Viral Relapse Following Treatment | Viral relapse was defined as HCV RNA ≥ 25 IU/mL in post-treatment after having achieved < LLOQ at last on-treatment measurement, confirmed with 2 consecutive values or last available measurement. | Up 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 2 (GT-2), HCV genotype 3 (GT-3)