SOF (Sovaldi®) +RBV for 16 or 24 Weeks and SOF+RBV+Peg-IFN for 12 Weeks in Adults With Genotype 2 or 3 Chronic HCV Infection

Study Overview
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Brief Summary
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This study will assess the efficacy, safety, and tolerability of 16 or 24 weeks of sofosbuvir (Sovaldi®; SOF) + ribavirin (RBV), and 12 weeks of SOF+RBV+ pegylated interferon (Peg-IFN) in treatment-naive and treatment-experienced adults with chronic genotype 3 hepatitis C virus (HCV) infection, and treatment-experienced adults with cirrhosis and chronic genotype 2 HCV infection.

Official Title
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A Phase 3B Randomized, Open-Label, Multi-Center Trial Assessing Sofosbuvir + Ribavirin for 16 or 24 Weeks and Sofosbuvir + Pegylated Interferon + Ribavirin for 12 Weeks in Subjects With Genotype 2 or 3 Chronic HCV Infection.

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: SOF
* Drug: RBV
* Drug: Peg-IFN


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female, age greater than or equal to 18 years. Confirmed chronic HCV infection. Subjects will have cirrhosis status assessment; liver biopsy may be required. Genotype 2 subjects must have cirrhosis of the liver to be eligible. Treatment-naive or prior treatment failure to ≥12 weeks of an interferon- based regimen that was not discontinued prematurely due to an adverse event Infection with HCV genotype 2 or 3 as determined at Screening Body mass index (BMI) greater than or equal to 18 kg/m^2 Screening laboratory values within predefined thresholds. Liver imaging (e.g., ultrasound) within 6 months of Baseline/Day 1 is required in cirrhotic patients to exclude hepatocellular carcinoma (HCC). In the event of intrahepatic lesions, triple phase CT scan or MRI should be performed to exclude HCC. Subject must be of generally good health as determined by the Investigator. Key Exclusion Criteria: Prior use of any other inhibitor of the HCV nonstructural protein (NS)5B polymerase Pregnant or nursing female or male with pregnant female partner History of any other clinically significant chronic liver disease. HIV or chronic hepatitis B virus (HBV) infection. Malignancy with the exception of certain resolved skin cancers. Chronic use of systemically administered immunosuppressive agents. Clinically-relevant drug or alcohol abuse. History of solid organ transplantation. Current or prior history of clinical hepatic decompensation. History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol. Known hypersensitivity to interferon, RBV, the study investigational medicinal product, the metabolites, or formulation excipients. 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: SOF+RBV 16 weeks<br>SOF+RBV for 16 weeks | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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+RBV 24 weeks<br>SOF+RBV for 24 weeks | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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+RBV+Peg-IFN 12 weeks<br>SOF+RBV+Peg-IFN for 12 weeks | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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>Drug: Peg-IFN<br>* 180 µg administered via subcutaneous injection once weekly<br>|
| Experimental: Retreatment Substudy<br>Participants from the SOF+RBV arms (16 weeks or 24 weeks) who experienced virologic failure on treatment, or during the posttreatment period at or before Posttreatment Week 24 may be eligible to enroll into the Retreatment Substudy to receive SOF+RBV+Peg-IFN for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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>Drug: Peg-IFN<br>* 180 µg administered via subcutaneous injection once weekly<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) 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 | 
| 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 SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR 24 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 HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 |  | Weeks 1, 2, 4, 8, 12, 16, 20, and 24 | 
| HCV RNA at Weeks 1, 2, 4, 8, and 12 |  | Weeks 1, 2, 4, 8, and 12 | 
| Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12 |  | Baseline; Weeks 1, 2, 4, 8, and 12 | 
| Percentage of Participants Experiencing On-Treatment Virologic Failure | On-treatment virologic failure was defined as: 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) | Up to 24 weeks | 
| Percentage of Participants Experiencing Viral Relapse | Viral relapse is 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GS-7977, 7977, PSI-7977, Sofosbuvir (SOF), Pegylated Interferon (Peg-IFN), Ribavirin (RBV)