Safety and Efficacy of Sofosbuvir and Ribavirin in Adults With Recurrent Chronic Hepatitis C Virus (HCV) Post Liver Transplant

Study Overview
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Brief Summary
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This is an open-label, single-arm study of sofosbuvir (GS-7977) and ribavirin (RBV) in adults who have had a liver transplant which has become re-infected with hepatitis C. The treatment period is 24 weeks with up to 48 weeks of follow up. The total time in this study will last up to 72 weeks not including the screening visit.

Official Title
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A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of GS-7977 and Ribavirin for 24 Weeks in Subjects With Recurrent Chronic HCV Post Liver Transplant

Conditions
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Recurrent Chronic Hepatitis C Virus, Post Liver Transplant

Intervention / Treatment
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* Drug: Sofosbuvir
* Drug: RBV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with evidence of chronic HCV (all genotypes) documented pretransplantation HCV RNA ≥ 10,000 IU/mL at screening Absence of organ rejection as documented by post transplant liver biopsy taken no more than 12 months prior to baseline/Day 1 visit Liver transplant ≥ 6 months and ≤ 12 years prior to screening Naive to all nucleotide/nucleoside treatments for chronic HCV infection Exclusion Criteria: Multiorgan transplant that includes heart or lung recipient Subjects with de novo or recurrent Hepatocellular Carcinoma(HCC) post transplant Current use of corticosteroids at any dose > 5mg of prednisone/day (or equivalent dose of corticosteroid) Infection with hepatitis B virus (HBV) or HIV at screening Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF+RBV<br>Participants will receive sofosbuvir+RBV for 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg tablet administered orally once daily<br>* Other names: Sovaldi®;Drug: RBV<br>* Ribavirin (RBV) 200-mg tablet(s) administered orally in a divided daily dose starting at 400 mg, subsequently adjusted (range: 200 to 1200 mg in a divided daily dose) based upon a number of factors including hemoglobin value, creatinine clearance, and weight.<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 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 25 IU/mL) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Percentage of Participants Who Discontinue Study Drug Due to an Adverse Event |  | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48) | SVR4, SVR 24, and SVR 48 were defined as HCV RNA < LLOQ 4, 24, and 48 weeks following the last dose of study drug, respectively. | Posttreatment Weeks 4, 24, and 48 | 
| Percentage of Participants With HCV RNA < LLOQ at Weeks 12 and 24 |  | Weeks 12 and 24 | 
| HCV RNA and Change From Baseline at Weeks 2, 4, and 8 |  | Baseline; Weeks 2, 4, and 8 | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as on-treatment virologic failure or virologic relapse. On-treatment virologic failure: HCV RNA < LLOQ during treatment with subsequent detectable HCV RNA while continuing treatment Virologic relapse: HCV RNA < LLOQ at last observed on-treatment HCV RNA measurement and HCV RNA ≥ LLOQ after stopping treatment (2 consecutive HCV RNA measurements or last available HCV RNA measurement) | Up to Posttreatment Week 24 |