Sofosbuvir/Velpatasvir Fixed-Dose Combination and Ribavirin for 12 or 24 Weeks in Participants With Chronic Genotype 1 or 2 Hepatitis C Virus Infection Who Have Previously Failed a Direct-Acting Antiviral-Containing Regimen

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the antiviral efficacy, safety, and tolerability of therapy with sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) and ribavirin (RBV) in participants with chronic genotype 1 or 2 hepatitis C virus (HCV) infection who have previously failed a direct-acting antiviral (DAA)-containing regimen.

Official Title
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A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination and Ribavirin for 12 or 24 Weeks in Subjects With Chronic Genotype 1 or 2 HCV Infection Who Have Previously Failed a Direct-Acting Antiviral-Containing Regimen

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: SOF/VEL
* Drug: RBV


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Genotype 1 or 2 HCV infection Chronic HCV infection (≥ 6 months prior to screening) documented by prior medical history or liver biopsy Previously treated with a DAA-containing regimen of at least 4 week duration Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 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/VEL FDC + RBV 12 weeks<br>SOF/VEL FDC + RBV for 12 weeks in participants with genotype 1 or 2 HCV infection | Drug: SOF/VEL<br>* 400/100 mg tablet administered orally once daily<br>* Other names: Epclusa®;Drug: RBV<br>* Capsules administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg)<br>* Other names: REBETOL®;|
| Experimental: SOF/VEL FDC + RBV 24 weeks<br>SOF/VEL FDC + RBV for 24 weeks in participants with genotype 1 or 2 HCV infection | Drug: SOF/VEL<br>* 400/100 mg tablet administered orally once daily<br>* Other names: Epclusa®;Drug: RBV<br>* Capsules administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg)<br>* Other names: REBETOL®;|

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 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment. | Posttreatment Week 4 | 
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | SVR 24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment. | Posttreatment Week 24 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 1 |  | Week 1 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 2 |  | Week 2 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 3 |  | Week 3 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 4 |  | Week 4 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 5 |  | Week 5 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 6 |  | Week 6 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 8 |  | Week 8 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 10 |  | Week 10 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 12 |  | Week 12 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 16 |  | Week 16 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 20 |  | Week 20 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 24 |  | Week 24 | 
| Change From Baseline in HCV RNA at Week 1 |  | Baseline; Week 1 | 
| Change From Baseline in HCV RNA at Week 2 |  | Baseline; Week 2 | 
| Change From Baseline in HCV RNA at Week 3 |  | Baseline; Week 3 | 
| Change From Baseline in HCV RNA at Week 4 |  | Baseline; Week 4 | 
| Change From Baseline in HCV RNA at Week 5 |  | Baseline; Week 5 | 
| Change From Baseline in HCV RNA at Week 6 |  | Baseline; Week 6 | 
| Change From Baseline in HCV RNA at Week 8 |  | Baseline; Week 8 | 
| Change From Baseline in HCV RNA at Week 10 |  | Baseline; Week 10 | 
| Change From Baseline in HCV RNA at Week 12 |  | Baseline; Week 12 | 
| Change From Baseline in HCV RNA at Week 16 |  | Baseline; Week 16 | 
| Change From Baseline in HCV RNA at Week 20 |  | Baseline; Week 20 | 
| Change From Baseline in HCV RNA at Week 24 |  | Baseline; Week 24 | 
| Percentage of Participants With Overall Virologic Failure | 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 |