Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination (FDC) and Sofosbuvir/Velpatasvir FDC and Ribavirin in Participants With Chronic Genotype 3 HCV Infection and Cirrhosis

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) and SOF/VEL FDC and ribavirin (RBV) for 12 weeks in participants with chronic genotype 3 hepatitis C virus (HCV) infection and compensated cirrhosis.

Official Title
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A Phase 2, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination (FDC) and Sofosbuvir/Velpatasvir FDC and Ribavirin in Subjects With Chronic Genotype 3 HCV Infection and Cirrhosis

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: Willing and able to provide written informed consent Individuals with chronic genotype 3 HCV infection and compensated cirrhosis Individuals with or without HIV-1 coinfection Key Exclusion Criteria: History of clinically significant illness or any other medical disorder that may interfere with individual's treatment assessment or compliance with the protocol Co-infection with active hepatitis B virus Laboratory results outside the acceptable ranges at screening Pregnant or nursing female Chronic liver disease not caused by HCV 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/VEL<br>SOF/VEL FDC for 12 weeks | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: Epclusa®;|
| Experimental: SOF/VEL + RBV<br>SOF/VEL FDC + RBV for 12 weeks | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: Epclusa®;Drug: RBV<br>* RBV 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 (SVR) 12 Weeks After Cessation 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 (Which Included SOF/VEL and RBV) Due to Any Adverse Event |  | Posttreatment Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Attain Sustained Virologic Response at 4 Weeks After Cessation of the Study Treatment Regimen (SVR4) | SVR4 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4 weeks after stopping study treatment. | Posttreatment Week 4 | 
| Percentage of Participants Who Have HCV RNA < LLOQ at Week 2 |  | Week 2 | 
| Percentage of Participants Who Have HCV RNA < LLOQ at Week 4 |  | Week 4 | 
| Percentage of Participants Who Have HCV RNA < LLOQ at Week 8 |  | Week 8 | 
| Percentage of Participants Who Have HCV RNA < LLOQ at Week 12 |  | Week 12 | 
| HCV RNA at Week 2 |  | Week 2 | 
| HCV RNA at Week 4 |  | Week 4 | 
| HCV RNA at Week 8 |  | Week 8 | 
| HCV RNA at Week 12 |  | Week 12 | 
| Change From Baseline in HCV RNA at Week 2 |  | Baseline; Week 2 | 
| Change From Baseline in HCV RNA at Week 4 |  | Baseline; Week 4 | 
| Change From Baseline in HCV RNA at Week 8 |  | Baseline; Week 8 | 
| Change From Baseline in HCV RNA at Week 12 |  | Baseline; Week 12 | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ on 2 consecutive measurements 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: 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 12 |