Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed-Dose Combination With or Without Ribavirin in Participants With Chronic Genotype 1 HCV Infection Previously Treated With a Direct Acting Antiviral Regimen

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy, safety, and tolerability of the treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed dose combination (FDC) ± ribavirin (RBV) in participants with chronic genotype 1 hepatitis C virus (HCV) infection and prior treatment experience with a direct acting antiviral (DAA).

Official Title
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A Phase 2, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir/GS-5816/GS-9857 Fixed-Dose Combination With or Without Ribavirin in Subjects With Chronic Genotype 1 HCV Infection Previously Treated With a Direct Acting Antiviral Regimen

Conditions
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Hepatitis C Virus Infection

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Individuals with chronic HCV genotype 1 infection Documented as treatment experienced with a direct acting antiviral-containing regimen without achieving sustained viral response Absence of cirrhosis or presence of compensated cirrhosis Screening laboratory values within defined thresholds Must use specific contraceptive methods if female of childbearing potential or sexually active male Key Exclusion Criteria: Co-infection with HIV or hepatitis B virus (HBV) Current or prior history of clinical hepatic decompensation Chronic use of systemic immunosuppressive agents History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol Pregnant or a nursing female 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/VOX<br>SOF/VEL/VOX for 12 weeks | Drug: SOF/VEL/VOX<br>* 400/100/100 mg FDC tablet administered orally once daily with food<br>* Other names: Vosevi®;|
| Experimental: SOF/VEL/VOX + RBV<br>SOF/VEL/VOX + RBV for 12 weeks | Drug: SOF/VEL/VOX<br>* 400/100/100 mg FDC tablet administered orally once daily with food<br>* Other names: Vosevi®;Drug: RBV<br>* Tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 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 Treatment (SVR12) | SVR12 is 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 SOF/VEL/VOX Due to an Adverse Event |  | Up to 12 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 are 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 on Treatment |  | Weeks 1, 2, 4, 8 and 12 | 
| HCV RNA Change From Baseline/Day 1 Through Week 12 |  | Weeks 1, 2, 4, 8, and 12 | 
| Percentage of Participants With Virologic Failure | Virologic failure is 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 |