Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir in Adults With Chronic HCV Infection Who Have Previously Received Treatment With Direct-Acting Antiviral Therapy

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the safety and efficacy of treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in adults with chronic hepatitis C virus (HCV) infection who have previously received treatment with direct-acting antiviral therapy. Participants randomized to placebo may be eligible for deferred treatment with active SOF/VEL/VOX.

Official Title
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A Phase 3, Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir/GS-9857 Fixed-Dose Combination for 12 Weeks in Direct-Acting Antiviral-Experienced Subjects With Chronic HCV Infection

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing and able to provide written informed consent HCV RNA ≥ 10^4 IU/mL at screening Chronic HCV infection (≥ 6 months) Treatment experienced with a direct acting antiviral medication for HCV Use of protocol specified methods of contraception Key Exclusion Criteria: Current or prior history of clinically significant illness that may interfere with participation in the study Screening ECG with clinically significant abnormalities Laboratory results outside of acceptable ranges at screening Pregnant or nursing female Chronic liver disease not caused by HCV Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF/VEL/VOX (Primary Study)<br>SOF/VEL/VOX for 12 weeks | Drug: SOF/VEL/VOX<br>* 400/100/100 mg fixed dose-combination (FDC) tablet administered orally once daily with food<br>* Other names: GS-7977/GS-5816/GS-9857;|
| Experimental: Placebo (Primary Study)<br>Placebo to match SOF/VEL/VOX for 12 weeks | Drug: Placebo<br>* Tablet administered orally once daily with food<br>|
| Experimental: SOF/VEL/VOX (Deferred Treatment Substudy)<br>SOF/VEL/VOX for 12 weeks for eligible participants initially randomized to receive placebo | Drug: SOF/VEL/VOX<br>* 400/100/100 mg fixed dose-combination (FDC) tablet administered orally once daily with food<br>* Other names: GS-7977/GS-5816/GS-9857;|

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) (Primary Study) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study) |  | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment, respectively. | Posttreatment Week 4 | 
| Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) |  | Weeks 1, 2, 4, 8 and 12 | 
| Change From Baseline in HCV RNA (Primary Study) |  | Baseline; Weeks 1, 2, 4, 8 and 12 | 
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study) | SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment. | Posttreatment Week 24 | 
| Percentage of Participants With Virologic Failure (Primary Study) | 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 | 
| Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) | SVR4, SVR12 and SVR24 was defined as HCV RNA < LLOQ at 4, 12 and 24 weeks after stopping study treatment, respectively. | Posttreatment Weeks 4, 12, and 24 (Deferred Treatment Substudy) | 
| Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) |  | Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy) | 
| Change From Baseline in HCV RNA (Deferred Treatment Substudy) |  | Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy) | 
| Percentage of Participants With Virologic Failure (Deferred Treatment Substudy) | 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 (Deferred Treatment Substudy) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C Infection