Safety and Efficacy of Voxilaprevir Plus Sofosbuvir/Velpatasvir Fixed Dose Combination in Adults With Chronic Genotype 1 HCV Infection

Study Overview
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Brief Summary
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This primary objectives of the study are to evaluate the safety, tolerability, and efficacy of voxilaprevir (VOX) plus sofosbuvir/velpatasvir (SOF/VEL) fixed dose combination (FDC) ± ribavirin (RBV) in adults with chronic genotype 1 hepatitis C virus (HCV) infection.

Official Title
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A Phase 2, Global, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of GS-9857 Plus Sofosbuvir/GS-5816 Fixed Dose Combination in Subjects With Chronic Genotype 1 HCV Infection

Conditions
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Hepatitis C Virus Infection

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Individuals with chronic HCV infection HCV RNA ≥10^4 IU/mL at screening HCV genotype 1 Cirrhosis determination; a liver biopsy may be required Screening laboratory values within defined thresholds Use of two contraception methods if female of childbearing potential or sexually active male Key Exclusion Criteria: Pregnant or nursing female Current or prior history of hepatic decompensation Hepatocellular carcinoma (HCC) or other clinically significant malignancy Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VOX+SOF/VEL 6 wk, TN, without cirrhosis<br>VOX + SOF/VEL for 6 weeks (treatment naive (TN), without cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL 8 wk, TN, without cirrhosis<br>VOX + SOF/VEL for 8 weeks (treatment naive, without cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL 6 wk, TN, with cirrhosis<br>VOX + SOF/VEL for 6 weeks (treatment naive, with cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL 8 wk, TN, with cirrhosis<br>VOX + SOF/VEL for 8 weeks (treatment naive, with cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL+RBV 8 wk, TN, with cirrhosis<br>VOX + SOF/VEL+RBV for 8 weeks (treatment naive, with cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;Drug: RBV<br>* 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>|
| Experimental: VOX+SOF/VEL 8 wk, DAA-E, without cirrhosis<br>VOX + SOF/VEL for 8 weeks (direct-acting antiviral experienced (DAA-E), without cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL 12 wk, DAA-E, without cirrhosis<br>VOX + SOF/VEL for 12 weeks (direct-acting antiviral experienced, without cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL 8 wk, DAA-E, with cirrhosis<br>GS-9857 + SOF/VEL for 8 weeks (direct-acting antiviral experienced, with cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL 12 wk, DAA-E, with cirrhosis<br>GS-9857 + SOF/VEL for 12 weeks (direct-acting antiviral experienced, with cirrhosis) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|
| Experimental: VOX+SOF/VEL 12 wk (GS-US-338-1121)<br>VOX + SOF/VEL for 12 weeks (participants who were previously enrolled in GS-US-338-1121 phase 1b study) | Drug: VOX<br>* 100 mg tablet(s) administered orally once daily with food<br>* Other names: GS-9857;Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily with food<br>* Other names: Epclusa®;|

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) 12 weeks following the last dose of study treatment. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |  | Up to 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With HCV RNA < LLOQ on Treatment |  | Baseline through end of treatment (Week 6, Week 8 or Week 12, as applicable) | 
| HCV RNA Change From Baseline |  | Baseline through end of treatment (Week 6, Week 8 or Week 12, as applicable) | 
| Percentage of Participants With Virologic Failure | 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 |