Efficacy and Safety of Oral Regimens for the Treatment of Chronic HCV Infection

Study Overview
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Brief Summary
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This study will evaluate the antiviral efficacy, safety, and tolerability of combination therapy with oral regimens for the treatment of chronic hepatitis C virus (HCV) infection.

Official Title
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A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Oral Regimens for the Treatment of Chronic HCV Infection

Conditions
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Chronic Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing and able to provide written informed consent Chronic HCV infection Cirrhosis determination (liver biopsy may be required) Screening laboratory values within specified limits Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Specific genotype, prior medical history, or concurrent disease as required by the specific study group Key Exclusion Criteria: History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol Pregnant or nursing female, or male with pregnant female partner Clinical hepatic decompensation (ie, ascites, encephalopathy or variceal hemorrhage) Use of any prohibited concomitant medications 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1)<br>Participants who previously received ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) for ≥ 12 weeks without achieving sustained virologic response at 12 weeks following treatment (SVR12) will receive LDV/SOF+RBV for 24 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;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: LDV/SOF+RBV 12 Weeks (Cohort 1 Group 2)<br>Participants who previously received a sofosbuvir-based regimen without achieving SVR12 were initially enrolled to receive LDV/SOF+RBV for 12 weeks (excluding participants who previously received LDV/SOF+RBV for ≥ 12 weeks). Participants who did not achieve sustained virologic response at 12 weeks were then moved to Cohort 1 Group 1. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;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: LDV/SOF 12 Weeks GT2 (Cohort 2 Group 1)<br>Participants with genotype 2 (GT2) HCV infection will receive LDV/SOF FDC for 12 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF 8 Weeks GT2 (Cohort 2 Group 2)<br>Participants with GT2 HCV infection will receive LDV/SOF FDC for 8 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF 12 Weeks GT1/GT2/GT4 (Cohort 3 Group 1)<br>Participants with genotypes 1 (GT1), 2 (GT2), or 4 (GT4) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC for 12 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2)<br>Participants with genotype 3 (GT3) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC plus RBV for 12 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;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: SOF/VEL+VOX 6 Weeks GT1 (Cohort 4)<br>Treatment-naive participants with GT1 HCV infection without cirrhosis will receive VOX only on Day 1 followed by sofosbuvir/velpatasvir (SOF/VEL) + voxilaprevir (VOX) for 6 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1)<br>Treatment-naive participants with GT1 HCV infection without cirrhosis will receive SOF/VEL+VOX for 4 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2)<br>Treatment-naive participants with GT1 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3)<br>Treatment-naive participants with GT3 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4)<br>Treatment-experienced participants with GT1 HCV infection with cirrhosis who were previously treated with pegylated interferon (Peg-IFN)+RBV will receive SOF/VEL+VOX for 6 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5)<br>Treatment-experienced participants with GT3 HCV infection with cirrhosis who were previously treated with Peg-IFN+RBV will receive SOF/VEL+VOX for 6 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6)<br>Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with non-structural protein (NS3/4A) protease inhibitor (PI) will receive SOF/VEL+VOX for 6 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7)<br>Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with direct-acting antivirals (DAA) will receive SOF/VEL+VOX for 6 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: GS-9857;|
| Experimental: SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8)<br>Treatment-experienced participants with GT3 HCV infection with or without cirrhosis who were previously treated with DAA will receive SOF/VEL+VOX for 8 weeks. | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;Drug: VOX<br>* 100 mg tablet administered orally once daily with food<br>* Other names: 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) | 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 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively. | Posttreatment Weeks 4 and 24 | 
| 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 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 HCV RNA < LLOQ While on Treatment by Study Visit |  | Weeks 1, 2, 4, 6, 8, 12, 16, 20, and 24 (depending on treatment duration; Week 6 data was not collected for Cohorts 1-3) |