Comparison of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks With Sofosbuvir and Ribavirin for 24 Weeks in Adults With Chronic Genotype 3 HCV Infection

Study Overview
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Brief Summary
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The primary objectives of this study are to compare the efficacy of treatment with sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) for 12 weeks with that of sofosbuvir (SOF) + ribavirin (RBV) for 24 weeks and to evaluate the safety and tolerability of each treatment regimen in participants with chronic genotype 3 hepatitis C virus (HCV) infection.

Official Title
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A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks With Sofosbuvir and Ribavirin for 24 Weeks in Subjects With Chronic Genotype 3 HCV Infection

Conditions
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Hepatitis C Virus Infection

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent HCV RNA ≥ 10^4 IU/mL HCV genotype 3 Chronic HCV infection (≥ 6 months) Females of childbearing potential must have a negative serum pregnancy test Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Exclusion Criteria: Current or prior history of clinically-significant illness (other than HCV) that may interfere with subject treatment, assessment or compliance with the protocol Screening ECG with clinically significant abnormalities Laboratory results outside of acceptable ranges at Screening Pregnant or nursing female or male with pregnant female partner Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

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 12 Weeks<br>SOF/VEL FDC for 12 weeks | Drug: SOF/VEL<br>* 400/100 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5816;|
| Experimental: SOF+RBV 24 Weeks<br>SOF+RBV for 24 weeks | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: PSI-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>|

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 SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |  | Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 | 
| Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |  | Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sofosbuvir, Velpatasvir, SOF/VEL, GS-5816, Hepatitis C, HCV, Cirrhosis, Genotype 3