Ledipasvir/Sofosbuvir Fixed-Dose Combination and Vedroprevir With or Without Ribavirin in Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection and Cirrhosis

Study Overview
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Brief Summary
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This study is to evaluate the antiviral efficacy, safety, and tolerability of combination therapy with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) + vedroprevir (VDV) ± ribavirin (RBV) for 8 weeks in treatment-experienced adults with chronic genotype 1 hepatitis C virus (HCV) infection and cirrhosis.

Official Title
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A Phase 2, Randomized, Open-Label Study of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Vedroprevir With or Without Ribavirin in Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection and Cirrhosis

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: LDV/SOF
* Drug: VDV
* Drug: RBV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years, with chronic HCV genotype 1 infection Documentation as treatment-experienced having received pegylated interferon (Peg-IFN) + RBV ≥ 4 weeks of duration without an additional agent in the regimen without achieving sustained viral response (SVR) Presence of compensated cirrhosis Screening laboratory values within defined thresholds Must use specific contraceptive methods if female of childbearing potential or sexually active male Not pregnant or a nursing female 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 subject treatment, assessment or compliance with the protocol

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: LDV/SOF+VDV<br>Participants will receive LDV/SOF+VDV for 8 weeks. | Drug: LDV/SOF<br>* LDV/SOF (90/400 mg) FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: VDV<br>* VDV 80 mg tablet administered orally once daily<br>* Other names: GS-9451;|
| Experimental: LDV/SOF+VDV+RBV<br>Participants will receive LDV/SOF+VDV+RBV for 8 weeks. | Drug: LDV/SOF<br>* LDV/SOF (90/400 mg) FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;Drug: VDV<br>* VDV 80 mg tablet administered orally once daily<br>* Other names: GS-9451;Drug: RBV<br>* RBV 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 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment. | Posttreatment Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis C, Gilead, GS-9451