Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination Tablet With Ribavirin for 12 Weeks in Treatment-naive Adults With Chronic HCV Genotype 3 Infection

Study Overview
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Brief Summary
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This study will evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) plus ribavirin (RBV) in treatment-naive adults with chronic genotype 3 hepatitis C virus (HCV) infection.

Official Title
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A Phase 2 Open- Label Study to Evaluate The Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination Tablet With Ribavirin for 12 Weeks in Treatment-naïve Patients With Chronic HCV Genotype 3 Infection

Conditions
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Hepatitis C Virus Infection

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Chronic genotype 3 HCV infection HCV treatment-naive HCV RNA > 10,000 IU/mL at screening Absence of cirrhosis or compensated cirrhosis Screening laboratory values within defined thresholds Use of two effective contraception methods if female of childbearing potential or sexually active male Key Exclusion Criteria: Pregnant or nursing female or male with pregnant female partner Coinfection 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 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF+RBV<br>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>|

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 12 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 | 
| Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8 and 12 |  | Weeks 1, 2, 4, 8, and 12 | 
| Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12 |  | Baseline; Weeks 1, 2, 4, 8, and 12 | 
| 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 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV genotype 3 (GT-3), HCV, Sustained Virologic Response, Direct Acting Antiviral, GS-7977, GS-5885, Ribavirin, Sofosbuvir, Ledipasvir, Hepatitis C, Hepatitis C, Chronic