Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects

Study Overview
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Brief Summary
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This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV), administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive, and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.

Official Title
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A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin in Subjects With Chronic Genotype 1 HCV Infection

Conditions
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Chronic Hepatitis C Virus

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years, with chronic genotype 1 HCV infection HCV RNA equal to or greater than 10,000 IU/mL at screening Cirrhosis determination; a liver biopsy may be required Screening laboratory values within defined thresholds Use of two effective contraception methods if female of childbearing potential or sexually active male Exclusion Criteria: Pregnant or nursing female or male with pregnant female partner Current or prior history of clinical hepatic decompensation Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) 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 8 Weeks (TN)<br>Treatment-naive (TN) participants will be randomized to receive LDV/SOF for 8 weeks. | Drug: LDV/SOF<br>* LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily<br>* Other names: Harvoni®;|
| Experimental: LDV/SOF+RBV 8 Weeks (TN)<br>Treatment-naive participants will be randomized to receive LDV/SOF plus RBV for 8 weeks. | Drug: LDV/SOF<br>* LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily<br>* Other names: Harvoni®;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>|
| Experimental: LDV/SOF 12 Weeks (TN)<br>Treatment-naive participants will be randomized to receive LDV/SOF for 12 weeks. | Drug: LDV/SOF<br>* LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily<br>* Other names: Harvoni®;|
| Experimental: LDV/SOF 12 Weeks (TE)<br>Treatment-experienced (TE) participants (had virologic failure following prior therapy with a protease-inhibitor [PI]+pegylated interferon [PEG]+RBV regimen) will be randomized to receive LDV/SOF for 12 weeks. | Drug: LDV/SOF<br>* LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily<br>* Other names: Harvoni®;|
| Experimental: LDV/SOF+RBV 12 Weeks (TE)<br>Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) will be randomized to receive LDV/SOF plus RBV for 12 weeks. | Drug: LDV/SOF<br>* LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily<br>* Other names: Harvoni®;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) at 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR2, SVR4, SVR8, and SVR24 was defined as HCV RNA < LLOQ at 2, 4, 8, and 24 weeks following the last dose of study drug, respectively. | Posttreatment Weeks 2, 4, 8, and 24 | 
| Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values. Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement. | Baseline to Posttreatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV genotype 1 (GT-1), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Open Label, Sofosbuvir, Treatment-Naïve, Protease Inhibitors, PI