Ledipasvir/Sofosbuvir Fixed-Dose Combination With Ribavirin or GS-9669 in Subjects With Chronic Genotype 1 HCV Infection

Study Overview
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Brief Summary
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This study will evaluate the antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) or LDV/SOF plus GS-9669 in treatment-naive or treatment-experienced participants with chronic genotype 1 hepatitis C virus (HCV) infection. A total of 90 participants are planned to be enrolled in the study for 8 weeks of treatment, approximately 60 having had prior treatment with a regimen containing pegylated interferon (PEG) and RBV for ≥ 12 weeks. Randomization will be stratified by treatment-naive versus treatment-experienced and by HCV genotype (1a versus 1b).

Official Title
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A Phase 2, Randomized, Open-Label Study of Sofosbuvir/Ledipasvir Fixed-Dose Combination With Ribavirin or GS-9669 250 mg or GS-9669 500 mg in Naive or Treatment-Experienced Cirrhotic Subjects With Chronic Genotype 1 HCV Infection

Conditions
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Chronic HCV Infection

Intervention / Treatment
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* Drug: LDV/SOF
* Drug: RBV
* Drug: GS-9669


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18, with chronic genotype 1 HCV infection Documented HCV treatment-naïve or treatment-experienced subjects who failed previous PEG+RBV regimen HCV RNA > 10,000 IU/mL at Screening Presence of compensated cirrhosis 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 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+RBV<br>Participants will receive LDV/SOF plus RBV for 8 weeks. | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5885;Drug: RBV<br>* Ribavirin (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>* Other names: Ribasphere®;|
| Experimental: LDV/SOF + GS-9669 250 mg<br>Participants will receive LDV/SOF plus GS-9669 250 mg for 8 weeks. | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5885;Drug: GS-9669<br>* GS-9669 tablet(s) administered orally once daily<br>|
| Experimental: LDV/SOF + GS-9669 500 mg<br>Participants will receive LDV/SOF plus GS-9669 500 mg (2 x 250 mg) for 8 weeks. | Drug: LDV/SOF<br>* Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-7977/GS-5885;Drug: GS-9669<br>* GS-9669 tablet(s) administered orally once daily<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) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Percentage of Participants Permanently Discontinuing 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 Sustained Virologic Response 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 On-treatment Virologic Failure | On-treatment virologic failure was defined as 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) | Up to 8 weeks | 
| Percentage of Participants Experiencing Viral Relapse | Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR. | Up 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, HCV, Sustained Virologic Response, Direct-Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Open Label, Sofosbuvir, Treatment-Naive, Protease Inhibitors, PI, Treatment experienced, Cirrhotic