Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.

Official Title
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A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination (FDC) +/- Ribavirin for 12 and 24 Weeks in Treatment-Naive 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, with chronic genotype 1 HCV infection HCV treatment-naive HCV RNA > 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 Co-infection with HIV or hepatitis B virus (HBV) 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 12 weeks<br>LDV/SOF administered for 12 weeks | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV 12 weeks<br>LDV/SOF+RBV administered for 12 weeks. | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;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 24 weeks<br>LDV/SOF administered for 24 weeks | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV 24 weeks<br>LDV/SOF+RBV administered for 24 weeks. | Drug: LDV/SOF<br>* LDV/SOF 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;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 Study Drug (SVR12) | SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug. | Posttreatment Week 12 | 
| Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug | The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized. | 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 Study Drug | SVR4 and SVR24 were defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 2 |  | Week 2 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 4 |  | Week 4 | 
| Percentage of Participants With HCV RNA < LLOQ at Week 8 |  | Week 8 | 
| Change From Baseline in HCV RNA at Week 2 |  | Baseline; Week 2 | 
| Change From Baseline in HCV RNA at Week 4 |  | Baseline; Week 4 | 
| Change From Baseline in HCV RNA at Week 8 |  | Baseline; Week 8 | 
| Percentage of Participants With Virologic Failure | On-treatment virologic failure was defined as: Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow- up values, OR Rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow-up values, OR Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment Virologic 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, Additional relevant MeSH terms:, Hepatitis, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections, Flaviviridae Infections, Antiviral Agents, Anti-Infective Agents, Therapeutic Uses, Pharmacologic Actions, Antimetabolites, Molecular Mechanisms of Pharmacological Action