Safety and Efficacy of Ledipasvir/Sofosbuvir in Adults With Chronic HCV Infection

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) with or without ribavirin (RBV) in adults with chronic hepatitis C virus (HCV) infection.

Official Title
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A Phase 3b, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of Ledipasvir/Sofosbuvir in Adults With Chronic HCV 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: Participants who failed treatment in Study GS-US-334-0119 who meet relevant inclusion/exclusion criteria are eligible for retreatment in this study Chronic genotype 1 HCV infection HCV treatment-naive HCV RNA > 10,000 IU/mL at screening Absence of 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 Infection with 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 For HIV-1/HCV co-infected individuals: Opportunistic infection within 6 months prior to screening Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline Treatment with an antiretroviral (ARV) regimen other than one of those listed in the study 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF<br>Treatment-naive participants with genotype 1 HCV infection without cirrhosis will receive LDV/SOF FDC for 8 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF Coinfected with HIV-1<br>Treatment-naive participants with genotype 1 HCV infection without cirrhosis and who are coinfected with HIV-1 will receive LDV/SOF FDC for 8 weeks. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV Retreatment<br>Participants with genotype 1 or 3 HCV infection who failed to achieve SVR12 in Gilead Study GS-US-334-0119 will receive LDV/SOF FDC + 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 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE) |  | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With HCV RNA < LLOQ on Treatment |  | Up to 12 weeks | 
| HCV RNA Change From Day 1 |  | Up to 12 weeks | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as On-treatment virologic failure confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment (ie, breakthrough), confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound), HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie, nonresponse) Relapse 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 | Up to Posttreatment Week 24 | 
| Percentage of HIV/HCV- Coinfected Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 |  | Up to Posttreatment Week 4 | 
| For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 |  | Up to Posttreatment Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV/HIV co-infection, HCV genotype 1, HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Sofosbuvir, ledipasvir, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Virus Diseases, Antiviral Agents