Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Participants With Chronic Genotype 1 HCV Who Participated in a Prior Gilead-Sponsored HCV Treatment Study

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV) in participants with chronic genotype 1 hepatitis C virus (HCV) infection who have participated in a prior Gilead-sponsored HCV treatment study, and who did not achieve sustained virologic response (SVR24), defined as HCV RNA < lower limit of quantification (LLOQ) 24 weeks after last dose of study drug (SVR24).

Official Title
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An Open-Label, Multicenter Study To Evaluate The Efficacy And Safety Of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin For 12 or 24 Weeks In Chronic Genotype 1 HCV Infected Subjects Who Participated In A Prior Gilead-Sponsored HCV Treatment Study

Conditions
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HCV 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: Willing and able to provide written informed consent Infection with HCV genotype 1 HCV RNA > LLOQ at screening Participation in a prior Gilead-sponsored study Screening laboratory values within defined thresholds Use of two effective contraception methods if female of childbearing potential or sexually active male Must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments Key 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 (Groups 1 and 2 only) Hepatocellular carcinoma (HCC) History of clinically significant illness or any other medical disorder that may interfere with subject 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF+RBV 12 weeks (Group 1)<br>Participants who failed a prior SOF+RBV ± pegylated interferon (Peg-IFN) regimen will receive LDV/SOF FDC plus RBV for 12 weeks. | Drug: LDV/SOF<br>* Tablet(s) 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) Participants in the LDV/SOF+RBV 24 weeks group will dose adjust RBV according to hemoglobin and renal status as stated in the RBV package insert.<br>|
| Experimental: LDV/SOF 24 weeks (Group 2)<br>Participants who failed a prior LDV/SOF ± RBV regimen will receive LDV/SOF FDC for 24 weeks. | Drug: LDV/SOF<br>* Tablet(s) administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF+RBV 24 weeks (Group 3)<br>Participants with advanced compensated or decompensated cirrhosis who failed a prior SOF+RBV regimen will receive LDV/SOF FDC plus RBV for 24 weeks. | Drug: LDV/SOF<br>* Tablet(s) 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) Participants in the LDV/SOF+RBV 24 weeks group will dose adjust RBV according to hemoglobin and renal status as stated in the RBV package insert.<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 treatment. | Post-treatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |  | Up to 24 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 treatment, respectively. | Posttreatment Weeks 4 and 24 | 
| Percentage of Participants With HCV RNA < LLOQ While on Treatment |  | Baseline to Week 24 | 
| Change in HCV RNA From Baseline |  | Baseline to Week 8 | 
| 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 confirmed with 2 consecutive values or last available posttreatment measurement | Up to posttreatment Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genotype 1