Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection

Phase 2

Completed

• Conditions: HCV Infection
• Interventions: Drug: LDV/SOF; Drug: Placebo to match RBV; Drug: RBV; Drug: Placebo to match LDV/SOF

• Registration Number: NCT01965535
• Lead Sponsor: Gilead Sciences

Brief Summary

This study is to determine the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) with and without ribavirin (RBV), and to evaluate the safety and tolerability of each regimen as assessed by review of the accumulated safety data. Approximately 150 participants with genotype 1 HCV infection, who have previously received treatment for HCV, and who have a diagnosis for cirrhosis will be enrolled. Participants will be randomized to 1 of 2 groups.

Group 1: SOF/LDV FDC tablet plus placebo to match RBV for 24 weeks

Group 2: Delayed treatment group: placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by SOF/LDV FDC once daily plus RBV in a divided daily dose for 12 weeks

Randomization will 1:1 to the two groups and will be stratified by HCV genotype (1a, 1b; mixed or other genotype 1 results will be stratified as genotype 1a), and prior HCV therapy treatment response (never achieved HCV RNA \< the lower limit of quantitation (LLOQ), or achieved HCV RNA \< LLOQ).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-10-16
• Study First Submitted QC: 2013-10-16
• Study First Posted: 2013-10-18
• Primary Completion: 2014-08
• Study Completion: 2014-11
• Results First Submitted: 2015-08-27
• Results First Submitted QC: 2015-08-27
• Results First Posted: 2015-09-28
• Status Verified: 2016-06
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

• Age equal to or greater than 18 years, with chronic genotype 1 HCV infection
• HCV RNA ≥ 10,000 IU/mL at screening
• Prior virological failure after treatment with pegylated interferon (PEG-IFN), RBV and a protease inhibitor following documented prior virology failure after treatment with a PEG-IFN + RBV regimen
• Evidence of cirrhosis
• Screening laboratory values within defined thresholds
• Use of two effective contraception methods if female of childbearing potential or sexually active male

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Exclusion Criteria

• Pregnant or nursing female or male with pregnant female partner
• Current or prior history of clinical hepatic decompensation
• Prior exposure to approved or experimental HCV specific direct-acting antivirals other than a nonstructural protein (NS)3/4A protease inhibitor
• History of solid organ transplantation, including liver transplant
• Hepatocellular carcinoma 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LDV/SOF + RBV	Placebo to match LDV/SOF	Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
LDV/SOF	LDV/SOF	LDV/SOF FDC tablet plus placebo to match RBV for 24 weeks
LDV/SOF	Placebo to match RBV	LDV/SOF FDC tablet plus placebo to match RBV for 24 weeks
LDV/SOF + RBV	LDV/SOF	Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
LDV/SOF + RBV	Placebo to match RBV	Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
LDV/SOF + RBV	RBV	Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, \< 25 IU/mL) 12 weeks following the last dose of study drug.; * 1 participant who was randomized to the LDV/SOF + RBV group who received placebo discontinued prior to receiving LDV/SOF + RBV and is excluded from the Full Analysis Set.; * 1 participant who was randomized to the LDV/SOF + RBV group received LDV/SOF + placebo, and is counted in the LDV/SOF group for the safety analysis, and in the LDV/SOF+RBV group for the efficacy analysis (ie, in the Full Analysis Set).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Percentage of Participants With HCV RNA < LLOQ (ie, < 25 IU/mL) at Weeks 1, 2, 4, 8, 12, and 24	Weeks 1, 2, 4, 8, 12, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12	Baseline; Weeks 1, 2, 4, 8, and 12
Percentage of Participants With Virologic Failure	Baseline to Posttreatment Week 24	Virologic failure is 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.