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

Phase 3

Completed

• Conditions: Chronic Hepatitis C Virus
• Interventions: Drug: LDV/SOF; Drug: RBV

• Registration Number: NCT01768286
• Lead Sponsor: Gilead Sciences

Brief Summary

This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir fixed dose combination (FDC) with or without ribavirin (RBV) administered for 12 or 24 weeks in treatment-experienced subjects with chronic genotype 1 hepatitis C virus (HCV) infection.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01
• Study First Submitted: 2013-01-10
• Study First Submitted QC: 2013-01-11
• Study First Posted: 2013-01-15
• Primary Completion: 2013-11
• Study Completion: 2014-02
• Status Verified: 2014-11
• Results First Submitted: 2014-11-21
• Results First Submitted QC: 2014-11-21
• Results First Posted: 2014-11-26
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 441

Inclusion Criteria

• Age > 18, with chronic genotype 1 HCV infection
• HCV treatment-experienced, including patients who have previously failed a nonstructural protein (NS)3/4A protease inhibitor plus pegylated interferon (PEG)/RBV regimen
• 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
• Coinfection with HIV or hepatitis B virus
• Current or prior history of clinical hepatic decompensation
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LDV/SOF 12 Weeks	LDV/SOF	Participants will receive LDV/SOF FDC for 12 weeks.
LDV/SOF+RBV 12 Weeks	LDV/SOF	Participants will receive LDV/SOF FDC plus RBV for 12 weeks.
LDV/SOF+RBV 12 Weeks	RBV	Participants will receive LDV/SOF FDC plus RBV for 12 weeks.
LDV/SOF 24 Weeks	LDV/SOF	Participants will receive LDV/SOF FDC for 24 weeks.
LDV/SOF+RBV 24 Weeks	LDV/SOF	Participants will receive LDV/SOF FDC plus RBV for 24 weeks.
LDV/SOF+RBV 24 Weeks	RBV	Participants will receive LDV/SOF FDC plus RBV for 24 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.
Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug	Up to 24 weeks	The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.

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 at Week 2	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 HCV RNA < LLOQ at Week 24	Week 24
Change From Baseline in HCV RNA at Week 2	Baseline; Week 2
Percentage of Participants With HCV RNA < LLOQ at Week 1	Week 1
Percentage of Participants With HCV RNA < LLOQ at Week 4	Week 4
Percentage of Participants With HCV RNA < LLOQ at Week 8	Week 8
Percentage of Participants With HCV RNA < LLOQ at Week 12	Week 12
Change From Baseline in HCV RNA at Week 1	Baseline; Week 1
Percentage of Participants With Virologic Failure	Baseline to posttreatment Week 24	Virologic failure was defined as on-treatment virologic failure or virologic relapse.; * 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); Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.