Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection

Phase 3

Completed

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

• Registration Number: NCT02073656
• Lead Sponsor: Gilead Sciences

Brief Summary

This study will evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) administered for 12 weeks in hepatitis C virus (HCV) treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic genotype 1 or 4 HCV infection who are co-infected with HIV-1.

Participants who experience confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 may be eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF plus ribavirin (RBV) for 24 weeks.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-02-25
• Study First Submitted QC: 2014-02-25
• Study First Posted: 2014-02-27
• Primary Completion: 2014-11
• Study Completion: 2015-12
• Status Verified: 2016-08
• Results First Submitted: 2016-08-30
• Results First Submitted QC: 2016-08-30
• Results First Posted: 2016-10-21
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 335

Inclusion Criteria

• HCV RNA ≥ 10,000 IU/mL at screening
• HCV genotype 1 or 4
• HIV-1 infection
• Cirrhosis determination, a fibroscan or liver biopsy may be required
• Screening laboratory values within defined thresholds
• Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male

Exclusion Criteria

• Clinically-significant illness (other than HCV or HIV) or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol
• Current or prior history of clinical hepatic decompensation, hepatocellular carcinoma (HCC), or other malignancy (with the exception of certain resolved skin cancers)
• Hepatitis B virus (HBV) infection
• Pregnant or nursing female
• Chronic use of systemically administered immunosuppressive agents

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LDV/SOF 12 Weeks	LDV/SOF	LDV/SOF for 12 weeks
Retreatment Substudy	LDV/SOF	LDV/SOF plus RBV for 24 weeks
Retreatment Substudy	RBV	LDV/SOF 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) at 12 weeks after stopping study treatment.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	Up to 12 weeks

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 SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12	Weeks 1, 2, 4, 6, 8, 10, and 12
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8	Baseline; Weeks 1, 2, 4, 6, and 8
Percentage of Participants With Virologic Failure	Up to Posttreatment Week 24	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.
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment	Weeks 4, 8, and 12
Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24	Baseline; Week 12, Posttreatment Weeks 12 and 24
For Participants in the Retreatment Substudy, Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)	Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy	SVR4, SVR12, and SVR 24 were defined as HCV RNA \< LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.
For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24	Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy
For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8	Baseline; Weeks 2, 4, and 8 of Retreatment Substudy
For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure	Up to Posttreatment Week 24 of Retreatment Substudy	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.