Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Participants Who Have Failed Prior Treatment With Sofosbuvir-based Therapies

Phase 3

Terminated

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

• Registration Number: NCT02600351
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of this study is to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) for 12 weeks with or without ribavirin (RBV) in participants without cirrhosis, and LDV/SOF FDC for 12 weeks with RBV or LDV/SOF FDC for 24 weeks without RBV in participants with cirrhosis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-05
• Study First Submitted QC: 2015-11-05
• Study First Posted: 2015-11-09
• Study Start: 2015-11-11
• Primary Completion: 2017-03-21
• Study Completion: 2017-05-29
• Results First Submitted: 2018-03-13
• Results First Submitted QC: 2018-03-13
• Results First Posted: 2018-04-11
• Status Verified: 2018-08
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 87

Inclusion Criteria

• HCV RNA > 15 IU/mL at screening
• HCV genotype 1 or 4
• Chronic HCV infection (≥ 6 months)
• Prior virologic failure after treatment with SOF in combination with simeprevir (SMV) ± RBV or with RBV ± pegylated interferon (PEG)
• Cirrhotic and non-cirrhotic as determined by standard methods
• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Key

Exclusion Criteria

• Prior exposure to approved or experimental non-structural protein (NS5A) inhibitors
• Prior exposure to nucleos(t)ide polymerase inhibitors, other than SOF
• 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 individual's treatment, assessment or compliance with the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LDV/SOF + RBV 12 weeks, with compensated cirrhosis	LDV/SOF	LDV/SOF + RBV for 12 weeks
LDV/SOF + RBV 12 weeks, without cirrhosis	LDV/SOF	LDV/SOF + RBV for 12 weeks
LDV/SOF 12 weeks, without cirrhosis	LDV/SOF	LDV/SOF for 12 weeks
LDV/SOF 24 weeks, with compensated cirrhosis	LDV/SOF	LDV/SOF for 24 weeks
LDV/SOF + RBV 12 weeks, without cirrhosis	RBV	LDV/SOF + RBV for 12 weeks
LDV/SOF + RBV 12 weeks, with compensated cirrhosis	RBV	LDV/SOF + RBV for 12 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 12 Weeks After Cessation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, \< 15 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Who Discontinued From Study Treatment for an Adverse Event	Up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Emerging Resistance	Up to Posttreatment Week 24	The full-length NS3, NS5A, and NS5B coding regions were deep sequenced at pretreatment (baseline) for all participants included in the Full Analysis Set, and at posttreatment for all participants who relapsed.
Percentage of Participants With HCV RNA < the Lower Limit of Quantitation (LLOQ) at 4 and 24 Weeks Posttreatment	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 Viral Relapse	Up to Posttreatment Week 24	Viral relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \<LLOQ at last on-treatment visit.
Percentage of Participants With Viral Breakthrough	Up to 24 weeks	Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment.