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

A Phase 3b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Subjects Who Have Failed Prior Treatment With Sofosbuvir-based Therapies

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.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: LDV/SOF; Drug: RBV

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1H2
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
    • Montreal, Quebec, Canada, H2l 4P9
• Puerto Rico
  • Ponce, Puerto Rico, 00716
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Los Angeles, California, United States, 90027
    • Pasadena, California, United States, 91105
    • Rialto, California, United States, 92377
    • Sacramento, California, United States, 95817
    • Ventura, California, United States, 93003
  • Connecticut
    • New Haven, Connecticut, United States, 06520
  • Florida
    • Largo, Florida, United States, 33777
    • Weston, Florida, United States, 33331
  • Illinois
    • Chicago, Illinois, United States, 60612
    • Skokie, Illinois, United States, 60076
  • Maryland
    • Baltimore, Maryland, United States, 21202
    • Columbia, Maryland, United States, 21045
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
  • Missouri
    • Kansas City, Missouri, United States, 64131
    • Saint Louis, Missouri, United States, 63110
  • New Jersey
    • Egg Harbor Township, New Jersey, United States, 08234
  • New York
    • Bronx, New York, United States, 10467
    • New York, New York, United States, 10032
    • New York, New York, United States, 10025
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
    • Charlotte, North Carolina, United States, 28204
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Cleveland, Ohio, United States, 44109
    • Columbus, Ohio, United States, 43212
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
  • Tennessee
    • Memphis, Tennessee, United States, 38104
    • Nashville, Tennessee, United States, 37232
  • Texas
    • Austin, Texas, United States, 78758
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75203
    • Dallas, Texas, United States, 75390
    • Houston, Texas, United States, 77030
  • Utah
    • Salt Lake City, Utah, United States, 84132
  • Virginia
    • Charlottesville, Virginia, United States, 22908
  • Washington
    • Seattle, Washington, United States, 98101
    • Seattle, Washington, United States, 98122

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDV/SOF 12 weeks, without cirrhosis; LDV/SOF for 12 weeks	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
Experimental: LDV/SOF + RBV 12 weeks, without cirrhosis; LDV/SOF + RBV for 12 weeks	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977; Drug: RBV; Tablets administered orally in a divided daily dose according to weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: LDV/SOF + RBV 12 weeks, with compensated cirrhosis; LDV/SOF + RBV for 12 weeks	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977; Drug: RBV; Tablets administered orally in a divided daily dose according to weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: LDV/SOF 24 weeks, with compensated cirrhosis; LDV/SOF for 24 weeks	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HCV RNA < the Lower Limit of Quantitation (LLOQ) at 4 and 24 Weeks Posttreatment	SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.	Posttreatment Weeks 4 and 24
Percentage of Participants With Viral Breakthrough	Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment.	Up to 24 weeks
Percentage of Participants With Viral Relapse	Viral relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA <LLOQ at last on-treatment visit.	Up to Posttreatment Week 24
Number of Participants With Emerging Resistance	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.	Up to Posttreatment Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Tam E, Luetkemeyer AF, Mantry PS, Satapathy SK, Ghali P, Kang M, Haubrich R, Shen X, Ni L, Camus G, Copans A, Rossaro L, Guyer B, Brown RS Jr; RESCUE and ACTG A5348 study investigators. Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir-experienced, NS5A treatment-naive patients: Findings from two randomized trials. Liver Int. 2018 Jun;38(6):1010-1021. doi: 10.1111/liv.13616. Epub 2017 Dec 5.
• Tam E, Brown RS, Satapathy S, Shen X, Camus G, Copans A, et al. Efficacy and Safety of Ledipasvir/Sofosbuvir (LDV/SOF), with or without Ribavirin (RBV), for Treatment of HCV-mono and HIV/HCV Co-infected Patients Who Have Failed Prior Treatment with Non-NS5A, SOF-based Therapies [Poster THU-265]. The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19-23 April; Amsterdam, the Netherlands.
• Tam E, Mantry PS, Satapathy SK, Ghali P, Shen X, Han LL, et al. A Phase 3b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir (LDV/SOF), with or without Ribavirin (RBV), in HCV Infected Subjects Who Have Failed Prior Treatment with Non-NS5A, SOF-based Therapies (RESCUE) [Poster PP0217]. Asian Pacific Association for the Study of the Liver (APASL); 2017 15-19 February; Shanghai, China.
• Tam E, Brown RS, Satapathy S, Camus G, Copans A, Rossaro L, et al. Ledipasvir/Sofosbuvir ± Ribavirin in HCV and HIV/HCV Prior SOF-based Virologic Failures (RESCUE and ACTG A5348 Studies) [Poster 568LB]. Conference on Retroviruses and Opportunistic Infections (CROI); 2017 13-16 February; Seattle, WA.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2015
• Primary Completion (Actual): March 21, 2017
• Study Completion (Actual): May 29, 2017

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (Estimate): November 9, 2015

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Ribavirin; Hepatitis C Virus (HCV); Ledipasvir/Sofosbuvir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: GS-US-337-1746

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes