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

Primary Purpose

Hepatitis C Virus Infection

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LDV/SOF
RBV
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C Virus Infection focused on measuring Hepatitis C Virus (HCV), Ledipasvir/Sofosbuvir, Ribavirin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

LDV/SOF 12 weeks, without cirrhosis

LDV/SOF + RBV 12 weeks, without cirrhosis

LDV/SOF + RBV 12 weeks, with compensated cirrhosis

LDV/SOF 24 weeks, with compensated cirrhosis

Arm Description

LDV/SOF for 12 weeks

LDV/SOF + RBV for 12 weeks

LDV/SOF + RBV for 12 weeks

LDV/SOF for 24 weeks

Outcomes

Primary Outcome Measures

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.
Percentage of Participants Who Discontinued From Study Treatment for an Adverse Event

Secondary Outcome Measures

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.
Percentage of Participants With Viral Breakthrough
Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment.
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.
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.

Full Information

First Posted
November 5, 2015
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02600351
Brief Title
Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Participants Who Have Failed Prior Treatment With Sofosbuvir-based Therapies
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Due to lack of feasibility of enrolling participants, the study was terminated early.
Study Start Date
November 11, 2015 (Actual)
Primary Completion Date
March 21, 2017 (Actual)
Study Completion Date
May 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus Infection
Keywords
Hepatitis C Virus (HCV), Ledipasvir/Sofosbuvir, Ribavirin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LDV/SOF 12 weeks, without cirrhosis
Arm Type
Experimental
Arm Description
LDV/SOF for 12 weeks
Arm Title
LDV/SOF + RBV 12 weeks, without cirrhosis
Arm Type
Experimental
Arm Description
LDV/SOF + RBV for 12 weeks
Arm Title
LDV/SOF + RBV 12 weeks, with compensated cirrhosis
Arm Type
Experimental
Arm Description
LDV/SOF + RBV for 12 weeks
Arm Title
LDV/SOF 24 weeks, with compensated cirrhosis
Arm Type
Experimental
Arm Description
LDV/SOF for 24 weeks
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
90/400 mg FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
Tablets administered orally in a divided daily dose according to weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After Cessation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame
Posttreatment Week 12
Title
Percentage of Participants Who Discontinued From Study Treatment for an Adverse Event
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With HCV RNA < the Lower Limit of Quantitation (LLOQ) at 4 and 24 Weeks Posttreatment
Description
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time Frame
Posttreatment Weeks 4 and 24
Title
Percentage of Participants With Viral Breakthrough
Description
Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment.
Time Frame
Up to 24 weeks
Title
Percentage of Participants With Viral Relapse
Description
Viral relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA <LLOQ at last on-treatment visit.
Time Frame
Up to Posttreatment Week 24
Title
Number of Participants With Emerging Resistance
Description
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.
Time Frame
Up to Posttreatment Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
City
Rialto
State/Province
California
ZIP/Postal Code
92377
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
City
Largo
State/Province
Florida
ZIP/Postal Code
33777
Country
United States
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Skokie
State/Province
Illinois
ZIP/Postal Code
60076
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21045
Country
United States
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
Egg Harbor Township
State/Province
New Jersey
ZIP/Postal Code
08234
Country
United States
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43212
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1H2
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4P9
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
City
Ponce
ZIP/Postal Code
00716
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.gilead.com/research/disclosure-and-transparency
Citations:
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
PubMed Identifier
29091342
Citation
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.
Results Reference
result

Learn more about this trial

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

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