search
Back to results

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

Primary Purpose

Hepatitis C Virus, HIV

Status
Completed
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 focused on measuring genotype 1, genotype 4, HIV

Eligibility Criteria

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

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

LDV/SOF 12 Weeks

Retreatment Substudy

Arm Description

LDV/SOF for 12 weeks

LDV/SOF plus RBV for 24 weeks

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
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

Secondary Outcome Measures

Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
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
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8
Percentage of Participants With Virologic Failure
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
Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at 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)
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
For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8
For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure
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.

Full Information

First Posted
February 25, 2014
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT02073656
Brief Title
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
Official Title
A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Co-infection
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus, HIV
Keywords
genotype 1, genotype 4, HIV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
335 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LDV/SOF 12 Weeks
Arm Type
Experimental
Arm Description
LDV/SOF for 12 weeks
Arm Title
Retreatment Substudy
Arm Type
Experimental
Arm Description
LDV/SOF plus RBV 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 package insert 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 (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Time Frame
Posttreatment Week 12
Title
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame
Up to 12 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description
SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Time Frame
Posttreatment Weeks 4 and 24
Title
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12
Time Frame
Weeks 1, 2, 4, 6, 8, 10, and 12
Title
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8
Time Frame
Baseline; Weeks 1, 2, 4, 6, and 8
Title
Percentage of Participants With Virologic Failure
Description
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.
Time Frame
Up to Posttreatment Week 24
Title
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment
Time Frame
Weeks 4, 8, and 12
Title
Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24
Time Frame
Baseline; Week 12, Posttreatment Weeks 12 and 24
Title
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)
Description
SVR4, SVR12, and SVR 24 were defined as HCV RNA < LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.
Time Frame
Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy
Title
For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24
Time Frame
Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy
Title
For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8
Time Frame
Baseline; Weeks 2, 4, and 8 of Retreatment Substudy
Title
For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure
Description
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.
Time Frame
Up to Posttreatment Week 24 of Retreatment Substudy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jenny Yang, PharmD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-2170
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304-5350
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20815
Country
United States
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34209
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30312
Country
United States
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
City
Santa Fe
State/Province
New Mexico
ZIP/Postal Code
87505
Country
United States
City
Bronx
State/Province
New York
ZIP/Postal Code
10468
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0595
Country
United States
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18102
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
City
Annandale
State/Province
Virginia
ZIP/Postal Code
22003
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0341
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 5B1
Country
Canada
City
Auckland
ZIP/Postal Code
1142
Country
New Zealand
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
City
San Juan
ZIP/Postal Code
00936-5607
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
Cooper C, Naggie S, Saag M, Yang JC, Stamm LM, Dvory-Sobol H, et al. Retreatment of Patients Who Failed 12 Weeks of Ledipasvir/Sofosbuvir-Based Regimens with Ledipasvir/Sofosbuvir with Ribavirin for 24 Weeks [Poster Presentation]. 23nd Conference on Retroviruses and Opportunistic Infections (CROI); 2016 February 22-25; Boston, MA.
Results Reference
result
PubMed Identifier
26196665
Citation
Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, Marks K, Luetkemeyer A, Baden RP, Sax PE, Gane E, Santana-Bagur J, Stamm LM, Yang JC, German P, Dvory-Sobol H, Ni L, Pang PS, McHutchison JG, Stedman CA, Morales-Ramirez JO, Brau N, Jayaweera D, Colson AE, Tebas P, Wong DK, Dieterich D, Sulkowski M; ION-4 Investigators. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21.
Results Reference
result
Citation
Naggie S, Cooper C, Saag M, Stamm LM, Yang JC, Pang PS, et al. Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected With HCV and HIV-1 [Oral Presentation]. 22nd Conference on Retroviruses and Opportunistic Infections (CROI); 2015 February 23-26; Seattle, WA.
Results Reference
result
PubMed Identifier
27225242
Citation
Cooper C, Naggie S, Saag M, Yang JC, Stamm LM, Dvory-Sobol H, Han L, Pang PS, McHutchison JG, Dieterich D, Sulkowski M. Successful Re-treatment of Hepatitis C Virus in Patients Coinfected With HIV Who Relapsed After 12 Weeks of Ledipasvir/Sofosbuvir. Clin Infect Dis. 2016 Aug 15;63(4):528-31. doi: 10.1093/cid/ciw349. Epub 2016 May 25.
Results Reference
result
PubMed Identifier
26743093
Citation
Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferriere V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study; Cohen J, Conway B, Cooper C, Cote P, Cox J, Gill J, Haider S, Harris M, Haase D, Hull M, Montaner J, Moodie E, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall JM, Vachon ML, Walmsley S, Wong D. How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World? Clin Infect Dis. 2016 Apr 1;62(7):919-926. doi: 10.1093/cid/civ1222. Epub 2016 Jan 6.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs