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Efficacy, Safety, and Tolerability of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Participants Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment (Co-STARs)

Primary Purpose

HIV-1 Infection, HCV Infection

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
E/C/F/TAF
F/R/TAF
LDV/SOF
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV-1 Infection focused on measuring HIV, HCV, Antiretroviral therapy, HCV direct acting antiviral(s) (DAA)

Eligibility Criteria

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

Key Inclusion Criteria:

  • Chronic genotype (GT) 1, HCV infected, male and non-pregnant/ non-lactating female individuals, without cirrhosis, treatment-naive or treatment-experienced with interferon (IFN) +/- ribavirin (RBV) +/- HCV protease inhibitor (PI).
  • Compensated cirrhotic individuals must be HCV treatment-naive.
  • No prior treatments with NS5A and NS5B or any HCV direct acting antivirals, except boceprevir, telaprevir and simeprevir, in combination with IFN and RBV
  • Currently on an ARV regimen (2 NRTI + a third agent) without change for 6 months prior to screening.
  • Documented plasma HIV-1 RNA levels < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 6 months preceding the screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values ("blips") of HIV-1 RNA ≥ 50 copies/mL followed by resuppression is allowed.

  • For individuals with 3 or more prior ARV regimens, a regimen history should be provided for approval by the Sponsor.

    • Note: Individuals that changed from TDF to TAF less than 6 months ago will be eligible as long as the TDF/ TAF change was the only change to the regimen.
  • Plasma HIV-1 RNA level < 50 copies/mL at the screening visit
  • Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype prior to first ARV is not available or individual had 3 or more prior ARV regimens, individual will have proviral genotype analysis for archived resistance prior to Day 1.
  • No history of HIV virologic failure
  • No evidence of Hepatitis B infection
  • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min as estimated by Cockcroft-Gault formula

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

Sites / Locations

  • University of Alabama at Birmingham
  • Spectrum Medical Group
  • Mills Clinical Research
  • Peter J Ruane MD Inc
  • University of California Davis
  • University of California San Diego
  • Kaiser Permanente
  • The George Washington University Medical Center
  • Whitman-Walker Health
  • Community AIDS Network
  • Gary Richmond, MD, PA, Inc.
  • Therafirst Medical Center
  • Midway Immunology & Research Center, LLC
  • AIDS Healthcare Foundation
  • University of Miami
  • AIDS Healthcare Foundation
  • Orlando Immunology Center
  • St. Josephs Comprehensive Research Institute
  • Triple O Research Institute PA
  • Rowan Tree Medical PA
  • AIDS Research Consortium of Atlanta
  • Emory University
  • Chatham County Health Department
  • The CORE Foundation
  • Be Well Medical Center
  • Kansas City Free Health Clinic
  • Saint Michael's Medical Center
  • Weill Cornell Medical College
  • University of North Carolina at Chapel Hill
  • Duke University
  • East Carolina University
  • Lehigh Valley Health Network, Network Office of Research and Innovation
  • Philadelphia FIGHT
  • University of Pennsylvania
  • Central Texas Clinical Research
  • UT Southwestern Medical Center
  • Gordon E. Crofoot MD PA
  • Therapeutics Concepts, PA
  • Clinical Alliance for Research & Education
  • Peter Shalit MD
  • Southern Cal
  • Community Health Care
  • Clinical Research Puerto Rico Inc

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

E/C/F/TAF + LDV/SOF

F/R/TAF + LDV/SOF

Arm Description

Part 1: Participants will switch from 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a third agent to E/C/F/TAF. Part 2: After 8 weeks of E/C/F/TAF treatment, the participants maintaining HIV-1 RNA < 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study.

Part 1: Participants will switch from 2 NRTI plus a third agent to F/R/TAF. Part 2: After 8 weeks of F/R/TAF treatment, the participants maintaining HIV-1 RNA < 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study.

Outcomes

Primary Outcome Measures

Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)
Sustained Virologic Response (SVR12) was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.

Secondary Outcome Measures

Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping LDV/SOF treatment.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment

Full Information

First Posted
March 9, 2016
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02707601
Brief Title
Efficacy, Safety, and Tolerability of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Participants Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment
Acronym
Co-STARs
Official Title
A Phase 3b Randomized, Open-label, Controlled Study of the Efficacy, Safety and Tolerability of 12 Weeks of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Subjects Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment, the HIV/HCV Co-STARs Study (Co-infection Treatment With Single Tablet Antiviral Regimens)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
April 1, 2016 (Actual)
Primary Completion Date
September 14, 2017 (Actual)
Study Completion Date
September 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
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate efficacy of ledipasvir/sofosbuvir (LDV/SOF) and safety and tolerability of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) from the current antiretroviral (ARV) therapy and in virologically-suppressed, HIV-1/HCV co-infected participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infection, HCV Infection
Keywords
HIV, HCV, Antiretroviral therapy, HCV direct acting antiviral(s) (DAA)

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
E/C/F/TAF + LDV/SOF
Arm Type
Experimental
Arm Description
Part 1: Participants will switch from 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a third agent to E/C/F/TAF. Part 2: After 8 weeks of E/C/F/TAF treatment, the participants maintaining HIV-1 RNA < 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study.
Arm Title
F/R/TAF + LDV/SOF
Arm Type
Experimental
Arm Description
Part 1: Participants will switch from 2 NRTI plus a third agent to F/R/TAF. Part 2: After 8 weeks of F/R/TAF treatment, the participants maintaining HIV-1 RNA < 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study.
Intervention Type
Drug
Intervention Name(s)
E/C/F/TAF
Other Intervention Name(s)
Genvoya®
Intervention Description
150/150/200/10 mg fixed dose combination (FDC) tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
F/R/TAF
Other Intervention Name(s)
Odefsey®
Intervention Description
200/25/25 mg FDC tablet administered orally once daily
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
Primary Outcome Measure Information:
Title
Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)
Description
Sustained Virologic Response (SVR12) was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.
Time Frame
HCV Posttreatment Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)
Description
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping LDV/SOF treatment.
Time Frame
HCV Posttreatment Week 4
Title
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm
Description
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame
24 weeks after start of HIV treatment
Title
Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment
Time Frame
Up to 32 weeks plus 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Chronic genotype (GT) 1, HCV infected, male and non-pregnant/ non-lactating female individuals, without cirrhosis, treatment-naive or treatment-experienced with interferon (IFN) +/- ribavirin (RBV) +/- HCV protease inhibitor (PI). Compensated cirrhotic individuals must be HCV treatment-naive. No prior treatments with NS5A and NS5B or any HCV direct acting antivirals, except boceprevir, telaprevir and simeprevir, in combination with IFN and RBV Currently on an ARV regimen (2 NRTI + a third agent) without change for 6 months prior to screening. Documented plasma HIV-1 RNA levels < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 6 months preceding the screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values ("blips") of HIV-1 RNA ≥ 50 copies/mL followed by resuppression is allowed. For individuals with 3 or more prior ARV regimens, a regimen history should be provided for approval by the Sponsor. Note: Individuals that changed from TDF to TAF less than 6 months ago will be eligible as long as the TDF/ TAF change was the only change to the regimen. Plasma HIV-1 RNA level < 50 copies/mL at the screening visit Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype prior to first ARV is not available or individual had 3 or more prior ARV regimens, individual will have proviral genotype analysis for archived resistance prior to Day 1. No history of HIV virologic failure No evidence of Hepatitis B infection Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min as estimated by Cockcroft-Gault formula 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:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Spectrum Medical Group
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Mills Clinical Research
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Peter J Ruane MD Inc
City
Los Angeles
State/Province
California
Country
United States
Facility Name
University of California Davis
City
Sacramento
State/Province
California
Country
United States
Facility Name
University of California San Diego
City
San Diego
State/Province
California
Country
United States
Facility Name
Kaiser Permanente
City
San Francisco
State/Province
California
Country
United States
Facility Name
The George Washington University Medical Center
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
Whitman-Walker Health
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
Community AIDS Network
City
Clearwater
State/Province
Florida
Country
United States
Facility Name
Gary Richmond, MD, PA, Inc.
City
Fort Lauderdale
State/Province
Florida
Country
United States
Facility Name
Therafirst Medical Center
City
Fort Lauderdale
State/Province
Florida
Country
United States
Facility Name
Midway Immunology & Research Center, LLC
City
Fort Pierce
State/Province
Florida
Country
United States
Facility Name
AIDS Healthcare Foundation
City
Miami Beach
State/Province
Florida
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
AIDS Healthcare Foundation
City
Miami
State/Province
Florida
Country
United States
Facility Name
Orlando Immunology Center
City
Orlando
State/Province
Florida
Country
United States
Facility Name
St. Josephs Comprehensive Research Institute
City
Tampa
State/Province
Florida
Country
United States
Facility Name
Triple O Research Institute PA
City
West Palm Beach
State/Province
Florida
Country
United States
Facility Name
Rowan Tree Medical PA
City
Wilton Manors
State/Province
Florida
Country
United States
Facility Name
AIDS Research Consortium of Atlanta
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Chatham County Health Department
City
Savannah
State/Province
Georgia
Country
United States
Facility Name
The CORE Foundation
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Be Well Medical Center
City
Berkley
State/Province
Michigan
Country
United States
Facility Name
Kansas City Free Health Clinic
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
Saint Michael's Medical Center
City
Newark
State/Province
New Jersey
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
East Carolina University
City
Greenville
State/Province
North Carolina
Country
United States
Facility Name
Lehigh Valley Health Network, Network Office of Research and Innovation
City
Allentown
State/Province
Pennsylvania
Country
United States
Facility Name
Philadelphia FIGHT
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Central Texas Clinical Research
City
Austin
State/Province
Texas
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Gordon E. Crofoot MD PA
City
Houston
State/Province
Texas
Country
United States
Facility Name
Therapeutics Concepts, PA
City
Houston
State/Province
Texas
Country
United States
Facility Name
Clinical Alliance for Research & Education
City
Annandale
State/Province
Virginia
Country
United States
Facility Name
Peter Shalit MD
City
Seattle
State/Province
Washington
Country
United States
Facility Name
Southern Cal
City
Spokane
State/Province
Washington
Country
United States
Facility Name
Community Health Care
City
Tacoma
State/Province
Washington
Country
United States
Facility Name
Clinical Research Puerto Rico Inc
City
San Juan
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
Ramgopal M, Jain M, Hinestrosa F, Asmuth D, Huhn G, Slim J, et al. HIV-1/HCV Coinfection Treatment with Single-Tablet Antiviral Regimens (CoSTARs): 12 Weeks of Ledipasvir/Sofosbuvir (LDV/SOF) after Randomized Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Rilpivirine/F/TAF (R/F/TAF) [Poster LB-12]. AASLD: The Liver Meeting 2017 20-24 October; Washington DC.
Results Reference
result
Citation
Huhn G, Jain M, Hinestrosa F, Asmuth D, Huhn G, Slim J, et al. HIV-1/HCV Coinfection Treatment with Single-Tablet Antiviral Regimens (CoSTARs): 12 Weeks of Ledipasvir/Sofosbuvir (LDV/SOF) after Randomized Switch to Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Rilpivirine/F/TAF (R/F/TAF) [Poster PE16/52]. European AIDS Conference 2017 25-27 October; Milan Italy.
Results Reference
result
PubMed Identifier
31995556
Citation
Huhn GD, Ramgopal M, Jain MK, Hinestrosa F, Asmuth DM, Slim J, Goldstein D, Applin S, Ryu JH, Jiang S, Cox S, Das M, Nguyen-Cleary T, Piontkowsky D, Guyer B, Rossaro L, Haubrich RH. HIV/HCV therapy with ledipasvir/sofosbuvir after randomized switch to emtricitabine-tenofovir alafenamide-based single-tablet regimens. PLoS One. 2020 Jan 29;15(1):e0224875. doi: 10.1371/journal.pone.0224875. eCollection 2020.
Results Reference
derived

Learn more about this trial

Efficacy, Safety, and Tolerability of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Participants Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment

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