Clinical trial NCT02707601: 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
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
HCV Infection
Keywords: HIV
HCV
Antiretroviral therapy
HCV direct acting antiviral(s) (DAA)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-03-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)
timeFrame: HCV Posttreatment Week 12
Secondary outcomes:
measure: Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)
timeFrame: HCV Posttreatment Week 4
measure: 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
timeFrame: 24 weeks after start of HIV treatment
measure: 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
timeFrame: Up to 32 weeks plus 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: Los Angeles
country: United States
facility: Peter J Ruane MD Inc
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: Washington
country: United States
facility: The George Washington University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Health
state: District of Columbia
city: Clearwater
country: United States
facility: Community AIDS Network
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA, Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology & Research Center, LLC
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tampa
country: United States
facility: St. Josephs Comprehensive Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute PA
state: Florida
city: Wilton Manors
country: United States
facility: Rowan Tree Medical PA
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Chicago
country: United States
facility: The CORE Foundation
state: Illinois
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Free Health Clinic
state: Missouri
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Health Network, Network Office of Research and Innovation
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Houston
country: United States
facility: Therapeutics Concepts, PA
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education
state: Virginia
city: Seattle
country: United States
facility: Peter Shalit MD
state: Washington
city: Spokane
country: United States
facility: Southern Cal
state: Washington
city: Tacoma
country: United States
facility: Community Health Care
state: Washington
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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.
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.
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.