Clinical trial NCT02600819: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Adults on Chronic Hemodialysis
Official title: A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: End stage renal disease
Hemodialysis
Open-label
HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-09
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV-1) infected adults with end-stage renal disease (ESRD) on chronic hemodialysis (HD).


Eligibility criteria: Key Inclusion Criteria:

* Currently on a stable antiretroviral regimen for ≥ 6 consecutive months
* Plasma HIV-1 ribonucleic acid (RNA) concentrations \< 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA \< 50 copies/mL at screening
* No documented history of HIV-1 resistance to elvitegravir (EVG), emtricitabine (FTC), lamivudine (3TC) or tenofovir (TFV) and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance
* Cluster determinant 4 (CD4+) T cell count ≥ 200 cells/μL
* ESRD with estimated glomerular filtration rate (eGFR) \< 15 mL/min by Cockcroft-Gault formula for creatinine clearance
* On chronic HD for ≥ 6 months prior to screening
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)

Key Exclusion Criteria:

* Hepatitis B co-infection
* Any clinical history, condition, or test result that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
* Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial.
* History or presence of allergy or intolerance to the study drugs or their components
* A new acquired immunodeficiency syndrome (AIDS)-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis
* Received solid organ or bone marrow transplant

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

Primary outcomes:
measure: GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48
timeFrame: First Dose Date Up to Week 48
Secondary outcomes:
measure: GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96
timeFrame: First Dose Date Up to Week 96
measure: GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm
timeFrame: Week 24
measure: GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm
timeFrame: Week 48
measure: GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm
timeFrame: Week 96
measure: Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV)
timeFrame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
measure: PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV
timeFrame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
measure: PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV
timeFrame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
measure: PK Parameter: Ctau of EVG, COBI, FTC, and TFV
timeFrame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
measure: GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach
timeFrame: Week 96
measure: GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach
timeFrame: Week 96
measure: BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach
timeFrame: Week 48 of the BVY OL Extension Phase
measure: GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96
timeFrame: Baseline; Week 96
measure: BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48 of the BVY OL Extension Phase
measure: GEN Phase: Change From Baseline in CD4 Percentage at Week 96
timeFrame: Baseline; Week 96
measure: BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48
timeFrame: Baseline; Week 48 of the BVY OL Extension Phase
Other outcomes:
Locations:
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: Fort Pierce
country: United States
facility: Midway Immunology & Research Center, LLC
state: Florida
city: Orlando
country: United States
facility: Infectious Disease Consultants, M.D., P.A. d/b/a Orlando Immunology Center
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute PA
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Newark
country: United States
facility: Prime Health Care Services - St Michael's LLC d/b/a Saint Michael's Medical Center
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill / UNC School of Medicine
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Med Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center IRB
state: Ohio
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants
state: Texas
city: Fort Worth
country: United States
facility: Trinity Health and Wellness Center
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Wien
country: Austria
facility: Otto Wagner Spital
city: Creteil
country: France
facility: Hopital Henri Mondor
city: NICE Cedex 03
country: France
facility: CHU de Nice-l Archet
city: Paris Cedex 10
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Bichat-Claude Bernard
city: Tourcoing Cedex
country: France
facility: Centre Hospitalier de Tourcoing
city: Munchen
country: Germany
facility: Klinikum rechts der Isar, TUM
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Eron JJ Jr, Lelievre JD, Kalayjian R, Slim J, Wurapa AK, Stephens JL, McDonald C, Cua E, Wilkin A, Schmied B, McKellar M, Cox S, Majeed SR, Jiang S, Cheng A, Das M, SenGupta D. Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1-infected adults with end-stage renal disease on chronic haemodialysis: an open-label, single-arm, multicentre, phase 3b trial. Lancet HIV. 2018 Dec 13:S2352-3018(18)30296-0. doi: 10.1016/S2352-3018(18)30296-0. Online ahead of print.