Clinical trial NCT02469246: Switch Study to Evaluate F/TAF in HIV-1 Infected Adults Who Are Virologically Suppressed on Regimens Containing ABC/3TC
Official title: A Phase 3b, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Infected Subjects Who Are Virologically Suppressed on Regimens Containing ABC/3TC
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV
HIV-1 Positive
Virologically-Suppressed
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-06-11
Enrollment: 567
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: The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching abacavir/lamivudine (ABC/3TC) fixed-dose combination (FDC) tablets to emtricitabine/tenofovir alafenamide (F/TAF) FDC tablets versus maintaining ABC/3TC in human immunodeficiency virus type 1 (HIV-1) infected adults who are virologically suppressed on regimens containing ABC/3TC.


Eligibility criteria: Key Inclusion Criteria:

* The ability to understand and sign a written informed consent form
* On antiretroviral regimen containing ABC/3TC FDC in combination with one 3rd agent for ≥ 6 consecutive months prior to screening
* Plasma HIV-1 RNA levels \< 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay) and without experiencing two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year
* Plasma HIV-1 RNA should be \< 50 copies/mL at the screening visit
* Normal ECG
* Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Females of childbearing potential and males must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug

Key Exclusion Criteria:

* A new AIDS-defining condition diagnosed within the 30 days prior to screening
* Hepatitis B surface antigen (HBsAg) positive
* Individuals experiencing decompensated cirrhosis
* Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis)
* Pregnant or lactating females
* Have an implanted defibrillator or pacemaker
* Current alcohol or substance use judged by the investigator to potentially interfere with study compliance
* A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit
* Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
* Participation in any other clinical trial (including observational trials) without prior approval
* Medications excluded due to the potential for interaction with emtricitabine (FTC), TAF, ABC or 3TC

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

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Hip BMD at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Spine BMD at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Spine BMD at Week 96
timeFrame: Baseline; Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Los Angeles
country: United States
facility: Anthony Mills, MD, Inc.
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, Inc.
state: California
city: Oakland
country: United States
facility: Highland Hospital - Alameda Health System
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: Washington
country: United States
facility: Capial Medical Associates
state: District of Columbia
city: Washington
country: United States
facility: Dupont Circle Physician's Group
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Health
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond,M.D.,P.A.
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute PA
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Kansas City
country: United States
facility: The KC CARE Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: AIDS Arms, Inc
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
city: Ghent
country: Belgium
facility: UZ Gent
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire CHU Sart Tilman Liege
city: Montreal
country: Canada
facility: Clinique medicale l'Actuel
city: Toronto
country: Canada
facility: Maple Leaf Research
city: Vancouver
country: Canada
facility: Spectrum Health
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care Centre Society
city: Copenhagen
country: Denmark
facility: Hvidovre Hospital
city: Bordeaux
country: France
facility: CHU - Groupe Saint-Andre
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Nantes
country: France
facility: C.H.U. de Nantes
city: Orleans
country: France
facility: CHR Orleans la Source
city: Tours
country: France
facility: Chu Tours
city: Bielefeld
country: Germany
facility: ICH Study Center Hamburg
city: Bonn
country: Germany
facility: Medizinische Universitatsklinik
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe-University Hospital
city: Hamburg
country: Germany
facility: ifi-Studien und Projekte GmbH an der Asklepiosklinik St. Georg
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Koln
country: Germany
facility: Klinikum der Universitaet Koln
city: Munich
country: Germany
facility: Universitätsklinikum München
city: Dublin 7
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Saint James's Hospital
city: Brescia
country: Italy
facility: University of Brescia
city: Milano
country: Italy
facility: Azienda Ospedaliera Luigi Sacco
city: Milano
country: Italy
facility: Fondazione IRCCS San Raffaele del Monte Tabor
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico di Modena
city: Roma
country: Italy
facility: Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
city: Torino
country: Italy
facility: Ospedale Amedeo di Savoia - Specializzato Malattie infettive
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: Hope Clinical Research Inc
city: Badalona
country: Spain
facility: Bonaventura
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Malaga
country: Spain
facility: Hospital Costa Del Sol
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: Imperial College
city: London
country: United Kingdom
facility: Kings College Hospital NHS Trust
city: London
country: United Kingdom
facility: Lewisham and Greenwich NHS Trust
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St. George's Hospital
city: Manchester
country: United Kingdom
facility: Manchester Centre for Sexual Health
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Winston A, Post FA, DeJesus E, Podzamczer D, Di Perri G, Estrada V, Raffi F, Ruane P, Peyrani P, Crofoot G, Mallon PWG, Castelli F, Yan M, Cox S, Das M, Cheng A, Rhee MS. Tenofovir alafenamide plus emtricitabine versus abacavir plus lamivudine for treatment of virologically suppressed HIV-1-infected adults: a randomised, double-blind, active-controlled, non-inferiority phase 3 trial. Lancet HIV. 2018 Apr;5(4):e162-e171. doi: 10.1016/S2352-3018(18)30010-9. Epub 2018 Feb 20.
citation: Gupta SK, Post FA, Arribas JR, Eron JJ Jr, Wohl DA, Clarke AE, Sax PE, Stellbrink HJ, Esser S, Pozniak AL, Podzamczer D, Waters L, Orkin C, Rockstroh JK, Mudrikova T, Negredo E, Elion RA, Guo S, Zhong L, Carter C, Martin H, Brainard D, SenGupta D, Das M. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS. 2019 Jul 15;33(9):1455-1465. doi: 10.1097/QAD.0000000000002223.