Switch Study to Evaluate F/TAF in HIV-1 Infected Adults Who Are Virologically Suppressed on Regimens Containing ABC/3TC

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: F/TAF; Drug: ABC/3TC Placebo; Drug: 3rd ARV agent; Drug: ABC/3TC; Drug: F/TAF Placebo

• Study Type: Interventional
• Enrollment (Actual): 567
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium
    • UZ Gent
  • Liege, Belgium
    • Centre Hospitalier Universitaire CHU Sart Tilman Liege
• Canada
  • Montreal, Canada
    • Clinique médicale l'Actuel
  • Toronto, Canada
    • Maple Leaf Research
  • Vancouver, Canada
    • Spectrum Health
  • Vancouver, Canada
    • Vancouver ID Research and Care Centre Society
• Denmark
  • Copenhagen, Denmark
    • Hvidovre Hospital
• France
  • Bordeaux, France
    • CHU de Bordeaux
  • Bordeaux, France
    • CHU - Groupe Saint-Andre
  • Nantes, France
    • C.H.U. de Nantes
  • Orleans, France
    • CHR Orléans La Source
  • Tours, France
    • Chu Tours
• Germany
  • Bielefeld, Germany
    • ICH Study Center Hamburg
  • Bonn, Germany
    • Medizinische Universitätsklinik
  • Essen, Germany
    • Universitätsklinikum Essen
  • Frankfurt, Germany
    • Johann Wolfgang Goethe-University Hospital
  • Hamburg, Germany
    • Universitätsklinikum Hamburg-Eppendorf
  • Hamburg, Germany
    • ifi-Studien und Projekte GmbH an der Asklepiosklinik St. Georg
  • Koln, Germany
    • Klinikum der Universitaet Koln
  • Munich, Germany
    • Universitätsklinikum München
• Ireland
  • Dublin, Ireland
    • Saint James's Hospital
  • Dublin 7, Ireland
    • Mater Misericordiae University Hospital
• Italy
  • Brescia, Italy
    • University of Brescia
  • Milano, Italy
    • Fondazione IRCCS San Raffaele del Monte Tabor
  • Milano, Italy
    • Azienda Ospedaliera Luigi Sacco
  • Modena, Italy
    • Azienda Ospedaliero Universitaria Policlinico di Modena
  • Roma, Italy
    • Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
  • Torino, Italy
    • Ospedale Amedeo di Savoia - Specializzato Malattie infettive
• Puerto Rico
  • San Juan, Puerto Rico
    • Clinical Research Puerto Rico
  • San Juan, Puerto Rico
    • Hope Clinical Research Inc
• Spain
  • Badalona, Spain
    • Bonaventura
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Clínico Universitario San Carlos
  • Malaga, Spain
    • Hospital Costa del Sol
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Heartlands Hospital
  • London, United Kingdom
    • Barts Health Nhs Trust
  • London, United Kingdom
    • Royal Free Hospital
  • London, United Kingdom
    • Imperial College
  • London, United Kingdom
    • Chelsea And Westminster Hospital
  • London, United Kingdom
    • St. George's Hospital
  • London, United Kingdom
    • Kings College Hospital NHS Trust
  • London, United Kingdom
    • Lewisham and Greenwich NHS Trust
  • Manchester, United Kingdom
    • Manchester Centre for Sexual Health
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Spectrum Medical Group
  • California
    • Beverly Hills, California, United States
      • Pacific Oaks Medical Group
    • La Jolla, California, United States
      • University of California San Diego (UCSD)
    • Los Angeles, California, United States
      • Anthony Mills, MD, Inc.
    • Los Angeles, California, United States
      • Peter J. Ruane, MD, Inc.
    • Oakland, California, United States
      • Highland Hospital - Alameda Health System
    • San Diego, California, United States
      • La Playa Medical Group and Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States
      • Whitman-Walker Health
    • Washington, District of Columbia, United States
      • Capial Medical Associates
    • Washington, District of Columbia, United States
      • Dupont Circle Physician's Group
  • Florida
    • Fort Lauderdale, Florida, United States
      • Gary J. Richmond,M.D.,P.A.
    • Fort Lauderdale, Florida, United States
      • Therafirst Medical Center
    • Fort Pierce, Florida, United States
      • Midway Immunology and Research Center
    • Orlando, Florida, United States
      • Orlando Immunology Center
    • West Palm Beach, Florida, United States
      • Triple O Research Institute PA
  • Georgia
    • Atlanta, Georgia, United States
      • Atlanta ID Group
  • Illinois
    • Chicago, Illinois, United States
      • Howard Brown Health Center
  • Kentucky
    • Louisville, Kentucky, United States
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States
      • LSU Health Sciences Center
  • Michigan
    • Berkley, Michigan, United States
      • Be Well Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Hennepin County Medical Center
  • Missouri
    • Kansas City, Missouri, United States
      • The KC CARE Clinic
    • Saint Louis, Missouri, United States
      • Southampton Healthcare, Inc.
  • New Jersey
    • Newark, New Jersey, United States
      • Saint Michael's Medical Center
    • Somers Point, New Jersey, United States
      • South Jersey Infectious Disease
  • New Mexico
    • Santa Fe, New Mexico, United States
      • Southwest CARE Center
  • New York
    • Bronx, New York, United States
      • Montefiore Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Philadelphia FIGHT
  • Texas
    • Austin, Texas, United States
      • Central Texas Clinical Research
    • Dallas, Texas, United States
      • AIDS Arms, Inc
    • Fort Worth, Texas, United States
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States
      • Gordon E. Crofoot MD PA
    • Houston, Texas, United States
      • Therapeutic Concepts, PA
  • Washington
    • Seattle, Washington, United States
      • Peter Shalit, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: F/TAF (Double-Blind); F/TAF + ABC/3TC placebo + allowed 3rd antiretroviral (ARV) agent for 96 weeks After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded.	Drug: F/TAF; 200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily; Other Names: Descovy®; Drug: ABC/3TC Placebo; Tablets administered orally once daily; Drug: 3rd ARV agent; An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).
Active Comparator: ABC/3TC (Double-Blind); ABC/3TC + F/TAF placebo + allowed 3rd ARV agent for 96 weeks After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded.	Drug: 3rd ARV agent; An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).; Drug: ABC/3TC; 600/300 mg FDC tablets administered orally once daily; Drug: F/TAF Placebo; Tablets administered orally once daily
Experimental: Open-Label F/TAF; After the unblinding visit, in countries where F/TAF FDC is not commercially available, participants (except in certain countries such as the UK) will be given the option to receive open-label F/TAF (200/10 mg or 200/25 mg) FDC and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country.	Drug: F/TAF; 200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily; Other Names: Descovy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was 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.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48		Baseline; Week 48
Percent Change From Baseline in Spine BMD at Week 48		Baseline; Week 48
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was 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.	Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was 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.	Week 96
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 was 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.	Week 96
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 48 was 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.	Week 48
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 was 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.	Week 96
Change From Baseline in CD4 Cell Count at Week 48		Baseline; Week 48
Change From Baseline in CD4 Cell Count at Week 96		Baseline; Week 96
Percent Change From Baseline in Hip BMD at Week 96		Baseline; Week 96
Percent Change From Baseline in Spine BMD at Week 96		Baseline; Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2015
• Primary Completion (Actual): December 11, 2017
• Study Completion (Actual): March 13, 2019

Study Registration Dates

• First Submitted: June 9, 2015
• First Submitted That Met QC Criteria: June 9, 2015
• First Posted (Estimate): June 11, 2015

Study Record Updates

• Last Update Posted (Actual): October 25, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: HIV; HIV-1 Positive; Virologically-Suppressed
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Lamivudine
• Other Study ID Numbers: GS-US-311-1717; 2015-000871-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No