Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF

A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF

This study will evaluate the efficacy of switching from emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide (F/TAF) FDC in HIV-1 positive participants who are virologically suppressed on regimens containing FTC/TDF.

This study will consist of a 96 week double-blind treatment period. After Week 96, all participants will continue on blinded study drug treatment and attend visits every 12 weeks until treatment assignments are unblinded. All participants will return for an unblinding visit and will be given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF is commercially available, or the sponsor terminates the F/TAF clinical development program.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: F/TAF; Drug: F/TAF Placebo; Drug: Allowed third antiretroviral agent; Drug: FTC/TDF Placebo; Drug: FTC/TDF

• Study Type: Interventional
• Enrollment (Actual): 668
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint-Pierre of Brussels
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Vancouver Infectious Disease Research and Care Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital-General Campus
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network/Toronto General Hospital
    • Toronto, Ontario, Canada, M5B 1L6
      • Maple Leaf Medical Clinic/Maple Leaf Research
• France
  • Montpellier, France, 34295
    • University Hospital of Montpellier (CHU-Gui de Chauliac)
  • Nantes, France, 44093
    • CHU de Nantes Hopital de l'Hotel Dieu
  • Paris, France, 75020
    • Hôpital Tenon
  • Paris, France, 75018
    • Hopital Bichat Claude Bernard
  • Tourcoing, France, 59208
    • Centre Hospitalier de Tourcoing
• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Milano, Italy, 20127
    • IRCCS Ospedale San Raffaele, Centro San Luigi
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico Inc
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico School of Medicine
  • San Juan, Puerto Rico, 00901
    • Hope Clinical Research
• United Kingdom
  • Brighton, United Kingdom, BN2 1ES
    • Brighton and Sussex University Hospitals
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, SW10 9TH
    • Chelsea and Westminster Hospital
  • London, United Kingdom, SE5 9RJ
    • King's College Hospital
  • London, United Kingdom, E1 1BB
    • Barts Health NHS Trust
  • Manchester, United Kingdom, M13 0FH
    • Manchester Centre for Sexual Health
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • California
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Medical Group
    • Hayward, California, United States, 94545
      • Kaiser Permanente
    • Los Angeles, California, United States, 90036
      • Tarrant County ID Associates
    • Los Angeles, California, United States, 90069
      • Southern California Men's Medical Group
    • Oakland, California, United States, 94602
      • Highland Hospital - Alameda Health System (formerly Alameda County medical Center)
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Sacramento Medical Center
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Group San Francisco
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
    • Denver, Colorado, United States, 80209
      • Apex Research LLC
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physician's Group
    • Washington, District of Columbia, United States, 20037
      • Medical Faculty Associates
    • Washington, District of Columbia, United States, 20009
      • Whitman-Walker Health
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond,M.D.,P.A.
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33133
      • Tarrant County Infectious Disease Associates
    • Miami Beach, Florida, United States, 33139
      • AIDS Healthcare Foundation
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Tampa, Florida, United States, 33602
      • AIDS Healthcare Foundation
    • Vero Beach, Florida, United States, 32960
      • AIDS Research & Treatment Center of the Treasure Coast
    • West Palm Beach, Florida, United States, 33401
      • Triple O Research Institute PA
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Atlanta, Georgia, United States, 30312
      • AIDS Research Consortium of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Community Research Initiative of New England
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • The Kc Care Clinic Site 5580
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University
    • Saint Louis, Missouri, United States, 63139
      • Southampton Healthcare, Inc.
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Prime Healthcare Services - St Michael's LLC d/b/a Saint Michael's Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • Flushing, New York, United States, 11355
      • New York Hospital Queens
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10011
      • Ricky K. Hsu, MD, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Infectious Disease Consultants, PA
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Clinical Research, Inc
    • Dallas, Texas, United States, 75215
      • AIDS Arms, Inc
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consulants
    • Fort Worth, Texas, United States, 76104
      • AIDS Arms, Inc./Trinity Health & Wellness Center
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, MD
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

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:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Currently receiving antiretroviral regimen containing FTC/TDF in combination with one third agent for ≥ 6 consecutive months prior to screening.
• Plasma HIV-1 RNA levels < 50 copies/mL for at least 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced 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 electrocardiogram (ECG)
• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (individuals with documented Gilbert's syndrome or with Atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 x ULN)
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active, or practice abstinence from screening throughout the duration of the study treatment and for 30 days following the last dose of the study drug.
• Females who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range.
• Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
• Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
• Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
• Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis)
• Females who are breastfeeding
• Positive serum pregnancy test
• 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
• Individuals receiving ongoing therapy with any of the medications not to be used with FTC, TAF, TDF or other antiretroviral third agents.

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 Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: F/TAF + 3rd Agent; Participants will receive F/TAF (200/25 mg or 200/10 mg) plus FTC/TDF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks. Dosing of F/TAF will be dependent on the third agent of the participants' pre-existing treatment regimen.	Drug: F/TAF; Tablets administered orally once daily; Other Names: Descovy®; Drug: Allowed third antiretroviral agent; An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted lopinavir (LPV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV; Sustiva®), rilpivirine (RPV; Edurant®), nevirapine (NVP;Viramune®), raltegravir (RAL; Isentress®), dolutegravir (DTG;Tivicay®), and maraviroc (MVC; Selzentry®).; Drug: FTC/TDF Placebo; Tablets administered orally once daily
Active Comparator: FTC/TDF + 3rd Agent; Participants will receive FTC/TDF plus F/TAF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.	Drug: F/TAF Placebo; Tablets administered orally once daily; Drug: Allowed third antiretroviral agent; An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted lopinavir (LPV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV; Sustiva®), rilpivirine (RPV; Edurant®), nevirapine (NVP;Viramune®), raltegravir (RAL; Isentress®), dolutegravir (DTG;Tivicay®), and maraviroc (MVC; Selzentry®).; Drug: FTC/TDF; 200/300 mg FDC tablets administered orally once daily; Other Names: Truvada®

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 Defined by the FDA Snapshot Analysis	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 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
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
Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.	Baseline; Week 48
Percentage Change From Baseline in Spine BMD at Week 48	Spine BMD was assessed by DXA scan.	Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis	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 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 Defined by the FDA Snapshot Analysis	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 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 Weeks 96 as Defined by the FDA Snapshot Analysis	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 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 Change From Baseline in Hip BMD at Week 96	Hip BMD was assessed by DXA scan.	Baseline; Week 96
Percentage Change From Baseline in Spine BMD at Week 96	Spine BMD was assessed by DXA scan.	Baseline; Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Gallant JE, Daar ES, Raffi F, Brinson C, Ruane P, DeJesus E, Johnson M, Clumeck N, Osiyemi O, Ward D, Morales-Ramirez J, Yan M, Abram ME, Plummer A, Cheng AK, Rhee MS. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV. 2016 Apr;3(4):e158-65. doi: 10.1016/S2352-3018(16)00024-2. Epub 2016 Mar 14.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2014
• Primary Completion (Actual): August 12, 2015
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: April 22, 2014
• First Posted (Estimate): April 24, 2014

Study Record Updates

• Last Update Posted (Actual): March 12, 2020
• Last Update Submitted That Met QC Criteria: February 28, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: HIV; HIV-1 Positive; Virologically-suppressed
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Anti-Retroviral Agents
• Other Study ID Numbers: GS-US-311-1089; 2013-005138-39 (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 https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
• 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