Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF
- Conditions
- HIV-1 Infection
- Interventions
- Drug: F/TAFDrug: FTC/TDFDrug: Allowed third antiretroviral agentDrug: FTC/TDF PlaceboDrug: F/TAF Placebo
- Registration Number
- NCT02121795
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 668
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FTC/TDF + 3rd Agent Allowed third antiretroviral 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. F/TAF + 3rd Agent F/TAF 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. F/TAF + 3rd Agent Allowed third antiretroviral 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. F/TAF + 3rd Agent FTC/TDF Placebo 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. FTC/TDF + 3rd Agent F/TAF Placebo 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. FTC/TDF + 3rd Agent FTC/TDF 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis Week 48 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.
- Secondary Outcome Measures
Name Time Method Percentage Change From Baseline in Spine BMD at Week 96 Baseline; Week 96 Spine BMD was assessed by DXA scan.
Change From Baseline in CD4+ Cell Count at Week 96 Baseline; Week 96 Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis Week 48 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.
Change From Baseline in CD4+ Cell Count at Week 48 Baseline; Week 48 Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis Week 96 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.
Percentage Change From Baseline in Hip BMD at Week 96 Baseline; Week 96 Hip BMD was assessed by DXA scan.
Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 Baseline; Week 48 Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis Week 96 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.
Percentage Change From Baseline in Spine BMD at Week 48 Baseline; Week 48 Spine BMD was assessed by DXA scan.
Trial Locations
- Locations (77)
National Jewish Health
🇺🇸Denver, Colorado, United States
Dupont Circle Physician's Group
🇺🇸Washington, District of Columbia, United States
Whitman-Walker Health
🇺🇸Washington, District of Columbia, United States
AIDS Healthcare Foundation
🇺🇸Tampa, Florida, United States
Hope Clinical Research
🇵🇷San Juan, Puerto Rico
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
Highland Hospital - Alameda Health System (formerly Alameda County medical Center)
🇺🇸Oakland, California, United States
Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
IRCCS Ospedale San Raffaele, Centro San Luigi
🇮🇹Milano, Italy
Capital Medical Associates
🇺🇸Washington, District of Columbia, United States
Southern California Men's Medical Group
🇺🇸Los Angeles, California, United States
TheraFirst Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Kaiser Permanente Sacramento Medical Center
🇺🇸Sacramento, California, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
King's College Hospital
🇬🇧London, United Kingdom
Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
CHU de Nantes Hopital de l'Hotel Dieu
🇫🇷Nantes, France
Manchester Centre for Sexual Health
🇬🇧Manchester, United Kingdom
Centre Hospitalier de Tourcoing
🇫🇷Tourcoing, France
Clinical Research Puerto Rico Inc
🇵🇷San Juan, Puerto Rico
University of Puerto Rico School of Medicine
🇵🇷San Juan, Puerto Rico
Brighton and Sussex University Hospitals
🇬🇧Brighton, United Kingdom
Gary J. Richmond,M.D.,P.A.
🇺🇸Fort Lauderdale, Florida, United States
Triple O Research Institute PA
🇺🇸West Palm Beach, Florida, United States
Atlanta ID Group
🇺🇸Atlanta, Georgia, United States
Prime Healthcare Services - St Michael's LLC d/b/a Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
AIDS Arms, Inc
🇺🇸Dallas, Texas, United States
Peter Shalit, MD
🇺🇸Seattle, Washington, United States
Southwest Infectious Disease Clinical Research, Inc
🇺🇸Dallas, Texas, United States
North Texas Infectious Diseases Consulants
🇺🇸Dallas, Texas, United States
University Health Network/Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
La Playa Medical Group and Clinical Research
🇺🇸San Diego, California, United States
Tarrant County Infectious Disease Associates
🇺🇸Miami, Florida, United States
Kaiser Permanente Medical Group San Francisco
🇺🇸San Francisco, California, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Kaiser Permanente Colorado
🇺🇸Denver, Colorado, United States
Apex Research LLC
🇺🇸Denver, Colorado, United States
Barts Health NHS Trust
🇬🇧London, United Kingdom
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
Tarrant County ID Associates
🇺🇸Los Angeles, California, United States
Kaiser Permanente
🇺🇸Hayward, California, United States
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
AIDS Research & Treatment Center of the Treasure Coast
🇺🇸Vero Beach, Florida, United States
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Mercer University School of Medicine
🇺🇸Macon, Georgia, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Southampton Healthcare, Inc.
🇺🇸Saint Louis, Missouri, United States
St. Louis University
🇺🇸Saint Louis, Missouri, United States
South Jersey Infectious Disease
🇺🇸Somers Point, New Jersey, United States
Southwest CARE Center
🇺🇸Santa Fe, New Mexico, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Ricky K. Hsu, MD, PC
🇺🇸New York, New York, United States
New York Hospital Queens
🇺🇸Flushing, New York, United States
Infectious Disease Consultants, PA
🇺🇸Charlotte, North Carolina, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Therapeutic Concepts, PA
🇺🇸Houston, Texas, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
AIDS Arms, Inc./Trinity Health & Wellness Center
🇺🇸Fort Worth, Texas, United States
Gordon E. Crofoot MD PA
🇺🇸Houston, Texas, United States
Premier Clinical Research
🇺🇸Spokane, Washington, United States
Vancouver Infectious Disease Research and Care Centre
🇨🇦Vancouver, British Columbia, Canada
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
CHU Saint-Pierre of Brussels
🇧🇪Brussels, Belgium
Ottawa Hospital-General Campus
🇨🇦Ottawa, Ontario, Canada
Maple Leaf Medical Clinic/Maple Leaf Research
🇨🇦Toronto, Ontario, Canada
University Hospital of Montpellier (CHU-Gui de Chauliac)
🇫🇷Montpellier, France
Hopital Bichat Claude Bernard
🇫🇷Paris, France
Hôpital Tenon
🇫🇷Paris, France
Chelsea and Westminster Hospital
🇬🇧London, United Kingdom
Community Research Initiative of New England
🇺🇸Boston, Massachusetts, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
The Kc Care Clinic Site 5580
🇺🇸Kansas City, Missouri, United States
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
Montefiore Medical Center
🇺🇸Bronx, New York, United States