Clinical trial NCT02121795: Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF
Official title: 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
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: 2014-04-24
Enrollment: 668
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis
timeFrame: Week 48
Secondary outcomes:
measure: Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline; Week 48
measure: Percentage Change From Baseline in Spine BMD at Week 48
timeFrame: Baseline; Week 48
measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis
timeFrame: Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48
measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis
timeFrame: Week 96
measure: Percentage Change From Baseline in Hip BMD at Week 96
timeFrame: Baseline; Week 96
measure: Percentage Change From Baseline in Spine BMD at Week 96
timeFrame: Baseline; Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 96
timeFrame: Baseline; Week 96
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
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: Hayward
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Tarrant County ID Associates
state: California
city: Los Angeles
country: United States
facility: Southern California Men's Medical Group
state: California
city: Oakland
country: United States
facility: Highland Hospital - Alameda Health System (formerly Alameda County medical Center)
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Sacramento Medical Center
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Group San Francisco
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
state: California
city: Denver
country: United States
facility: Kaiser Permanente Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Denver
country: United States
facility: Apex Research LLC
state: Colorado
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: Washington
country: United States
facility: Capital Medical Associates
state: District of Columbia
city: Washington
country: United States
facility: Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: TheraFirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond,M.D.,P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Miami
country: United States
facility: Tarrant County Infectious Disease Associates
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tampa
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research & Treatment Center of the Treasure Coast
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: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
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 Site 5580
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Newark
country: United States
facility: Prime Healthcare Services - St Michael's LLC d/b/a 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: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Flushing
country: United States
facility: New York Hospital Queens
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Ricky K. Hsu, MD, PC
state: New York
city: Charlotte
country: United States
facility: Infectious Disease Consultants, PA
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: AIDS Arms, Inc
state: Texas
city: Dallas
country: United States
facility: Southwest Infectious Disease Clinical Research, Inc
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consulants
state: Texas
city: Fort Worth
country: United States
facility: AIDS Arms, Inc./Trinity Health & Wellness Center
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Brussels
country: Belgium
facility: CHU Saint-Pierre of Brussels
city: Vancouver
country: Canada
facility: Vancouver Infectious Disease Research and Care Centre
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital-General Campus
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic/Maple Leaf Research
state: Ontario
city: Toronto
country: Canada
facility: University Health Network/Toronto General Hospital
state: Ontario
city: Montpellier
country: France
facility: University Hospital of Montpellier (CHU-Gui de Chauliac)
city: Nantes
country: France
facility: CHU de Nantes Hopital de l'Hotel Dieu
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Paris
country: France
facility: Hôpital Tenon
city: Tourcoing
country: France
facility: Centre Hospitalier de Tourcoing
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele, Centro San Luigi
city: San Juan
country: Puerto Rico
facility: Hope Clinical Research
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster 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: 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.