Clinical trial NCT02842086: Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection
Official title: A Phase 3, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Pre-Exposure Prophylaxis of HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-07-22
Enrollment: 5399
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the rates of HIV-1 infection in Men (MSM) and transgender women (TGW) who have sex with men and who are administered daily emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) with a minimum follow-up of 48 weeks and at least 50% of participants have 96 weeks of follow-up after randomization.


Eligibility criteria: Key Inclusion Criteria:

* Must be at high risk of sexual acquisition of HIV
* HIV-1 negative status
* MSM and TGW (male at birth) who have at least one of the following:

  * condomless anal intercourse with at least two unique male partners in the past 12 weeks (partners must be either HIV-infected or of unknown HIV status)
  * documented history of syphilis in the past 24 weeks
  * documented history of rectal gonorrhea or chlamydia in the past 24 weeks
* Adequate renal function: estimated glomerular filtration rate ≥ 60 mL/min according to the Cockcroft-Gault formula
* Adequate liver and hematologic function:

  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) and total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
  * Absolute neutrophil count ≥ 1000/mm\^3; platelets ≥ 75,000/mm\^3; hemoglobin ≥ 10 g/dL

Key Exclusion Criteria

* Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or not clinically manageable.

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

Primary outcomes:
measure: Incidence of HIV-1 Infection Per 100 Person Years (PY)
timeFrame: When all participants completed minimum follow-up of 48 weeks and at least 50% of the participants completed 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 125 weeks)
Secondary outcomes:
measure: Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase
timeFrame: Baseline, Week 48
measure: Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase
timeFrame: Baseline, Week 48
measure: Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase
timeFrame: Baseline, Week 48
measure: Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase
timeFrame: Baseline, Week 48
measure: Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase
timeFrame: Baseline, Week 48
measure: Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase
timeFrame: Baseline, Week 48
measure: Incidence of HIV-1 Infection Per 100 PY
timeFrame: When all participants have 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 157 weeks)
measure: Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase
timeFrame: Baseline, Week 96
measure: Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase
timeFrame: Baseline, Week 96
measure: Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase
timeFrame: Baseline, Week 96
measure: Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase
timeFrame: Baseline, Week 96
measure: Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase
timeFrame: Baseline, Week 96
measure: Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase
timeFrame: Baseline, Week 96
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
measure: Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality
timeFrame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Oakland
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Torrance
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: New Haven
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Washington
country: United States
state: District of Columbia
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Pierce
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: New Orleans
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Berkley
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: Somers Point
country: United States
state: New Jersey
city: Santa Fe
country: United States
state: New Mexico
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Huntersville
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Graz
country: Austria
city: Vienna
country: Austria
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Montréal
country: Canada
state: Quebec
city: Hvidovre
country: Denmark
state: Region Hovedstaden
city: Aarhus N
country: Denmark
state: Region Midtjylland
city: Copenhagen
country: Denmark
state: RegionH
city: Odense
country: Denmark
city: Nice
country: France
state: Alpe Maritimes
city: Marseille
country: France
state: Provence
city: Paris
country: France
state: Provence
city: Paris cedex 10
country: France
city: Munich
country: Germany
state: Bavaria
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Dublin 7
country: Ireland
state: Dublin
city: Dublin
country: Ireland
city: Milan
country: Italy
city: Roma
country: Italy
city: Amsterdam
country: Netherlands
city: Badalona
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Vigo
country: Spain
city: Soho
country: United Kingdom
state: London
city: Whitechapel
country: United Kingdom
state: London
city: Edinburgh
country: United Kingdom
state: Scotland
city: Brighton
country: United Kingdom
state: Sussex
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Hare B. The Phase 3 DISCOVER Study: Daily F/TAF or F/TDF for HIV Preexposure Prophylaxis [Presentation]. Conference on Retroviruses and Opportunistic Infections (CROI); 2019 04-07 March; Seattle, WA.
citation: Mayer KH, Molina JM, Thompson MA, Anderson PL, Mounzer KC, De Wet JJ, DeJesus E, Jessen H, Grant RM, Ruane PJ, Wong P, Ebrahimi R, Zhong L, Mathias A, Callebaut C, Collins SE, Das M, McCallister S, Brainard DM, Brinson C, Clarke A, Coll P, Post FA, Hare CB. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020 Jul 25;396(10246):239-254. doi: 10.1016/S0140-6736(20)31065-5.
citation: Ogbuagu O, Ruane PJ, Podzamczer D, Salazar LC, Henry K, Asmuth DM, Wohl D, Gilson R, Shao Y, Ebrahimi R, Cox S, Kintu A, Carter C, Das M, Baeten JM, Brainard DM, Whitlock G, Brunetta JM, Kronborg G, Spinner CD; DISCOVER study team. Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV. 2021 Jul;8(7):e397-e407. doi: 10.1016/S2352-3018(21)00071-0.
citation: Glidden DV, Das M, Dunn DT, Ebrahimi R, Zhao Y, Stirrup OT, Baeten JM, Anderson PL. Using the adherence-efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background hiv incidence: a secondary analysis of a randomized, controlled trial. J Int AIDS Soc. 2021 May;24(5):e25744. doi: 10.1002/jia2.25744.