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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 (DISCOVER)

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ClinicalTrials.gov Identifier: NCT02842086
Recruitment Status : Active, not recruiting
First Posted : July 22, 2016
Results First Posted : March 17, 2020
Last Update Posted : January 12, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE July 20, 2016
First Posted Date  ICMJE July 22, 2016
Results First Submitted Date  ICMJE January 29, 2020
Results First Posted Date  ICMJE March 17, 2020
Last Update Posted Date January 12, 2021
Actual Study Start Date  ICMJE September 2, 2016
Actual Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
Incidence of HIV-1 Infection Per 100 Person Years (PY) [ Time Frame: 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) ]
The incidence of HIV-1 infection rate per 100 PY was calculated as the number of participants who became HIV infected during the study after the first dose of study drug divided by the sum of all participants' years (where a year is 365.25 days) of follow-up while at risk of HIV infection during the study. HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab:
  • Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or
  • Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or
  • Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results)
Original Primary Outcome Measures  ICMJE
 (submitted: July 20, 2016)
Incidence of Seroconversions per 100 Person Years (PY) as Defined by the HIV-1 RNA by Polymerase Chain Reaction (PCR) [ Time Frame: When the last participant has a minimum of 48 weeks of follow-up and at least 50% of the participants have at least 96 weeks of follow-up after randomization ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
  • Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase [ Time Frame: Baseline, Week 48 ]
    Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.
  • Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase [ Time Frame: Baseline, Week 48 ]
    Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.
  • Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase [ Time Frame: Baseline, Week 48 ]
    Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
  • Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase [ Time Frame: Baseline, Week 48 ]
    Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
  • Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase [ Time Frame: Baseline, Week 48 ]
    The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.
  • Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase [ Time Frame: Baseline, Week 48 ]
  • Incidence of HIV-1 Infection Per 100 PY [ Time Frame: When all participants have 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 157 weeks) ]
    The incidence of HIV-1 infection rate per 100 PY was calculated as the number of participants who became HIV infected during the study after the first dose of study drug divided by the sum of all participants' years (where a year is 365.25 days) of follow-up while at risk of HIV infection during the study. HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab:
    • Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or
    • Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or
    • Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results)
  • Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase [ Time Frame: Baseline, Week 96 ]
    Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.
  • Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase [ Time Frame: Baseline, Week 96 ]
    Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.
  • Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase [ Time Frame: Baseline, Week 96 ]
    Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
  • Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase [ Time Frame: Baseline, Week 96 ]
    Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
  • Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase [ Time Frame: Baseline, Week 96 ]
    The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.
  • Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase [ Time Frame: Baseline, Week 96 ]
  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks) ]
  • Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality [ Time Frame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2016)
  • Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase in a Subset of Participants [ Time Frame: Baseline; Week 48 ]
  • Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase in a Subset of Participants [ Time Frame: Baseline; Week 48 ]
  • Percent Change From Baseline in Renal Biomarkers of Urine Retinol-Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase [ Time Frame: Baseline; Week 48 ]
  • Percent Change From Baseline in Renal Biomarkers of Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase [ Time Frame: Baseline; Week 48 ]
  • Percent Change From Baseline in Renal Biomarkers of Urine Protein-to-Creatinine Ratio (UPCR) at Week 48 in the Blinded Phase [ Time Frame: Baseline; Week 48 ]
  • Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase [ Time Frame: Baseline; Week 48 ]
  • Incidence of Seroconversions per 100 PY as Defined by the HIV RNA-1 by PCR at the end of the Blinded Phase [ Time Frame: At least 96 weeks ]
  • Percent Change from Baseline in Hip BMD at Week 96 in the Blinded Phase in a Subset of Participants [ Time Frame: Baseline; Week 96 ]
  • Percent Change from Baseline in Spine BMD at Week 96 in the Blinded Phase in a Subset of Participants [ Time Frame: Baseline; Week 96 ]
  • Percent Change From Baseline in Renal Biomarkers of Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase [ Time Frame: Baseline; Week 96 ]
  • Percent Change From Baseline in Renal Biomarkers of Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase [ Time Frame: Week 96 ]
  • Percent Change From Baseline in Renal Biomarkers of Urine Protein-to-Creatinine Ratio (UPCR) at Week 96 in the Blinded Phase [ Time Frame: Week 96 ]
  • Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase [ Time Frame: Week 96 ]
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: At least 144 weeks plus 30 days ]
  • Incidence of Treatment-Emergent Laboratory Toxicities [ Time Frame: At least 144 weeks plus 30 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Pre-Exposure Prophylaxis of HIV-1 Infection
Intervention  ICMJE
  • Drug: F/TAF
    200/25 mg tablet administered orally once daily
    Other Name: Descovy®
  • Drug: F/TDF
    200/300 mg tablet administered orally once daily
    Other Name: Truvada®
  • Drug: F/TAF Placebo
    Tablet administered orally once daily
  • Drug: F/TDF Placebo
    Tablet administered orally once daily
Study Arms  ICMJE
  • Experimental: F/TAF
    F/TAF+ F/TDF placebo for at least 96 weeks
    Interventions:
    • Drug: F/TAF
    • Drug: F/TDF Placebo
  • Experimental: F/TDF
    F/TDF+ F/TAF placebo for at least 96 weeks
    Interventions:
    • Drug: F/TDF
    • Drug: F/TAF Placebo
  • Experimental: Open-label Extension
    Once all participants have been on blinded treatment for at least 96 weeks, the study will be unblinded and participants will be offered the option to continue on open-label F/TAF treatment in the open-label extension for 48 weeks.
    Intervention: Drug: F/TAF
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 3, 2020)
5399
Original Estimated Enrollment  ICMJE
 (submitted: July 20, 2016)
5000
Estimated Study Completion Date  ICMJE December 2022
Actual Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: Men and Transgender Women
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   Denmark,   France,   Germany,   Ireland,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02842086
Other Study ID Numbers  ICMJE GS-US-412-2055
2016-001399-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP