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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 : December 21, 2023
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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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.

Condition or disease Intervention/treatment Phase
Pre-Exposure Prophylaxis of HIV-1 Infection Drug: F/TAF Drug: F/TDF Drug: F/TAF Placebo Drug: F/TDF Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5399 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 2, 2016
Actual Primary Completion Date : January 31, 2019
Estimated Study Completion Date : September 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: F/TAF
F/TAF+ F/TDF placebo for at least 96 weeks
 Drug: F/TAF
200/25 mg tablet administered orally once daily
Other Name: Descovy®

Drug: F/TDF Placebo
Tablet administered orally once daily
Experimental: F/TDF
F/TDF+ F/TAF placebo for at least 96 weeks
 Drug: F/TDF
200/300 mg tablet administered orally once daily
Other Name: Truvada®

Drug: F/TAF Placebo
Tablet administered orally once daily
Experimental: Open-label
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 for 96 weeks.
 Drug: F/TAF
200/25 mg tablet administered orally once daily
Other Name: Descovy®
Experimental: Open-Label Extension
Participants who remain on study at Open-label Week 96 will have the option to continue on open-label F/TAF treatment in the Open-label extension phase for 408 weeks.
 Drug: F/TAF
200/25 mg tablet administered orally once daily
Other Name: Descovy®


Outcome Measures
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Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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%.

  2. 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%.

  3. 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.


  4. 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.


  5. 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.

  6. Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase [ Time Frame: Baseline, Week 48 ]
  7. 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)

  8. 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%.

  9. 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%.

  10. 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.


  11. 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.


  12. 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.

  13. Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase [ Time Frame: Baseline, Week 96 ]
  14. 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) ]
  15. 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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Men and Transgender Women
Accepts Healthy Volunteers:   Yes
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02842086


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] October 19, 2021
Statistical Analysis Plan  [PDF] December 11, 2019

More Information
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Additional Information:

Publications of Results:
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02842086    
Other Study ID Numbers: GS-US-412-2055
2022-501763-40 ( Other Identifier: European Medicines Agency )
2016-001399-31 ( EudraCT Number )
First Posted: July 22, 2016    Key Record Dates
Results First Posted: March 17, 2020
Last Update Posted: December 21, 2023
Last Verified: December 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infections
Communicable Diseases
HIV Infections
Disease Attributes
Pathologic Processes
Blood-Borne Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Genital Diseases
 Urogenital Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Emtricitabine tenofovir alafenamide
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents