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)

Gilead Sciences

Status and phase: Active, not recruiting; Phase 3

Conditions: Pre-Exposure Prophylaxis of HIV-1 Infection

Treatments: Drug: F/TDF Placebo; Drug: F/TAF Placebo; Drug: F/TDF; Drug: F/TAF

Study type: Interventional

Funder types: Industry

Identifiers

NCT02842086

GS-US-412-2055

2022-501763-40 (EudraCT Number)

2016-001399-31 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 5,399 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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5,399 participants in 4 patient groups

F/TAF

Experimental group

Description:

F/TAF+ F/TDF placebo for at least 96 weeks

Treatment:

Drug: F/TAF

Drug: F/TDF Placebo

F/TDF

Experimental group

Description:

F/TDF+ F/TAF placebo for at least 96 weeks

Treatment:

Drug: F/TDF

Drug: F/TAF Placebo

Open-label

Experimental group

Description:

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.

Treatment:

Drug: F/TAF

Open-Label Extension

Experimental group

Description:

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.

Treatment:

Drug: F/TAF