Oral Islatravir (MK-8591) Once-Monthly as Preexposure Prophylaxis (PrEP) in Men and Transgender Women Who Have Sex With Men and Are at High Risk for HIV-1 Infection (MK-8591-024)

Purpose

The main purpose of the study is to evaluate the efficacy and safety of oral Islatravir (ISL) once monthly (QM) as Preexposure Prophylaxis (PrEP) in cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men and who are at high risk of HIV-1 infection with a minimum follow-up of 48 weeks and at least 50% of participants have 96 weeks of follow-up after randomization. The primary hypothesis of the study is that the administration of ISL QM as PreP reduces the incidence rate per year of the confirmed HIV-1 infections compared to the background incidence rates.

Condition

  • HIV Preexposure Prophylaxis

Eligibility

Eligible Ages
Over 16 Years
Eligible Genders
Male
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Has confirmed Human Immunodeficiency Virus (HIV) uninfected based on negative HIV-1/HIV-2 test result before randomization - Is sexually active with male or transgender women (TGW) partners defined as having anal sexual intercourse with a man or TGW at least once in the past month - Is at high risk for sexually acquiring HIV-1 infection based on self-report of at least 1 of the following: a) Condomless receptive anal intercourse in the 6 months prior to screening occurring outside a mutually monogamous HIV seronegative concordant relationship b) More than 5 partners (anal intercourse) in the 6 months prior to screening c) Any unprescribed stimulant drug use in the 6 months prior to screening d) Rectal or urethral gonorrhea or chlamydia or incident syphilis in the 6 months prior to screening - Participants 16 or 17 years of age must weigh ≥35 kg. Enrollment for 16- to 17-year-old participants will begin only after completion of the Sentinel Cohort IA and review of IA results by the external data monitoring committee (eDMC) - Has no plans to relocate or travel away from the site for ≥4 consecutive weeks during study participation

Exclusion Criteria

  • Has hypersensitivity or other contraindication to any component of the study interventions as determined by the investigator - Has chronic HBV infection or past HBV infection which could indicate risk for Hepatitis B reactivation - Has known current or chronic history of liver disease or known hepatic or biliary abnormalities, unless the participant has stable liver function tests and no evidence of hepatic synthetic dysfunction - Has a history of malignancy within 5 years of screening except for adequately treated basal cell or squamous cell skin cancer or in situ anal cancers - Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to enroll - Has taken cabotegravir, lenacapavir, or any other long-acting HIV prevention product at any time - Is currently receiving or is anticipated to require any prohibited therapies outlined in the study from 30 days prior to Day 1 through the duration of the study - Is currently participating in or has participated in an interventional or prevention clinical study with an investigational compound or device, within 30 days prior to Day 1 through the duration of the study - Has exclusionary laboratory values within 45 days prior to Day 1

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Double (Participant, Investigator)
Masking Description
Double-blind with in-house blinding

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Islatravir (ISL) Once Monthly (QM) Group
Participants receive 60 mg tablet of ISL QM, orally plus Placebo to Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) tablet once daily (QD) or Placebo to Emtricitabine/Tenofovir Alafenamide (FTC/TAF) tablet QD, orally for up to 24 months of treatment duration.
  • Drug: ISL
    ISL 60 mg tablet, QM, orally for up to 24 months
    Other names:
    • MK-8591
  • Drug: Placebo to FTC/TDF
    Placebo FTC/TDF 0 mg tablets QD, orally for up to 24 months
  • Drug: Placebo to FTC/TAF
    Placebo FTC/TAF 0 mg tablets QD, orally for up to 24 months
Active Comparator
FTC/TDF or FTC/TAF QD Group
Participants receive 200/245 mg or 200/300 mg of FTC/TDF combination tablet, QD, orally or 200/25 mg of FTC/TAF combination tablet, QD, orally at investigator's discretion plus Placebo to ISL tablet QM, orally for up to 24 months of treatment duration.
  • Drug: FTC/TDF
    Participants receive 200/245 mg or 200/300 mg of FTC/TDF combination tablet, QD, orally for up to 24 months
    Other names:
    • Truvada
    • Emtricitabine/Tenofovir Disoproxil Fumarate
  • Drug: FTC/TAF
    Participants receive 200/25 mg of FTC/TAF combination tablet, QD, orally for up to 24 months
    Other names:
    • Descovy
    • Emtricitabine/Tenofovir Alafenamide
  • Drug: Placebo to ISL
    Placebo ISL 0 mg tablets QM, orally for up to 24 months.

Recruiting Locations

University of Alabama at Birmingham-UAB 1917 Research Clinic ( Site 0007)
Birmingham, Alabama 35222
Contact:
Study Coordinator
205-934-7492

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@merck.com