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

NCT ID: NCT04652700

Last Updated: 2025-01-13

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

494 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-15

Study Completion Date

2023-08-04

Brief Summary

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The main purpose of the study is to evaluate the safety and tolerability 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 48 or 96 weeks of treatment and a minimum follow-up of 42 days.

Detailed Description

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Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021. Blinded assessments conducted prior to then are designated as Study Part 1. During Study Part 2, participants from Part 1 were switched to PrEP therapy with emtricitabine/tenofovir disoproxil (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF) while continuing in the study, but participants, investigators, and Sponsor personnel remained blinded to the Part 1 treatment. In Part 3, participants, investigators, and all Sponsor personnel are unblinded to participant's original randomized intervention group, and participants may continue to receive unblinded FTC/TDF or FTC/TAF.

Conditions

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HIV Preexposure Prophylaxis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators
In Study Part 1, double-blind with in-house blinding is used.

In Study Part 2, sponsor personnel not directly involved with blinded safety monitoring will be unblinded to participants' randomized study intervention in Part 1 (personnel involved with Part 2 will remain blinded).

In Study Part 3, al participants, investigators, and Sponsor personnel are unblinded as to the participant's original randomized intervention group.

Study Groups

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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.

Group Type EXPERIMENTAL

ISL

Intervention Type DRUG

ISL 60 mg tablet, QM, orally for up to 24 months

Placebo to FTC/TDF

Intervention Type DRUG

Placebo FTC/TDF 0 mg tablets QD, orally for up to 24 months

Placebo to FTC/TAF

Intervention Type DRUG

Placebo FTC/TAF 0 mg tablets QD, orally for up to 24 months

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.

Group Type ACTIVE_COMPARATOR

FTC/TDF

Intervention Type DRUG

Participants receive 200/245 mg of FTC/TDF combination tablet, QD, orally for up to 24 months

FTC/TAF

Intervention Type DRUG

Participants receive 200/25 mg of FTC/TAF combination tablet, QD, orally for up to 24 months

Placebo to ISL

Intervention Type DRUG

Placebo ISL 0 mg tablets QM, orally for up to 24 months.

Interventions

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ISL

ISL 60 mg tablet, QM, orally for up to 24 months

Intervention Type DRUG

FTC/TDF

Participants receive 200/245 mg of FTC/TDF combination tablet, QD, orally for up to 24 months

Intervention Type DRUG

FTC/TAF

Participants receive 200/25 mg of FTC/TAF combination tablet, QD, orally for up to 24 months

Intervention Type DRUG

Placebo to ISL

Placebo ISL 0 mg tablets QM, orally for up to 24 months.

Intervention Type DRUG

Placebo to FTC/TDF

Placebo FTC/TDF 0 mg tablets QD, orally for up to 24 months

Intervention Type DRUG

Placebo to FTC/TAF

Placebo FTC/TAF 0 mg tablets QD, orally for up to 24 months

Intervention Type DRUG

Other Intervention Names

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MK-8591 Truvada Emtricitabine/Tenofovir Disoproxil Fumarate Descovy Emtricitabine/Tenofovir Alafenamide

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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University of Alabama at Birmingham-UAB 1917 Research Clinic ( Site 0007)

Birmingham, Alabama, United States

Site Status

UCLA Center for Clinical AIDS Research and Education ( Site 0011)

Los Angeles, California, United States

Site Status

Global Research Institute ( Site 0031)

Los Angeles, California, United States

Site Status

Bridge HIV - San Francisco Department of Public Health ( Site 0003)

San Francisco, California, United States

Site Status

The GW Medical Faculty Associates-Medicine ( Site 0033)

Washington D.C., District of Columbia, United States

Site Status

Midway Immunology and Research Center ( Site 0014)

Ft. Pierce, Florida, United States

Site Status

University of Miami Miller School of Medicine-Infectious Disease ( Site 0029)

Miami, Florida, United States

Site Status

Orlando Immunology Center ( Site 0010)

Orlando, Florida, United States

Site Status

Ponce De Leon Center Grady Health ( Site 0032)

Atlanta, Georgia, United States

Site Status

Howard Brown Health Center ( Site 0004)

Chicago, Illinois, United States

Site Status

The University of Mississippi Medical Center ( Site 0012)

Jackson, Mississippi, United States

Site Status

Rutgers New Jersey Medical School-Clinical Research Center ( Site 0017)

Newark, New Jersey, United States

Site Status

The University of North Carolina at Chapel Hill ( Site 0019)

Chapel Hill, North Carolina, United States

Site Status

Central Texas Clinical Research ( Site 0002)

Austin, Texas, United States

Site Status

The Crofoot Research Center ( Site 0025)

Houston, Texas, United States

Site Status

Centro de Referência e Treinamento DST/AIDS ( Site 0351)

São Paulo, , Brazil

Site Status

Hôpital Saint-Louis-Infectious Diseases and tropical diseases ( Site 0151)

Paris, Île-de-France Region, France

Site Status

Center Hospital of the National Center for Global Health and Medicine ( Site 0101)

Shinjyuku-ku, Tokyo, Japan

Site Status

Via Libre ( Site 0404)

Lima, , Peru

Site Status

Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0203)

Johannesburg, Gauteng, South Africa

Site Status

Wits Reproductive Health and HIV Institute (WRHI)-Research Center ( Site 0201)

Johannesburg, Gauteng, South Africa

Site Status

Desmond Tutu HIV Foundation ( Site 0202)

Cape Town, Western Cape, South Africa

Site Status

Chulalongkorn University-Pediatrics ( Site 0051)

Bangkok, Bangkok, Thailand

Site Status

HIV Netherlands Australia Thailand Research Collaboration ( Site 0056)

Bangkok, Bangkok, Thailand

Site Status

Research Institute for Health Sciences-Research Institute for Health Sciences Building 1 ( Site 0052

Chiang Mai, , Thailand

Site Status

Countries

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United States Brazil France Japan Peru South Africa Thailand

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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MK-8591-024

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2031200419

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-003309-79

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591-024

Identifier Type: -

Identifier Source: org_study_id

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