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)

NCT04652700 | Terminated Phase 3 Results DMC FDA Drug

• 4 other identifiers: 8591-024MK-8591-024jRCT20312004192020-003309-79
• Study Type: interventional
• Target: 494
• Locations: 7 countries
• Sites: 25

Brief Summary

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.

Conditions

HIV Preexposure Prophylaxis

Keywords

Preexposure prophylaxis (PrEP); Prevention

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE will be reported for each treatment arm.

  Up to approximately 10.5 months

• Number of Participants Who Discontinued From Blinded Study Treatment Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE will be reported for each treatment arm.

  Up to approximately 9 months

Secondary Outcomes (1)

• Number of Participants With Confirmed HIV-1 Infection

  Up to approximately 10.5 months

Study Arms (2)

Islatravir (ISL) Once Monthly (QM) Group

EXPERIMENTAL

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; Drug: Placebo to FTC/TDF; Drug: Placebo to FTC/TAF

FTC/TDF or FTC/TAF QD Group

ACTIVE COMPARATOR

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; Drug: FTC/TAF; Drug: Placebo to ISL

Interventions

Placebo to FTC/TDF DRUG

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

Islatravir (ISL) Once Monthly (QM) Group

Placebo to FTC/TAF DRUG

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

Islatravir (ISL) Once Monthly (QM) Group

ISL DRUG

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

Also known as: MK-8591

Islatravir (ISL) Once Monthly (QM) Group

FTC/TDF DRUG

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

Also known as: Truvada, Emtricitabine/Tenofovir Disoproxil Fumarate

FTC/TDF or FTC/TAF QD Group

FTC/TAF DRUG

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

Also known as: Descovy, Emtricitabine/Tenofovir Alafenamide

FTC/TDF or FTC/TAF QD Group

Placebo to ISL DRUG

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

FTC/TDF or FTC/TAF QD Group

Eligibility Criteria

• Age: 16 Years+
• Gender Eligibility Details: Male participants and transgender women (TGW) who are at high risk for HIV-1 infection
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (25)

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

Birmingham, Alabama, 35222, United States

Location

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

Los Angeles, California, 90035, United States

Location

Global Research Institute ( Site 0031)

Los Angeles, California, 90036, United States

Location

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

San Francisco, California, 94102, United States

Location

The GW Medical Faculty Associates-Medicine ( Site 0033)

Washington D.C., District of Columbia, 20037, United States

Location

Midway Immunology and Research Center ( Site 0014)

Ft. Pierce, Florida, 34982, United States

Location

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

Miami, Florida, 33136, United States

Location

Orlando Immunology Center ( Site 0010)

Orlando, Florida, 32803, United States

Location

Ponce De Leon Center Grady Health ( Site 0032)

Atlanta, Georgia, 30308, United States

Location

Howard Brown Health Center ( Site 0004)

Chicago, Illinois, 60613, United States

Location

The University of Mississippi Medical Center ( Site 0012)

Jackson, Mississippi, 39216, United States

Location

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

Newark, New Jersey, 07103, United States

Location

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

Chapel Hill, North Carolina, 27599, United States

Location

Central Texas Clinical Research ( Site 0002)

Austin, Texas, 78705, United States

Location

The Crofoot Research Center ( Site 0025)

Houston, Texas, 77098, United States

Location

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

São Paulo, 04121-000, Brazil

Location

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

Paris, Île-de-France Region, 75010, France

Location

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

Shinjyuku-ku, Tokyo, 162-8655, Japan

Location

Via Libre ( Site 0404)

Lima, 15001, Peru

Location

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

Johannesburg, Gauteng, 1864, South Africa

Location

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

Johannesburg, Gauteng, 2000, South Africa

Location

Desmond Tutu HIV Foundation ( Site 0202)

Cape Town, Western Cape, 7925, South Africa

Location

Chulalongkorn University-Pediatrics ( Site 0051)

Bangkok, Bangkok, 10330, Thailand

Location

HIV Netherlands Australia Thailand Research Collaboration ( Site 0056)

Bangkok, Bangkok, 10330, Thailand

Location

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

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• Landovitz RJ, Pinedo Y, Hinestrosa F, Crofoot GE, Brinson C, Buchbinder S, Molina JM, Gravett RM, Brock JB, Ramgopal MN, Rosengren AL, Ofotokun I, Valdez Madruga J, Liegeon G, Panchia R, Supparatpinyo K, Avihingsanon A, Creticos C, Swaminathan S, Doblecki-Lewis S, Rodriguez J, Siegel M, Oka S, Puthanakit T, Grinsztejn B, Sanders EJ, Lama JR, Lombaard J, Ndlovu N, Hwang P, Du J, Jackson B, Homony B, Evans B, Sklar P, Robertson MN, Plank RM. Safety and Tolerability of Oral Islatravir Once Monthly as Pre-Exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study. Clin Infect Dis. 2026 Mar 14:ciag171. doi: 10.1093/cid/ciag171. Online ahead of print.

  PMID: 41830344 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

islatravir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; emtricitabine tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Clinical Trials Disclosure
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 3, 2020
• Study Start: March 15, 2021
• Primary Completion: August 4, 2023
• Study Completion: August 4, 2023
• Last Updated: May 5, 2026
• Results First Posted: December 11, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (1); BR (1); US (15); FR (1); ZA (3); TH (3); PE (1)