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) (Impower-024)

A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy and Safety of Oral Islatravir Once-Monthly as Preexposure Prophylaxis in Cisgender Men and Transgender Women Who Have Sex With Men, and Are at High Risk for HIV-1 Infection

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.

Study Overview

• Status: Completed
• Conditions: HIV Preexposure Prophylaxis
• Intervention / Treatment: Drug: ISL; Drug: Placebo to FTC/TDF; Drug: Placebo to FTC/TAF; Drug: FTC/TDF; Drug: FTC/TAF; Drug: Placebo to ISL

Detailed Description

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. 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. Screening and randomization of new participants have stopped, with no new participants being enrolled in Part 2 or Part 3.

• Study Type: Interventional
• Enrollment (Actual): 494
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04121-000
    • Centro de Referência e Treinamento DST/AIDS ( Site 0351)
• France
  • Ile-de-France
    • Paris, Ile-de-France, France, 75010
      • Hôpital Saint-Louis-Infectious Diseases and tropical diseases ( Site 0151)
• Japan
  • Tokyo
    • Shinjyuku-ku, Tokyo, Japan, 162-8655
      • Center Hospital of the National Center for Global Health and Medicine ( Site 0101)
• Peru
  • Lima, Peru, 15001
    • Via Libre ( Site 0404)
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1864
      • Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0203)
    • Johannesburg, Gauteng, South Africa, 2000
      • Wits Reproductive Health and HIV Institute (WRHI)-Research Center ( Site 0201)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Desmond Tutu HIV Foundation ( Site 0202)
• Thailand
  • Chiang Mai, Thailand, 50200
    • Research Institute for Health Sciences-Research Institute for Health Sciences Building 1 ( Site 0052
  • Krung Thep Maha Nakhon
    • Bangkok, Krung Thep Maha Nakhon, Thailand, 10330
      • Chulalongkorn University-Pediatrics ( Site 0051)
    • Bangkok, Krung Thep Maha Nakhon, Thailand, 10330
      • HIV Netherlands Australia Thailand Research Collaboration ( Site 0056)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • University of Alabama at Birmingham-UAB 1917 Research Clinic ( Site 0007)
  • California
    • Los Angeles, California, United States, 90035
      • UCLA Center for Clinical AIDS Research and Education ( Site 0011)
    • Los Angeles, California, United States, 90036
      • Global Research Institute ( Site 0031)
    • San Francisco, California, United States, 94102
      • Bridge HIV - San Francisco Department of Public Health ( Site 0003)
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The GW Medical Faculty Associates-Medicine ( Site 0033)
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center ( Site 0014)
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Infectious Disease ( Site 0029)
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center ( Site 0010)
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Ponce De Leon Center Grady Health ( Site 0032)
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center ( Site 0004)
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • The University of Mississippi Medical Center ( Site 0012)
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School-Clinical Research Center ( Site 0017)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill ( Site 0019)
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research ( Site 0002)
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center ( Site 0025)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced an Adverse Event (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 percentage of participants who experienced an AE will be reported for each treatment arm.	Up to approximately 26 months
Percentage of Participants Who Discontinued 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 percentage of participants who experienced an AE will be reported for each treatment arm.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate Per Year of Confirmed HIV-1 infection Among Participants	Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status. The secondary incidence analysis to compare the incidence rate per year of confirmed HIV-1 Infections between the ISL QM arm and the FTC/TDF or FTC/TAF QD arm participants. HIV serology tests and PCR tests will be done at pre-specified timepoints to confirm HIV-1 infection.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Actual): August 4, 2023
• Study Completion (Actual): August 4, 2023

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Prevention; Preexposure prophylaxis (PrEP)
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: 8591-024; MK-8591-024 (Other Identifier: Merck); jRCT2031200419 (Registry Identifier: jRCT); 2020-003309-79 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No