Clinical trial NCT04652700: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV Preexposure Prophylaxis
Keywords: Preexposure prophylaxis (PrEP)
Prevention
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-12-03
Enrollment: 494
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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, 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment
timeFrame: Up to approximately 10.5 months
measure: Number of Participants Who Discontinued From Blinded Study Treatment Due to an AE
timeFrame: Up to approximately 9 months
Secondary outcomes:
measure: Number of Participants With Confirmed HIV-1 Infection
timeFrame: Up to approximately 10.5 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham-UAB 1917 Research Clinic ( Site 0007)
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Center for Clinical AIDS Research and Education ( Site 0011)
state: California
city: Los Angeles
country: United States
facility: Global Research Institute ( Site 0031)
state: California
city: San Francisco
country: United States
facility: Bridge HIV - San Francisco Department of Public Health ( Site 0003)
state: California
city: Washington
country: United States
facility: The GW Medical Faculty Associates-Medicine ( Site 0033)
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center ( Site 0014)
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Infectious Disease ( Site 0029)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 0010)
state: Florida
city: Atlanta
country: United States
facility: Ponce De Leon Center Grady Health ( Site 0032)
state: Georgia
city: Chicago
country: United States
facility: Howard Brown Health Center ( Site 0004)
state: Illinois
city: Jackson
country: United States
facility: The University of Mississippi Medical Center ( Site 0012)
state: Mississippi
city: Newark
country: United States
facility: Rutgers New Jersey Medical School-Clinical Research Center ( Site 0017)
state: New Jersey
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill ( Site 0019)
state: North Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research ( Site 0002)
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center ( Site 0025)
state: Texas
city: Sao Paulo
country: Brazil
facility: Centro de Referência e Treinamento DST/AIDS ( Site 0351)
city: Paris
country: France
facility: Hôpital Saint-Louis-Infectious Diseases and tropical diseases ( Site 0151)
state: Ile-de-France
city: Shinjyuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 0101)
state: Tokyo
city: Lima
country: Peru
facility: Via Libre ( Site 0404)
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0203)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute (WRHI)-Research Center ( Site 0201)
state: Gauteng
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation ( Site 0202)
state: Western Cape
city: Bangkok
country: Thailand
facility: Chulalongkorn University-Pediatrics ( Site 0051)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: HIV Netherlands Australia Thailand Research Collaboration ( Site 0056)
state: Krung Thep Maha Nakhon
city: Chiang Mai
country: Thailand
facility: Research Institute for Health Sciences-Research Institute for Health Sciences Building 1 ( Site 0052
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: