Clinical trial NCT04644029: Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection (MK-8591-022)
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 Women at High Risk for HIV-1 Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV-I
Human Immunodeficiency Virus Type 1
Prophylaxis
Keywords: Preexposure prophylaxis (PrEP)
Prevention
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-11-25
Enrollment: 730
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate whether oral islatravir (ISL) is effective in preventing Human Immunodeficiency Virus Type 1 (HIV-1) infection in women at high-risk for HIV-1 infection. The study will compare oral ISL taken once a month with standard-of-care medication for prevention of HIV-1 infection, emtricitabine/tenofovir disoproxil (FTC/TDF), taken once per day. The primary hypothesis is that oral ISL is more effective than FTC/TDF at reducing the incidence rate per year of confirmed HIV-1 infections.

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 and screening and randomization of new participants was ended. Blinded assessments conducted prior to this date are designated as Study Part 1. During Study Part 2, participants from Part 1 have the option to receive daily open-label FTC/TDF while continuing in the study for safety monitoring. Study Part 3 was added to unblind each participant's Part 1 study intervention assignment, continue participants on FTC/TDF, and monitor safety.

Eligibility criteria: Inclusion Criteria:

* Confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results before randomization.
* Sexually active (vaginal and/or anal sex) with a male sexual partner in the 30 days prior to screening.
* High risk for HIV-1 infection.
* Not pregnant or breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or is a WOCBP and is using an acceptable contraceptive method during the intervention period and for at least 42 days after the last dose.
* A WOCBP must have a negative pregnancy test within 24 hours prior to the first dose of study intervention.

Exclusion Criteria:

* Hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
* Findings of chronic hepatitis B virus (HBV) infection or past HBV.
* Current or chronic history of liver disease.
* History of malignancy within 5 years of screening except for adequately-treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
* Past or current use of cabotegravir, lenacapavir, or any other long-acting HIV prevention product.
* Currently participating in or has participated in an interventional clinical study with an investigational compound or device, within 30 days prior to Day 1.
* Expecting to conceive or donate eggs at any time during the study.

Primary outcomes:
measure: Incidence Rate Per Year of Confirmed HIV-1 Infection Among Participants During Blinded Treatment +42 Days Post-Blind
timeFrame: Up to approximately 325 days
measure: Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind
timeFrame: Up to approximately 325 days
measure: Number of Participants Who Discontinued Blinded Study Treatment Due to an AE
timeFrame: Up to 283 days
Secondary outcomes:
measure: Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 Infection Among ISL-Treated Participants
timeFrame: Up to approximately 237 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)
state: Alabama
city: Washington
country: United States
facility: MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 0068)
state: Florida
city: Atlanta
country: United States
facility: Ponce De Leon Center Grady Health ( Site 0066)
state: Georgia
city: Jackson
country: United States
facility: The University of Mississippi Medical Center ( Site 0065)
state: Mississippi
city: Kansas City
country: United States
facility: KC CARE Health Center-Clinical Trials ( Site 0059)
state: Missouri
city: Newark
country: United States
facility: Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)
state: New Jersey
city: Bronx
country: United States
facility: Bronx Prevention Center ICAP ( Site 0062)
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill-Medicine ( Site 0056)
state: North Carolina
city: Columbia
country: United States
facility: Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)
state: South Carolina
city: Dallas
country: United States
facility: Prism Health North Texas, Oak Cliff Health Center ( Site 0070)
state: Texas
city: Morgantown
country: United States
facility: West Virginia University-Department of Medicine ( Site 0061)
state: West Virginia
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002
state: Gauteng
city: Johannesburg
country: South Africa
facility: Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)
state: Gauteng
city: Tshwane
country: South Africa
facility: Setshaba Research Centre ( Site 0016)
state: Gauteng
city: Chatsworth
country: South Africa
facility: SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)
state: Kwazulu-Natal
city: Durban
country: South Africa
facility: Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)
state: Kwazulu-Natal
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo Research Clinic ( Site 0017)
state: Kwazulu-Natal
city: Brits
country: South Africa
facility: Madibeng Centre for Research ( Site 0019)
state: North-West
city: Klerksdorp
country: South Africa
facility: Aurum Institute Klerksdorp CRS ( Site 0029)
state: North-West
city: Rustenburg
country: South Africa
facility: Aurum Institute - Rustenburg ( Site 0022)
state: North-West
city: Kampala
country: Uganda
facility: MU-JHU Care Limited-Clinic ( Site 0041)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: