Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection (MK-8591-022)

Phase 3TerminatedNCT04644029

Merck Sharp & Dohme LLC730 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

730

Conditions

HIV-I Human Immunodeficiency Virus Type 1

Interventions

IslatravirDRUG

Oral 60 mg tablet administered once monthly during Part 1.

Placebo to FTC/TDFDRUG

0 mg tablet administered once daily during Part 1.

FTC/TDFDRUG

Each tablet contains 200 mg emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg tenofovir disoproxil fumarate or 201.22 mg tenofovir disproxil phosphate), administered orally once daily in Parts 1, 2, and 3.

Placebo to ISLDRUG

0 mg tablet administered orally once monthly in Part 1.

Eligibility

Sex: FEMALEMin age: 16 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (24)

University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)

Birmingham, Alabama, United States

MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si

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

University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)

Miami, Florida, United States

Orlando Immunology Center ( Site 0068)

Orlando, Florida, United States

Ponce De Leon Center Grady Health ( Site 0066)

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Incidence Rate Per Year of Confirmed HIV-1 Infection Among Participants During Blinded Treatment +42 Days Post-Blind

Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned primary statistical analysis was removed via amendment when open-label treatment was initiated.

Time frame: Up to approximately 325 days

Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind

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.

Time frame: Up to approximately 325 days

Number of Participants Who Discontinued 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 discontinued blinded study treatment due to an AE will be reported for each treatment arm.

Time frame: Up to 283 days

Secondary Outcomes

Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 Infection Among ISL-Treated Participants

Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned secondary statistical analysis was removed via amendment when open-label treatment was initiated.

Time frame: Up to approximately 237 days