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

Phase 3

Terminated

Interventions: Drug: FTC/TDF
Drug: Islatravir
Drug: Placebo to FTC/TDF
Drug: Placebo to ISL

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
ISL QM	Placebo to FTC/TDF	ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF administered once daily.
FTC/TDF QD	FTC/TDF	FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
FTC/TDF QD	Placebo to ISL	FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
ISL QM	Islatravir	ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF administered once daily.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Discontinued Blinded Study Treatment Due to an AE	Up to 283 days	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.
Incidence Rate Per Year of Confirmed HIV-1 Infection Among Participants During Blinded Treatment +42 Days Post-Blind	Up to approximately 325 days	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.
Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind	Up to approximately 325 days	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.

Secondary Outcome Measures

Name	Time	Method
Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 Infection Among ISL-Treated Participants	Up to approximately 237 days	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.

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, 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
The University of Mississippi Medical Center ( Site 0065)
🇺🇸
Jackson, Mississippi, United States
KC CARE Health Center-Clinical Trials ( Site 0059)
🇺🇸
Kansas City, Missouri, United States
Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)
🇺🇸
Newark, New Jersey, United States
Bronx Prevention Center ICAP ( Site 0062)
🇺🇸
Bronx, New York, United States
The University of North Carolina at Chapel Hill-Medicine ( Site 0056)
🇺🇸
Chapel Hill, North Carolina, United States
Scroll for more (14 remaining)
University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)
🇺🇸Birmingham, Alabama, United States