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

NCT04644029 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: 8591-022MK-8591-0222021-001289-39
• Study Type: interventional
• Target: 730
• Locations: 3 countries
• Sites: 24

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.

Conditions

HIV-I; Prophylaxis; Human Immunodeficiency Virus Type 1

Keywords

Preexposure prophylaxis (PrEP); Prevention

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to 283 days

Secondary Outcomes (1)

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

  Up to approximately 237 days

Study Arms (2)

ISL QM

EXPERIMENTAL

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.

Drug: Islatravir; Drug: Placebo to FTC/TDF

FTC/TDF QD

ACTIVE COMPARATOR

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.

Drug: FTC/TDF; Drug: Placebo to ISL

Interventions

Islatravir DRUG

Oral 60 mg tablet administered once monthly during Part 1.

Also known as: MK-8591

ISL QM

Placebo to FTC/TDF DRUG

0 mg tablet administered once daily during Part 1.

ISL QM

FTC/TDF DRUG

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.

Also known as: TRUVADA™, Emtricitabine/Tenofovir disoproxil, Emtricitabine/Tenofovir disoproxil fumarate

FTC/TDF QD

Placebo to ISL DRUG

0 mg tablet administered orally once monthly in Part 1.

FTC/TDF QD

Eligibility Criteria

• Age: 16 Years - 45 Years
• Gender Eligibility Details: Assigned female sex at birth and is cisgender
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (24)

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

Birmingham, Alabama, 35205, United States

Location

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

Washington D.C., District of Columbia, 20010, United States

Location

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

Miami, Florida, 33136, United States

Location

Orlando Immunology Center ( Site 0068)

Orlando, Florida, 32803, United States

Location

Ponce De Leon Center Grady Health ( Site 0066)

Atlanta, Georgia, 30308, United States

Location

The University of Mississippi Medical Center ( Site 0065)

Jackson, Mississippi, 39216, United States

Location

KC CARE Health Center-Clinical Trials ( Site 0059)

Kansas City, Missouri, 64111, United States

Location

Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)

Newark, New Jersey, 07103, United States

Location

Bronx Prevention Center ICAP ( Site 0062)

The Bronx, New York, 10451, United States

Location

The University of North Carolina at Chapel Hill-Medicine ( Site 0056)

Chapel Hill, North Carolina, 27599, United States

Location

Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)

Columbia, South Carolina, 29203, United States

Location

Prism Health North Texas, Oak Cliff Health Center ( Site 0070)

Dallas, Texas, 75208, United States

Location

West Virginia University-Department of Medicine ( Site 0061)

Morgantown, West Virginia, 26506, United States

Location

Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)

Johannesburg, Gauteng, 1864, South Africa

Location

Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002

Johannesburg, Gauteng, 2000, South Africa

Location

Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)

Johannesburg, Gauteng, 2092, South Africa

Location

Setshaba Research Centre ( Site 0016)

Pretoria, Gauteng, 0152, South Africa

Location

SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)

Chatsworth, KwaZulu-Natal, 4092, South Africa

Location

Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)

Durban, KwaZulu-Natal, 4001, South Africa

Location

Qhakaza Mbokodo Research Clinic ( Site 0017)

Ladysmith, KwaZulu-Natal, 3370, South Africa

Location

Madibeng Centre for Research ( Site 0019)

Brits, North West, 0250, South Africa

Location

Aurum Institute Klerksdorp CRS ( Site 0029)

Klerksdorp, North West, 2571, South Africa

Location

Aurum Institute - Rustenburg ( Site 0022)

Rustenburg, North West, 0299, South Africa

Location

MU-JHU Care Limited-Clinic ( Site 0041)

Kampala, 10216, Uganda

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

islatravir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: In Study Part 1, a double-blinding technique with in-house blinding will be used. ISL and FTC/TDF will be packaged identically relative to their matching placebos so that blind is maintained. The participant, the investigator, and Sponsor personnel or delegate(s) who are involved in the study intervention administration or clinical evaluation of the participants are unaware of the intervention assignments. In Study Part 2, sponsor personnel not directly involved with blinded safety monitoring will be unblinded to participants' randomized study intervention in Part 1. In Study Part 3, participants, investigators, and all Sponsor personnel will be unblinded to the participants' original randomized study intervention group.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: November 25, 2020
• Study Start: February 24, 2021
• Primary Completion: July 18, 2023
• Study Completion: June 11, 2024
• Last Updated: February 4, 2026
• Results First Posted: August 9, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

ZA (10); UG (1); US (13)