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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prophylaxis; Human Immunodeficiency Virus Type 1; HIV-I
• Intervention / Treatment: Drug: Islatravir; Drug: Placebo to FTC/TDF; Drug: FTC/TDF; Drug: Placebo to ISL

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 FTC/TDF while continuing in the study. 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
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1864
      • Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)
    • Johannesburg, Gauteng, South Africa, 2000
      • Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002
    • Johannesburg, Gauteng, South Africa, 2092
      • Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)
    • Tshwane, Gauteng, South Africa, 0152
      • Setshaba Research Centre ( Site 0016)
  • Kwazulu-Natal
    • Chatsworth, Kwazulu-Natal, South Africa, 4092
      • SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)
    • Durban, Kwazulu-Natal, South Africa, 4001
      • Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)
    • Ladysmith, Kwazulu-Natal, South Africa, 3370
      • Qhakaza Mbokodo Research Clinic ( Site 0017)
  • North-West
    • Brits, North-West, South Africa, 0250
      • Madibeng Centre for Research ( Site 0019)
    • Klerksdorp, North-West, South Africa, 2571
      • Aurum Institute Klerksdorp CRS ( Site 0029)
    • Rustenburg, North-West, South Africa, 0299
      • Aurum Institute - Rustenburg ( Site 0022)
• Uganda
  • Kampala, Uganda, 10216
    • MU-JHU Care Limited-Clinic ( Site 0041)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center ( Site 0068)
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Ponce De Leon Center Grady Health ( Site 0066)
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • The University of Mississippi Medical Center ( Site 0065)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC CARE Health Center-Clinical Trials ( Site 0059)
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)
  • New York
    • Bronx, New York, United States, 10451
      • Bronx Prevention Center ICAP ( Site 0062)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill-Medicine ( Site 0056)
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)
  • Texas
    • Dallas, Texas, United States, 75208
      • Prism Health North Texas, Oak Cliff Health Center ( Site 0070)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University-Department of Medicine ( Site 0061)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 43 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ISL QM; ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily during Part 1.	Drug: Islatravir; Oral 60 mg tablet administered once monthly during Part 1.; Other Names: MK-8591; Drug: Placebo to FTC/TDF; 0 mg tablet administered once daily during Part 1.
Active Comparator: FTC/TDF QD; FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily in Parts 1, 2, and 3. Placebo to ISL (islatravir) also administered once monthly during Part 1.	Drug: FTC/TDF; 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.; Other Names: TRUVADA™; Emtricitabine/Tenofovir disoproxil; Emtricitabine/Tenofovir disoproxil fumarate; Drug: Placebo to ISL; 0 mg tablet administered orally once monthly in Part 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate Per Year of Confirmed HIV-1 Infections	Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections divided by the total person-years of follow-up time to HIV-1 infection status. The primary analysis will compare the incidence rate per year of confirmed HIV-1 Infections between the ISL QM arm participants and incidence rate per year of confirmed HIV-1 Infections in the FTC/TDF QD arm participants. HIV serology tests and polymerase chain reaction (PCR) tests will be done at pre-specified timepoints to confirm HIV-1 infection.	Up to approximately 36 months
Percentage of Participants Who Experienced One or More Adverse Events	An adverse event (AE) is any untoward medical occurrence in a study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign, symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 37 months
Percentage of Participants Who Discontinued Treatment Due to an Adverse Event	An adverse event (AE) is any untoward medical occurrence in a study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign, symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate per Year of Confirmed HIV-1 Infections Among Participants	Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections divided by the total person-years of follow-up time to HIV-1 infection status. The secondary analysis will compare the incidence rate per year of confirmed HIV-1 Infections between the ISL QM arm participants and the background incidence rate calculated from screened participants. The background incidence rate will be estimated using tests based on biomarkers that can differentiate "recent" from "nonrecent" infections in the population screened for this study.	Up to approximately 36 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): July 18, 2023
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: November 23, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Prevention; Preexposure prophylaxis (PrEP)
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Islatravir
• Other Study ID Numbers: 8591-022; MK-8591-022 (Other Identifier: Merck); 2021-001289-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No