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

Prophylaxis Clinical Trial

— Impower-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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04644029
• Other study ID #: 8591-022
• Secondary ID: MK-8591-0222021-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 24, 2021
• Est. completion date: July 1, 2024

Study information

• Verified date: October 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 730
• Est. completion date: July 1, 2024
• Est. primary completion date: July 18, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 45 Years

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• HIV-I
• Human Immunodeficiency Virus Type 1
• Prophylaxis

Intervention

Drug:
• Islatravir
Oral 60 mg tablet administered once monthly during Part 1.
• Placebo to FTC/TDF
0 mg tablet administered once daily during Part 1.
• 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.
• Placebo to ISL
0 mg tablet administered orally once monthly in Part 1.

Locations

Country	Name	City	State
South Africa	Madibeng Centre for Research ( Site 0019)	Brits	North-West
South Africa	SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)	Chatsworth	Kwazulu-Natal
South Africa	Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)	Durban	Kwazulu-Natal
South Africa	Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)	Johannesburg	Gauteng
South Africa	Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)	Johannesburg	Gauteng
South Africa	Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002	Johannesburg	Gauteng
South Africa	Aurum Institute Klerksdorp CRS ( Site 0029)	Klerksdorp	North-West
South Africa	Qhakaza Mbokodo Research Clinic ( Site 0017)	Ladysmith	Kwazulu-Natal
South Africa	Aurum Institute - Rustenburg ( Site 0022)	Rustenburg	North-West
South Africa	Setshaba Research Centre ( Site 0016)	Tshwane	Gauteng
Uganda	MU-JHU Care Limited-Clinic ( Site 0041)	Kampala
United States	Ponce De Leon Center Grady Health ( Site 0066)	Atlanta	Georgia
United States	University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)	Birmingham	Alabama
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	Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)	Columbia	South Carolina
United States	Prism Health North Texas, Oak Cliff Health Center ( Site 0070)	Dallas	Texas
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	University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)	Miami	Florida
United States	West Virginia University-Department of Medicine ( Site 0061)	Morgantown	West Virginia
United States	Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)	Newark	New Jersey
United States	Orlando Immunology Center ( Site 0068)	Orlando	Florida
United States	MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  South Africa,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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

External Links

•   Merck Clinical Trials Information