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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 3

Conditions: Prophylaxis; HIV-I; Human Immunodeficiency Virus Type 1

Treatments: Drug: Islatravir; Drug: Placebo to ISL; Drug: FTC/TDF; Drug: Placebo to FTC/TDF

Study type: Interventional

Funder types: Industry

Identifiers

NCT04644029

2021-001289-39 (EudraCT Number)

MK-8591-022 (Other Identifier)

8591-022

Details and patient eligibility

About

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.

Full 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.

Enrollment: 730 patients

Sex: Female

Ages: 16 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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730 participants in 2 patient groups

ISL QM

Experimental group

Description:

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.

Treatment:

Drug: Placebo to FTC/TDF

Drug: Islatravir

FTC/TDF QD

Active Comparator group

Description:

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.

Treatment:

Drug: FTC/TDF

Drug: Placebo to ISL