Pharmacy and Poisons Board
Protocol No: ECCT/25/08/02 Date of Protocol: 28-04-2025
Study Title:

A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy and Safety of MK-8527 Oral Once-Monthly as HIV-1 Preexposure Prophylaxis in Women.
Study Objectives:

Primary Objectives.

1. To evaluate the efficacy of MK-8527 qm compared to FTC/TDF qd for the prevention of HIV-1 infection as assessed by the incidence rate per year of adjudicated HIV-1 infections.

2. To evaluate the safety and tolerability of MK-8527 qm compared to FTC/TDF qd.

Secondary Objectives.

- None

Tertiary/Exploratory Objectives

1. To evaluate aspects of treatment with MK-8527 qm and FTC/TDF qd on participant-reported outcomes.
2. To evaluate the pharmacokinetics of MK-8527 qm using sparse PK sampling
3. To evaluate adherence to MK-8527 qm and FTC/TDF qd
4. To assess association between adherence to MK-8527 qm and efficacy in a nested casecontrol study
5. To evaluate the impact of MK-8527 qm on renal function compared to FTC/TDF qd as measured by the change from baseline in renal biomarkers at Weeks 24 and 48
6. To evaluate viral drug resistance in participants who seroconvert to HIV-1
7. To measure the plasma concentrations of ENG, MPA, and NET among participants who use an ENG-releasing implant or injectable depot MPA or injectable NETEN
8. To evaluate the PK of MK-8527 in pregnant participants
9. To evaluate the impact of MK-8527 qm on body weight and body mass index compared to FTC/TDF qd as measured by the change from baseline through Week 48
10. To explore the relationship between genetic variation and response to the treatment(s) administered, and mechanisms of disease. Variation across the human genome may be analyzed for association with clinical data collected in the study.

 
Laymans Summary:

HIV remains a major global health challenge, with nearly 40 million people living with the virus and over 1.3 million new infections reported in 2023. Women and girls account for a large share of these infections, especially in sub-Saharan Africa, where young women aged 15–24 are particularly affected—over 3,000 become infected every week in that region alone. To help prevent HIV, medications called PrEP (pre-exposure prophylaxis) are used. These are usually daily pills, but taking a pill every day can be hard for some people. New injectable options are available, but are not widely accessible and may not be preferred by everyone. This study is testing a new HIV prevention pill called MK-8527, which is taken once a month. It may be easier to use and more appealing for women who struggle with daily pills or dislike injections. The study involves over 4,500 HIV-negative cisgender women (assigned female sex at birth) aged 16 to 30 who are at higher risk of HIV infection.

This study will be conducted at the KEMRI-CMR-RCTP Lumumba site in Kisumu County, Kenya. Upto 150 cisgender women (assigned female sex at birth) aged 16 to 30 who are at higher risk of HIV infection will be enrolled at this site. Participants will be randomly assigned to take either MK-8527 once a month or the standard daily PrEP pill. They will attend monthly follow-up visits for HIV testing, health check-ups, and medication monitoring over 24 months, with a short follow-up at day 28 and day 42 after treatment ends. Participants who become pregnant and continue with the study medication will have additional assessments, including blood sample collection. Participants will be recruited from within Kisumu County from HIV testing points, learning institutions, safe spaces, drop-in centres, bars and beaches, and from social media.

If successful, MK-8527 could offer a simpler and more acceptable HIV prevention method for women, especially in areas where HIV rates are high and daily pill-taking is difficult.
Abstract of Study:

Background: MK-8527 is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) with potent antiretroviral activity against HIV-1, being developed for the prevention of HIV-1 infection because of its potent antiviral activity, long half-life, and favorable safety profile as demonstrated in early-phase clinical studies. Nonclinical and clinical data indicate that MK-8527 is generally well tolerated. The convenience and discretion of monthly oral administration of MK-8527 may facilitate adherence and access to PrEP for women at high risk for HIV-1 infection, ultimately leading to greater effectiveness for HIV-1 prevention than what is currently observed with daily oral emtricitabine/tenofovir disoproxil (FTC/TDF).

Objectives: The primary objective of this study is to evaluate the efficacy, safety, and tolerability of MK-8527 monthly compared to FTC/TDF daily for the prevention of HIV-1 infection as assessed by the incidence rate per year of adjudicated HIV-1 infections and the number of adverse events reported leading to discontinuation of study intervention.

Methods: This is a randomized, active-controlled, parallel-group, multisite, double-blind, double-dummy study to evaluate the efficacy and safety of monthly oral MK-8527 in cisgender women (assigned female sex at birth) 16 to 30 years of age, who are at a greater likelihood of HIV-1 exposure. The active comparator for this study will be oral daily FTC/TDF. Approximately 4580 participants from Africa will be randomized and stratified by age in a 1:1 ratio to receive either MK-8527 or FTC/TDF for the duration of the study. Approximately 80% of participants will be ≤25 years of age. Enrolment is competitive, and sites will enrol participants consecutively until the global target sample size is achieved. Our site will enroll upto 150 participants. Participants will be assessed every month till month 24, with an additional follow-up at day 28 and day 42 post-end of treatment.

Expected results: The primary hypothesis is that oral monthly MK-8527 is superior to oral daily FTC/TDF with respect to the hazard ratio for HIV-1 infection and the number of adverse events reported leading to discontinuation of the study intervention.