Pharmacy and Poisons Board
Protocol No: ECCT/25/08/01 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. Hypothesis: MK-8527

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

 

Tertiary 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 assess association between adherence to MK-8527 qm and efficacy in a nested case control study
  4. To evaluate adherence to MK-8527 qm and FTC/TDF qd
  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 NET EN
  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 Week48
  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:

 Lay Summary

HIV remains a major global health problem.  Around 40 million people are living with the virus, and more than 1.3 million new cases were reported in 2023. Women and girls make up a large number of these cases, especially in sub-Saharan Africa. In this region, young women aged 15 to 24 are hit the hardest, with over 3,000 new infections happening each week.

To help prevent HIV, medications called PrEP (pre-exposure prophylaxis) are used. These are usually taken as daily pills, but taking a pill every day can be difficult  for some people.  Injections are now available as another option, but they aren’t easy for everyone to get and some people might not like them.

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 attractive for women who find it hard to take a pill every day, or don’t like getting injections. The study involves over 4,500 HIV-negative cisgender women (assigned female sex at birth and identify as a woman) aged 16 to 30, who have a higher chance of getting HIV infection.

Methods:
Participants in the study will be randomly placed into one of two groups:  one will take the monthly pill (MK-8527)  , and the other will take  the standard daily PrEP pill (FTC/TDF). They will come in once a month for 24 months for HIV tests, health check-ups, and to track how the medicine is working, with a short follow-up after treatment ends.
If a participant becomes pregnant and decides to keep taking the study medicine, she will have some extra health checks, including blood sample tests.

 Outcome:
If successful, MK-8527 could provide an easier and more preferred way for women to prevent HIV—especially in places where HIV is common and taking a pill every day is hard
Abstract of Study:

Abstract

Background:
HIV-1 infection remains a persistent global epidemic. In 2023, 39.9 million people were living with HIV, with 1.3 million new infections reported globally. Women and girls accounted for 44% of new HIV infections globally, and in sub-Saharan Africa, they represented 62%. Approximately 4000 adolescent girls and young women aged 15–24 became infected every week, with 3100 of these cases in sub-Saharan Africa. HIV requires lifelong treatment and poses multiple health risks, creating a growing healthcare burden. While WHO-recommended daily oral PrEP, including FTC/TDF and FTC/TAF, is effective, its success depends heavily on strict adherence—often a challenge in high-risk populations. Recently approved injectable PrEP like cabotegravir has improved efficacy but faces access and acceptability barriers. Thus, a long-acting oral PrEP alternative like MK-8527 could address these limitations. The trial tests the efficacy of MK-8527 administered once monthly (qm) compared to FTC/TDF administered once daily (qd) for the prevention of HIV-1 infection, as measured by the annual incidence rate of adjudicated HIV-1 infections. Additionally, the study evaluates the safety and tolerability of MK-8527 qm in comparison to FTC/TDF qd.

Methodology:
This Phase 3 randomized, double-blind, active-controlled clinical trial compares once-monthly oral MK-8527 to once-daily FTC/TDF for HIV-1 pre-exposure prophylaxis in cisgender women aged 16–30 at risk of HIV infection. Approximately 4580 participants will be enrolled and followed for up to 24 months, with a 28-day follow-up. Participants will be randomized to receive either MK-8527 or FTC/TDF under blinded design. The primary endpoint is the incidence rate of adjudicated HIV-1 infections.

Outcomes:
An interim analysis will occur after ≥24 primary endpoint cases are accrued. MK-8527's long intracellular half-life supports a monthly dosing strategy aimed at improving adherence and acceptability among women. This study may lead to a more practical and preferred HIV prevention option for women at high risk, especially in low-resource and high-burden settings.