| Protocol No: | ECCT/25/11/07 | Date of Protocol: | 28-04-2025 |
| Study Title: | Protocol 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 |
| Study Objectives: | 1. To evaluate the efficacy of MK-8527 qm compared to FTC/TDF ad for the prevention of HIV-1 infection as assessed by the incidence rate per year of adjudicated HIV-1 infections. Hypothesis (H1): MK-8527 qm is noninferior to FTC/TDF qd with respect to the hazard ratio for HIV-1 infection. Hypothesis (H2): MK-8527 qm is superior to FTC/TDF qd with respect to the hazard ratio for HIV-1 infection.
2. To evaluate the safety and tolerability of MK-8527 qm compared to FTC/TDF qd.
Tertiary objectives
1. To evaluate the efficacy of MK-8527 qm in reducing the incidence per year of HIV-1 infection relative to the background rate.
2. To evaluate aspects of treatment with MK-8527 qm and FTC/TDF qd on participant-reported outcomes.
3. To evaluate the pharmacokinetics of MK-8527 qm using sparse PK sampling.
4. To evaluate adherence to MK-8527 qm and FTC/TDF qd.
5. To assess association between adherence to MK-8527 qm and efficacy in a nested case-control study.
6. 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.
7. 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.
8. To evaluate viral drug resistance in participants who seroconvert to HIV-1.
9. 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.
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| Laymans Summary: | This study is testing a new medication called MK-8527, taken as a pill once a month, to see if it is safe and effective in preventing Human Immunodeficiency Virus (HIV) infection among people at higher risk of getting HIV. The study will include people aged 16 years and older who were born male and have sex with other people who were also born male. This group includes men whose gender matches the sex they were born with (cisgender men), transgender women (people who were born male but identify as women), transgender men (people who were born female but identify as men), and gender-diverse individuals who do not identify strictly as male or female. The research compares MK-8527 to the standard daily HIV prevention pill called tenofovir disoproxil fumarate/ emitriciatbine (FTC/TDF). Participants will be randomly placed into two groups.
Neither the participants nor the researchers know which treatment each person is receiving. This is called a double-blind study, and it helps ensure fair and accurate results. The study will take place at multiple locations with around 4,390 participants. Each participant may be involved for up to 30 months, with regular clinic visits for HIV testing and safety checks. If someone becomes pregnant or chooses to breastfeed, they may be switched to FTC/TDF in a way where both the participant and the study team know what medicine is being given. Mainly the study aims to find out if MK-8527 works as well as or better than the daily FTC/TDF pill in preventing HIV and also to check if MK-8527 causes any side effects or health problems. Researchers hope that this new once-a-month pill will provide a more convenient HIV prevention option and encourage more people to stay protected. |
| Abstract of Study: | Protocol 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 Short Title: MK-8527 as HIV-1 PrEP Objectives: The following primary objectives will be evaluated in cisgender men, transgender women (TGW), transgender men (TGM), and gender non-binary (GNB) people ≥16 years of age who have sex with partners assigned male sex at birth and are at greater likelihood of HIV-1 exposure.
Number of Participants: The trial will rapidly enrol and individually randomize approximately 4,390 participants globally. The Kenya Impact Research and Development Organization Clinical Research Site (K-IRDO CRS) will enrol at least 80 participants. Study Design: This is a randomized, active-controlled, parallel-group, multisite, double-blind, double dummy study to evaluate the efficacy and safety of MK-8527 oral qm as PrEP in cisgender men, TGW, TGM, and GNB people ≥16 years of age who have sex with partners assigned male sex at birth and are at greater likelihood of HIV-1 exposure. The active comparator in this study will be FTC/TDF qd. Approximately 4,390 participants will be randomized in a 1:1 ratio to 1 of 2 intervention groups, the MK-8527 qm group or the FTC/TDF qd group. Study Site: The study will be conducted in Kenya. The K-IRDO CRS will be one of the sites in Kisumu. K-IRDO CRS is located within Tuungane Hospital, Mito Jura Road, Tom Mboya Estate, approximately 100m off Kisumu-Kakamega highway. K-IRDO has strong networks and excellent working relationships with county governments and health departments of the counties from where we will draw study participants. Estimated Duration of Study: The Sponsor estimates that the study will require approximately 33 months from the time the first participant (or their legally acceptable representative) provides documented informed consent until the last participant’s last study-related contact. Because this is an endpoint-driven study, 33 months is an estimate of study duration. Duration of Participation: Because this is an endpoint-driven study, participation times will vary depending on when the participant is enrolled and time for HIV-1 infection case accrual. Participants will be enrolled over an approximately 12-month period with study intervention administered for up to 30 months, based on estimated accrual of primary endpoint cases. Participants who discontinue study intervention, become pregnant, or decide to breast/chestfeed will be followed as described in the protocol. Analysis: The primary efficacy objective will be assessed based on the incidence rate of adjudicated HIV-1 infections while the safety and tolerability objective will be assessed by clinical review of all relevant parameters including adverse Events (AEs), laboratory test values, and vital signs. |