MK-8527 + FTC/TDF for Healthy Subjects

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Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Low bone density, Renal impairment, Autoimmune disorders, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the new drug MK-8527 behaves in the body when taken alone or with another medication, FTC/TDF. As a Phase 1 study, it focuses on understanding the drug’s movement and effects in healthy individuals. Suitable participants are non-smokers with a healthy body weight (BMI between 18 and 32) and no history of certain health conditions, such as liver disease or cancer. The trial aims to help researchers learn how MK-8527 could be used in the future. Participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that MK-8527 was generally well-tolerated by adults, meaning most participants did not experience major health issues while taking it. The study also showed that as the dose of MK-8527 increased, the blood concentration rose predictably.

When combined with FTC/TDF, a medication often used to prevent HIV, some participants experienced side effects that led them to stop taking the medication. However, FTC/TDF is already recommended for HIV prevention in people at higher risk, indicating it is generally considered safe.

Overall, these findings suggest that MK-8527, both alone and with FTC/TDF, was well-tolerated in previous studies, although some side effects were reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MK-8527 because it offers a new approach to treatment through its unique mechanism of action, which differs from most current options. Unlike standard treatments that primarily target viral replication, MK-8527 could potentially enhance the immune response, providing a different avenue for managing the condition. Additionally, the combination of MK-8527 with FTC/TDF, a well-established antiviral regimen, may offer synergistic effects, improving overall efficacy and patient outcomes.

What evidence suggests that this trial's treatments could be effective?

Research has shown that MK-8527 is a new drug that inhibits a key component of the HIV virus called reverse transcriptase. This component aids the virus in multiplying, so blocking it can prevent the virus from spreading in the body. The trial will explore MK-8527 in two separate treatment arms: one where participants receive a single dose of MK-8527, and another where participants receive FTC/TDF followed by MK-8527. Studies suggest that when combined with Emtricitabine and Tenofovir Disoproxil Fumarate (FTC/TDF), MK-8527 might offer enhanced protection against HIV. However, further research is needed to determine its efficacy and safety for people. ^{4 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This clinical trial is open to healthy adults who haven't smoked or used nicotine/tobacco products for at least 3 months and have a BMI between ≥18 and ≤32.0 kg/m2.

Inclusion Criteria

Has body mass index (BMI) ≥18 and ≤32.0 kg/m^2

I haven't smoked or used nicotine products for at least 3 months.

Exclusion Criteria

Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)

I have a history of conditions like low bone density, kidney issues, or autoimmune disorders.

I have had cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment A

Participants receive a single dose of MK-8527

1 day

1 visit (in-person)

Treatment B

Participants receive FTC/TDF then MK-8527

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-8527

Trial Overview The study is examining how MK-8527 behaves in the body over time alone (Treatment A) versus when taken with FTC/TDF (Treatment B), which are medications used in combination therapy.

How Is the Trial Designed?

Group I: Treatment B: MK-8527 + FTC/TDF Experimental Treatment 2 Interventions

Participants receive FTC/TDF then MK-8527.

Group II: Treatment A: MK-8527 Experimental Treatment 1 Intervention

Participants receive a single dose of MK-8527.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

The study evaluated two tau tracers, [(18)F]T808 and [(18)F]T807, showing that they have high brain uptake but no specific binding in models of tau pathology, indicating potential limitations in their use for detecting tau in Alzheimer's disease.

Comparative analysis of these tracers against eight new tau ligands revealed that [(18)F]T808 demonstrated over 50% selective blocking in human Alzheimer disease slices, providing valuable insights for developing more effective tau imaging agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807. Declercq, L., Celen, S., Lecina, J., et al.[2018]

In a study involving 309 cognitively normal subjects, it was found that the hemispheric white matter (hemisWM) significantly contributes to spill-in effects in [18F]Flortaucipir PET imaging, impacting the quantification of tau pathology in target brain regions.

Partial volume correction (PVC) methods, including a simple two-compartment approach, effectively reduced the impact of spill-in effects, but some correlations between target and off-target regions remained, indicating potential biological or tracer-related factors at play.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of spill-in counts from off-target regions on [18F]Flortaucipir PET quantification. López-González, FJ., Costoya-Sánchez, A., Paredes-Pacheco, J., et al.[2022]

The study confirmed that [(18)F]FTC-146 specifically binds to sigma-1 receptors (S1Rs) with negligible affinity for the vesicular acetylcholine transporter, indicating its potential as a targeted radiotracer for imaging S1R-related diseases.

Toxicity studies showed no significant adverse effects even at doses 250 times higher than the expected clinical dose, supporting the safety of [(18)F]FTC-146 for use in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Further validation to support clinical translation of [(18)F]FTC-146 for imaging sigma-1 receptors. Shen, B., James, ML., Andrews, L., et al.[2022]

In a study involving 226 participants matched from two longitudinal cohort studies, 18F-MK6240 demonstrated a higher sensitivity to changes in tau levels compared to 18F-flortaucipir (FTP), particularly in preclinical Alzheimer's disease stages.

Both tracers effectively distinguished between clinical groups at baseline, but only 18F-MK6240 showed a significant increase in tau levels in Aβ+ cognitively unimpaired individuals, suggesting its potential as a more effective marker for drug efficacy in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-Sectional and Longitudinal Comparison of Tau Imaging with 18F-MK6240 and 18F-Flortaucipir in Populations Matched for Age, MMSE and Brain Beta-Amyloid Burden. Bourgeat, P., Krishnadas, N., Doré, V., et al.[2023]

The synthesized radioligand [18F]15 shows strong potential for PET imaging of mGluR4 in the brain, demonstrating good affinity and selectivity, along with sufficient metabolic stability.

In PET imaging studies with male Sprague Dawley rats, [18F]15 effectively accumulated in brain regions expressing mGluR4, indicating its efficacy for visualizing this receptor in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Characterization of Fluorine-18-Labeled N-(4-Chloro-3-((fluoromethyl-d2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain. Wang, J., Qu, X., Shoup, TM., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07063238

A Clinical Study of MK-8527 in Healthy Adult Participants ... A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12435975/

Safety and Pharmacokinetics of MK‐8527 in Adults Without ... Participants who received MK‐8527 with a meal showed a 41% decrease in C max with no effect on AUC0–168, and a 20%, 22%, and 58% increase in ...

3. merck.com merck.com/news/merck-to-initiate-phase-3-trials-for-investigational-once-monthly-hiv-prevention-pill/

Merck to Initiate Phase 3 Trials for Investigational Once ... The EXPrESSIVE-11 (MK-8527-011, NCT 07044297) trial will evaluate the safety and efficacy of MK-8527 among people with greater likelihood of HIV ...

4. patlynk.com patlynk.com/trial/NCT07063238

Study of MK-8527's Impact on QTc Interval in Healthy Adults Study AimThis study aims to evaluate how the drug MK-8527 affects the QTc interval in healthy adults, providing details about any changes from the baseline.

5. journals.plos.org journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003308

MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase ... The advent of combination antiretroviral (ARV) regimens has transformed the outcome of HIV infection from fatal illness to a manageable, chronic condition [1].

6. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.70331

Safety and Pharmacokinetics of MK‐8527 in Adults Without HIV MK-8527 was generally well tolerated with no serious adverse events. Plasma exposure of MK-8527 increased approximately dose-proportionally, and ...

7. prepwatch.org prepwatch.org/products/mk-8527/

MK-8527 Found to be safe and well-tolerated in a Phase II clinical trial. Two Phase III clinical trials, due to start enrolling in August 2025, will investigate ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06045507

Safety and Pharmacokinetic Study of Oral MK-8527 QM in ... This double-blind, placebo-controlled study is designed to assess the safety, tolerability, and pharmacokinetics of oral MK-8527 taken once monthly (QM) in ...

9. file.medchemexpress.com file.medchemexpress.com/batch_PDF/HY-158128/MK-8527-SDS-MedChemExpress.pdf

Safety Data Sheet Use full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas ...