MK-2214 for Alzheimer's Disease

No longer recruiting at 16 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Anti-amyloid therapy, Immunosuppressants

Disqualifiers: Suicidal ideation, Cancer, HIV, others

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, MK-2214, to determine its safety and how it moves through the body in individuals with early-stage Alzheimer's Disease or mild cognitive impairment. The goal is to assess if the drug can be tolerated and effective at certain levels in the spinal fluid. Participants will receive either the drug or a placebo (a harmless substance) through an IV on specific days. This trial may suit individuals who have noticed a gradual decline in memory and thinking skills over the past year. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving aducanumab or another anti-amyloid therapy, or if you are on systemic immunosuppression.

Is there any evidence suggesting that MK-2214 is likely to be safe for humans?

Research shows that MK-2214 is under study to determine its safety and effectiveness in treating Alzheimer's disease. Early results from past studies suggest that participants tolerated MK-2214 well, with no serious side effects reported, which is encouraging.

This is a Phase 1 trial, indicating that MK-2214 is in the early stages of human testing. At this stage, researchers primarily focus on assessing the drug's safety and understanding how the body processes it. Although detailed data is limited, testing MK-2214 in humans suggests it showed promise in earlier lab and animal studies.

Participation in this trial will help researchers gather more detailed safety information. This will aid in determining if MK-2214 could become a safe treatment option for people with Alzheimer's disease in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard treatments for Alzheimer's, which typically focus on managing symptoms or slowing disease progression through medications like donepezil or memantine, MK-2214 offers a fresh approach. MK-2214 is unique because it is administered intravenously and is being evaluated for its potential to impact the disease through a new mechanism, possibly targeting underlying disease processes more directly. Researchers are excited about MK-2214 as it could represent a shift from symptomatic relief to a treatment that modifies the disease itself, offering new hope for those affected by Alzheimer's.

What evidence suggests that MK-2214 might be an effective treatment for Alzheimer's Disease?

Research shows that MK-2214, which participants in this trial may receive, might help slow brain changes in people with Alzheimer's disease. Earlier patients showed promising results, suggesting that MK-2214 could benefit those with early Alzheimer's or mild cognitive impairment (MCI). This treatment targets specific brain processes linked to these conditions. Early studies examined its safety and ability to reach the brain at effective levels. While more information is needed, the initial findings offer hope for its potential effectiveness. ^{1 3 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with mild cognitive impairment or mild-to-moderate Alzheimer's Disease who are in good health, have a BMI between 18.5 and 35 kg/m2, and show a history of gradual cognitive decline over at least one year. Participants must score within certain ranges on mental state and ischemic assessments.

Inclusion Criteria

Participant is in overall good health based on medical history and laboratory safety tests

BMI between 18.5 and 35 kg/m^2

Have a Mini-Mental State Examination (MMSE) >12 at the prestudy visit

Exclusion Criteria

Based on clinical interview and Columbia-Suicide Severity Rating Scale (C-SSRS), has reported suicidal ideation with intent, with or without a plan or method

History of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food

I am on ongoing medication for an active autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-2214 or placebo as an IV infusion on Days 1, 29, and 57

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

approximately 42 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-2214
• Placebo

Trial Overview The study tests the safety and effects of MK-2214 on patients with Alzheimer's-related cognitive issues. It measures how much drug reaches the brain fluid and its impact compared to a placebo (a substance with no therapeutic effect).

How Is the Trial Designed?

Group I: MK-2214 Experimental Treatment 1 Intervention

Participants will receive MK-2214 administered in escalating doses as an intravenous (IV) infusion on Days 1, 29, and 57.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo as an IV infusion on Days 1, 29, and 57.

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

In a 30-week study involving 663 patients with mild to moderate Alzheimer's disease, high-dose tacrine (up to 160 mg/d) showed significant improvements in cognitive function and quality of life compared to placebo, particularly on measures like the Clinician Interview-Based Impression (CIBI) and Alzheimer's Disease Assessment Scale (ADAS-Cog).

While tacrine was effective, it was associated with some adverse effects, including liver enzyme elevations and gastrointestinal issues, which were reversible upon stopping the medication, indicating a need for monitoring but not necessarily compromising its overall safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group. Knapp, MJ., Knopman, DS., Solomon, PR., et al.[2022]

AF267B, a selective M1 muscarinic agonist, has shown promise in reducing key Alzheimer's disease (AD) hallmarks, such as beta-amyloid levels and tau hyperphosphorylation, while also improving cognitive deficits in various animal models, indicating its potential efficacy as a treatment.

The compound demonstrated a wide safety margin and effectively penetrated the central nervous system, making it a unique candidate for clinical trials aimed at addressing multiple aspects of AD pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

M1 muscarinic agonists target major hallmarks of Alzheimer's disease--an update. Fisher, A.[2022]

Tacrolimus (FK506), an FDA-approved calcineurin inhibitor, can be safely delivered to APP/PS1 mice using time-release pellets, leading to normalization of calcineurin activity and significant reduction of Alzheimer's disease (AD) pathologies such as synapse loss and neuroinflammation.

The treatment with FK506 not only alleviated cognitive impairment and neuroinflammation but also preserved normal immune responses, suggesting it could be a promising early intervention for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer's phenotypes without blocking peripheral T cell IL-2 response. Stallings, NR., O'Neal, MA., Hu, J., et al.[2023]

In an 11-week study involving 181 patients with mild to moderate Alzheimer's disease, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 did not show significant improvement in cognitive function compared to placebo, as measured by the ADAS-Cog scale.

While there were some marginal improvements in neuropsychiatric symptoms after 8 weeks of treatment, the overall safety profile was similar between LY451395 and placebo, with most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Chappell, AS., Gonzales, C., Williams, J., et al.[2022]

In a preliminary study of 16 patients with early Alzheimer's disease, the p38α kinase inhibitor neflamapimod showed potential to improve episodic memory function, with significant increases in memory scores observed at 28 and 84 days.

While there were no overall group effects on brain amyloid plaque load, a responder analysis indicated that some patients experienced a reduction in amyloid signal, suggesting a possible impact on β-amyloid production that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory clinical study of p38α kinase inhibition in Alzheimer's disease. Scheltens, P., Prins, N., Lammertsma, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07033494

NCT07033494 | A Clinical Study of MK-2214 in People ... Researchers want to know if the study treatment called MK-2214 works to slow certain changes in the brains of people with Alzheimer's disease (AD).

2. memory.ucsf.edu memory.ucsf.edu/research-trials/mk-2214

A Clinical Study of MK-2214 in People with Early Alzheimer's ... The purpose of this Phase 2 clinical study is to evaluate the efficacy and safety of MK-2214, a potential treatment for early Alzheimer's disease. Researchers ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05466422

NCT05466422 | A Study of MK-2214 in Adults With Mild ... The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of MK-2214 in adults with mild cognitive ...

4. alzheimer-europe.org alzheimer-europe.org/research/clinical-trials/mk-2214-004?language_content_entity=en

MK-2214-004 The study will evaluate the safety and efficacy of MK-2214 in people with early Alzheimer's disease. Researchers want to know if giving MK-2214 can slow the ...

5. drug-dev.com drug-dev.com/merck-advances-neuroscience-pipeline-with-novel-therapies-in-phase-2-studies-for-treatment-of-alzheimers-disease/

Merck Advances Neuroscience Pipeline With Novel ... MK-2214 is currently being evaluated in a Phase 2 clinical trial for the treatment of early mild cognitive impairment (MCI) or mild Alzheimer's ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05466422

NCT05466422 | A Study of MK-2214 in Adults With Mild ... The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of MK-2214 in adults with mild cognitive impairment ...

7. merckclinicaltrials.com merckclinicaltrials.com/trial/nct05466422/

A Study of MK-2214 in Adults With Mild Cognitive Impairment ... The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of MK-2214 in adults with mild cognitive impairment ...