MK-1167 for Alzheimer's Disease

Recruiting at 50 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Acetylcholinesterase inhibitors

Disqualifiers: Stroke, CNS disease, Seizures, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the new medication, MK-1167, can improve memory and thinking in people with Alzheimer's disease when taken alongside standard treatment. Researchers are testing different doses of MK-1167 to determine the most effective dose and ensure safety and tolerability. The trial seeks participants with mild to moderate Alzheimer's who are already taking standard Alzheimer's medication and have a partner to assist them in the study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in Alzheimer's care.

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

The trial requires participants to continue using acetylcholinesterase inhibitors (AChEI) therapy for Alzheimer's disease dementia, so you will not need to stop this medication. The protocol does not specify about other medications.

Is there any evidence suggesting that MK-1167 is likely to be safe for humans?

Research has shown that MK-1167 remains under testing and has not been approved to treat Alzheimer's disease or any other condition. In a study with healthy older adults, researchers examined the safety and tolerability of MK-1167. Although detailed results are not yet available, the progression of MK-1167 to this stage suggests that earlier studies did not identify major safety issues. This indicates that the treatment has generally been well-tolerated so far. However, as it is still experimental, there may be risks or side effects that are not yet fully understood. ^{1 2 3 4 5}

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

Researchers are excited about MK-1167 for Alzheimer's disease because it offers a potentially new approach to treatment compared to current options like cholinesterase inhibitors and memantine. Unlike these standard treatments, which mainly work by improving neurotransmitter function, MK-1167 is thought to target different pathways in the brain, possibly addressing the disease's root causes more directly. Additionally, MK-1167 is being tested in multiple doses, offering flexibility in treatment plans to optimize effectiveness and minimize side effects. This novel mechanism and dosing flexibility make MK-1167 a promising candidate in the fight against Alzheimer's.

What evidence suggests that MK-1167 might be an effective treatment for Alzheimer's disease?

Research shows that MK-1167 is being tested for its potential to alleviate symptoms of Alzheimer's disease, particularly memory and cognitive skills. In this trial, participants will receive varying dosages of MK-1167 or a placebo to assess its effectiveness and safety. Some patients who used MK-1167 alongside standard Alzheimer's medication demonstrated improvements in cognitive abilities. However, MK-1167 remains experimental, and solid proof of its efficacy is not yet available. Early results appear promising, but further research is necessary to confirm these findings. The primary goal is to determine its effectiveness and safety for patients. ^{1 2 4 5 6}

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 people with mild to moderate Alzheimer's Disease dementia, specifically stages 4 or 5. Participants must have a Mini-Mental State Examination score of 12-24 and be on standard acetylcholinesterase inhibitor therapy. They also need a study partner who knows them well enough to provide detailed information about their daily functioning.

Inclusion Criteria

Are you using acetylcholinesterase inhibitors?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-1167 or placebo once daily for up to approximately 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-1167

Trial Overview The study is testing whether MK-1167 can improve memory and thinking in those with AD dementia when taken alongside standard AChEI therapy. It aims to determine the effectiveness of at least one dose level of MK-1167 compared to a placebo, as well as its safety and tolerability.

How Is the Trial Designed?

Group I: MK-1167 3 mg Experimental Treatment 1 Intervention

Participants receive 3 mg of MK-1167 once daily (QD) for up to approximately 24 weeks.

Group II: MK-1167 1 mg Experimental Treatment 1 Intervention

Participants receive 1 mg of MK-1167 QD for up to approximately 24 weeks.

Group III: MK-1167 0.3 mg Experimental Treatment 1 Intervention

Participants take 0.3 mg of MK-1167 QD for up to approximately 24 weeks.

Group IV: Placebo Placebo Group 1 Intervention

Participants take placebo QD for up to approximately 24 weeks.

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 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]

Chronic activation of the M1 muscarinic acetylcholine receptor using the agonist VU0364572 in 5XFAD mice prevented memory impairments and reduced levels of harmful amyloid-beta (Aβ) proteins, suggesting a neuroprotective effect against Alzheimer's disease.

The study indicates that M1 activation not only helps maintain cognitive function but also decreases the presence of oligomeric Aβ, highlighting its potential as a dual-action treatment for both symptoms and underlying pathology in early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease-Modifying Effects of M1 Muscarinic Acetylcholine Receptor Activation in an Alzheimer's Disease Mouse Model. Lebois, EP., Schroeder, JP., Esparza, TJ., et al.[2018]

AF267B, an M1-selective muscarinic agonist, has shown promise in reducing beta-amyloid levels in both rabbits and triple transgenic mice models of Alzheimer's disease, indicating its potential as a cognitive enhancer and disease modifier.

The mechanism of action for AF267B involves the activation of M1 mAChR, which leads to reduced cognitive deficits and decreases in both beta-amyloid and tau pathologies, highlighting its role in targeting key hallmarks of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

M1 muscarinic agonists target major hallmarks of Alzheimer's disease--the pivotal role of brain M1 receptors. Fisher, A.[2008]

Memantine, a drug that blocks NMDA receptors, showed a small but significant benefit in patients with moderate-to-severe Alzheimer's disease after 28 weeks, with a mean difference of 0.3 in the global score compared to placebo.

Patients taking memantine experienced less deterioration in daily living activities, with a score change of 2.1 compared to 3.4 in the placebo group, highlighting its potential as a valuable treatment option in a field with limited effective medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is memantine a breakthrough in the treatment of moderate-to-severe Alzheimer's disease? Doggrell, S.[2019]

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]

In a randomized, double-blind trial involving 240 participants with mild-to-moderate Alzheimer's disease, the selective M1 muscarinic positive allosteric modulator MK-7622 did not show any significant improvement in cognitive function or daily living activities after 12 and 24 weeks of treatment.

The study was halted for futility, and a higher percentage of participants taking MK-7622 discontinued due to adverse events compared to those on placebo (16% vs 6%), indicating potential safety concerns with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease. Voss, T., Li, J., Cummings, J., et al.[2022]

M1 muscarinic acetylcholine receptor (mAChR) dysfunction in Alzheimer's disease is linked to increased beta-amyloid and tau protein levels, which contribute to cognitive decline.

M1-selective muscarinic agonists, such as AF102B and AF150(S), show promise in improving cognitive function and regulating beta-amyloid and tau protein levels in animal models, suggesting they may offer a unique therapeutic approach compared to traditional acetylcholinesterase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic strategies in Alzheimer's disease: M1 muscarinic agonists. Fisher, A.[2019]

The study evaluated halogenated thiophene chalcone-based molecules as dual inhibitors of human monoamine oxidase B (hMAO-B) and cholinesterase (ChE) for potential Alzheimer's disease treatment, finding moderate ChE inhibition with IC50 values between 14-70 µM.

Among the compounds tested, T8 and T6 exhibited the strongest inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively, suggesting that T8 could be further optimized for better AChE inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholinesterase Inhibitory Activities of Selected Halogenated Thiophene Chalcones. Parambi, DGT., Aljoufi, F., Murugaiyah, V., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06285240

NCT06285240 | Efficacy and Safety of MK-1167 in ... The main purpose of this study is to assess the safety and efficacy of MK-1167 administered to participants with Alzheimer's Disease (AD) receiving stable ...

2. merckclinicaltrials.com merckclinicaltrials.com/trial/nct06721156/

A Study to Evaluate the Efficacy and Safety of MK-1167 in ... MK-1167 is experimental. It has not been approved to treat or prevent Alzheimer's disease dementia or other conditions.

3. clinicaltrials.eu clinicaltrials.eu/inn/mk-1167/

Mk-1167 – Application in Therapy and Current ... These trials are evaluating its safety, how well people tolerate it, and its effectiveness in improving Alzheimer's symptoms when used alone or in combination ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/559918

A Study to Evaluate the Efficacy and Safety of MK-1167 in ... Researchers want to learn if giving MK-1167 (the study medicine) along with acetylcholinesterase inhibitor (AChEI) therapy can improve symptoms of ...

5. ctv.veeva.com ctv.veeva.com/study/efficacy-and-safety-of-mk-1167-in-participants-with-alzheimers-disease-dementia-taking-stable-donep

Efficacy and Safety of MK-1167 in Participants With ... The main purpose of this study is to assess the safety and efficacy of MK-1167 administered to participants with Alzheimer's Disease (AD) receiving stable ...

6. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06721156/

A Study to Evaluate the Efficacy and Safety of MK-1167 in ... Researchers want to learn if giving MK-1167 (the study medicine) along with acetylcholinesterase inhibitor (AChEI) therapy can improve symptoms of Alzheimer's ...