A Study of MK-2214 in Adults With Mild Cognitive Impairment or Mild-to-Moderate Alzheimer's Disease (MK-2214-002)

NCT05466422 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2214-002MK-2214-002
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of MK-2214 in adults with mild cognitive impairment (MCI) or mild-to-moderate Alzheimer's Disease (AD). The primary hypothesis (Part 1) is that at a generally well tolerated dose level, the true geometric mean concentration at Day 85 of MK-2214 in cerebrospinal fluid is \>0.3 nanomolar (nM).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (9)

• Number of Participants Who Experience At Least One Adverse Event (AE)

  An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.

  Up to approximately 297 days

• Number of Participants Who Discontinue Study Treatment Due to an AE

  An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

  Up to approximately 57 days

• Serum Area Under the Concentration-Time Curve of MK-2214 from Time 0 to 28 Hours (AUC0-28) After First and Third Dose

  AUC is a measure of the extrapolated mean concentration in serum. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine AUC0-28 of MK-2214.

  At designated time points (up to 85 days)

• Serum Maximum Concentration (Cmax) of MK-2214 After First and Third Dose

  Cmax is the maximum concentration of the drug observed in plasma. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Cmax of MK-2214.

  At designated time points (up to 85 days)

• Serum Time to Maximum Concentration (Tmax) of MK-2214 After First and Third Dose

  Tmax is the amount of time required to reach Cmax. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Tmax of MK-2214.

  At designated time points (up to 85 days)

• Serum Apparent Terminal Half-Life (t1/2) of MK-2214 After First and Third Dose

  t1/2 is the time required for 50% of drug to be cleared from serum. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine t1/2 of MK-2214.

  At designated time points (up to 85 days)

• Concentration of MK-2214 in Cerebrospinal Fluid (CSF) at Day 85 (C85d)

  CSF concentration of MK-2214 will be presented for Day 85.

  Day 85

• Percentage change from baseline to Day 29 in free phospho-tau in CSF

  Free phospho-tau in CSF will be determined for participants using the individual percent of baseline values (100\* free phospho-tau / baseline).

  Baseline and Day 29 pre-dose

• Percentage change from baseline to Day 85 in free phospho-tau in CSF

  Free phospho-tau in CSF will be determined for participants using the individual percent of baseline values (100\* free phospho-tau / baseline).

  Baseline and Day 85

Study Arms (2)

MK-2214

EXPERIMENTAL

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

Biological: MK-2214

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

MK-2214 BIOLOGICAL

MK-2214 in escalating doses as an IV infusion on Days 1, 29, and 57

MK-2214

Placebo DRUG

Placebo as an IV infusion on Days 1, 29, and 57

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is in overall good health based on medical history and laboratory safety tests
• BMI between 18.5 and 35 kg/m\^2
• Part 1 (MCI and Mild to Moderate AD) Only:
• History of cognitive and functional decline with gradual onset and slow progression for at least one year before Screening
• Have an Mini-Mental State Examination (MMSE) \>12 at the prestudy visit
• Modified Hachinski Ischemic Score (MHIS) score \<4 at the prestudy visit

You may not qualify if:

• 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 unstable or poorly controlled endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, renal, respiratory, or genitourinary abnormalities or diseases
• History of clinically significant active neurological disease (except for AD or MCI for participants in Part 1)
• History of clinically significant active autoimmune disease requiring ongoing systemic immunosuppressant therapy
• History of cancer (malignancy)
• 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
• Positive test(s) for Hepatitis B Surface Antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV)
• Has had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy visit
• Has a contraindication to lumbar dural puncture, such as coagulopathy, concomitant anticoagulation beyond low dose aspirin, thrombocytopenia, or other factors that could preclude safe lumbar puncture
• Currently receiving or has received aducanumab or another anti-amyloid therapy within the last 6 months
• Has a history of receiving biological therapy within 3 months or 5 half-lives (whichever is longer) or any human immunoglobulin preparation within the last year
• Has received any non-live vaccine starting from 14 days prior to first study intervention or is scheduled to receive any non-live vaccine through 14 days following the final dose of study intervention. Exception: COVID-19 and influenza vaccines may be administered
• Is receiving systemic immunosuppression, including corticosteroids exceeding physiologic replacement doses

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (12)

California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0007)

Glendale, California, 91206, United States

Location

Collaborative Neuroscience Research, LLC ( Site 0009)

Los Alamitos, California, 90720, United States

Location

NRC Research Institute ( Site 0015)

Orange, California, 92868, United States

Location

Velocity Clinical Research, Hallandale Beach ( Site 0001)

Hallandale, Florida, 33009, United States

Location

Research Centers of America ( Hollywood ) ( Site 0004)

Hollywood, Florida, 33024, United States

Location

K2 Medical Research ( Site 0005)

Maitland, Florida, 32751, United States

Location

Charter Research - Winter Park ( Site 0012)

Orlando, Florida, 32803, United States

Location

Progressive Medical Research-Alzheimer's Team ( Site 0013)

Port Orange, Florida, 32127, United States

Location

Charter Research - Lady Lake ( Site 0011)

The Villages, Florida, 32162, United States

Location

CenExel iResearch, LLC ( Site 0002)

Decatur, Georgia, 30030, United States

Location

Global Medical Institutes LLC; Princeton Medical Institute ( Site 0003)

Princeton, New Jersey, 08540, United States

Location

Neuro-Behavioral Clinical Research ( Site 0016)

North Canton, Ohio, 44720, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 20, 2022
• Study Start: September 20, 2022
• Primary Completion: July 3, 2025
• Study Completion: July 3, 2025
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (12)