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Completed

NCT Number: NCT05466422

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

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).

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Key information

Conditions

Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

50 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0007), Glendale, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

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

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 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

Treatment and study plan

MK-2214

Biological

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

Placebo

Drug

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

Primary outcomes

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

    Time frame: Up to approximately 297 days

    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.

  2. Number of Participants Who Discontinue Study Treatment Due to an AE

    Time frame: Up to approximately 57 days

    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.

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

    Time frame: At designated time points (up to 85 days)

    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.

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

    Time frame: At designated time points (up to 85 days)

    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.

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

    Time frame: At designated time points (up to 85 days)

    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.

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

    Time frame: At designated time points (up to 85 days)

    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.

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

    Time frame: Day 85

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

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

    Time frame: Baseline and Day 29 pre-dose

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

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

    Time frame: Baseline and Day 85

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

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Multiple Ascending Dose Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-2214 in Adults With Mild Cognitive Impairment or Mild-to-Moderate Alzheimer's Disease

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Jul 20, 2022
Registry last updated
Aug 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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