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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, and pharmacodynamics of MK-2214 in adults with mild cognitive impairment or mild-to-moderate Alzheimer's Disease. 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

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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

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About this study

As specified by Phase 1 flexible language in the protocol, modifications to the dose or dosing regimen could be made to achieve the scientific goals of the trial objectives and/or ensure appropriate safety of the trial participants. The proposed doses could be adjusted based on evaluation of safety, tolerability, and pharmacokinetic data observed in previous panels.

Part 2 was optional and was not conducted.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

  • Participant is in overall good health based on medical history and laboratory safety tests
  • Body mass index between 18.5 and 35 kg/m^2

Part 1 (Mild Cognitive Impairment [MCI] and Mild-to-Moderate Alzheimer's Disease [AD]) Only:

  • History of cognitive and functional decline with gradual onset and slow progression for at least one year before Screening
  • Mini-Mental State Examination (MMSE) score >12 at the prestudy visit
  • Modified Hachinski Ischemic Score (MHIS) <4 at the prestudy visit

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

  • 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: coronavirus disease of 2019 (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

IV infusion

Placebo

Drug

IV infusion

Primary outcomes

  1. Number of Participants Who Experienced an Adverse Event (AE)

    Time frame: Up to approximately 297 days

    An AE was 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 experienced at least one AE was reported.

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

    Time frame: Up to approximately 57 days

    An AE was 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 discontinued study treatment due to an AE was reported.

  3. Area Under the Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) of MK-2214 in Serum After First Dose (Day 1)

    Time frame: Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post first dose (Day 1), Day 4, Day 8, Day 15, and predose on Day 29

    AUC0-28 was defined as the area under the concentration-time curve from time 0 to 28 days of MK-2214 in serum. Blood samples were collected at prespecified time points to determine AUC0-28 of MK-2214 in serum after first dose (Day 1).

  4. AUC0-28 of MK-2214 in Serum After Third Dose (Day 57)

    Time frame: Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297

    AUC0-28 was defined as the area under the concentration-time curve from time 0 to 28 days of MK-2214 in serum. Blood samples were collected at prespecified time points to determine AUC0-28 of MK-2214 in serum after third dose (Day 57).

  5. Maximum Serum Concentration (Cmax) of MK-2214 After First Dose (Day 1)

    Time frame: Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post first dose (Day 1), Day 4, Day 8, Day 15, and predose on Day 29

    Cmax was defined as the maximum concentration of MK-2214 observed in serum. Blood samples were collected at prespecified time points to determine Cmax of MK-2214 after first dose (Day 1).

  6. Cmax of MK-2214 After Third Dose (Day 57)

    Time frame: Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297

    Cmax was defined as the maximum concentration of MK-2214 observed in serum. Blood samples were collected at prespecified time points to determine Cmax of MK-2214 after third dose (Day 57).

  7. Time of Maximum Serum Concentration (Tmax) of MK-2214 After First Dose (Day 1)

    Time frame: Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post first dose (Day 1), Day 4, Day 8, Day 15, and predose on Day 29

    Tmax was defined as the time to maximum serum concentration of MK-2214. Blood samples were collected at prespecified time points to determine Tmax of MK-2214 in serum after first dose (Day 1).

  8. Tmax of MK-2214 After Third Dose (Day 57)

    Time frame: Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297

    Tmax was defined as the time to maximum serum concentration of MK-2214. Blood samples were collected at prespecified time points to determine Tmax of MK-2214 in serum after third dose (Day 57).

  9. Apparent Half-Life (T1/2) of MK-2214 in Serum After Third Dose (Day 57)

    Time frame: Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297

    T1/2 was defined as the apparent half-life of MK-2214 observed in serum. Blood samples were collected at prespecified time points to determine t1/2 of MK-2214 in serum after third dose (Day 57).

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

    Time frame: Day 85

    Concentration of MK-2214 in CSF was defined as the CSF exposure of MK-2214. A CSF sample was to be collected on Day 85.

  11. Free Phospho-Tau Concentration in CSF

    Time frame: Day 85

    Concentration of free phospo-tau in CSF was defined as free phospho-tau levels in CSF after study treatment administration (MK-2214 or placebo). A CSF sample was to be collected on Day 85.

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
Sep 3, 2026

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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