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

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

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

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Biological: MK-2214

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0007)
    • Los Alamitos, California, United States, 90720
      • Collaborative Neuroscience Research, LLC ( Site 0009)
    • Orange, California, United States, 92868
      • NRC Research Institute ( Site 0015)
  • Florida
    • Hallandale, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0001)
    • Hollywood, Florida, United States, 33024
      • Research Centers of America ( Hollywood ) ( Site 0004)
    • Maitland, Florida, United States, 32751
      • K2 Medical Research ( Site 0005)
    • Orlando, Florida, United States, 32803
      • Charter Research - Winter Park ( Site 0012)
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research-Alzheimer's Team ( Site 0013)
    • The Villages, Florida, United States, 32162
      • Charter Research - Lady Lake ( Site 0011)
  • Georgia
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch, LLC ( Site 0002)
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes LLC; Princeton Medical Institute ( Site 0003)
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research ( Site 0016)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: MK-2214 20 mg; Participants were randomized to receive MK-2214 20 mg as an intravenous (IV) infusion every month (qm) for 3 months (on Days 1, 29, and 57).	Biological: MK-2214; IV infusion
Experimental: Panel B: MK-2214 100 mg; Participants were randomized to receive MK-2214 100 mg as an IV infusion qm for 3 months (on Days 1, 29, and 57).	Biological: MK-2214; IV infusion
Experimental: Panel C: MK-2214 500 mg; Participants were randomized to receive MK-2214 500 mg as an IV infusion qm for 3 months (on Days 1, 29, and 57).	Biological: MK-2214; IV infusion
Experimental: Panel D: MK-2214 2000 mg; Participants were randomized to receive MK-2214 2000 mg as an IV infusion qm for 3 months (on Days 1, 29, and 57).	Biological: MK-2214; IV infusion
Placebo Comparator: Placebo; Participants were randomized to receive placebo as an IV infusion qm for 3 months (on Days 1, 29, and 57).	Drug: Placebo; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced an Adverse Event (AE)	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.	Up to approximately 297 days
Number of Participants Who Discontinued Study Treatment Due to an AE	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.	Up to approximately 57 days
Area Under the Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) of MK-2214 in Serum After First Dose (Day 1)	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).	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 of MK-2214 in Serum After Third Dose (Day 57)	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).	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
Maximum Serum Concentration (Cmax) of MK-2214 After First Dose (Day 1)	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).	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 of MK-2214 After Third Dose (Day 57)	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).	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
Time of Maximum Serum Concentration (Tmax) of MK-2214 After First Dose (Day 1)	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).	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 of MK-2214 After Third Dose (Day 57)	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).	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
Apparent Half-Life (T1/2) of MK-2214 in Serum After Third Dose (Day 57)	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).	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
Concentration of MK-2214 in Cerebrospinal Fluid (CSF) at 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.	Day 85
Free Phospho-Tau Concentration in CSF	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.	Day 85

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Actual): July 3, 2025
• Study Completion (Actual): July 3, 2025

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 2214-002; MK-2214-002 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No