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 (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). Optional healthy older participants (Part 2) may receive MK-2214 at dose levels determined by criteria met in Part 1.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Recruiting
      • California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0007)
      • Contact: Study Coordinator; Phone Number: 800-239-4367
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Collaborative Neuroscience Research, LLC ( Site 0009)
      • Contact: Study Coordinator; Phone Number: 844-424-9494
    • Orange, California, United States, 92868
      • Recruiting
      • NRC Research Institute ( Site 0015)
      • Contact: Study Coordinator; Phone Number: 714-289-1100
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Recruiting
      • Velocity Clinical Research, Hallandale Beach ( Site 0001)
      • Contact: Study Coordinator; Phone Number: 954-455-5757
    • Hollywood, Florida, United States, 33024
      • Completed
      • Research Centers of America ( Hollywood ) ( Site 0004)
    • Maitland, Florida, United States, 32751
      • Recruiting
      • K2 Medical Research ( Site 0005)
      • Contact: Study Coordinator; Phone Number: 407-500-5252
    • Port Orange, Florida, United States, 32127
      • Recruiting
      • Progressive Medical Research-Alzheimer's Team ( Site 0013)
      • Contact: Study Coordinator; Phone Number: 386-304-7070
    • The Villages, Florida, United States, 32162
      • Recruiting
      • Charter Research - Lady Lake ( Site 0011)
      • Contact: Study Coordinator; Phone Number: 352-441-2000
    • Winter Park, Florida, United States, 32792
      • Recruiting
      • Charter Research - Winter Park ( Site 0012)
      • Contact: Study Coordinator; Phone Number: 407-337-3000
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Recruiting
      • CenExel iResearch, LLC ( Site 0002)
      • Contact: Study Coordinator; Phone Number: 404-537-1281
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Recruiting
      • Global Medical Institutes LLC; Princeton Medical Institute ( Site 0003)
      • Contact: Study Coordinator; Phone Number: 609-921-3555
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Recruiting
      • Neuro-Behavioral Clinical Research ( Site 0016)
      • Contact: Study Coordinator; Phone Number: 330-493-1118

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-2214; Participants will receive MK-2214 administered in escalating doses as an intravenous (IV) infusion on Days 1, 29, and 57.	Biological: MK-2214; MK-2214 in escalating doses as an IV infusion on Days 1, 29, and 57
Placebo Comparator: Placebo; Participants will receive placebo as an IV infusion on Days 1, 29, and 57.	Drug: Placebo; Placebo as an IV infusion on Days 1, 29, and 57

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

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 (Estimated): May 16, 2025
• Study Completion (Estimated): May 16, 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): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: 2214-002; MK-2214-002 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/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