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

Alzheimer Disease Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05466422
• Other study ID #: 2214-002
• Secondary ID: MK-2214-002
• Status: Recruiting
• Phase: Phase 1
• Start date: September 20, 2022
• Est. completion date: May 16, 2025

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: May 16, 2025
• Est. primary completion date: May 16, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction

Intervention

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

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	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

External Links

•   Merck Clinical Trials Information