Clinical trial NCT05466422: A Study of MK-2214 in Adults With Mild Cognitive Impairment or Mild-to-Moderate Alzheimer's Disease (MK-2214-002)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-07-20
Enrollment: 48
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experience At Least One Adverse Event (AE)
timeFrame: Up to approximately 297 days
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 57 days
measure: Serum Area Under the Concentration-Time Curve of MK-2214 from Time 0 to 28 Hours (AUC0-28) After First and Third Dose
timeFrame: At designated time points (up to 85 days)
measure: Serum Maximum Concentration (Cmax) of MK-2214 After First and Third Dose
timeFrame: At designated time points (up to 85 days)
measure: Serum Time to Maximum Concentration (Tmax) of MK-2214 After First and Third Dose
timeFrame: At designated time points (up to 85 days)
measure: Serum Apparent Terminal Half-Life (t1/2) of MK-2214 After First and Third Dose
timeFrame: At designated time points (up to 85 days)
measure: Concentration of MK-2214 in Cerebrospinal Fluid (CSF) at Day 85 (C85d)
timeFrame: Day 85
measure: Percentage change from baseline to Day 29 in free phospho-tau in CSF
timeFrame: Baseline and Day 29 pre-dose
measure: Percentage change from baseline to Day 85 in free phospho-tau in CSF
timeFrame: Baseline and Day 85
Secondary outcomes:
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0007)
state: California
city: Los Alamitos
country: United States
facility: Collaborative Neuroscience Research, LLC ( Site 0009)
state: California
city: Orange
country: United States
facility: NRC Research Institute ( Site 0015)
state: California
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach ( Site 0001)
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood ) ( Site 0004)
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research ( Site 0005)
state: Florida
city: Orlando
country: United States
facility: Charter Research - Winter Park ( Site 0012)
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research-Alzheimer's Team ( Site 0013)
state: Florida
city: The Villages
country: United States
facility: Charter Research - Lady Lake ( Site 0011)
state: Florida
city: Decatur
country: United States
facility: CenExel iResearch, LLC ( Site 0002)
state: Georgia
city: Princeton
country: United States
facility: Global Medical Institutes LLC; Princeton Medical Institute ( Site 0003)
state: New Jersey
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research ( Site 0016)
state: Ohio
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: