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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: MK-2214
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The key Inclusion Criteria include but are not limited to the following: Participant is in overall good health based on medical history and laboratory safety tests BMI between 18.5 and 35 kg/m2 Part 1 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 and <28 at the prestudy visit Modified Hachinski Ischemic Score (MHIS) score <4 at the prestudy visit Exclusion Criteria: The key 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: COVID-19 and influenza vaccines may be administered Is receiving systemic immunosuppression, including corticosteroids exceeding physiologic replacement doses

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |