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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Alzheimer Disease

Treatments: Drug: Placebo; Biological: MK-2214

Study type: Interventional

Funder types: Industry

Identifiers

NCT05466422

MK-2214-002 (Other Identifier)

2214-002

Details and patient eligibility

About

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

Full 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.

Enrollment: 34 patients

Sex: All

Ages: 50 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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34 participants in 5 patient groups, including a placebo group

Panel A: MK-2214 20 mg

Experimental group

Description:

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).

Treatment:

Biological: MK-2214

Panel B: MK-2214 100 mg

Experimental group

Description:

Participants were randomized to receive MK-2214 100 mg as an IV infusion qm for 3 months (on Days 1, 29, and 57).

Treatment:

Biological: MK-2214

Panel C: MK-2214 500 mg

Experimental group

Description:

Participants were randomized to receive MK-2214 500 mg as an IV infusion qm for 3 months (on Days 1, 29, and 57).

Treatment:

Biological: MK-2214

Panel D: MK-2214 2000 mg

Experimental group

Description:

Participants were randomized to receive MK-2214 2000 mg as an IV infusion qm for 3 months (on Days 1, 29, and 57).

Treatment:

Biological: MK-2214

Placebo

Placebo Comparator group

Description:

Participants were randomized to receive placebo as an IV infusion qm for 3 months (on Days 1, 29, and 57).

Treatment:

Drug: Placebo