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
Overview
- Phase
- Phase 1
- Intervention
- MK-2214
- Conditions
- Alzheimer Disease
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 34
- Locations
- 12
- Primary Endpoint
- Number of Participants Who Experience At Least One Adverse Event (AE)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
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).
Investigators
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
Arms & Interventions
MK-2214
Participants will receive MK-2214 administered in escalating doses as an intravenous (IV) infusion on Days 1, 29, and 57.
Intervention: MK-2214
Placebo
Participants will receive placebo as an IV infusion on Days 1, 29, and 57.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants Who Experience At Least One Adverse Event (AE)
Time Frame: Up to approximately 297 days
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.
Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame: Up to approximately 57 days
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.
Serum Area Under the Concentration-Time Curve of MK-2214 from Time 0 to 28 Hours (AUC0-28) After First and Third Dose
Time Frame: At designated time points (up to 85 days)
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.
Concentration of MK-2214 in Cerebrospinal Fluid (CSF) at Day 85 (C85d)
Time Frame: Day 85
CSF concentration of MK-2214 will be presented for Day 85.
Percentage change from baseline to Day 29 in free phospho-tau in CSF
Time Frame: Baseline and Day 29 pre-dose
Free phospho-tau in CSF will be determined for participants using the individual percent of baseline values (100\* free phospho-tau / baseline).
Percentage change from baseline to Day 85 in free phospho-tau in CSF
Time Frame: Baseline and Day 85
Free phospho-tau in CSF will be determined for participants using the individual percent of baseline values (100\* free phospho-tau / baseline).
Serum Maximum Concentration (Cmax) of MK-2214 After First and Third Dose
Time Frame: At designated time points (up to 85 days)
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.
Serum Apparent Terminal Half-Life (t1/2) of MK-2214 After First and Third Dose
Time Frame: At designated time points (up to 85 days)
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.
Serum Time to Maximum Concentration (Tmax) of MK-2214 After First and Third Dose
Time Frame: At designated time points (up to 85 days)
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.