Alzheimer Disease
Conditions
Brief summary
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
Detailed 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.
Interventions
BIOLOGICALMK-2214
IV infusion
DRUGPlacebo
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 297 days | An AE was 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 experienced at least one AE was reported. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 57 days | An AE was 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 discontinued study treatment due to an AE was reported. |
| Area Under the Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) of MK-2214 in Serum After First Dose (Day 1) | Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post first dose (Day 1), Day 4, Day 8, Day 15, and predose on Day 29 | AUC0-28 was defined as the area under the concentration-time curve from time 0 to 28 days of MK-2214 in serum. Blood samples were collected at prespecified time points to determine AUC0-28 of MK-2214 in serum after first dose (Day 1). |
| AUC0-28 of MK-2214 in Serum After Third Dose (Day 57) | Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297 | AUC0-28 was defined as the area under the concentration-time curve from time 0 to 28 days of MK-2214 in serum. Blood samples were collected at prespecified time points to determine AUC0-28 of MK-2214 in serum after third dose (Day 57). |
| Maximum Serum Concentration (Cmax) of MK-2214 After First Dose (Day 1) | Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post first dose (Day 1), Day 4, Day 8, Day 15, and predose on Day 29 | Cmax was defined as the maximum concentration of MK-2214 observed in serum. Blood samples were collected at prespecified time points to determine Cmax of MK-2214 after first dose (Day 1). |
| Cmax of MK-2214 After Third Dose (Day 57) | Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297 | Cmax was defined as the maximum concentration of MK-2214 observed in serum. Blood samples were collected at prespecified time points to determine Cmax of MK-2214 after third dose (Day 57). |
| Time of Maximum Serum Concentration (Tmax) of MK-2214 After First Dose (Day 1) | Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post first dose (Day 1), Day 4, Day 8, Day 15, and predose on Day 29 | Tmax was defined as the time to maximum serum concentration of MK-2214. Blood samples were collected at prespecified time points to determine Tmax of MK-2214 in serum after first dose (Day 1). |
| Tmax of MK-2214 After Third Dose (Day 57) | Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297 | Tmax was defined as the time to maximum serum concentration of MK-2214. Blood samples were collected at prespecified time points to determine Tmax of MK-2214 in serum after third dose (Day 57). |
| Apparent Half-Life (T1/2) of MK-2214 in Serum After Third Dose (Day 57) | Predose, 0.5, 1, 2, 4, 8, 12, and 24 hours post third dose (Day 57), Day 60, Day 64, Day 71, Day 85, Day 141, Day 197, Day 247, and Day 297 | T1/2 was defined as the apparent half-life of MK-2214 observed in serum. Blood samples were collected at prespecified time points to determine t1/2 of MK-2214 in serum after third dose (Day 57). |
| Concentration of MK-2214 in Cerebrospinal Fluid (CSF) at Day 85 | Day 85 | Concentration of MK-2214 in CSF was defined as the CSF exposure of MK-2214. A CSF sample was to be collected on Day 85. |
| Free Phospho-Tau Concentration in CSF | Day 85 | Concentration of free phospo-tau in CSF was defined as free phospho-tau levels in CSF after study treatment administration (MK-2214 or placebo). A CSF sample was to be collected on Day 85. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
Thirty-four participants were randomized and received study treatment in 1 of 4 panels (Part 1: Panels A through D). In each panel, participants received MK-2214 or placebo. As specified by Phase 1 flexible dose regimen in the protocol, MK-2214 dose in Panel D was modified to obtain additional pharmacokinetic and pharmacodynamic data. Part 2 (Panels E and F) was optional and was not conducted.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.9 Years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 25 |
| other Total, other adverse events | 5 / 7 | 5 / 6 | 4 / 6 | 5 / 6 | 7 / 9 | 19 / 25 |
| serious Total, serious adverse events | 0 / 7 | 1 / 6 | 2 / 6 | 0 / 6 | 1 / 9 | 3 / 25 |
Outcome results
None listed