A Clinical Study of MK-2214 in People With Early Alzheimer's Disease (MK-2214-004)
- Registration Number
- NCT07033494
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Researchers want to know if the study treatment called MK-2214 works to slow certain changes in the brains of people with Alzheimer's disease (AD). AD is a type of dementia that can cause loss of memory, communication (such as speech), and decision-making skills. It can limit a person's ability to do daily tasks. MK-2214 is a study treatment designed to slow down AD.
The goals of the study are to learn:
* If MK-2214 slows the spread of tau in the brain compared to placebo. Tau is a protein that accumulates in AD \& damages brain cells. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment.
* About the safety of MK-2214 and if people tolerate it
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 340
The main inclusion criteria include but are not limited to the following:
- Has mild cognitive impairment (MCI) or mild dementia due to Alzheimer's Disease (AD)
- Has a designated study partner who can fulfill the requirements of this study
- If on an approved AD therapy for symptomatic AD, the dosing regimen must have been stable for 3 months prior to screening
The main exclusion criteria include but are not limited to the following:
- Has a known history of stroke or cerebrovascular disease
- Has diagnosis of a clinically relevant central nervous system disease other than AD or other condition that negatively impacts cognition or cognitive status chronically
- Has structural brain disease
- Has a history of seizures or epilepsy within 5 years before screening
- Has any other major central nervous system trauma, or infections that affect brain function
- Has major medical illness or unstable medical condition within 3 months before screening
- Has a severe, acute, or chronic medical or psychiatric condition or laboratory abnormality
- Has any immunological disease, which is not adequately controlled, or which requires treatment with biologics and/or immunosuppressants during the study
- Has a bleeding disorder that is not under adequate control
- Has a history of malignancy occurring within 5 years of screening
- Has a risk factor for corrected QT interval (QTc) prolongation
- Has liver disease
- Is unwilling or unable to undergo computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) scan
- Resides in a nursing home or assisted care facility with need for direct continuous medical care and nursing supervision
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MK-2214 MK-2214 Participants will receive MK-2214 via intravenous (IV) infusion every 4 weeks (q4w) during the study. Placebo Placebo Participants will receive a placebo via IV infusion q4w during the study.
- Primary Outcome Measures
Name Time Method Change from Baseline in Tau PET Standardized Uptake Value Ratio (SUVr) Baseline, up to approximately 23 months Participants will have tau PET imaging to assess tau pathology. Tau is a protein that accumulates in AD \& damages brain cells. SUVr is SUV in the region of interest divided by SUV in a reference region (cerebellum). The change from baseline in tau PET SUVr will be reported.
Number of Participants Who Experience One or More Adverse Events (AEs) Up to approximately 26 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience one or more AEs will be reported.
Number of Participants Who Discontinue Study Intervention Due to an AE Up to approximately 23 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study intervention due to an AE will be reported.
- Secondary Outcome Measures
Name Time Method Change from Baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) Total Score Baseline, up to approximately 23 months The CDR-SB is used for cognitive assessment in people with AD. The CDR is a clinical scale that describes 5 degrees of impairment in performance on each of 6 categories of function including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The ratings of degree of impairment obtained on each of the 6 categories of function are synthesized into 1 global rating of dementia CDR score ranging from 0 (normal) to 3 (severe). A total score is calculated as the sum of the category scores, with a range of 0 (normal) to 18 (severe). Higher scores indicate more impairment. The change from baseline in CDR-SB total score will be reported.
Change from Baseline in the Composite Tau PET SUVr in Braak Region III and IV Baseline, up to approximately 23 months Participants will have tau PET imaging to assess tau pathology. Tau is a protein that accumulates in AD \& damages brain cells. SUVr is SUV in the region of interest, divided by SUV in a reference region (cerebellum). Braak staging ranges from Braak I to VI. Description for Braak III includes amygdala, parahippocampal gyrus, fusiform gyrus, \& lingual gyrus, and Braak IV includes insula, inferior temporal, lateral temporal, posterior cingulate, \& inferior parietal. The composite tau PET SUVr is a weighted average of tau PET SUVr values obtained from multiple brain regions, with weights being the percentage volume of each region within the composite. The change from baseline in composite tau PET SUVr in Braak regions III and IV will be reported.
Change from Baseline in the Composite Tau PET SUVr Baseline, up to approximately 23 months Participants will have tau PET imaging to assess tau pathology. Tau is a protein that accumulates in AD \& damages brain cells. SUVr is SUV in the region of interest, divided by SUV in a reference region (cerebellum). The composite tau PET SUVr is a weighted average of tau PET SUVr values obtained from multiple brain regions, with weights being the percentage volume of each region within the composite. The change from baseline in composite tau PET SUVr will be reported.
Change from Baseline in the Composite Tau PET SUVr in Braak Region I to VI Baseline, up to approximately 23 months Participants will have tau PET imaging to assess tau (protein that accumulates in AD \& damages brain cells) pathology. SUVr is SUV in the region of interest, divided by SUV in a reference region (cerebellum). Braak staging ranges from I-VI (Braak I (transentorhinal); II (entorhinal \& hippocampus); III (amygdala, parahippocampal gyrus, fusiform gyrus, \& lingual gyrus); IV (insula, inferior temporal, lateral temporal, posterior cingulate, \& inferior parietal); V (orbitofrontal, superior temporal, inferior frontal, cuneus, anterior cingulate, supramarginal gyrus, lateral occipital, precuneus, superior parietal, superior frontal, \& rostro medial frontal); VI (paracentral, postcentral, precentral, \& pericalcarine)). Composite tau PET SUVr is weighted average of tau PET SUVr values from multiple brain regions, with weights being percentage volume of each region. The change from baseline in composite tau PET SUVr in Braak region I to IV will be reported.
Change from Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale13 (ADAS-Cog13) Total Score Baseline, up to approximately 23 months The ADAS-Cog13 is a structured scale that evaluates memory (word recall, delayed word recall, and word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). In addition, ratings of spoken language, language comprehension, word finding difficulty, ability to remember test instructions, and number cancellation will be obtained. Per protocol, score range will be from 0 (no impairment) to 85 (maximum impairment) points. Higher scores indicate more impairment. The change from baseline in ADAS-Cog13 total score will be reported.
Change from Baseline in the Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL-MCI) Total Score Baseline, up to approximately 23 months ADCS-ADL-MCI evaluates the ability of individuals to perform various daily activities including basic activities of daily living (BADL; personal care tasks like bathing, dressing and eating) and instrumental activities of daily living (IADL; complex tasks such as managing finances, preparing meals, using telephone) administered through caregiver or family member to access severity of cognitive decline in the past 4 weeks. Each item is scored on a scale of 0 (unable to do) to 2 (independent). The total score is calculated by summing scores of all items and ranges from 0 (poor functioning) to 68 (better functioning). Higher scores indicate better functional ability. The change from baseline in ADCS-ADL-MCI total score will be reported.
Change from Baseline in Modified Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score Baseline, up to approximately 23 months The modified iADRS is a composite tool to measure cognition and function. The modified iADRS is a linear combination of total scores from the ADAS-Cog and the ADCS-ADL-MCI. The modified iADRS composite score is calculated by subtracting the ADAS-Cog13 score from 85 and then adding the ADCS-ADL-MCI score. Composite score ranges from 0 (maximum impairment) to 144 (greater independent, healthy functioning and cognition). Lower scores indicate more impairment. The change from baseline in modified iADRS total score will be reported.
Trial Locations
- Locations (9)
Irvine Clinical Research ( Site 1041)
🇺🇸Irvine, California, United States
Syrentis Clinical Research ( Site 1001)
🇺🇸Santa Ana, California, United States
Neuropsychiatric Research Center of Southwest Florida ( Site 1003)
🇺🇸Fort Myers, Florida, United States
ClinCloud LLC ( Site 1039)
🇺🇸Melbourne, Florida, United States
Aqualane Clinical Research ( Site 1035)
🇺🇸Naples, Florida, United States
Charter Research - Orlando ( Site 1051)
🇺🇸Orlando, Florida, United States
JEM Research Institute ( Site 1046)
🇺🇸Atlantis, Florida, United States
Axiom Brain Health ( Site 1029)
🇺🇸Tampa, Florida, United States
Conquest Research LLC ( Site 1053)
🇺🇸Winter Park, Florida, United States
Irvine Clinical Research ( Site 1041)🇺🇸Irvine, California, United StatesStudy CoordinatorContact949-753-1663