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A Multiple Dose Trial of Emraclidine in Elderly Participants and in Participants With Dementia Due to Alzheimer's Disease
A Phase 1, Randomized, Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Emraclidine Following Multiple Oral Doses in Healthy Elderly Participants (Part A) and to Evaluate the Safety and Tolerability of Emraclidine in Participants With Dementia Due to Alzheimer's Disease (Part B)
Lead sponsor
Asset
Emraclidine
Listed sites
11
Recruiting sites
-
Enrollment
17
actual
Study population
Alzheimer’s disease
Key I/E criteria
•Alzheimer's disease•MMSE 8-26•AD symptomatic therapy: stable
Primary endpoints
•Part•Part B
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Drug assets
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
Cohorts 1 to 5 (Part A)
1. Male participants and female participants of nonchildbearing potential, ages 65 to 85 years, inclusive.
2. Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
3. Body mass index of 17.5 to 32.0 kilograms per square meter (kg/m^2), inclusive, and total body weight >45 kg (100 pounds [lb]) at Screening.
4. Female participants will be of nonchildbearing potential, defined as follows:
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause, and confirmed with a serum follicle-stimulating hormone level >40 international units per milliliter (IU/mL).
5. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the full protocol.
Cohort 6 (Part B)
1. Male participants and female participants of nonchildbearing potential, ages 55 to 90 years, inclusive.
2. Have a clinical diagnosis of possible or probable Alzheimer's disease dementia according to the 2011 National Institute on Aging - Alzheimer's Association (NIA-AA) clinical criteria at the Screening Visit; diagnosis must be stable for at least 6 months prior to signing the ICF.
3. Have a Mini-Mental State Examination (MMSE) score of 8 through 26, inclusive, at the Screening Visit.
4. Have prior neuroimaging evidence (Computed Tomography [CT] or Magnetic resonance imaging [MRI] completed within the 3 years prior to signing the ICF) collected during or subsequent to the onset of dementia symptoms to rule out other central nervous system disorders that could account for the dementia syndrome.
5. Currently receiving oral symptomatic treatment for dementia (i.e., cholinesterase inhibitor and/or memantine), must have been on a stable regimen for at least 6 weeks prior to signing ICF and be willing to maintain a stable dose for the duration of the trial.
6. Body mass index of 17.5 to 40.0 kg/m2, inclusive, and total body weight >45 kg (100 lb) at Screening
Exclusion criteria
All Cohorts
1. "Yes" responses for any of the following items on the C-SSRS (within the past 6 months):
2. Diagnosis of moderate to severe substance or alcohol-use disorder (excluding nicotine or caffeine) as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria within 12 months prior to signing the ICF.
3. Positive drug screen or a positive test for alcohol at Screening or Baseline Visits.
4. Any of the following clinical laboratory test results at the Screening Visit (as assessed by the central laboratory) and at Check-in (Day -1; as assessed by the local laboratory), and confirmed by a single repeat measurement, if deemed necessary:
Cohorts 1 to 5 (Part A)
1. Current or past history of significant pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator), hematological, immunological, neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
2. Current or past history of significant cardiovascular disease.
3. Estimated glomerular filtration rate <60 milliliters per minute (mL/min)/1.73 m^2, as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation at the Screening Visit or Check-in (Day -1).
Cohort 6 (Part B)
1. Has either of the following:
2. Has evidence of a clinically relevant neurological disorder other than possible or probable Alzheimer's disease such as, but not limited to, the following:
3. Estimated glomerular filtration rate <60 mL/min/1.73 m2, as calculated using the CKD-EPI 2021 equation the Screening Visit.
NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
Endpoints (23)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Behavior / neuropsychiatric
1 endpointPart A: Changes in Suicidality Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame:Up to Day 17
descriptive
Safety / tolerability / PK
11 endpointsPart A: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame:Up to Day 28
event count, event
Part A: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Time frame:Up to Day 17
event count, event
Part A: Number of Participants With Clinically Significant Changes in Vital Sign Measurements
Time frame:Up to Day 17
event count, event
Part B: Number of Participants With TEAEs, Clinically Significant Changes in ECG Parameters, Laboratory Assessments, Vital Sign Measurements, and Physical and Neurological Examination Results
Time frame:Up to Day 28
event count, event
Part B: Changes in Suicidality Assessed Using the C-SSRS
Time frame:Up to Day 28
descriptive
Part A: Maximum Observed Plasma Concentration (Cmax) of Emraclidine and its Metabolite CV-0000364
Time frame:Days 1 and 14
concentration, descriptive
Part A: Time to Maximum Plasma Concentration (Tmax) of Emraclidine and its Metabolite CV-0000364
Time frame:Days 1 and 14
time to event, event
Part A: Area Under the Plasma Concentration-time Curve (AUC) of Emraclidine and its Metabolite CV-0000364
Time frame:Days 1 and 14
concentration, descriptive
Part A: Trough Plasma Concentration (Ctrough) of Emraclidine and its Metabolite CV-0000364
Time frame:Days 1 and 14
concentration, descriptive
Part A: Apparent Terminal Half-life (t1/2) of Emraclidine and its Metabolite CV-0000364
Time frame:Days 1 and 14
concentration, descriptive
Part A: Accumulation Ratio (Rac) of Emraclidine and its Metabolite CV-0000364
Time frame:Day 14
concentration, descriptive
Other (unclassified)
11 endpointsPart A: Number of Participants With Clinically Significant Changes in Laboratory Assessments
Time frame:Up to Day 17
event count, event
Part A: Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results
Time frame:Up to Day 17
event count, event
Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Simpson Angus Scale (SAS)
Time frame:Up to Day 14
event count, event
Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Abnormal Involuntary Movement Scale (AIMS)
Time frame:Up to Day 14
event count, event
Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Barnes Akathisia Rating Scale (BARS)
Time frame:Up to Day 14
event count, event
Part B: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms
Time frame:Up to Day 28
event count, event
Part A: Peak to Trough Ratio (PTR) of Emraclidine and its Metabolite CV-0000364
Time frame:Day 14
ratio, descriptive
Part A: Apparent Clearance of Drug From Plasma (CL/F) of Emraclidine
Time frame:Days 1 and 14
descriptive
Part A: Apparent Volume of Distribution During Terminal Phase (Vz/F) of Emraclidine
Time frame:Days 1 and 14
descriptive
Part A: Metabolite to Parent Ratio of Emraclidine and its Metabolite CV-0000364
Time frame:Days 1 and 14
ratio, descriptive
Part B: Plasma Concentrations of Emraclidine and its Metabolite CV-0000364
Time frame:Days 1 to 28
concentration, descriptive
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.