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CompletedPhase 1

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

AbbVie

Asset

Emraclidine

Listed sites

11

Recruiting sites

-

Enrollment

17

actual

Study population

Alzheimer’s disease

Key I/E criteria

Alzheimer's diseaseMMSE 8-26AD symptomatic therapy: stable

Primary endpoints

PartPart 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

Org study IDCVL-231-1006
NCT IDNCT05644977

Timeline

Milestones

Study start2022-12-02actual
Study first posted2022-12-09actual
Primary completion2025-04-14actual
Study completion2025-04-14actual
Last update posted2025-05-02actual

Assets

Drug assets

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years
Maximum age90 Years
SexAll
Healthy volunteersAccepted

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):

-Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan)
-Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) "Yes" responses for any of the following items on the C-SSRS (within past 2 years):
-Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior). Serious risk of suicide in the opinion of the investigator is also exclusionary.

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:

-aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.0 × upper limit normal (ULN)
-Total bilirubin >1.5 × ULN. If Gilbert's syndrome is suspected, total bilirubin >1.5 × ULN is acceptable if the conjugated or direct bilirubin fraction is <20% of total bilirubin.

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:

-History of major depressive episode with psychotic features during the 12 months prior to signing the ICF
-History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder

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:

-History of ischemic stroke within 12 months prior to signing the ICF or any evidence of hemorrhagic stroke
-History of cerebral amyloid angiopathy, epilepsy, or central nervous system neoplasm

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

Safety / tolerability / PK
11
Other (unclassified)
11
Behavior / neuropsychiatric
1

Behavior / neuropsychiatric

1 endpoint
Primary/protocol endpoint

Part 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 endpoints
Primary/protocol endpoint

Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Time frame:Up to Day 28

event count, event

Primary/protocol endpoint

Part A: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters

Time frame:Up to Day 17

event count, event

Primary/protocol endpoint

Part A: Number of Participants With Clinically Significant Changes in Vital Sign Measurements

Time frame:Up to Day 17

event count, event

Primary/protocol endpoint

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

Primary/protocol endpoint

Part B: Changes in Suicidality Assessed Using the C-SSRS

Time frame:Up to Day 28

descriptive

Secondary/protocol endpoint

Part A: Maximum Observed Plasma Concentration (Cmax) of Emraclidine and its Metabolite CV-0000364

Time frame:Days 1 and 14

concentration, descriptive

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

Part A: Trough Plasma Concentration (Ctrough) of Emraclidine and its Metabolite CV-0000364

Time frame:Days 1 and 14

concentration, descriptive

Secondary/protocol endpoint

Part A: Apparent Terminal Half-life (t1/2) of Emraclidine and its Metabolite CV-0000364

Time frame:Days 1 and 14

concentration, descriptive

Secondary/protocol endpoint

Part A: Accumulation Ratio (Rac) of Emraclidine and its Metabolite CV-0000364

Time frame:Day 14

concentration, descriptive

Other (unclassified)

11 endpoints
Primary/protocol endpoint/low confidence

Part A: Number of Participants With Clinically Significant Changes in Laboratory Assessments

Time frame:Up to Day 17

event count, event

Primary/protocol endpoint/low confidence

Part A: Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results

Time frame:Up to Day 17

event count, event

Primary/protocol endpoint/low confidence

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

Primary/protocol endpoint/low confidence

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

Primary/protocol endpoint/low confidence

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

Primary/protocol endpoint/low confidence

Part B: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms

Time frame:Up to Day 28

event count, event

Secondary/protocol endpoint/low confidence

Part A: Peak to Trough Ratio (PTR) of Emraclidine and its Metabolite CV-0000364

Time frame:Day 14

ratio, descriptive

Secondary/protocol endpoint/low confidence

Part A: Apparent Clearance of Drug From Plasma (CL/F) of Emraclidine

Time frame:Days 1 and 14

descriptive

Secondary/protocol endpoint/low confidence

Part A: Apparent Volume of Distribution During Terminal Phase (Vz/F) of Emraclidine

Time frame:Days 1 and 14

descriptive

Secondary/protocol endpoint/low confidence

Part A: Metabolite to Parent Ratio of Emraclidine and its Metabolite CV-0000364

Time frame:Days 1 and 14

ratio, descriptive

Secondary/protocol endpoint/low confidence

Part B: Plasma Concentrations of Emraclidine and its Metabolite CV-0000364

Time frame:Days 1 to 28

concentration, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableno registry results posted yet

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.