A Multiple Dose Trial of Emraclidine in Elderly Participants and in Participants With Dementia Due to Alzheimer's Disease

Last updated: April 30, 2025
Sponsor: AbbVie
Overall Status: Completed

Phase

1

Condition

Dementia

Treatment

Emraclidine

Placebo

Clinical Study ID

NCT05644977
CVL-231-1006
  • Ages 55-90
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

The primary purpose of the study is to evaluate the safety and tolerability of emraclidine administered orally to healthy elderly participants in Part A (multiple ascending doses) and participants with dementia due to Alzheimer's disease (AD) in Part B.

Eligibility Criteria

Inclusion

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 psychiatrichistory, physical and neurological examinations, ECG, vital sign measurements, andlaboratory 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, andtotal 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 mensesfor at least 12 consecutive months with no alternative pathological or physiologicalcause, and confirmed with a serum follicle-stimulating hormone level >40international units per milliliter (IU/mL).

  1. Capable of giving signed informed consent, which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thefull 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 dementiaaccording 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 6months prior to signing the ICF.

  3. Have a Mini-Mental State Examination (MMSE) score of 8 through 26, inclusive, at theScreening Visit.

  4. Have prior neuroimaging evidence (Computed Tomography [CT] or Magnetic resonanceimaging [MRI] completed within the 3 years prior to signing the ICF) collectedduring or subsequent to the onset of dementia symptoms to rule out other centralnervous system disorders that could account for the dementia syndrome.

  5. Currently receiving oral symptomatic treatment for dementia (i.e., cholinesteraseinhibitor and/or memantine), must have been on a stable regimen for at least 6 weeksprior to signing ICF and be willing to maintain a stable dose for the duration ofthe trial.

  6. Body mass index of 17.5 to 40.0 kg/m2, inclusive, and total body weight >45 kg (100lb) at Screening.

Exclusion

Exclusion Criteria:

All Cohorts

  1. "Yes" responses for any of the following items on the C-SSRS (within the past 6months):
  • 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 andIntent) "Yes" responses for any of the following items on the C-SSRS (withinpast 2 years):

  • Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt,Aborted Attempt, Preparatory Acts or Behavior). Serious risk of suicide in theopinion of the investigator is also exclusionary.

  1. Diagnosis of moderate to severe substance or alcohol-use disorder (excludingnicotine or caffeine) as per Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition (DSM-5) criteria within 12 months prior to signing the ICF.

  2. Positive drug screen or a positive test for alcohol at Screening or Baseline Visits.

  3. Any of the following clinical laboratory test results at the Screening Visit (asassessed by the central laboratory) and at Check-in (Day -1; as assessed by thelocal laboratory), and confirmed by a single repeat measurement, if deemednecessary:

  • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.0 × upperlimit 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 thediscretion of the investigator), hematological, immunological, neurological, orpsychiatric 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

  1. 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 12months prior to signing the ICF

  • History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffectivedisorder

  1. Has evidence of a clinically relevant neurological disorder other than possible orprobable Alzheimer's disease such as, but not limited to, the following:
  • History of ischemic stroke within 12 months prior to signing the ICF or anyevidence of hemorrhagic stroke

  • History of cerebral amyloid angiopathy, epilepsy, or central nervous systemneoplasm

  1. Estimated glomerular filtration rate <60 mL/min/1.73 m2, as calculated using theCKD-EPI 2021 equation the Screening Visit.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Total Participants: 17
Treatment Group(s): 2
Primary Treatment: Emraclidine
Phase: 1
Study Start date:
December 02, 2022
Estimated Completion Date:
April 14, 2025

Connect with a study center

  • Cypress, California

    Cypress, California 90630
    United States

    Site Not Available

  • San Diego, California

    San Diego, California 92103
    United States

    Site Not Available

  • Hialeah, Florida

    Hialeah, Florida 33014
    United States

    Site Not Available

  • Decatur, Georgia

    Decatur, Georgia 30030
    United States

    Site Not Available

  • Honolulu, Hawaii

    Honolulu, Hawaii 96817
    United States

    Site Not Available

  • Overland Park, Kansas

    Overland Park, Kansas 66212
    United States

    Site Not Available

  • Farmington Hills, Michigan

    Farmington Hills, Michigan 48334
    United States

    Site Not Available

  • Marlton, New Jersey

    Marlton, New Jersey 08053
    United States

    Site Not Available

  • Princeton, New Jersey

    Princeton, New Jersey 08540
    United States

    Site Not Available

  • Staten Island, New York

    Staten Island, New York 10314
    United States

    Site Not Available

  • North Canton, Ohio

    North Canton, Ohio 44720
    United States

    Site Not Available

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