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Healthy ParticipantsPhase 1NCT05644977

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

A Phase 1 study testing Emraclidine in people with Healthy Participants and Alzheimer's Disease Dementia, run by AbbVie at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 55 to 90 yearsHealthy volunteers can take part
What is being tested?
Emraclidine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
17 participants
Where
11 sitesUnited States
Study dates
2 Dec 2022to 14 Apr 2025
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 90 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Cohorts 1 to 5 (Part A)
  • Male participants and female participants of nonchildbearing potential, ages 65 to 85 years, inclusive.
  • 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.
  • 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.
  • 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).
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  • 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)
  • Male participants and female participants of nonchildbearing potential, ages 55 to 90 years, inclusive.
  • 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.
  • Have a Mini-Mental State Examination (MMSE) score of 8 through 26, inclusive, at the Screening Visit.
  • 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.
  • 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.
  • Body mass index of 17.5 to 40.0 kg/m2, inclusive, and total body weight >45 kg (100 lb) at Screening.

Who cannot join

  • All Cohorts
  • "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.
  • 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.
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  • Positive drug screen or a positive test for alcohol at Screening or Baseline Visits.
  • 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)
  • 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.
  • Current or past history of significant cardiovascular disease.
  • 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)
  • 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
  • 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
  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Cypress, California

    Cypress, California, 90630

  • Decatur, Georgia

    Decatur, Georgia, 30030

  • Farmington Hills, Michigan

    Farmington Hills, Michigan, 48334

  • Hialeah, Florida

    Hialeah, Florida, 33014

  • Honolulu, Hawaii

    Honolulu, Hawaii, 96817

  • Marlton, New Jersey

    Marlton, New Jersey, 08053

  • North Canton, Ohio

    North Canton, Ohio, 44720

  • Overland Park, Kansas

    Overland Park, Kansas, 66212

  • Princeton, New Jersey

    Princeton, New Jersey, 08540

  • San Diego, California

    San Diego, California, 92103

  • Staten Island, New York

    Staten Island, New York, 10314

Other trials in United States

About this study

Official title: 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)

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.

Being tested
Emraclidine, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EmraclidineDrug

    Also called CVL-231, PF-06852231

    Oral tablets

  • PlaceboDrug

    Oral tablets

Study groups in NCT05644977
Study groupRoleWhat they receive
Part A: Cohort 1: Emraclidine Dose 1ExperimentalParticipants will receive emraclidine dose 1 or emraclidine-matching placebo tablets, orally, once daily (QD) up to Day 14.
Receives: Drug: Emraclidine; Drug: Placebo
Part A: Cohort 2: Emraclidine Dose 2ExperimentalParticipants will receive emraclidine dose 2 or emraclidine-matching placebo tablets, orally, QD up to Day 14.
Receives: Drug: Emraclidine; Drug: Placebo
Part A: Cohort 3: Emraclidine Dose 3ExperimentalParticipants will receive emraclidine dose 3 or emraclidine-matching placebo tablets, orally, QD up to Day 14.
Receives: Drug: Emraclidine; Drug: Placebo
Part A: Cohort 4: Emraclidine Dose 4ExperimentalParticipants will receive emraclidine dose 4 or emraclidine-matching placebo tablets, orally, QD up to Day 14.
Receives: Drug: Emraclidine; Drug: Placebo
Part A: Cohort 5: Emraclidine Dose 5ExperimentalParticipants will receive emraclidine dose 5 or emraclidine-matching placebo tablets, orally, QD up to Day 14.
Receives: Drug: Emraclidine; Drug: Placebo
Part B: Cohort 6: Emraclidine Dose 6ExperimentalParticipants with dementia due to AD will receive emraclidine dose 6 or emraclidine-matching placebo tablets, orally, QD up to Day 28.
Receives: Drug: Emraclidine; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to Day 28

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

    Measured: Up to Day 17

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

    Measured: Up to Day 17

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

    Measured: Up to Day 17

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

    Measured: Up to Day 17

  6. Part A: Changes in Suicidality Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)

    The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk.

    Measured: Up to Day 17

  7. Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Simpson Angus Scale (SAS)

    The SAS consists of a list of 10 symptoms of parkinsonism. Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms and a score of 4 representing a severe condition. The SAS total score is the sum of the scores for all 10 items.

    Measured: Up to Day 14

  8. Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Abnormal Involuntary Movement Scale (AIMS)

    The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness, severe distress). In addition, the AIMS includes 2 yes/no questions that address the participant's dental status.

    Measured: Up to Day 14

  9. Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Barnes Akathisia Rating Scale (BARS)

    The BARS consists of 4 items related to akathisia. The first 3 items are rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation is made on a 6-point scale, with a score of 0 representing absence of symptom and a score of 5 representing severe akathisia.

    Measured: Up to Day 14

  10. Part B: Number of Participants With TEAEs, Clinically Significant Changes in ECG Parameters, Laboratory Assessments, Vital Sign Measurements, and Physical and Neurological Examination Results

    Measured: Up to Day 28

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

    Measured: Up to Day 28

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

    Extrapyramidal symptoms will be evaluated using SAS, AIMS, and BARS scales.

    Measured: Up to Day 28

Secondary outcomes (11)

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

    Measured: Days 1 and 14

  2. Part A: Time to Maximum Plasma Concentration (Tmax) of Emraclidine and its Metabolite CV-0000364

    Measured: Days 1 and 14

  3. Part A: Area Under the Plasma Concentration-time Curve (AUC) of Emraclidine and its Metabolite CV-0000364

    Measured: Days 1 and 14

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

    Measured: Days 1 and 14

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

    Measured: Day 14

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

    Measured: Days 1 and 14

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

    Measured: Days 1 and 14

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

    Measured: Days 1 and 14

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

    Rac would be calculated from AUC and Cmax of emraclidine and its metabolite.

    Measured: Day 14

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

    Measured: Days 1 and 14

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

    Measured: Days 1 to 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2022
  2. Study start2 Dec 2022
  3. Primary completion14 Apr 2025
  4. Study completion14 Apr 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05644977
Sponsor's protocol ID
CVL-231-1006
Status last verified
Apr 2025
First submitted
1 Dec 2022
Last updated
2 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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