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

NCT05644977 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CVL-231-1006
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Healthy Participants; Alzheimer's Disease Dementia

Outcome Measures

Primary Outcomes (12)

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

  Up to Day 28

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

  Up to Day 17

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

  Up to Day 17

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

  Up to Day 17

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

  Up to Day 17

• 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.

  Up to Day 17

• 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.

  Up to Day 14

• 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.

  Up to Day 14

• 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.

  Up to Day 14

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

  Up to Day 28

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

  Up to Day 28

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

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

  Up to Day 28

Secondary Outcomes (11)

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

  Days 1 and 14

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

  Days 1 and 14

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

  Days 1 and 14

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

  Days 1 and 14

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

  Day 14

Study Arms (6)

Part A: Cohort 1: Emraclidine Dose 1

EXPERIMENTAL

Participants will receive emraclidine dose 1 or emraclidine-matching placebo tablets, orally, once daily (QD) up to Day 14.

Drug: Emraclidine; Drug: Placebo

Part A: Cohort 2: Emraclidine Dose 2

EXPERIMENTAL

Participants will receive emraclidine dose 2 or emraclidine-matching placebo tablets, orally, QD up to Day 14.

Drug: Emraclidine; Drug: Placebo

Part A: Cohort 3: Emraclidine Dose 3

EXPERIMENTAL

Participants will receive emraclidine dose 3 or emraclidine-matching placebo tablets, orally, QD up to Day 14.

Drug: Emraclidine; Drug: Placebo

Part A: Cohort 4: Emraclidine Dose 4

EXPERIMENTAL

Participants will receive emraclidine dose 4 or emraclidine-matching placebo tablets, orally, QD up to Day 14.

Drug: Emraclidine; Drug: Placebo

Part A: Cohort 5: Emraclidine Dose 5

EXPERIMENTAL

Participants will receive emraclidine dose 5 or emraclidine-matching placebo tablets, orally, QD up to Day 14.

Drug: Emraclidine; Drug: Placebo

Part B: Cohort 6: Emraclidine Dose 6

EXPERIMENTAL

Participants with dementia due to AD will receive emraclidine dose 6 or emraclidine-matching placebo tablets, orally, QD up to Day 28.

Drug: Emraclidine; Drug: Placebo

Interventions

Emraclidine DRUG

Oral tablets

Also known as: CVL-231, PF-06852231

Part A: Cohort 1: Emraclidine Dose 1; Part A: Cohort 2: Emraclidine Dose 2; Part A: Cohort 3: Emraclidine Dose 3; Part A: Cohort 4: Emraclidine Dose 4; Part A: Cohort 5: Emraclidine Dose 5; Part B: Cohort 6: Emraclidine Dose 6

Placebo DRUG

Oral tablets

Part A: Cohort 1: Emraclidine Dose 1; Part A: Cohort 2: Emraclidine Dose 2; Part A: Cohort 3: Emraclidine Dose 3; Part A: Cohort 4: Emraclidine Dose 4; Part A: Cohort 5: Emraclidine Dose 5; Part B: Cohort 6: Emraclidine Dose 6

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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):
• 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.
• 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:

Sponsors & Collaborators

• AbbVie: lead

Study Sites (11)

Cypress, California

Cypress, California, 90630, United States

Location

San Diego, California

San Diego, California, 92103, United States

Location

Hialeah, Florida

Hialeah, Florida, 33014, United States

Location

Decatur, Georgia

Decatur, Georgia, 30030, United States

Location

Honolulu, Hawaii

Honolulu, Hawaii, 96817, United States

Location

Overland Park, Kansas

Overland Park, Kansas, 66212, United States

Location

Farmington Hills, Michigan

Farmington Hills, Michigan, 48334, United States

Location

Marlton, New Jersey

Marlton, New Jersey, 08053, United States

Location

Princeton, New Jersey

Princeton, New Jersey, 08540, United States

Location

Staten Island, New York

Staten Island, New York, 10314, United States

Location

North Canton, Ohio

North Canton, Ohio, 44720, United States

Location

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: December 9, 2022
• Study Start: December 2, 2022
• Primary Completion: April 14, 2025
• Study Completion: April 14, 2025
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)