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A Study to Evaluate the Safety, Tolerability, and Blood Levels of ACU193 in Participants With MCI or Mild AD (INTERCEPT-AD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04931459
Recruitment Status : Recruiting
First Posted : June 18, 2021
Last Update Posted : November 19, 2021
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Acumen Pharmaceuticals

Brief Summary:
This Phase 1 study is a single ascending dose (SAD) and multiple ascending dose (MAD), placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenous ACU193 when administered to participants diagnosed with Mild Cognitive Impairment (MCI) or Mild Dementia due to Alzheimer's disease (AD).

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: ACU193 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Study ACU-001 is a placebo-controlled study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple escalating doses of intravenous ACU193. A two-part single-ascending dose (SAD)/multiple-ascending dose (MAD) study design will be conducted in a population of individuals with early AD (MCI or mild dementia due to AD).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Placebo-Controlled, Single- and Multiple-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous ACU193 in Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease
Actual Study Start Date : June 21, 2021
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: ACU193 Administration
Participants will receive 1 to 3 doses of ACU193 by intravenous (IV) infusion.
Drug: ACU193
Intravenous ACU193

Placebo Comparator: Placebo Administration

Participants receive 1 to 3 doses of matching ACU193 placebo by intravenous (IV) infusion.

2 participants per cohort will receive placebo.

Drug: Placebo
Intravenous Placebo

Primary Outcome Measures :
  1. Incidence and Nature of Treatment-Related Adverse Events (AE) or Serious Adverse Events (SAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Baseline up to 20 weeks (SAD); 24 or 28 weeks (MAD) ]
    Proportion of participants with AE, discontinuations due to AE or SAE, and withdrawals from the study due to AE

  2. Change in Clinical Laboratory Tests [ Time Frame: Baseline up to 20 weeks (SAD); 24 or 28 weeks (MAD) ]
    Incidence and clinically significant abnormal changes in clinical laboratory assessments (hematology, clinical chemistry, urinalysis)

  3. Changes in 12-Lead ECGs [ Time Frame: Baseline up to 20 weeks (SAD); 24 or 28 weeks (MAD) ]
    Clinically significant abnormal changes in 12-Lead ECGs for PR, QRS, QT, QTcF, and QTcB

  4. Changes in the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline up to 20 weeks (SAD); 24 or 28 weeks (MAD) ]
    Presence of suicidal ideation as defined by a positive response to Question 5 on the C-SSRS suicide ideation section

  5. Changes in Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline (predose) up to 20 weeks (SAD); 24 or 28 weeks (MAD) ]
    Brain magnetic resonance imaging (MRI) findings to assess amyloid-related imaging abnormalities (ARIA), including incidence of ARIA-E (edema) or ARIA-H (hemosiderosis)

Secondary Outcome Measures :
  1. Estimate Blood Levels of ACU193 [ Time Frame: Up to 140 days post dose ]
    Area under the concentration-time curve (AUC) from time zero to the time of last measurable concentration (AUCt)

  2. Estimate Maximum Blood Levels of ACU193 [ Time Frame: Up to 140 days post dose. ]
    Maximum observed blood concentration Cmax(obs).

  3. Estimate Time to Reach Maximum Blood Levels of ACU193 [ Time Frame: Up to 140 days post dose. ]
    Time to reach Tmax(obs)

  4. Estimate Blood Levels of ACU193 [ Time Frame: Up to 140 days post dose. ]
    Area under the plasma concentration-time curve from time 0 to infinity (AUC∞)

  5. Estimate Clearance of ACU193 [ Time Frame: Up to 140 days post dose ]
    Clearance (CL)

  6. Estimate Volume of Distribution of ACU193 [ Time Frame: Up to 140 days post dose ]
    Apparent volume of distribution at terminal phase (Vz)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males or females ages 55 to 85 (inclusive).
  2. Participant weighs at least 41 kg (90 lbs) and no more than 113 kg (250 lbs) before study drug administration.
  3. Female participants must be surgically sterile or be at least two years post-menopausal or at least one year post-menopausal with an elevated follicle stimulating hormone (FSH). Male participants with a female partner of child-bearing potential must use adequate contraception.
  4. Individual (or the participant's Legally Authorized Representative [LAR]) is able to give informed consent.
  5. Are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  6. Must meet all of the following clinical criteria for MCI due to AD or mild AD at Screening:

    1. Participant meets NIA-Alzheimer's Association (NIA-AA)criteria for MCI due to AD or probable AD.
    2. A global Clinical Dementia Rating (CDR) of 0.5 or 1.0.
    3. A Mini-Mental State Examination (MMSE) score between 20 and 30 (inclusive).
    4. A positive amyloid positron emission tomography (PET) scan.
  7. Must consent to apolipoprotein E (APOE) genotyping.
  8. If using cholinesterase inhibitors or memantine to treat symptoms related to AD, doses must be stable for at least four weeks prior to Baseline and willing to be stable during the study.
  9. Must have a reliable informant or caregiver who is willing and able to perform all caregiver roles as specified in the caregiver Informed Consent Form (ICF).

Exclusion Criteria:

  1. Receipt of any investigational biological drug within less than one year of Baseline or of any investigational small molecule drug within less than six months of Baseline.
  2. Currently receiving or likely to require the following types of anticoagulants: coumarins and indandiones, Factor Xa inhibitors, heparins, thrombin inhibitors.
  3. Has known humanized monoclonal antibody allergy or hypersensitivity.
  4. History of significant neurological disease, other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson´s disease, or adult epilepsy.
  5. Has had magnetic resonance imaging (MRI) or computerized tomography (CT) of brain within previous two years showing pathology that would be inconsistent with a diagnosis of AD.
  6. Has MRI with results showing greater than four amyloid-related imaging abnormalities hemorrhage/hemosiderin deposition (ARIA-H), presence of any amyloid-related imaging abnormalities edema/effusions (ARIA-E), or superficial siderosis.
  7. Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI.
  8. Current serious or unstable clinically important illness that, in the judgment of the Investigator, is likely to affect cognitive assessment including visual and hearing impairment, deteriorate, or affect the participant's safety or ability to complete the study, including psychiatric, hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrinological, immunologic, or hematologic disorders.
  9. Has an ongoing or new clinically significant laboratory abnormality, as determined by the Investigator.
  10. Has a history or presence of clinically significant abnormal 12-lead electrocardiogram (ECG) or an ECG with QT interval corrected using Fridericia's formula (QTcF) >470 msec for female participants or >450 msec for male participants.
  11. Within one year before Screening, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptom of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (eg, significant valvular disease, hypertrophic cardiomyopathy), or hospitalization for arrhythmia.
  12. History of seizure, transient ischemic attack (TIA), or stroke within the last 18 months.
  13. History of clinically significant carotid or vertebrobasilar stenosis or plaque.
  14. History of a malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen posttreatment within the last five years.
  15. Current symptoms meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for major depressive disorder or any current primary psychiatric diagnosis other than AD if, in the judgment of the Investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the participant´s ability to complete the study.
  16. Are a suicide risk, as determined by meeting any of the following criteria:

    1. Suicide attempt within the six months prior to Baseline.
    2. Suicidal ideation as defined by a positive response to Question 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation section.
    3. Significant risk of suicide, as judged by the site Investigator.
  17. History of multiple concussions, significant head trauma, or objective change in neuropsychological function within the last five years.
  18. History of human immunodeficiency virus (HIV).
  19. History of alcohol or drug abuse/dependence within the last five years.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04931459

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Contact: Clinical Trials 463-235-7482

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United States, Arizona
Clinical Endpoints Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Brian Martin    480-566-9090   
Contact: Donnell Carmichael, Psy.D.    480-566-9090   
Principal Investigator: Allan Block, MD         
United States, Florida
Velocity Clinical Research Recruiting
Hallandale Beach, Florida, United States, 33009
Contact: Evelyn Quiles    954-455-5757   
Principal Investigator: Beth Safirstein, MD         
Charter Research Recruiting
Lady Lake, Florida, United States, 32159
Contact: Tina Blair    352-775-1000   
Principal Investigator: Jeffrey Norton, MD         
Combined Research Orlando Phase I-IV Recruiting
Orlando, Florida, United States, 32807
Contact: Yenilady Estevez    407-440-4493   
Principal Investigator: Eric Carbonell, MD         
Santos Research Center Recruiting
Tampa, Florida, United States, 33615
Contact: Sherley R. Valdez-Arroyo, MD    813-249-9100   
Principal Investigator: Sherley R Valdez-Arroyo, MD         
United States, Georgia
iResearch Atlanta Recruiting
Decatur, Georgia, United States, 30030
Contact: Tamara Nelson    404-537-1281   
Contact: Monica Mahathre    404-537-1281   
Principal Investigator: Kimball Johnson, MD         
United States, Ohio
Neuro-Behavioral Clinical Research, Inc. Not yet recruiting
North Canton, Ohio, United States, 44720
Contact: Megan Smith, MA    330-493-1118   
Contact: Shandell Mooney, RN    330-493-1118   
Principal Investigator: Shishuka Malhotra, MD         
Sponsors and Collaborators
Acumen Pharmaceuticals
National Institute on Aging (NIA)
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Principal Investigator: Eric Siemers, MD Acumen Pharmaceuticals, Inc.
Study Director: James Senetar, PharmD Acumen Pharmaceuticals, Inc.
Study Director: Russell Barton, MS Acumen Pharmaceuticals, Inc.
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Responsible Party: Acumen Pharmaceuticals Identifier: NCT04931459    
Other Study ID Numbers: ACU-001
3U01AG053247 ( U.S. NIH Grant/Contract )
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: November 19, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Acumen Pharmaceuticals:
Alzheimer's Diseases
Mild Cognitive Impairment
Mild dementia
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders