A Multiple Ascending Dose Study in Healthy Volunteers and Patients With Alzheimer's Disease

NCT05804383 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: ALX-923-102R01AG073177
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase 1b Multiple Ascending Dose Study of the Safety and Tolerability of BMS-984923 in Healthy Older Adults and Patients with Alzheimer's Disease

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease; Synapses; Cognition; Neuroprotection; Neurons; mGluR5

Outcome Measures

Primary Outcomes (4)

• Stage 1 and Stage 2 Incidence of treatment-emergent adverse events (TEAEs)

  Safety

  Up to 10 days after last dose

• Stage 1 and Stage 2 Incidence of clinically significant lab abnormalities

  Safety

  Up to 10 days after last dose

• Stage 1 Incidence of clinically significant changes in safety assessments

  Vital signs, physical exam, electrocardiogram \[ECG\], Neuropsychiatric Inventory-Questionnaire \[NPI Q\], Geriatric Depression Scale \[GDS\], Glasgow Coma Scale \[GCS\], Montreal Cognitive Assessment \[MOCA\])

  Up to 10 days after last dose

• Stage 2 Incidence of clinically significant changes in safety assessments

  Vital signs, physical exam, ECG, NPI Q, GDS, MOCA, and Functional Assessment Questionnaire \[FAQ\])

  Up to 10 days after last dose

Secondary Outcomes (4)

• Stage 1 and Stage 2 Trough plasma drug concentration at steady state

  Up to 10 days after last dose

• Stage 1 and Stage 2 Area under the curve for the first 24 hours of dosing (AUC24h) and at steady state as determined by PK modeling

  Up to 10 days after last dose

• Stage 2 Change from baseline in synaptic density PET

  Up to 24 hours after last dose

• Stage 2 Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale 14 Score range of 0-90, with higher scores indicating greater cognitive impairment.

  Up to 7 days after the last dose

Study Arms (11)

50 mg active

EXPERIMENTAL

BMS-984923 50 mg in healthy participants

Drug: BMS-984923

50 mg Placebo

PLACEBO COMPARATOR

Placebo 50 mg in healthy participants

Drug: Placebo

100 mg Active

EXPERIMENTAL

BMS-984923 100 mg in healthy participants

Drug: BMS-984923

100 mg Placebo

PLACEBO COMPARATOR

Placebo 100 mg in healthy participants

Drug: Placebo

100 mg Active 20d

EXPERIMENTAL

BMS-984923 100 mg in healthy participants 20 days

Drug: BMS-984923

100 mg Placebo 20d

PLACEBO COMPARATOR

Placebo 100 mg in healthy participants 20 days

Drug: Placebo

150 mg Active 20d

EXPERIMENTAL

BMS-984923 150 mg in healthy participants 20 days

Drug: BMS-984923

150 mg Placebo 20d

PLACEBO COMPARATOR

Placebo 150 mg in healthy participants 20 days

Drug: Placebo

50 mg Active-AD

EXPERIMENTAL

BMS-984923 50 mg

Drug: BMS-984923

100 mg Active-AD

EXPERIMENTAL

BMS-984923 100 mg

Drug: BMS-984923

Placebo-AD

PLACEBO COMPARATOR

Placebo matching

Drug: Placebo

Interventions

BMS-984923 DRUG

Capsules

Also known as: Active

100 mg Active; 100 mg Active 20d; 100 mg Active-AD; 150 mg Active 20d; 50 mg Active-AD; 50 mg active

Placebo DRUG

Capsules

Also known as: Inactive

100 mg Placebo; 100 mg Placebo 20d; 150 mg Placebo 20d; 50 mg Placebo; Placebo-AD

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women between the ages of 50 and 80 years, inclusive
• No history of cognitive impairment
• Capable of providing written informed consent and willing to comply with all study requirements and procedures
• Participant is not pregnant, lactating, or of childbearing potential
• Non-childbearing potential for women is defined as postmenopausal (last natural menses greater than 24 months prior; menopausal status will be documented with serum follicle-stimulating hormone (FSH) or documentation of bilateral tubal ligation or hysterectomy
• Male participants who are sexually active with a woman of childbearing potential must agree to use condoms during the trial and for 3 months after the last dose unless the woman is using an acceptable means of birth control. Acceptable forms of birth control include abstinence, birth control pills, or any double combination of intrauterine device (IUD), male or female condom, diaphragm, sponge, and cervical cap.
• Male participants must also agree not to donate sperm for 90 days after the last dose.
• Montreal Cognitive Assessment (MOCA) \>25

You may not qualify if:

• Body mass index (BMI) \>38 kg/m2 or body weight \<50 kg.
• Any significant neurologic disease, such as AD, Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
• A current Diagnostic and Statistical Manual of Mental Disorders, Fifth revision (DSM V) diagnosis of active major depression, schizophrenia or bipolar disorder. Participants with depressive symptoms successfully managed by a stable dose of an antidepressant are allowed entry.
• Current nicotine use or positive urine cotinine test.
• History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
• Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the PI, may either put the participant at risk because of participation in the study, or influence the results, or the participant's ability to participate in the study.
• Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs (e.g., small bowel disease, Crohn's disease, celiac disease, or liver disease.)
• Seropositive for human immunodeficiency virus (HIV).
• History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen \[HbsAg\] or anti-hepatitis C \[HCV\] antibody).
• Use of psychoactive medications (typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity) within 2 weeks or 5 half-lives (whichever is greater) prior to study drug administration and for the duration of the trial.
• Use of medications with potential drug-drug interactions (see Appendix A for a list of these medications) within 2 weeks or 5 half-lives (whichever is greater) prior to study drug administration and for the duration of the trial.
• Use of anticoagulants within 30 days or 5 half-lives (whichever is greater) prior to study drug administration and for the duration of the trial.
• Use of another investigational agent within 30 days or 5 half-lives (whichever is greater) prior to screening and for the duration of the trial.
• Neutropenia defined as absolute neutrophils count of \<1,500/microliter.
• Thrombocytopenia defined as platelet count \<100,000/microliter.

Sponsors & Collaborators

• Allyx Therapeutics: lead
• Yale University: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Yale University

New Haven, Connecticut, 06511, United States

Location

Spaulding Clinical Research

West Bend, Wisconsin, 53095, United States

Location

Related Publications (2)

• Haas LT, Salazar SV, Smith LM, Zhao HR, Cox TO, Herber CS, Degnan AP, Balakrishnan A, Macor JE, Albright CF, Strittmatter SM. Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer's Mouse Phenotypes. Cell Rep. 2017 Jul 5;20(1):76-88. doi: 10.1016/j.celrep.2017.06.023.

  PMID: 28683325 BACKGROUND

• Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Perez-Canamas A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Sci Transl Med. 2022 Jun;14(647):eabi8593. doi: 10.1126/scitranslmed.abi8593. Epub 2022 Jun 1.

  PMID: 35648810 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Exercise

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Adam Mecca, MD, PhD

  Yale University

  STUDY DIRECTOR

• Stephanie Post, MD

  Spaulding Clinical Research (Stage 1)

  PRINCIPAL INVESTIGATOR

• Adam Mecca, MD, PhD

  Yale University (Stage 2)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo capsules
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2023
• First Posted: April 7, 2023
• Study Start: March 28, 2023
• Primary Completion: July 15, 2025
• Study Completion: October 15, 2025
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (2)