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Alzheimer's DiseasePhase 1NCT05804383

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

A Phase 1 study testing BMS-984923 in people with Alzheimer's Disease, run by Allyx Therapeutics at 2 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

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 Read more about this study

Who is it for?
Ages 50 to 80 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
BMS-984923
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
51 participants
Where
2 sitesUnited States
Study dates
28 Mar 2023to 15 Oct 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 50 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Male participants must also agree not to donate sperm for 90 days after the last dose.
  • Montreal Cognitive Assessment (MOCA) >25
  • Men or women between the ages of 50 and 85 years, inclusive, at the time of first dose of investigational product (IP).
  • Diagnosis of either amnestic mild cognitive impairment (aMCI) or mild dementia due to AD as defined by
  • Mild dementia due to AD
  • National Institute on Aging (NIA)-Alzheimer's Association core clinical criteria for dementia due to probable AD (McKhann 2011) and,
  • Mini Mental Status Exam (MMSE) score between 18 and 26 (inclusive)
  • Clinical Dementia Rating (CDR) global score of 0.5 or 1
  • aMCI due to AD
  • Subjective memory complaint preferably corroborated by an informant and,
  • Normal activities of daily living
  • CDR global score of 0.5
  • aMCI (Petersen 2004) as evidenced by abnormal memory function documented by scoring 1.5 SD below the education adjusted cutoff on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised (the maximum score is 25), and
  • 8 for 16 or more years of education
  • 4 for 8 15 years of education
  • 2 for 0 7 years of education
  • Stable pharmacological treatment of any other chronic conditions for at least 4 weeks prior to baseline.
  • Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of AD as defined in Criteria 2 and without findings of significant exclusionary abnormalities (see Section 6.2.2, exclusion criteria, Number 4).
  • Study partner is available who has frequent contact with the participant (e.g., average of 10 hours per week or more), and can participate in all study partner assessments for the duration of the protocol.
  • Generally healthy with mobility (ambulatory or ambulatory-aided, i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient for compliance with testing procedures as determined by the PI.
  • Must be able to complete all screening evaluations
  • Living at home or in the community (assisted living acceptable)
  • Ability to swallow study medication.
  • Modified Hachinski score ≤4
  • 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 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 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.

Who cannot join

  • 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.
  • Positive urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, tetrahydrocannabinol (THC), ethanol or cotinine (stable prescribed amphetamines or benzodiazepines for a non-exclusionary medical condition are permitted) or positive alcohol breathalyzer test
  • Current nicotine use or positive urine cotinine test.
  • History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
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  • 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.
  • Clinically significant abnormalities in screening laboratories, including aspartate aminotransferase (AST) >1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) >1.5 times ULN; total bilirubin >1.5 times ULN; serum creatinine >2.0 times ULN.
  • Geriatric Depression Scale (GDS) score of ≥5 and symptoms consistent with a current episode of major depression.
  • Hospitalization or change of chronic concomitant medication within 4 weeks prior to baseline
  • BMI >38 kg/m2 or body weight <50 kg
  • Any contraindications for MRI studies, such as claustrophobia, the presence of metal (ferromagnetic) implants, metal fragments or foreign objects in the eyes, skin, or body or a cardiac pacemaker.
  • Living in a continuous care nursing facility
  • Screening MRI of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct >1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, or space-occupying lesion (e.g., abscess or brain tumor such as meningioma)
  • Clinical or laboratory findings consistent with:
  • Other primary neurodegenerative disease or cognitive disorder (Lewy body disease, frontotemporal lobar disease, Huntington's disease, Jacob-Creutzfeld Disease, Down's syndrome, Parkinson's disease, amyotrophic lateral sclerosis, etc.)
  • Seizure disorder
  • Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 deficiency, other laboratory abnormalities, etc.)
  • A current 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.
  • Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease that in the opinion of the PI, may either put the participant at risk because of participation in the study, or influence the results, or impair the participant's ability to participate in the study.
  • Disability that may prevent the participant from completing all study requirements (e.g., blindness, deafness, severe language difficulty, etc.)
  • 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.)
  • Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine) for 12 weeks prior to baseline
  • History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
  • Suspected or known allergy to any components of the study treatments
  • Any condition, which in the opinion of the investigator or Project Director (PD) makes the participant unsuitable for inclusion
  • Clinically significant abnormalities in B12 or thyroid function tests (TFTs) that might interfere with the study
  • 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 investigational amyloid lowering therapies within 2 months 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.
  • Clinically significant abnormalities in screening laboratories, including AST >1.5 times ULN; ALT >1.5 times ULN; total bilirubin >1.5 times ULN; serum creatinine >2.0 times ULN
  • GDS score of ≥5 and symptoms consistent with a current episode of major depression.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Yale University

    New Haven, Connecticut, 06511

  • Spaulding Clinical Research

    West Bend, Wisconsin, 53095

Other trials in United States

About this study

Official title: 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

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

Read the detailed description

This double-blind placebo-controlled study will be completed in 2 stages. The first stage will evaluate 10-days of BID dosing in four ascending dose cohorts in healthy older adults and Stage 2 will examine BMS-984923 dosed BID for 28 days at two dose levels in comparison to Placebo in participants with early AD.

This research study will assess the safety and tolerability of multiple doses of BMS-984923 for the treatment of early Alzheimer's Disease (AD) and investigate the use of synaptic density, measured with positron emission tomography (PET), as an early marker of therapeutic response to treatments that target synapse restoration.

Being tested
BMS-984923, Placebo
Keywords
Alzheimer's Disease, Synapses, Cognition, Neuroprotection, Neurons, mGluR5
Medical subject headings
Alzheimer Disease

What participants receive

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

  • BMS-984923Drug

    Also called Active

    Capsules

  • PlaceboDrug

    Also called Inactive

    Capsules

Study groups in NCT05804383
Study groupRoleWhat they receive
50 mg activeExperimentalBMS-984923 50 mg in healthy participants
Receives: Drug: BMS-984923
50 mg PlaceboPlacebo comparatorPlacebo 50 mg in healthy participants
Receives: Drug: Placebo
100 mg ActiveExperimentalBMS-984923 100 mg in healthy participants
Receives: Drug: BMS-984923
100 mg PlaceboPlacebo comparatorPlacebo 100 mg in healthy participants
Receives: Drug: Placebo
100 mg Active 20dExperimentalBMS-984923 100 mg in healthy participants 20 days
Receives: Drug: BMS-984923
100 mg Placebo 20dPlacebo comparatorPlacebo 100 mg in healthy participants 20 days
Receives: Drug: Placebo
150 mg Active 20dExperimentalBMS-984923 150 mg in healthy participants 20 days
Receives: Drug: BMS-984923
150 mg Placebo 20dPlacebo comparatorPlacebo 150 mg in healthy participants 20 days
Receives: Drug: Placebo
50 mg Active-ADExperimentalBMS-984923 50 mg
Receives: Drug: BMS-984923
100 mg Active-ADExperimentalBMS-984923 100 mg
Receives: Drug: BMS-984923
Placebo-ADPlacebo comparatorPlacebo matching
Receives: Drug: Placebo

What is being measured

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

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

    Safety

    Measured: Up to 10 days after last dose

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

    Safety

    Measured: Up to 10 days after last dose

  3. 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])

    Measured: Up to 10 days after last dose

  4. Stage 2 Incidence of clinically significant changes in safety assessments

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

    Measured: Up to 10 days after last dose

Secondary outcomes (4)

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

    plasma concentration as determined by pharmacokinetic modeling

    Measured: Up to 10 days after last dose

  2. 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

    Total plasma concentration as determined by pharmacokinetic modeling

    Measured: Up to 10 days after last dose

  3. Stage 2 Change from baseline in synaptic density PET

    Pharmacodynamics

    Measured: Up to 24 hours after last dose

  4. 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.

    Assessment of cognitive impairment.

    Measured: Up to 7 days after the last dose

Timeline

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

  1. First posted7 Apr 2023
  2. Study start28 Mar 2023
  3. Primary completion15 Jul 2025
  4. Study completion15 Oct 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
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05804383
Sponsor's protocol ID
ALX-923-102
Other IDs
R01AG073177
Status last verified
Nov 2025
First submitted
27 Mar 2023
Last updated
6 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 28683325

  • 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.

    PubMed 35648810

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BMS-984923 in people with Alzheimer's Disease, run by Allyx Therapeutics at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Stage 1 and Stage 2 Incidence of treatment-emergent adverse events (TEAEs) (time frame: Up to 10 days after last dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05804383, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2025; AzTrials last refreshed its copy on 6 Nov 2026.

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