Starting soon
Phase 1
A Study to Evaluate the Drug Levels, Absolute Bioavailability, Safety, Tolerability, and Immunogenicity of Single-Dose of BMS-986446 in Healthy Adults After Single-dose Administration, and Participants With Early Alzheimer's Disease After Multiple Dose Administration
Condition(s) studied
Alzheimer's DiseaseHealthy Participants
Investigational drug(s) / intervention(s)
BMS-986446
BMS-986446: Specified dose on specified days
Study summary
The purpose of this study is to evaluate the drug levels, absolute bioavailability, safety, tolerability, and immunogenicity of single-Dose of BMS-986446 in healthy adults after single-dose administration, and participants with early Alzheimer's Disease after multiple dose administration
Eligibility
Inclusion Criteria
* Participants must have a BMI of 18.0 to 35.0 kg/m2.
* For Parts A and B: Participants must be healthy as determined by medical history, Physical Examination (PE), neurological examination, vital signs, 12-lead ECG, Columbia Suicide-Severity Rating Scale (C-SSRS), and clinical laboratory evaluations.
* For Part C: Participants must meet diagnostic criteria for MCI or mild AD dementia, consistent with the National Institute on Aging and the Alzheimer's Association (NIA-AA) diagnostic criteria.
* For Part C: Participants must have an Mini Mental State Examination (MMSE) score of ≥ 20 to 28 (inclusive).
* For Part C: Participants must have evidence of positive plasma pTau217.
Exclusion Criteria
* For Parts A and B: Participants must not have a general history of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, immune-mediated disorder, hematological, ongoing allergic disorder requiring treatment, metabolic disorder, cancer, or cirrhosis.
* For Parts A and B: Participants must not have donated or lost 500 mL blood or more within 60 days prior to study intervention administration.
* For Part C: Participants must not have a neurological condition that in the opinion of the investigator may be contributing to cognitive impairment aside from the AD diagnosis, including but not limited to: Parkinson's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, long COVID, or baseline intellectual disability.
* For Part C: Participants must not have any current primary psychiatric diagnosis (eg, major depression, schizoaffective disorder or bipolar disorder) other than AD or symptoms (eg, hallucination or delusions).
* Other protocol-defined Inclusion/Exclusion criteria apply.
Primary outcome measure(s)
- Absolute bioavailability estimated from geometric mean ratio (GMR) of area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-986446 after subcutaneous (SC) infusion — Up to approximately 5 months
- Absolute bioavailability estimated from GMR of AUC(INF) of BMS-986446 after intravenous (IV) infusion — Up to approximately 5 months
- Maximum observed concentration (Cmax) — Up to approximately 5 months
- Time of maximum observed concentration (Tmax) — Up to approximately 5 months
- Area under the concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) — Up to approximately 5 months
- Area under the serum concentration-time curve from time zero to 672 hours (AUC(0-672)) — Up to approximately 5 months
- AUC(INF) — Up to approximately 5 months
- Half-life (T-HALF) — Up to approximately 5 months
- Apparent total body clearance in SC administration (CLT/F) — Up to approximately 5 months
- Total body clearance in IV infusion (CLT) — Up to approximately 5 months
- Apparent volume of distribution of terminal phase in SC administration (Vz/F) — Up to approximately 5 months
- Volume of distribution of terminal phase (VZ) — Up to approximately 5 months
Trial sites (1)
| Facility | City | Region | Status |
| Local Institution - 0001 |
Anaheim |
California |
|