Alzheimer's Disease, Healthy Participants
Conditions
Keywords
Healthy Participants, Early Alzheimer's Disease, BMS-986446, Subcutaneous Administration, IV administration
Brief 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
Interventions
DRUGBMS-986446
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AEs) | Up to approximately 5 months | — |
| Serious adverse events (SAEs) | Up to approximately 5 months | — |
| AEs reported as related to BMS-986446 | Up to approximately 5 months | — |
| Incidence of anti-drug antibody (ADA) | Up to approximately 5 months | — |
| Local tolerance evaluation | Up to approximately 5 months | This evaluation will assess pain, itching, burning, pressure, and soreness/tenderness (using a Numeric Rating Scale) at the injection site location. |
| GMR of Panel B1 vs Panel A3 for Cmax | Up to approximately 5 months | — |
| GMR of Panel B1 vs Panel A3 for area under the concentration-time curve (AUC) | Up to approximately 5 months | — |
| GMR of Panel B2 vs Panel A3 for Cmax | Up to approximately 5 months | — |
| GMR of Panel B2 vs Panel A3 for AUC | Up to approximately 5 months | — |
| Cmax | Up to approximately 5 months | Panel B1, Panel B2, Panel C1 |
| Tmax | Up to approximately 5 months | Panel B1, Panel B2, Panel C1 |
| AUC(0-T) | Up to approximately 5 months | Panel B1, Panel B2 |
| AUC(0-672) | Up to approximately 5 months | Panel B1, Panel B2 |
| AUC(INF) | Up to approximately 5 months | Panel B1, Panel B2 |
| T-HALF | Up to approximately 5 months | Panel B1, Panel B2, Panel C1 |
| CLT/F | Up to approximately 5 months | Panel B1, Panel B2, Panel C1 |
| Vz/F | Up to approximately 5 months | Panel B1, Panel B2, Panel C1 |
| Trough observed plasma concentration (Ctrough) | Up to approximately 5 months | Panel C1 |
| Concentration at the end of a dosing interval (Ctau) | Up to approximately 5 months | Panel C1 |
| Area under the concentration-time curve within a dosing interval (AUC(TAU)) | Up to approximately 5 months | Panel C1 |
Countries
United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed