A Phase 1, Open-label, Multi-part Study to Evaluate Pharmacokinetics, Absolute Bioavailability, Safety, Tolerability, and Immunogenicity of Single-Dose of BMS-986446 Following Intravenous and Subcutaneous Administrations in Healthy Adults and Multiple Doses of BMS-986446 in Participants With Early Alzheimer's Disease.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 7
- 主要终点
- Half-life (T-HALF)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must have a BMI of 18.0 to 35.0 kg/m
- •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.
排除标准
- •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.
研究组 & 干预措施
Panel A1: BMS986446
干预措施: BMS-986446 (Drug)
Panel B2: BMS986446
干预措施: BMS-986446 (Drug)
Panel A2: BMS986446
干预措施: BMS-986446 (Drug)
Panel A3: BMS986446
干预措施: BMS-986446 (Drug)
Panel B1: BMS986446
干预措施: BMS-986446 (Drug)
Panel C1: BMS986446
干预措施: BMS-986446 (Drug)
结局指标
主要结局
Half-life (T-HALF)
时间窗: Up to approximately 5 months
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
时间窗: Up to approximately 5 months
Absolute bioavailability estimated from GMR of AUC(INF) of BMS-986446 after intravenous (IV) infusion
时间窗: Up to approximately 5 months
Maximum observed concentration (Cmax)
时间窗: Up to approximately 5 months
Time of maximum observed concentration (Tmax)
时间窗: Up to approximately 5 months
Area under the concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))
时间窗: Up to approximately 5 months
Area under the serum concentration-time curve from time zero to 672 hours (AUC(0-672))
时间窗: Up to approximately 5 months
AUC(INF)
时间窗: Up to approximately 5 months
Apparent total body clearance in SC administration (CLT/F)
时间窗: Up to approximately 5 months
Total body clearance in IV infusion (CLT)
时间窗: Up to approximately 5 months
Apparent volume of distribution of terminal phase in SC administration (Vz/F)
时间窗: Up to approximately 5 months
Volume of distribution of terminal phase (VZ)
时间窗: Up to approximately 5 months
次要结局
- Incidence of anti-drug antibody (ADA)(Up to approximately 5 months)
- 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)
- Local tolerance evaluation(Up to approximately 5 months)
- 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)
- Tmax(Up to approximately 5 months)
- AUC(0-T)(Up to approximately 5 months)
- AUC(0-672)(Up to approximately 5 months)
- AUC(INF)(Up to approximately 5 months)
- T-HALF(Up to approximately 5 months)
- CLT/F(Up to approximately 5 months)
- Vz/F(Up to approximately 5 months)
- Trough observed plasma concentration (Ctrough)(Up to approximately 5 months)
- Concentration at the end of a dosing interval (Ctau)(Up to approximately 5 months)
- Area under the concentration-time curve within a dosing interval (AUC(TAU))(Up to approximately 5 months)