A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Aducanumab (BIIB037) in Japanese Subjects With Mild to Moderate Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Clinically significant changes in vital signs and 12-lead electrocardiogram (ECG) data; abnormalities in neurological and physical examinations
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of single and multiple intravenous (IV) infusions of Aducanumab in Japanese participants with mild to moderate Alzheimer's Disease (AD). The secondary objectives of this study are as follows: To evaluate the serum pharmacokinetics (PK) of Aducanumab after single and multiple intravenous (IV) infusions of Aducanumab; To evaluate the effect of single and multiple IV infusions of Aducanumab on immunogenicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be ambulatory
- •Must have a clinical diagnosis of mild to moderate AD
- •Must be in good health as determined by the Investigator, based on medical history and Screening assessments
- •Must have a caregiver who, understands the study and assents to accompany the subject to all study site visits, provide information to the Investigator/study site staff, specifically about cognitive abilities and AEs/SAEs and return for per-protocol follow-up visits and procedures
- •Must consent to blood sample collection for deoxyribonucleic acid (DNA; genotyping) and ribonucleic acid (RNA; for potential future analysis).
排除标准
- •Any medical or neurological condition (other than AD) that in the opinion of the Investigator could be a contributing cause of the subject's dementia
- •Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening
- •Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within the 3 months prior to Day 1
- •History of unstable angina, myocardial infarction, chronic heart failure
- •Chronic, uncontrolled hypertension
- •History of seizure within 3 years prior to Screening
- •History within the past 6 months or evidence of clinically significant psychiatric illness
- •History of severe allergic or anaphylactic reactions, or history of hypersensitivity to any of the inactive ingredients in the drug product
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Cohort 1
IV infusion in cohorts assigned to low dose 1; 1 participant per cohort will receive placebo
干预措施: Aducanumab (Drug)
Cohort 1
IV infusion in cohorts assigned to low dose 1; 1 participant per cohort will receive placebo
干预措施: Placebo (Drug)
Cohort 4
IV infusion in cohorts assigned to mid dose; 1 participant per cohort will receive placebo
干预措施: Aducanumab (Drug)
Cohort 2
IV infusion in cohorts assigned to low dose 2; 1 participant per cohort will receive placebo
干预措施: Aducanumab (Drug)
Cohort 2
IV infusion in cohorts assigned to low dose 2; 1 participant per cohort will receive placebo
干预措施: Placebo (Drug)
Cohort 3
IV infusion in cohorts assigned to high dose; 1 participant per cohort will receive placebo
干预措施: Aducanumab (Drug)
Cohort 3
IV infusion in cohorts assigned to high dose; 1 participant per cohort will receive placebo
干预措施: Placebo (Drug)
Cohort 4
IV infusion in cohorts assigned to mid dose; 1 participant per cohort will receive placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Clinically significant changes in vital signs and 12-lead electrocardiogram (ECG) data; abnormalities in neurological and physical examinations
时间窗: Up to week 42
Brain magnetic resonance imaging (MRI) findings to assess amyloid-related imaging abnormalities (ARIA), including incidence of ARIA-E (edema) or ARIA-H (hemosiderosis)
时间窗: Up to week 42
Incidence and nature of adverse events (AE) / serious adverse events(SAE)
时间窗: Up to week 42
次要结局
- Area under the concentration-time curve (AUC) from time zero extrapolated to infinity (AUC0-∞)(Up to 8 weeks post dosing)
- AUC from time zero to time of the last measurable concentration (AUC0-last)(Up to 8 weeks post dosing)
- Maximum observed concentration (Cmax)(Up to 8 weeks post dosing)
- Time to Cmax (Tmax)(Up to 8 weeks post dosing)
- Elimination half-life (t1/2)(Up to 8 weeks post dosing)
- Volume of distribution at steady state (Vss)(Up to 8 weeks post dosing)
- Clearance (CL) after a single IV infusion of aducanumab(Up to 8 weeks post dosing)
- Incidence of anti-aducanumab antibodies in serum(Up to week 42)