A Randomized, Double-Blinded, Placebo-Controlled Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB037 in Subjects With Prodromal or Mild Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 197
- 试验地点
- 32
- 主要终点
- Number of Participants with Adverse Events
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of multiple doses of Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) in participants with prodromal or mild Alzheimer's Disease (AD). The secondary objectives of this study are to assess the effect on cerebral amyloid plaque content as measured by florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging, to assess the multiple dose serum concentrations of Aducanumab and to evaluate the immunogenicity of Aducanumab after multiple dose administration in this population.
详细描述
The study consists of a placebo-controlled period to study week 54, followed by a long-term extension to study week 518. The placebo-controlled period is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel, 2 additional treatment arms beginning in parallel, and the last 2 treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period for up to 42 additional doses of active drug for the first 3 years of LTE. Furthermore, up until the last participant in Arms 8 and 9 has had his or her last dose in the fifth year of the LTE, eligible participants will be able to continue treatment beyond the third year of the LTE.
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
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be ambulatory.
- •Participants must meet the following core clinical criteria as determined by the Investigator:
- •Prodromal Alzheimer's Disease (AD) (all of the criteria must apply):
- •Mini Mental State Examination (MMSE) scores between 24-30 (inclusive)
- •a spontaneous memory complaint
- •objective memory loss defined as a free recall score of ≤27 on the Free and Cued Selective Reminding Test (FCSRT)
- •a global Clinical Dementia Rating Scale (CDR) score of 0.5
- •absence of significant levels of impairment in other cognitive domains
- •essentially preserved activities of daily living, and an absence of dementia. OR
- •Mild Alzheimer's Disease (AD) criteria (all criteria must apply):
- •Mini Mental State Examination (MMSE) scores between 20-26 (inclusive)
- •a global Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0
- •meeting the National Institute on Aging-Alzheimer's Association core clinical criteria for probable AD.
- •Participants must have a positive florbetapir positron emission tomography (PET) amyloid scan.
- •Participants must consent to apolipoprotein E (ApoE) genotyping.
- •Apart from clinical diagnosis of Alzheimer's Disease (AD), participant must be in good health.
- •Must have a reliable informant or caregiver.
排除标准
- •Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the participant's cognitive impairment.
- •Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year.
- •Clinically significant psychiatric illness in past 6 months.
- •Seizure in the past 3 years.
- •Poorly controlled diabetes mellitus.
- •History of unstable angina, myocardial infarction, chronic heart failure, or clinical significant conduction abnormalities within 1 year prior to Screening.
- •Indication of impaired renal or liver function.
- •Have human immunodeficiency virus (HIV) infection.
- •Have a significant systematic illness or infection in past 30 days.
- •Brain MRI showing evidence of acute or sub-acute micro or macrohemorrhage, greater than 4 microhemorrhages, cortical infarct or greater than one 1 lunar infarct.
- •Any contraindications to brain MRI or positron emission tomography (PET) scans.
- •Negative positron emission tomography (PET) scan with any amyloid-targeting ligand within 48 weeks of Screening.
- •Clinically significant 12-lead electrocardiogram (ECG) abnormalities.
- •Alcohol or substance abuse in past 1 year.
- •Taking blood thinners (except for aspirin at a prophylactic dose or less)
- •Have changes in medications or doses of medication in past 4 weeks.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Low-dose #1 Aducanumab
Intravenous doses of low-dose level #1 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Low-dose #2 Aducanumab
Intravenous doses of low-dose level #2 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Placebo (low dose group)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Placebo (low dose group)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Placebo (Drug)
Mid-dose Aducanumab
Intravenous doses of mid-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Placebo (mid dose group)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Placebo (mid dose group)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Placebo (Drug)
High-dose Aducanumab
Intravenous doses of high-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Placebo (high dose group)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Placebo (high dose group)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Placebo (Drug)
Aducanumab Titration
Intravenous doses of Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) (Drug)
Placebo (Titration Group)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with Adverse Events
时间窗: Baseline to week 518
次要结局
- Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.(Up to week 518)
- Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas.(Day 1, Weeks 26, 54, End of year 2, 3, and 4)
- Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab(Up to week 518)