A Phase 2, Multicenter, Randomized, Parallel-Group, Double-Blind, Controlled Study of Aducanumab (BIIB037) in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Subjects With Asymptomatic Amyloid-Related Imaging Abnormalities
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 52
- 试验地点
- 21
- 主要终点
- Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA)
研究概览
简要总结
The primary objective of the study is to assess the safety impact of continuing aducanumab dosing in asymptomatic Amyloid-related Imaging Abnormalities (ARIA) in participants with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or with mild AD dementia. The secondary objective of the study is to characterize ARIA, from both the imaging and the clinical perspective and to characterize the safety, tolerability, pharmacokinetics (PK), and immunogenicity of aducanumab.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability of the participant or his/her legally authorized representative to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- •Must have at least 6 years of education or work experience to exclude mental deficits other than MCI due to AD or mild AD dementia.
- •Must have evidence of cerebral Aβ accumulation, based on a positive PET scan of the brain. Previously obtained positron emission tomography (PET) scan (within 12 months of screening) is permissible. Previous PET scan images must be submitted to the central imaging vendor to confirm that study inclusion criteria are met.
- •Must consent to apolipoprotein E (ApoE) genotyping.
- •Must meet all of the following clinical criteria for MCI due to AD or mild AD dementia according to NIA-AA criteria [Albert 2011; McKhann 2011], and must have the following: MCI due to AD (a CDR global score of 0.5, and an MMSE score between 24 and 30 (inclusive)), or Mild AD dementia (a CDR global score of 0.5 or 1, and as MMSE score between 20 and 26 (inclusive)).
排除标准
- •Any uncontrolled medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment (e.g., substance abuse, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, Lewy body dementia, frontotemporal dementia, head trauma).
- •Clinically significant unstable psychiatric illness (e.g., uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder) within 6 months prior to Screening.
- •Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening.
- •Vaccinations within 10 days prior to randomization (Day 1).
- •Female participants who are pregnant or currently breastfeeding.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Group 1
Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
干预措施: Aducanumab (Drug)
Group 1
Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
干预措施: Placebo (Drug)
Group 2
Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
干预措施: Aducanumab (Drug)
结局指标
主要结局
Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA)
时间窗: up to Week 54
次要结局
- Number of Participants With Antiaducanumab Antibodies in Serum(up to Week 54)
- Time to Resolution of Symptomatic ARIA(up to Week 54)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(up to Week 54)
- Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54(Baseline, Week 54)
- Number of Participants With Aducanumab Concentration in Serum(up to Week 54)
- Time to Onset of ARIA as Obtained on MRI(up to Week 54)
- Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI)(up to Week 54)
- Time to Resolution of ARIA as Obtained on MRI(up to Week 54)
- Number of Participants With Symptomatic ARIA by Severity(up to Week 54)
- Time to Onset of Symptomatic ARIA(up to Week 54)