A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects With Early Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 1,653
- 试验地点
- 155
- 主要终点
- Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78
研究概览
简要总结
The primary objective of the study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with early AD. Secondary objectives are to assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (13 items) [ADAS-Cog 13], and AD Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) [ADCS-ADL-MCI].
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
- •Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have:
- •A Clinical Dementia Rating (CDR)-Global Score of 0.
- •Objective evidence of cognitive impairment at screening
- •An MMSE score between 24 and 30 (inclusive)
- •Must have a positive amyloid Positron Emission Tomography (PET) scan
- •Must consent to apolipoprotein E (ApoE) genotyping
- •If using drugs to treat symptoms related to AD, doses must be stable for at least 8 weeks prior to screening visit 1
- •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 subject's cognitive impairment
- •Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year
- •Clinically significant unstable psychiatric illness in past 6 months
- •History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically 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
- •Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
- •Any contraindications to brain magnetic resonance imaging (MRI) or PET scans
- •Alcohol or substance abuse in past 1 year
- •Taking blood thinners (except for aspirin at a prophylactic dose or less)
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
High Dose
Monthly intravenous (IV) infusion
干预措施: Placebo (Drug)
Low Dose
Monthly intravenous (IV) infusion
干预措施: Aducanumab (BIIB037) (Drug)
Low Dose
Monthly intravenous (IV) infusion
干预措施: Placebo (Drug)
High Dose
Monthly intravenous (IV) infusion
干预措施: Aducanumab (BIIB037) (Drug)
结局指标
主要结局
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78
时间窗: Baseline, Week 78
CDR-SB integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic patient examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. Prespecified severity anchors range from none = 0, questionable = 0.5, mild = 1, moderate = 2 to severe = 3 (the personal care domain omits the 0.5 score). "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18 that can change in increments of 0.5 or greater. Higher scores indicate greater disease severity. Mixed model for repeated measures (MMRM) analysis was used to analyze change from baseline in CDR-SB. A positive change from baseline indicates clinical decline.
次要结局
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at Week 78(Baseline, Week 78)
- Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment Version) (ADCS-ADL-MCI) Score at Week 78(Baseline, Week 78)
- Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 78(Baseline, Week 78)