A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy And Safety Trial Of Bapineuzumab (Aab-001, Eln115727) In Subjects With Mild to Moderate Alzheimer Disease Who Are Apolipoprotein E 4 Non-carriers
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 901
- 试验地点
- 331
- 主要终点
- The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78
研究概览
简要总结
This is a study to evaluate the efficacy and safety of multiple doses of bapineuzumab in patients with mild to moderate Alzheimer Disease. Patients will receive either bapineuzumab or placebo. Each patient's participation will last approximately 1.5 years.
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 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of probable Alzheimer Disease (AD), with Mini Mental State Examination (MMSE) score of 16-26, and brain magnetic resonance imaging (MRI) consistent with the diagnosis of AD
- •Concurrent use of cholinesterase inhibitor or memantine allowed, if stable
- •Caregiver will participate and be able to attend clinic visits with patient
排除标准
- •Significant neurological disease other than AD
- •Major psychiatric disorder
- •Contraindication to undergo brain MRI [e.g., pacemaker, cerebrospinal fluid (CSF) shunt, or foreign metal objects in the body]
- •Women of childbearing potential
研究组 & 干预措施
Bapineuzumab 0.5 mg/kg
干预措施: bapineuzumab (Drug)
Bapineuzumab 1.0 mg/kg
干预措施: bapineuzumab (Drug)
Placebo
干预措施: placebo (Drug)
结局指标
主要结局
The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78
时间窗: 78 weeks
The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4) constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8) remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension. This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.
The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78
时间窗: 78 weeks
The DAD measures instrumental and basic activities of daily living in participants with Alzheimer's Disease (AD). The DAD is administered to the participants'caregiver in the form of an interview. This scale had to be administered by a trained and certified global rater who did not have access to any information regarding adverse events experienced by the participant. This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement.
次要结局
- Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)(78 weeks)
- Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78(78 Weeks)
- The Change From Baseline in Phospho-tau Levels in the Cerebrospinal Fluid (CSF) at Week 71.(71 Weeks)
- Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78(39 Weeks)
- Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan)(78 Weeks)
- Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan)(78 weeks)
- Change From Baseline in Dependence Scale Total Score at Week 78(78 Weeks)
- Time to Median Placebo Deterioration on DAD Total Score(78 Weeks)
- Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)(78 Weeks)
- Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan)(78 Weeks)
- The Change From Baseline in Brain Amyloid Burden at Week 71.(71 Weeks)
- The Change From Baseline in Brain Volume at Week 71(71 Weeks)
- Divergence of Effect on the DAD Total Scores From Week 39 to Week 78(39 weeks)
- Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)(78 Weeks)
- Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan)(78 Weeks)