Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,169
- 试验地点
- 108
- 主要终点
- Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score
研究概览
简要总结
The purpose of this study is to test whether an investigational drug called solanezumab can slow the progression of memory problems associated with brain amyloid (protein that forms plaques in the brains of people with Alzheimer Disease [AD]).
详细描述
The A4 study is a clinical trial for older individuals who have evidence of amyloid plaque build-up in their brains who may be at risk for memory loss and cognitive decline due to Alzheimer's disease. The A4 study will test an anti-amyloid investigational drug in older individuals who do not yet show symptoms of Alzheimer's disease cognitive impairment or dementia with the aim of slowing memory and cognitive decline. The A4 study will also test whether anti-amyloid treatment can delay the progression of AD related brain injury on imaging and other biomarkers.
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
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a Mini-Mental State Examination (MMSE) score at screening of 25 to 30
- •Has a global Clinical Dementia Rating (CDR) scale score at screening of 0
- •Has a Logical Memory II score at screening of 6 to 18
- •Has a florbetapir positron emission tomography (PET) scan that shows evidence of brain amyloid pathology at screening
- •Has a study partner that is willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or electronic communication)
排除标准
- •Is receiving a prescription acetylcholinesterase inhibitor (AChEI) and/or memantine at screening or baseline
- •Lacks good venous access, such that intravenous drug delivery or multiple blood draws would be precluded
- •Has current serious or unstable illness including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study
- •Has had a history within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis) or head trauma resulting in protracted loss of consciousness
- •Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of any in situ cancer that was appropriately treated and is being appropriately monitored, such as resected cutaneous squamous cell carcinoma in situ or in situ prostate cancer with normal prostate-specific antigen post-treatment
- •Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis)
- •Is clinically judged by the investigator to be at serious risk for suicide
- •Has a history within the past 2 years of major depression or bipolar disorder as defined by the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM)
- •Has a history within the past 5 years of chronic alcohol or drug abuse/dependence as defined by the most current version of the DSM
- •Open-Label Inclusion Criteria:
- •All participants who complete the placebo-controlled period will be allowed to continue into the open-label period
研究组 & 干预措施
Placebo/Solanezumab
Participants received placebo administered IV Q4W for approximately 240 weeks in double-blind period.
Participants begin open label extension period and received 1600 mg solanezumab Q4W for 204 weeks (from week 240 to week 444).
干预措施: Solanezumab (Drug)
Placebo/Solanezumab
Participants received placebo administered IV Q4W for approximately 240 weeks in double-blind period.
Participants begin open label extension period and received 1600 mg solanezumab Q4W for 204 weeks (from week 240 to week 444).
干预措施: Placebo (Drug)
Solanezumab/Solanezumab
Participants received 400 milligram (mg) solanezumab followed by 800 mg solanezumab and then 1600 milligram solanezumab administered intravenously (IV) every 4 weeks (Q4W) for approximately 240 weeks in double-blind placebo-controlled period.
Participants begin open label extension and received 1600 mg solanezumab Q4W for 204 weeks (from week 240 to week 444).
干预措施: Solanezumab (Drug)
结局指标
主要结局
Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score
时间窗: Baseline, Week 336
PACC has 4 components: Free and Cued Selective Reminding Test (0 (worst)-96 (best recall); Delayed Paragraph Recall test (Range 0 (worst)-25 (best recall); Wechsler Adult Intelligence scale: Digit Symbol Substitution Test (DSST): (ranges 0 \[none\]-91 \[best performance\]) and Mini Mental State Examination (Range 0 \[worst\] - 30 \[best performance\]). Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.
Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score
时间窗: Baseline, Week approximately 240
PACC has 4 components: Free and Cued Selective Reminding Test (0 (worst)-96 (best recall); Delayed Paragraph Recall test (Range 0 (worst)-25 (best recall); Wechsler Adult Intelligence scale: Digit Symbol Substitution Test (DSST): (ranges 0 \[none\]-91 \[best performance\]) and Mini Mental State Examination (Range 0 \[worst\] - 30 \[best performance\]). Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.
次要结局
- Change From Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score(Baseline, Week 336)
- Change From Baseline in Mean Composite Standardized Uptake Value Ratio (SUVr)(Baseline, Week approximately 240)
- Change From Baseline in Cerebrospinal Fluid (CSF) Tau Biomarkers(Baseline, Week approximately 240)
- Change From Baseline on the Clinical Dementia Rating-Sum of Boxes Score (CDR-SB)(Baseline, Week 336)
- Change From Baseline of Cerebrospinal Fluid (CSF) Concentrations of Amyloid Beta (Aβ)(Baseline, Week approximately 240)
- Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)(Baseline, Week approximately 240)
- Change From Baseline in Cognitive Function Index (CFI)(Baseline, Week 336)
- Change From Baseline on the Computerized Cognitive Composite (C3)(Baseline, Week 336)
- Change From Baseline in Cognitive Function Index (CFI)(Baseline, Week approximately 240)
- Change From Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score(Baseline, Week approximately 240)