A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of CNP520 in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (AD).
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1,145
- 试验地点
- 36
- 主要终点
- Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
研究概览
简要总结
The purpose of this study is to determine the effects of CNP520 on cognition, global clinical status, and underlying AD pathology, as well as the safety of CNP520, in people at risk for the onset of clinical symptoms of AD based on their age, APOE genotype and elevated amyloid.
详细描述
This trial was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned in cognitively unimpaired participants aged 60 to 75 years, with at least one apolipoprotein E allele (APOE4), (homozygotes (HMs) or heterozygotes (HTs)) and, if HTs, with evidence of elevated brain amyloid. The participants were randomized to either CNP520 50 mg, CNP520 15 mg or placebo a 2:1:2 ratio and was stratified based on amyloid status. The planned treatment period of 5 to 8 years was not achieved due to early study termination.
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
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype and, if Heterozygotes, evidence of elevated brain amyloid.
- •Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential
- •Cognitively unimpaired as evaluated by memory tests performed at screening.
- •Participant's willingness to have a study partner.
- •Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as measured by CSF Abeta or amyloid PET imaging).
排除标准
- •Any disability that could have prevented the participants from completing all study requirements. -
- •Current medical or neurological condition that could have impacted cognition or performance on cognitive assessments.
- •Advanced, severe progressive or unstable disease that could have interfered with the safety, tolerability and study assessments, or put the participant at special risk.
- •History of malignancy of any organ system, treated or untreated, within the past 60 months.
- •Indication for, or current treatment with ChEIs and/or another AD treatment (e.g. memantine).
- •Contraindication or intolerance to MRI.
- •Brain MRI results showing findings unrelated to AD that, in the opinion of the Investigator might be a leading cause to future cognitive decline, could have posed a risk to the participant, or could have prevented a satisfactory MRI assessment for safety monitoring.
- •Suicidal Ideation in the past six months, or Suicidal Behavior in the past two years.
- •A positive drug screen at Screening, if, in the Investigator's opinion, was is due to drug abuse.
- •Significantly abnormal laboratory results at Screening, not as a result of a temporary condition.
- •Current clinically significant ECG findings.
- •Clinically relevant depigmenting or hypopigmenting conditions (e.g. albinism, vitiligo) or active / history of chronic urticaria in the past year.
研究组 & 干预措施
CNP520 50 mg
50 mg capsule taken orally once daily
干预措施: CNP520 50mg (Drug)
CNP520 15 mg
15 mg capsule taken orally once daily
干预措施: CNP520 15mg (Drug)
Placebo
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
干预措施: Matching placebo (Other)
结局指标
主要结局
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
时间窗: Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
APCC is a composite score derived from the specific scores from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE) and the Raven's Progressive Matrices. The APCC score is a weighted score with ranges from from 0 to 100 where higher scores correspond to better cognitive performance.
Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
时间窗: Baseline to last cognitive assessment performed (up to day 648)
Event was defined as the first confirmed diagnosis of MCI due to Alzheimer's disease (AD) or dementia due to AD (whichever occurred first) after adjudication by the progression adjudication committee (PAC) as triggered either by an investigator diagnosis or an increase in the Clinical Dementia Rating (CDR) global score. An event had to be confirmed by the PAC at two consecutive visits. In case no confirmed event was observed for a participant, the observation was censored, and the censoring date was defined as the last date where the diagnostic classification was assessed. The Study was terminated and only confirmed events collected up to the data cut-off point were counted. Due to the early termination of the study only a small number of events were observed and time-to-event could not be analyzed. Kaplan-Meyer (KM) estimates were provided to estimate probability that a subject would have an event prior to the specified visit.
次要结局
- Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score(Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648))
- Change in the Everyday Cognition Scale (ECog-Informant) Total Scores(Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648))
- Change in the Total and Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)(Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648))
- Change in the Everyday Cognition Scale (ECog-Subject) Total Scores(Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648))
- Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)(Baseline up to study termination approximately 617 days)
- Annualized Percent Change on Volume of Brain Regions(Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648))
- Change in CSF Levels of Amyloid Beta 40 (Aβ40)(Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648))
- Change in CSF Levels of Amyloid Beta 42 (Aβ42)(Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648))
- Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)(Baseline to Months 24 and 60)
- Change in Amyloid Deposition as Measured by Standardized Uptake Ratio (SUVR) of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer(Baseline to Months 24 and 60)
- Change in CSF Levels of Total Tau and Phosphorylated Tau(Baseline to Last on-treatment (Day 547) Baseline to Last off-treatment (Day 648))
- Change in Serum Neurofilaments(Baseline to Week 26, baseline to Last on-treatment (Day 547) Baseline to Last off-treatment (Day 648))
- Number of Suicidal Ideation or Behavior Events(Baseline up to study termination approximately 617 days)