A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of ASN51 in Adults With Early Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 123
- 试验地点
- 5
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
The main purpose of this study is to evaluate the safety, tolerability, and effect on biomarkers of disease pathophysiology and pathology, pharmacokinetics (PK), and preliminary effects on measures of clinical efficacy of multiple doses of ASN51 in adult participants with early Alzheimer's disease (AD).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female age 50 to 80 years.
- •A clinical diagnosis of Alzheimer's disease (AD) at either the mild cognitive impairment or mild AD dementia stage per National Institute on Aging and the Alzheimer's Association, consistent with Stage 3 and Stage 4 in the Food and Drug Administration (FDA) draft guidance for early AD.
- •Mini-Mental State Examination score of 20 to 28 (inclusive).
- •A plasma pTau217 result consistent with the presence of amyloid pathology.
- •Must have a care partner who, in the investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities. The care partner must be literate and provide informed consent.
排除标准
- •Any medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment (e.g., current history of substance abuse, uncontrolled vitamin B12 deficiency or abnormal thyroid function, stroke or other cerebrovascular condition, normal pressure hydrocephalus, Parkinson's Disease, Lewy body dementia, cerebral amyloid angiopathy, frontotemporal dementia) or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns.
- •Non-amnestic presentation of AD as judged by the investigator.
- •Woman of childbearing potential.
- •Any prior or ongoing exposure to active or passive anti-amyloid immunotherapy, anti-tau immunotherapy, an anti-tau antisense oligonucleotide or gene therapy, or O-linked-β-N-acetylglucosaminidase (O-GlcNAcase) inhibitor.
- •Other protocol defined inclusion and exclusion criteria could apply.
研究组 & 干预措施
ASN51: Low Dose
Participants were to receive low dose of ASN51 orally, once daily (QD) for up to 24 weeks in the double-blind placebo-controlled intervention period or up to 36 weeks long-term extension period.
干预措施: ASN51 (Drug)
ASN51: High Dose
Participants were to receive high dose of ASN51 orally, QD for up to 24 weeks in the double-blind placebo-controlled intervention period or up to 36 weeks long-term extension period.
干预措施: ASN51 (Drug)
Placebo
Participants were to receive ASN51 matching placebo orally, QD for up to 24 weeks in the double-blind placebo-controlled intervention period.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: From first dose up to end of the study up to Week 28
An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Baseline up to Week 28
C-SSRS is used to assess the suicidality of participants and assessment includes "yes" or "no" responses for 5 questions, each related to suicidal ideation and suicidal behavior. Numeric ratings are provided for suicidal ideation (score ranges from 1 to 5, where higher scores indicate more suicidal ideation) and suicidal behavior (score ranges from 0 to 4 where higher total scores indicate more suicidal behavior).
次要结局
- Change From Baseline in Plasma pTau217 Through Week 24(Baseline through Week 24)
- Trough Plasma Concentration (Cmin) of ASN51 in Plasma at Steady State(Pre-dose on Day 1 and at multiple time points post-dose up to Week 24)
- Maximum Plasma Concentration (Cmax) of ASN51 at Steady State(Pre-dose on Day 1 and at multiple time points post-dose up to Week 24)
- Change From Baseline in MK-6240 Tau Positron Emission Tomography (PET) Signal Through Week 24(Baseline through Week 24)
- Change From Baseline in Cerebrospinal Fluid (CSF) Plasma Tau Phosphorylated at Threonine-217 (pTau217) Through Week 24(Baseline through Week 24)
- Change From Baseline in CSF Total Tau Protein Through Week 24(Baseline through Week 24)