A Pilot Electroencephalography (EEG) Study to Evaluate the Effect of CT1812 Treatment on Synaptic Activity in Subjects with Mild to Moderate Alzheimerʼs Disease

一项旨在评估 CT1812 治疗对轻度至中度阿尔茨海默病受试者突触活动影响的脑电图 (EEG) 试验研究

• 批准号: 10651320
• 负责人: ANTHONY O CAGGIANO
• 金额: $ 214.44万
• 依托单位: COGNITION THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10651320
• 关键词: Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease patient; Amyloid beta-Protein; Binding; Biological Markers; Brain; Cerebrospinal Fluid; Clinical Trials; Cognition; Data; Development; Disease; Double-Blind Method; Electroencephalography; Funding; Future; Measures; Memory Loss; Methods; Neurons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase Ib Clinical Trial; Pilot Projects; Placebo Control; Proteins; Randomized; Synapses; Therapeutic; Work; abeta oligomer; antagonist; base; design; drug candidate; efficacy study; novel; patient response; pilot trial; protein oligomer; receptor; sigma-2 receptor; small molecule; synaptic function

ABSTRACT. Cognition Therapeutics, Inc. (CogRx) is developing ElaytaTM (CT1812), a disease-modifying drug for Alzheimer’s disease (AD). CT1812 is the first highly brain penetrant selective sigma-2 receptor antagonist small molecule. This first-in-class drug candidate selectively displaces amyloid-β oligomers bound to neuronal receptors at synapses and protects synapses from toxic oligomer effects, clearing them from the brain into the cerebrospinal fluid (CSF). When administered once daily for 28 days to mild to moderate AD patients, CT1812 significantly reduces concentrations of synaptic degeneration markers in AD patient CSF. Based on our review of publicly-disclosed clinical trial data, no other therapeutic currently in development selectively targets the most toxic form of the Aβ protein – oligomers. No other AD drug candidate reduces synaptic damage markers as much, and as rapidly, as CT1812 in Alzheimer's patients. Our Aim in the proposed trial is to identify non-invasive measures to quantify the CNS impact of CT1812 demonstrated ability to reduce synaptic damage in AD patients. This pilot trial project proposes to evaluate the effect of one month of CT1812 treatment on quantitative EEG in a Phase 1b randomized double-blind, placebo-controlled, crossover clinical trial in AD patients. We hypothesize that the rapid reduction in synaptic damage CSF biomarkers seen in previous clinical trials will be accompanied by a reduction in global theta power and provide information on the suitability of this sensitive non-invasive qEEG method of measuring synaptic function for measuring patient response to drug treatment in future efficacy studies. Completion of this pilot study in AD patients will inform the design and methods of the subsequent Phase 2a proof of concept trials with CT1812.

抽象的。认知治疗公司（COGRX）正在开发Elaytatm（CT1812），这是一种调整疾病的药物 对于阿尔茨海默氏病（AD）。 CT1812是第一个高度脑穿透性选择性Sigma-2受体拮抗剂 小分子。这位第一类候选药物选择性地置换了与神经元结合的淀粉样蛋白-β低聚物 突触处的受体并保护突触免受有毒的低聚物影响，将其从大脑清除到 脑脊液（CSF）。当每天一次给予轻度至中度AD患者28天28天时，CT1812 显着降低了AD患者CSF中突触变性标记的浓度。根据我们的评论 公开披露的临床试验数据，目前没有其他治疗方法有选择地针对 Aβ蛋白 - 低聚物的大多数有毒形式。没有其他AD候选药物可以减少合成损伤标记 在阿尔茨海默氏症患者中，与CT1812一样迅速。 我们在拟议的试验中的目标是确定无创措施来量化CT1812的中枢神经系统影响 表现出减少AD患者突触损伤的能力。该试点审判项目提案，以评估 CT1812处理一个月的影响对1B期随机双盲的定量脑电图的影响， AD患者的安慰剂对照，跨界临床试验。我们假设突触的快速减少 在以前的临床试验中看到的损害CSF生物标志物将通过减少全球theta来实现 权力并提供有关这种敏感的非侵入性QEEG测量方法的适用性信息 在未来的效率研究中，用于测量患者对药物治疗的反应的突触功能。完成此操作 AD患者的试点研究将告知随后的2A概念证明的设计和方法 CT1812试验。