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。 Cognition Therapeutics, Inc. (CogRx) 正在开发 ElaytaTM (CT1812)，一种疾病缓解药物 用于阿尔茨海默病（AD）。 CT1812是第一个高脑渗透性选择性sigma-2受体拮抗剂 小分子。这种一流的候选药物选择性取代与神经元结合的淀粉样蛋白-β寡聚体 突触上的受体并保护突触免受有毒寡聚物的影响，将它们从大脑清除到大脑中 脑脊液（CSF）。当轻度至中度 AD 患者每日一次连续 28 天给药时，CT1812 显着降低 AD 患者脑脊液中突触变性标记物的浓度。根据我们的评论 根据公开披露的临床试验数据，目前正在开发的其他治疗方法没有选择性地针对 Aβ 蛋白毒性最强的形式——寡聚物。没有其他 AD 候选药物能够降低突触损伤标记物 与阿尔茨海默病患者中的 CT1812 一样多、一样快。 我们拟议试验的目标是确定非侵入性措施来量化 CT1812 对 CNS 的影响 已证明能够减少 AD 患者的突触损伤。该试点项目建议评估 在 1b 期随机双盲试验中，CT1812 治疗一个月对定量脑电图的影响， AD 患者的安慰剂对照、交叉临床试验。我们假设突触的快速减少 先前临床试验中发现的脑脊液生物标志物损伤将伴随着全局θ的减少 功率并提供有关这种敏感的非侵入性 qEEG 测量方法的适用性的信息 突触功能，用于在未来的疗效研究中测量患者对药物治疗的反应。完成此 AD 患者的试点研究将为后续 2a 阶段概念验证的设计和方法提供信息 CT1812 试验。