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

抽象的。认知治疗公司(CogRx)正在开发一种疾病修改药物ElaytaTM(CT1812) 治疗阿尔茨海默氏症(AD)。CT1812是第一个具有高度脑渗透性的选择性Sigma-2受体拮抗剂 小分子。这种一流的候选药物选择性地取代与神经元结合的淀粉样蛋白-β寡聚体 突触上的受体保护突触免受有毒寡聚体的影响，将它们从大脑清除到 脑脊液(CSF)。轻中度AD患者每天给药一次，连续28天，CT1812 显著降低AD患者脑脊液中突触变性标志物的浓度。根据我们的评论 在公开披露的临床试验数据中，目前没有其他正在开发的治疗方法选择性地针对 最具毒性的Aβ蛋白形式-寡聚体。没有其他AD候选药物能降低突触损伤标志物 与阿尔茨海默氏症患者体内的CT1812一样多，也一样快。 我们在拟议的试验中的目标是确定非侵入性措施来量化CT1812对中枢神经系统的影响 证实有能力减少AD患者的突触损伤。这一试点试验项目建议评估 CT1812治疗1个月对1b期随机双盲定量脑电的影响 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 在以前的临床试验中看到的脑脊液生物标记物的损伤将伴随着全局theta的减少 并提供关于这种灵敏的非侵入性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衡量患者对药物治疗的反应。完成这项工作 AD患者的先导性研究将为后续阶段2a概念验证的设计和方法提供信息 CT1812试验。

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.