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.

摘要。Cognition Therapeutics，Inc.（CogRx）正在开发Elayta TM（CT 1812），一种改善疾病的药物 阿尔茨海默病（AD）。CT 1812是第一个高脑渗透选择性σ-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β淀粉样蛋白低聚物 受体，并保护突触免受有毒寡聚体的影响，将它们从大脑清除到大脑中。 脑脊液（CSF）。当对轻度至中度AD患者每日一次给药28天时，CT 1812 显著降低AD患者CSF中突触变性标志物的浓度。根据我们的审阅 根据公开披露的临床试验数据，目前还没有其他正在开发的治疗药物选择性地靶向 最具毒性的Aβ蛋白寡聚体。没有其他AD候选药物减少突触损伤标记物 就像CT 1812在老年痴呆症患者中的作用一样迅速。 我们在拟议试验中的目的是确定非侵入性措施，以量化CT 1812对CNS的影响 证明了减少AD患者突触损伤的能力。该试点项目建议评估 在一项1b期随机双盲研究中， 在AD患者中进行的安慰剂对照、交叉临床试验。我们假设突触的快速减少 在先前的临床试验中观察到的CSF生物标志物损伤将伴随着总体θ的降低， 功率和提供这种敏感的非侵入性qEEG测量方法的适用性信息 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。完成本 在AD患者中进行的初步研究将为随后的2a期概念验证的设计和方法提供信息 使用CT 1812进行试验。