A Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Phase II Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Mild to Moderate Alzheimerʼs Disease

一项随机、双盲、安慰剂对照、平行组、II 期研究，旨在评估 CT1812 在轻度至中度阿尔茨海默病受试者中的安全性和有效性

• 批准号: 10208480
• 负责人: ANTHONY O CAGGIANO
• 金额: $ 1363.45万
• 依托单位: COGNITION THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10208480
• 关键词: Alzheimer' s Disease; Alzheimer' s disease patient; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Australia; Award; Binding; Biological Markers; Brain; Budgets; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Clinical Trials Design; Cognition; Cognitive; Development; Disease; Disease Progression; Dose; Double-Blind Method; Enrollment; Funding; Future; Goals; Grant; Impaired cognition; Measures; Methods; Modification; Neurons; Outcome; Patients; Performance; Pharmacodynamics; Pharmacological Treatment; Phase; Placebos; Plasma; Proteins; Randomized; Request for Applications; Research Design; S-nitro-N-acetylpenicillamine; Safety; Structure; Synapses; Synaptic Receptors; Therapeutic; Viola; abeta oligomer; clinical development; clinical outcome assessment; clinical research site; cognitive function; cognitive performance; cost; design; drug candidate; improved; monomer; neurogranin; novel; phase 2 study; phase III trial; potential biomarker; primary outcome; protein oligomer; receptor; safety outcomes; small molecule; targeted biomarker; tau-1

ABSTRACT. Soluble oligomers of beta amyloid (Aβ) protein are the most potent neuroactive structural form of this protein and evidence suggests they cause the synaptotoxic changes resulting in cognitive decline in Alzheimer's disease (AD) (Selkoe and Hardy 2016, Viola and Klein 2015). Cognition Therapeutics, Inc. (CogRx) is developing CT1812, the first brain penetrant small molecule that selectively clears toxic oligomers from the brain into the cerebrospinal fluid (CSF). This drug candidate displaces AβOs bound to neuronal receptors at synapses and protects synapses from toxic oligomer effects. 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, and phospho-tau. CT1812's mechanism of action can potentially halt or slow cognitive decline, significantly alleviating the suffering of AD patients. An ongoing study COG0201 (SHINE) funded by the NIA under the award AG058660 is evaluating the safety and efficacy of two doses of CT1812 on cognitive function in a Phase 2 randomized, double-blind, placebo-controlled parallel group clinical trial in mild to moderate AD patients. This important proof of concept trial will be critical for CT1812's continued development. Excellent progress has been made on this study and award. Study COG0201 is proceeding well at nine clinical research sites across the US and Australia. Regulatory interactions have resulted in changes to the study design which have increased per patient costs; this competing revision application requests additional funds to enroll sufficient patients and reach the appropriate number of patients per group and adequately measure changes in cognitive function (N=48/group) and complete a fully powered trial (revised AIM 1). Adequately powered assessment of clinical outcomes is vital to CT1812's further development. Completion of this study in AD patients will inform the design and methods of the subsequent disease modification Phase III trials with CT1812. Advancement of CT1812 clinical development would substantially improve the lives of the 50 million people worldwide suffering from AD, for whom no disease-modifying pharmacological treatments exist.

抽象的。β-淀粉样蛋白的可溶性寡聚体(A-β)是最有效的神经活性结构形式 这种蛋白质和证据表明，它们导致突触毒素变化，导致认知能力下降 阿尔茨海默病(AD)(Selkoe和Hardy 2016，Viola和Klein 2015)。认知治疗公司 (CogRx)正在开发CT1812，这是第一种选择性清除有毒低聚物的脑穿透性小分子 从大脑进入脑脊液(CSF)。这种候选药物取代了与神经元结合的βOS 突触上的受体和保护突触免受有毒寡聚体的影响。每天给药一次，共28次 轻至中度AD患者的天数，CT1812显著降低突触变性的浓度 AD患者脑脊液和磷酸化tau的标志物。CT1812的S作用机制可能会停止或减缓 认知功能下降，明显缓解了AD患者的痛苦。正在进行的研究COG0201(SIRE) 由NIA资助的AG058660正在评估两剂CT1812的安全性和有效性 轻症患者认知功能的2期随机、双盲、安慰剂平行对照临床试验 至中度AD患者。S继续说，这一重要的概念验证试验将对CT1812至关重要 发展。在这项研究和奖励方面取得了很好的进展。COG0201研究进展顺利 在美国和澳大利亚的九个临床研究地点。监管方面的相互作用导致了 增加了每个患者的成本的研究设计；这一竞争性修订申请要求 额外资金，以招募足够的患者并达到每组适当的患者数量，以及 充分测量认知功能的变化(N=48/组)并完成全功率试验(修订版 目标1)。充足的临床结果评估对CT1812型S的进一步发展至关重要。 在AD患者中完成这项研究将为后续疾病的设计和方法提供参考 CT1812的第三阶段改装试验。CT1812临床开发的进展将大大 改善全球5000万阿尔茨海默病患者的生活，他们无法改变疾病 药物治疗是存在的。