Combination anti-amyloid therapy for preclinical Alzheimer's disease

临床前阿尔茨海默病的抗淀粉样蛋白联合治疗

• 批准号: 9786200
• 负责人: Paul S. Aisen
• 金额: $ 873.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9786200
• 关键词: Activities of Daily Living; Address; Alzheimer' s Disease; Alzheimer' s disease therapeutic; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Antibodies; Atrophic; Award; Binding; Biological Markers; Biometry; Blood; Brain; Cerebrospinal Fluid; Clinic; Clinical; Clinical Trials; Clinical assessments; Cognition; Cognitive; Collaborations; Combined Modality Therapy; Committee Membership; Data; Development; Disease; Disease Progression; Enrollment; Epidemic; Futility; Generations; Hippocampus (Brain); Image; Impaired cognition; Individual; Intervention; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Modification; Monitor; Neocortex; Nerve Degeneration; Neurobiology; Neurons; Oral; Participant; Pathologic; Pathology; Pathway interactions; Patient Self-Report; Pharmaceutical Preparations; Pharmacologic Substance; Placebos; Plasma; Positron-Emission Tomography; Prevention; Randomized; Randomized Controlled Trials; Regimen; Research Personnel; Safety; Sampling; Senile Plaques; Site; Symptoms; Testing; Therapeutic; Therapeutic Agents; Therapeutic Human Experimentation; Therapeutic Trials; Therapy trial; Treatment Protocols; Ventricular; Work; amyloid peptide; arm; asymptomatic Alzheimer' s disease; beta secretase; beta-site APP cleaving enzyme 1; clinical development; cognitive function; computerized; cooperative study; data management; design; drug development; effective therapy; efficacy evaluation; exosome; experience; high risk; improved; indexing; inhibitor/antagonist; instrument; neurofilament protein L; pre-clinical; pre-clinical therapy; prevent; primary outcome; secondary outcome; success; tau Proteins; tau-1; tool; uptake

PROJECT SUMMARY This is a multi-PI application for an R01 award under PAR-18-513. The proposed project titled “Combination Anti-Amyloid Therapy in Preclinical Alzheimer's Disease” is a multicenter randomized placebo-controlled two arm clinical trial of a combination anti-amyloid therapy: an anti-fibrillar amyloid antibody for the initial 18 months combined with BACE inhibition therapy for 4 years, in preclinical AD, defined as asymptomatic individuals with elevated brain amyloid as determined by florbetapir PET scanning. The primary outcome will be a cognitive composite (a modified version of the Preclinical Alzheimer's Cognitive Composite, PACC5), with functional and clinical assessments along with volumetric MR and tau PET as secondary outcomes (and, in a subset, CSF biomarkers). The specific Aims of the proposed study are; 1. to evaluate the impact of a combination anti-amyloid regimen on fibrillar amyloid in brain as indicated by amyloid PET SUVr, 2. to evaluate the efficacy and safety of a combination anti-amyloid regimen in individuals with preclinical AD, and 3. to evaluate the impact of the combination anti-amyloid regimen on AD biomarkers. Drs. Sperling and Aisen will share responsibility for scientific oversight of the clinical design and execution of the study and Imaging oversight will be provided by Dr. Johnson. The ACTC will provide the administrative and operational support, data capture and data management, clinical monitoring and site management, safety oversight, biostatistical support, and biomarker sample processing storage and support. Final selection of therapeutic agents for this trial will be made by a compound selection committee composed of field experts. Committee membership will include external experts in AD drug development and AD neurobiology, appointed in concert with NIA. The study team will work collaboratively with the pharmaceutical company researchers who have clinical experience with these therapeutics in development. This will be the first study of its kind: a potentially synergistic combination approach to dramatically reducing amyloid from asymptomatic individuals on the AD spectrum. Combination therapy trials are increasingly proposed by investigators and regulators to improve the likelihood of success in trials aiming for disease-modification. This approach could ultimately prevent the onset of AD symptoms

项目概要 这是 PAR-18-513 下的 R01 奖项的多 PI 申请。拟议的项目名为 “临床前阿尔茨海默病的抗淀粉样蛋白联合治疗”是一项多中心随机研究 抗淀粉样蛋白联合治疗的安慰剂对照双臂临床试验：抗纤维淀粉样蛋白 在临床前 AD 中，最初 18 个月的抗体结合 4 年的 BACE 抑制疗法， 定义为通过氟倍䑳 PET 测定大脑淀粉样蛋白升高的无症状个体 扫描。主要结果将是认知综合（临床前测试的修改版本） 阿尔茨海默氏症认知综合，PACC5），以及功能和临床评估 体积 MR 和 tau PET 作为次要结果（以及一部分脑脊液生物标志物）。具体的 拟议研究的目的是： 1. 评估联合抗淀粉样蛋白治疗方案对 2. 淀粉样蛋白 PET SUVr 表明大脑中存在纤维状淀粉样蛋白，以评估 3. 临床前 AD 个体的联合抗淀粉样蛋白治疗方案，以及评估 针对 AD 生物标志物的联合抗淀粉样蛋白治疗方案。博士。斯珀林和艾森将分担责任 对临床设计和研究执行的科学监督以及影像学监督将 由约翰逊博士提供。 ACTC 将提供行政和运营支持、数据 捕获和数据管理、临床监测和现场管理、安全监督、生物统计 支持，以及生物标志物样品处理存储和支持。治疗药物的最终选择 此次试验将由由现场专家组成的化合物选择委员会进行。委员会 成员将包括 AD 药物开发和 AD 神经生物学方面的外部专家，任命于 与NIA的音乐会。研究团队将与制药公司合作 具有开发这些疗法的临床经验的研究人员。 这将是此类研究中的第一项：一种潜在的协同组合方法，可显着 减少 AD 谱系中无症状个体的淀粉样蛋白。联合治疗试验是 研究人员和监管机构越来越多地提出提高试验成功的可能性 以疾病缓解为目标。这种方法最终可以预防 AD 症状的出现