Combination anti-amyloid therapy for preclinical Alzheimer's disease

项目总结 这是一个符合PAR-18-513的R01奖项的多PI申请。拟议的项目名为 《联合抗淀粉样蛋白治疗临床前阿尔茨海默病》是一项多中心随机研究 一种联合抗淀粉样蛋白治疗的安慰剂对照双臂临床试验：一种抗纤维淀粉样蛋白 在临床前AD中，最初18个月的抗体联合BACE抑制治疗4年， 经FLOBETAPIR PET确定为脑淀粉样蛋白升高的无症状个体 扫描中。主要结果将是认知复合体(临床前的修改版本 阿尔茨海默氏症认知复合体，以及功能和临床评估，以及 作为次要结果的体积MR和tau PET(以及，在子集中，脑脊液生物标记物)。具体的 这项研究的目的是：1.评估联合抗淀粉样蛋白疗法对 脑内纤维状淀粉样蛋白PET SUVR显示，2.评价一种药物的疗效和安全性 联合抗淀粉样蛋白方案治疗临床前AD患者，以及3.评估 联合抗淀粉样蛋白治疗对AD生物标志物的影响。斯珀林博士和艾森博士将共同承担责任 对于临床设计和研究执行的科学监督和成像监督将是 由约翰逊博士提供。反恐委员会将提供行政和业务支持、数据 捕获和数据管理、临床监测和现场管理、安全监督、生物统计学 支持、生物标记物样品的加工、存储和支持。治疗剂的最终选择 这次审判将由一个由现场专家组成的复合型遴选委员会进行。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，于 与NIA的音乐会。研究小组将与制药公司合作 对这些疗法有临床经验的研究人员正在开发中。 这将是此类研究的第一次：一种潜在的协同组合方法，以显著 减少AD频谱上无症状个体的淀粉样蛋白。联合治疗试验是 调查人员和监管机构越来越多地提出提高试验成功可能性的建议 以治未病为目标。这种方法最终可以防止AD症状的出现

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