Combination anti-amyloid therapy for preclinical Alzheimer's disease

项目摘要 这是PAR-18-513下R 01奖项的多PI申请。项目名称： “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 一项联合抗淀粉样蛋白治疗的安慰剂对照两组临床试验：抗纤维淀粉样蛋白 在临床前AD中，最初18个月的抗体联合4年的BACE抑制治疗， 定义为通过florbetapir PET确定脑淀粉样蛋白升高的无症状个体 扫描。主要结局将是认知复合（临床前研究的修改版本）。 阿尔茨海默氏症认知综合征，PACC 5），功能和临床评估沿着， 体积MR和tau PET作为次要结局（以及子集中的CSF生物标志物）。具体 本研究的目的是：1。评估联合抗淀粉样蛋白治疗方案对 如淀粉样蛋白PET SUVr所示，2.评价一种新的治疗方法的有效性和安全性， 在患有临床前AD的个体中的组合抗淀粉样蛋白方案，和3.的影响进行评估 联合抗淀粉样蛋白方案对AD生物标志物的影响。Sperling博士和Aisen博士将共同负责 对研究的临床设计和执行进行科学监督，并进行成像监督。 由约翰逊医生提供。ACTC将提供行政和业务支持， 采集和数据管理、临床监查和研究中心管理、安全性监督、生物统计 支持物和生物标志物样品处理存储和支持物。治疗药物的最终选择 将由一个由实地专家组成的化合物筛选委员会进行。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， 与NIA的音乐会研究团队将与制药公司合作 在开发这些疗法方面具有临床经验的研究人员。 这将是同类研究中的第一项：一种潜在的协同组合方法， 减少AD谱上无症状个体的淀粉样蛋白。联合治疗试验是 越来越多的研究人员和监管机构提出，以提高试验成功的可能性 目的是改变疾病。这种方法最终可以预防AD症状的发作

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