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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos s disease therapeutic Alzheimer&apos 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&apos 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

项目摘要

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，拟议项目名为“R01 奖项”。 “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）。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 Sperling 博士和 Aisen 博士将共同负责 AD 生物标志物的联合抗淀粉样蛋白治疗。对临床设计和研究执行的科学监督以及影像学监督将由 Johnson 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治疗剂的最终选择。此次试验将由由现场专家组成的化合物选择委员会进行。成员将包括 AD 药物开发和 AD 神经生物学方面的外部专家，任命于研究小组将与制药公司合作。拥有这些正在开发的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的联合治疗试验正在进行中。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这种方法的目的是改善疾病，最终可以预防 AD 症状的发生。