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: 10666411
• 负责人: Paul S. Aisen
• 金额: $ 872.31万
• 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/10666411
• 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; Country; Data; Dementia; Development; Disease; Disease Progression; Enrollment; Epidemic; Futility; Generations; Hippocampus; 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; Placebo Control; Placebos; Plasma; Positron-Emission Tomography; Prevention; Randomized; Randomized, Controlled Trials; Regimen; Research Personnel; Safety; Sampling; Senile Plaques; Site; Symptoms; Testing; Therapeutic; Therapeutic Agents; Therapeutic Research; 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; instrument; monomer; neocortical; 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

项目摘要 这是根据PAR-18-513的R01奖项的多PI申请。拟议的项目标题为 “临床前阿尔茨海默氏病中的抗淀粉样疗法组合”是多中心随机的 安慰剂对照的两臂抗淀粉样疗法的两臂临床试验：抗纤维淀粉样蛋白 最初18个月的抗体与BACE抑制疗法相结合4年，在临床前AD中， 由Florbetapir PET确定为无症状的脑淀粉样蛋白升高的个体 扫描。主要结果将是认知复合材料（临床前的修改版本 阿尔茨海默氏症的认知复合材料PACC5），具有功能和临床评估以及 体积MR和Tau PET作为次要结果（在子集中是CSF生物标志物）。具体 拟议研究的目的是； 1。评估组合抗淀粉样蛋白的影响 如淀粉样蛋白PET SUVR所示的大脑中的纤维淀粉样蛋白，2。 临床前AD个体的抗淀粉样疗法组合，3。 AD生物标志物上的抗淀粉样疗法组合。博士。 Sperling和Aisen将分担责任 为了科学监督研究的临床设计和执行和成像监督 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，临床监控和现场管理，安全监督，生物统计学 支持以及生物标志物样品处理存储和支持。最终选择治疗剂 对于此试验，将由一个由现场专家组成的复合选择委员会成立。委员会 会员资格将包括被任命为AD药物开发和AD神经生物学的外部专家 与Nia音乐会。研究团队将与制药公司合作 在开发中具有临床经验的研究人员。 这将是同类研究的第一个研究：一种潜在的协同组合方法 从AD光谱上的不对称个体中还原淀粉样蛋白。联合疗法试验是 研究人员和监管机构越来越提出，以提高试验成功的可能性 瞄准疾病调整。这种方法最终可以防止AD症状发作