Phase 1 Clinical Trial of CMS121, a Novel Therapeutic Candidate for Alzheimer's Disease

摘要 本申请要求补充资金的资助赠款，1 R 01 AG 074447 -01，支持 CMS 121的首次人体临床试验，CMS 121是治疗阿尔茨海默病的候选药物。之日起 在提交父母补助金申请之后，有必要进行修改。两 第一种修改优化了从试验中获得的信息，第三种修改提供了NIA强制要求的数据 安全监测委员会（DSMB）。这些修改在提交报告时是没有预料到的。 家长补助申请 Escherion的临床试验预算已被修改，主要是为了解决与以下方面相关的额外费用： 将老年队列从单次给药剂量递增（SAD）方案转换为多次给药剂量递增方案 (MAD)协议，这一变化提供了多种优势。Escherion的方法单独预算 由于需要一项附加议定书， 测量血浆和尿液中的CMS 121和三种CMS代谢物。另一个意想不到的增长 NIA要求为NIA资助的所有临床试验建立DSMB， 包括第一阶段试验 试验设计的主要改进和测量的必要改进CMS 121 血浆和尿液中的CMS 121代谢物将提供否则将被遗漏的有价值的数据。 此外，这些数据将与CMS 121下一阶段临床试验的设计直接相关。 NIA要求的DSMB将为NIA工作人员提供对试验进展的额外监督。

Abstract This application requests supplemental funds for the funded grant, 1 R01 AG074447-01, which supports a first-in-human clinical trial of CMS121, a drug candidate for treatment of Alzheimer's Disease. Since the date of submission of the application for the parent grant, modifications have become necessary. Two of the modifications optimize the information obtained from the trial and the third provides an NIA-mandated Data and Safety Monitoring Board (DSMB). These modifications were unanticipated at the time of submission of the parent grant application. Celerion's clinical trial budget has been amended primarily to address the additional costs associated with shifting the elderly cohort from the single ascending dose (SAD) protocol to the multiple ascending dose (MAD) protocol, a change that provides multiple advantages. Celerion's separate budget for methods development now includes additional costs due to the necessity for an additional protocol to provide accurate measurements of CMS121 and three CMS metabolites in plasma and urine. Another unanticipated increase in costs results from the NIA requirement that a DSMB be established for all clinical trials funded by NIA, including Phase I trials. The major enhancement in the trial design and the necessary improvement in the measurements CMS121 and CMS121 metabolites in plasma and urine will provide valuable data that would otherwise be missed. Furthermore, these data will be directly relevant for the design of the next phase clinical trial for CMS121. The NIA-required DSMB will provide NIA staff additional oversight of the trial's progress.