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

摘要 本申请请求资助补助金 1 R01 AG074447-01 的补充资金，该补助金支持 CMS121 的首次人体临床试验，CMS121 是一种治疗阿尔茨海默病的候选药物。自该日期起 提交家长补助金申请后，有必要进行修改。其中两个 修改优化了从试验中获得的信息，第三个提供了 NIA 规定的数据 和安全监察委员会（DSMB）。这些修改是在提交时未预料到的 家长补助金申请。 Celerion 的临床试验预算已进行修改，主要是为了解决与以下相关的额外费用 将老年人群从单次递增剂量 (SAD) 方案改为多次递增剂量 (MAD) 协议，这一变化提供了多种优势。 Celerion 方法的单独预算 由于需要额外的协议来提供准确的信息，开发现在包括额外的成本 血浆和尿液中 CMS121 和三种 CMS 代谢物的测量。又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。 试验设计的重大改进和测量的必要改进 CMS121 血浆和尿液中的 CMS121 代谢物将提供有价值的数据，否则这些数据将被错过。 此外，这些数据将直接与 CMS121 下一阶段临床试验的设计相关。 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.