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

摘要 本申请要求为资助拨款1 R01 AG074447-01提供补充资金，该拨款支持 治疗阿尔茨海默病的候选药物CMS121的首次人体临床试验。自日期起 在提交父母赠款申请后，必须进行修改。其中两个 修改优化了从试验中获得的信息，第三个修改提供了NIA授权的数据 和安全监测委员会(DSMB)。这些修改在提交时是意想不到的 家长拨款申请。 Celerion的临床试验预算已经修改，主要是为了解决与以下方面相关的额外成本 将老年队列从单一递增剂量(SAD)方案转变为多个递增剂量 (MAD)协议，这一变化提供了多种优势。Celerion的方法单独预算 开发现在包括额外的成本，因为需要额外的协议来提供准确的 CMS121及三种CMS代谢物在血浆和尿液中的测定又一次意想不到的增长 由于NIA要求为NIA资助的所有临床试验建立一个DSMB， 包括I期试验。 试验设计的主要改进和测量CMS121的必要改进 血浆和尿液中的CMS121代谢物将提供有价值的数据，否则这些数据将被遗漏。 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.