TREATMENT WITH HOKT3YL (ALA-ALA) IN TYPE 1 DIABETES MELLITUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们提出了一项多中心、随机、双臂、开放标签的II期试验，其中81名诊断为T1 DM的6周内的参与者以2：1的比例随机分配接受hOKT 3 1（Ala-Ala）加标准糖尿病管理或仅接受标准糖尿病管理。分配接受hOKT 3 1（Ala-Ala）的参与者将在研究入组时接受14天的疗程，如果符合条件，可以在13个月时接受第二个疗程。总研究持续时间约为4年（2年累积和2年随访）。如方案所述，免疫学检测可在研究开始后长达5年进行。两组都将接受MMTT刺激的C肽试验，并按照相同的时间表采集血液用于机制研究。糖尿病相关的目的是评估药物是否具有延长的临床疗效，并评估hOKT 3的作用。1例（Ala-Ala）选择的次要临床结局。安全性和药代动力学目标包括确定hOKT 3的药代动力学和作用机制？1（Ala-Ala），并获得有关hOKT 3？1（Ala-Ala）。机制研究的目的是确定药物如何改变一般和糖尿病特异性免疫反应，并确定hOKT 3的作用机制？1（Ala-Ala）维持？-细胞功能

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a multicenter, randomized, two-arm, open-label phase II trial in which 81 participants within 6 weeks of diagnosis with T1DM are randomly assigned at a 2:1 ratio to receive hOKT3 1 (Ala-Ala) plus standard diabetes management or standard diabetes management alone. Participants assigned to receive hOKT3 1 (Ala-Ala) will be given a 14-day course at study entry and may, if eligible, be given a second course at 13 months. Total study duration is approximately 4 years (a 2-year accrual and a 2-year follow-up). Immunologic testing may occur for up to 5 years post study initiation as outlined in the protocol. Both groups will undergo the MMTT stimulated C-peptide test and have blood collected for mechanistic studies on the same schedule. Diabetes-related objectives are to assess whether the drug has prolonged clinical efficacy and to assess the effect of hOKT3?1 (Ala-Ala) on selected secondary clinical outcomes. Safety and pharmacokinetics objectives include to determine the pharmacokinetics and mechanism of action for hOKT3?1 (Ala-Ala) and to gain additional information about the safety of hOKT3?1 (Ala-Ala). Mechanistic studies are aimed at determining how the drug alters general and diabetes-specific immune responses and determining the mechanism of action for hOKT3?1 (Ala-Ala) in maintenance of ?-cell function.