Glucose-Responsive Self-Regulated Insulin Delivery

描述（由申请人提供）： 具有里程碑意义的糖尿病控制和并发症试验（DCCT）和英国前瞻性糖尿病 研究（UKPDS）已经临床证明，如通过较低的糖化血红蛋白A1 c（HbAlc）水平所测量的，更严格的血糖控制显著降低了长期糖尿病并发症的发生率。 真正的血糖控制需要提供血浆葡萄糖调节的胰岛素替代治疗。 SmartCells通过提供SmartInsulin来满足这一需求，SmartInsulin是唯一一种以临床相关方式感知和响应血清葡萄糖水平变化的产品。 为了向FDA提交SmartInsulin IND并启动人体临床试验，第1年和第2年的安全性和有效性研究将使用链脲佐菌素诱导的糖尿病Sprague-Dawley（SD）大鼠模型解决以下关键问题： - 将SmartInsulin从4 L批次规模扩大至40 L批次，同时保留通过体外葡萄糖设定点和体内葡萄糖耐量试验确定的性能 - 设计SmartInsulin皮下注射相容性，并使用标准组织学评分验证不存在纤维化和坏死组织以及巨噬细胞和淋巴细胞浸润 - 根据注射后药代动力学和药效学关键参数测量，定制SmartInsulin以实现快速吸收、作用和消除 - 优化SmartInsulin配方，使用单次给药控制空腹和餐时血糖水平 - 通过每日注射优化的SmartInsulin降低60天HbA 1c水平

DESCRIPTION (provided by applicant): The landmark Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS), have clinically proven that tighter glycemic control, as measured by lower glycosylated hemoglobin A1c (HbAlc) levels, significantly reduces the incidence of long term diabetic complications. True glycemic control requires treatments that provide plasma glucose-regulated insulin replacement. SmartCells is addressing this need by offering Smartlnsulin, the only product to both sense and respond to altered serum glucose levels in a clinically relevant way. In order to file a Smartlnsulin IND with the FDA and initiate human clinical trials, safety and efficacy studies in Years 1 and 2 will address the following critical issues using streptozotocin-induced diabetic Sprague-Dawley (SD) rat models: - Scale-up Smartlnsulin from 4L to 40L batches while preserving performance as determined by in vitro glucose set point and in vivo glucose tolerance tests - Engineer Smartlnsulin subcutaneous injection compatibility and verify absence of fibrotic and necrotic tissue and macrophage and lymphocyte infiltration using standard histology scoring - Tailor Smartlnsulin for rapid absorption, action, and elimination as measured by key post-injection pharmacokinetic and pharmacodynamic parameters - Optimize Smartlnsulin formulation to control fasting and mealtime glucose levels using a single dose - Reduce 60-day HbA1c levels with daily injections of optimized Smartlnsulin