Home Use of MD-Logic Automated Insulin Delivery System: Safety and Efficacy

 描述(申请人提供)：这个名为MD2Go的项目的目的是解决测试人工胰腺(AP)系统的挑战，为1型糖尿病(T1D)患者开发一种商业上可用的自动胰岛素输送解决方案。由以色列施耐德儿童医学中心糖尿病技术中心开发的MD-Logic自动胰岛素释放系统是一种AP系统，它通过应用模糊逻辑理论来模仿糖尿病护理人员的推理路线来建立血糖控制。该系统提供了一种具有实时学习能力的个性化治疗方法，有效地跟踪了血糖-胰岛素动力学和 相应地调整胰岛素。MD-Logic系统已经在斯洛文尼亚、德国和以色列的一个多中心联盟中进行了研究。它已经被用于越来越具有挑战性的环境中，包括在住院环境中过夜，在糖尿病营地环境中过夜，以及在家里过夜。最近，该系统在家中进行了一天24小时、一周7天(24/7)、周末(60小时)和2周的测试。这些初步研究证明了MD-Logic与传感器增强泵(SAP)系统在不同条件下的可行性、安全性和有效性。用于控制血糖水平的软件在欧洲获得了CE标志，使其成为世界上第一个获得监管批准的AP软件。只有通过一项旨在产生美国食品和药物管理局(FDA)批准的结果的研究，才能充分推进商业化。MD2Go研究方案是这样设计的，如果假设是正确的，研究结果将直接推动AP技术走向商业化。我们的3阶段研究将FDA从之前的提交前会议中获得的指导与创新技术、出色的临床场地和顶级协调中心结合在一起。第一阶段包括在成人中进行MD-Logic的试点测试，以评估在有监督、有监测的运动和营养挑战期间的安全性和可靠性，同时通过黄泉仪(YSI)的等效比较确认连续血糖监测仪的准确性。然后，试验对象将继续使用全天候混合闭环系统，为期3个月。在得到数据安全和监测委员会的批准后，相同的试验性测试将在12至21岁的受试者中重复进行(FDA推荐的正式和严格的儿科定义)。第二阶段将是一项大规模、多中心、多国的第三阶段随机临床试验，在240名12岁至21岁的年轻人中进行MD-Logic和SAP的比较。主要结果是疗效，定义为血糖传感器读数在目标范围70-180 mg/dL的百分比，安全性定义为血糖传感器读数低于70 mg/dL的百分比，以及持续混合闭环使用6个月后HbA1c变化的次要疗效结果。第三阶段是关于MD-Logic在成人中作为一个完整的闭环系统使用的概念验证研究。从整体上看，这一前沿研究项目有可能成为T1D患者全天候治疗的全封闭环路解决方案商业化道路上的一个重要里程碑。

 DESCRIPTION (provided by applicant): The purpose of this project, called MD2Go, is to address the challenge of testing an artificial pancreas (AP) system to develop a commercially available automated insulin-delivery solution for people living with type 1 diabetes (T1D). The MD-Logic Automated Insulin Delivery (MD-Logic) system, developed by the Diabetes Technology Center, Schneider Children's Medical Center of Israel, is an AP system that establishes glucose control by applying fuzzy logic theory to imitate lines of reasoning of diabetes caregivers. This system provides a personalized treatment approach with real-time learning ability that effectively tracks the unpredictable behavior of glucose-insulin dynamics and adjusts insulin accordingly. The MD-Logic system has been studied in a multicenter consortium in Slovenia, Germany, and Israel. It has been used in increasingly challenging settings, including overnight in an inpatient setting, a diabetes camp setting, and in the home overnight. Recently, the system was tested at home for 24 hours a day, 7 days a week (24/7); over the weekend (60 hours); and for 2 weeks. These preliminary studies demonstrate the feasibility, safety, and efficacy of MD-Logic compared with a sensor-augmented pump (SAP) system under different conditions. The software for controlling glucose levels has received a CE Mark in Europe, making it the first AP software to receive regulatory approval in the world. Commercialization will be adequately advanced only with a study designed to yield U.S. Food and drug Administration (FDA) approvable outcomes. The MD2Go study protocol is designed so that, if the hypotheses are correct, the findings will directly advance AP technology toward commercialization. Our 3-phase study incorporates FDA guidance acquired from prior pre-submission meetings with innovative technology, excellent clinical sites, and a top coordinating center. Phase 1 includes pilot testing of MD-Logic in adults to assess safety and reliability during supervised, monitored exercise and nutritional challenges with concurrent confirmation of continuous glucose monitor accuracy with Yellow Springs Instrument (YSI) equivalent comparisons. Then the pilot subjects will continue use 24/7 as a hybrid closed-loop system for 3 months. With approval from a Data Safety and Monitoring Board, the identical pilot testing will be repeated in subjects age 12 to 21 years (the FDA's recommended formal and strict definition of pediatrics). Phase 2 will be a large- scale, multicenter, multinational phase III randomized clinical trial of MD-Logic compared with SAP in 240 youth aged 12 to 21. The primary outcomes are efficacy, defined as the percentage of blood glucose sensor readings in the target range of 70-180 mg/dL, safety defined as the percentage of blood glucose sensor readings below 70 mg/dL, and a secondary efficacy outcome of change in HbA1c over 6 months of continued hybrid closed-loop use. Phase 3 is a proof-of-concept study for MD-Logic's use as a full closed-loop system in adults. In its entirety, this cutting-edge research project has potential to become a major milestone on the pathway to commercialization of a full closed-loop solution for 24/7 treatment in patients with T1D.