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

 描述（由申请人提供）：该项目名为MD 2Go，旨在解决测试人工胰腺（AP）系统的挑战，为1型糖尿病（T1 D）患者开发商用自动胰岛素输送解决方案。由以色列施耐德儿童医疗中心糖尿病技术中心开发的MD-Logic自动胰岛素输送（MD-Logic）系统是一种AP系统，其通过应用模糊逻辑理论来模仿糖尿病护理人员的推理线来建立葡萄糖控制。该系统提供了一种具有实时学习能力的个性化治疗方法，该方法有效地跟踪葡萄糖-胰岛素动力学的不可预测行为， 相应地调整胰岛素。在斯洛文尼亚、德国和以色列的一个多中心联盟中对MD-Logic系统进行了研究。它已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，糖尿病营地环境，以及在家中过夜。最近，该系统在家中进行了测试，每周7天，每天24小时（24/7）;周末（60小时）;以及2周。这些初步研究证明了MD-Logic与传感器增强泵（SAP）系统相比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已在欧洲获得CE认证，成为全球首个获得监管批准的AP软件。只有通过一项旨在产生美国食品和药物管理局（FDA）批准结果的研究，商业化才能充分推进。MD 2Go研究方案的设计是为了，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期研究结合了从之前的预提交会议中获得的FDA指南，包括创新技术，优秀的临床研究中心和顶级协调中心。第1阶段包括在成人中进行MD-Logic的试点测试，以评估在监督、监测的运动和营养挑战期间的安全性和可靠性，同时通过Yellow Springs Instrument（YSI）等效比较确认动态血糖监测仪的准确性。然后，试点受试者将继续使用24/7作为混合闭环系统3个月。在获得数据安全和监测委员会的批准后，将在12至21岁的受试者中重复相同的试点测试（FDA推荐的正式和严格的儿科定义）。II期将是一项在240名12至21岁的青年中进行的比较MD-Logic与SAP的大规模、多中心、多国III期随机临床试验。主要结局为有效性（定义为血糖传感器读数在70-180 mg/dL目标范围内的百分比）、安全性（定义为血糖传感器读数低于70 mg/dL的百分比）和次要有效性结局（持续混合闭环使用6个月期间HbA 1c的变化）。第3阶段是MD-Logic作为成人全闭环系统使用的概念验证研究。总的来说，这个尖端的研究项目有可能成为T1 D患者全天候治疗的全闭环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.