Final clinical studies for submission of a pre-market approval application to the FDA for a Bionic Pancreas that automates type 1 diabetes management

 描述（由申请人提供）：我们已经在1型糖尿病（T1 D）患者的住院和真实门诊研究中构建并广泛测试了我们的双激素仿生胰腺（BP）。通过波士顿大学（BU）和马萨诸塞州总医院（MGH）之间为期八年的合作，我们已经完成了三项为期1天和2天的住院研究，测试了笔记本电脑版本的BP，以及三项为期5天的门诊研究，测试了iPhone版本的BP在T1 D成人中的应用（在波士顿市中心），患有T1 D的青少年（在糖尿病营地）和患有T1 D的青少年（在糖尿病营地）。在BU、MGH、马萨诸塞州大学医学中心、斯坦福大学和查佩尔山的北卡罗来纳州大学的合作下，我们在T1 D成人中完成了一项为期11天的仿生胰腺多中心门诊研究，在家中和工作场所测试iPhone版本的BP，不限制活动或锻炼。我们最近根据III类医疗器械标准构建了一个新的双激素BP设备平台，该平台集成了一个微精密双输注泵，该泵（1）分别输送胰岛素和胰高血糖素，（2）用作FDA批准的连续葡萄糖监测仪（CGM）的接收器，以及（3）包括我们经过临床测试的数学控制算法套件，该算法可根据以下参数自动确定和控制胰岛素和胰高血糖素的剂量：CGM血糖数据。这个新的设备平台提供了一个交钥匙解决方案，将标准化，简化和改善T1 D治疗。在这里，我们建议进行仿生胰腺移植试验（BPPT），该试验将招募480名患有T1 D的儿童和成人（8岁及以上，HbA 1c <11%），以测试和鉴定BP的完全集成版本，并提供向FDA申请上市前批准（PMA）所需的所有临床数据。我们建议通过以下具体目标实现这一目标：（1）在人为因素研究中评价BP的可用性，必要时根据研究结果完善器械和用户界面，并在小型门诊可行性研究中对其功能进行鉴定（仿生胰腺桥接研究）;以及（2）进行BPPT，以测试最终BP系统在控制压力方面的安全性和有效性（HbA 1c和CGM葡萄糖测量值< 60 mg/dl的百分比的共同主要结局），以评价我们的技术相对于常规护理的行为和心理社会影响，并提供关于长期胰高血糖素给药安全性的数据，足以用于该器械的新使用适应症。

 DESCRIPTION (provided by applicant): We have built and extensively tested our bihormonal bionic pancreas (BP) in inpatient and real-world outpatient studies in subjects with type 1 diabetes (T1D). Through an eight-year collaboration between Boston University (BU) and the Massachusetts General Hospital (MGH), we have completed three 1- and 2-day inpatient studies testing a laptop version of the BP and three 5-day outpatient studies testing an iPhone version of the BP in adults with T1D (in downtown Boston), adolescents with T1D (in a diabetes camp), and pre-adolescents with T1D (in a diabetes camp). In collaboration among BU, MGH, the University of Massachusetts Medical Center, Stanford University, and the University of North Carolina, Chapel Hill, we completed an 11-day Bionic Pancreas Multi-Center outpatient study in adults with T1D testing the iPhone version of the BP at home and in the workplace without restrictions on activity or exercise. We have recently built a new bihormonal BP device platform in accordance with Class III medical device standards that integrates a microprecision dual-infusion pump that (1) separately delivers insulin and glucagon, (2) acts as a receiver for an FDA-cleared continuous glucose monitor (CGM), and (3) includes our clinically tested suite of mathematical control algorithms that autonomously determines and commands doses of insulin and glucagon based on CGM glucose data. This new device platform provides a turnkey solution that will standardize, simplify, and improve T1D therapy. Here we propose to conduct the Bionic Pancreas Pivotal Trial (BPPT), which will enroll 480 children and adults with T1D (ages 8 and older, HbA1c <11%) to test and qualify the fully integrated version of the BP and to provide all of the clinical data necessary for a pre-market approval (PMA) application to the FDA. We propose to achieve this objective with the following specific aims: (1) to evaluate the usability of the BP in a human factors study, to refine the device and user interface, if necessary, based on the study results, and to qualify its functionality in a small outpatient feasibility study (the Bionic Pancreas Bridging Study); and (2) to conduct the BPPT to test the safety and efficacy of the final BP system in controlling glycemia (with co-primary outcomes of HbA1c and percentage of CGM glucose measurements < 60 mg/dl), to evaluate the behavioral and psychosocial impact of our technology relative to usual care, and to provide data on the safety of chronic glucagon administration sufficient for a new use indication for this device.