The Insulin-Only Bionic Pancreas Pivotal Trial

Primary Objective • To compare the efficacy and safety of the insulin-only configuration of the iLet BP System (using insulin lispro, insulin aspart) the BP System using Fiasp (BPFiasp) \[adults only\]) in maintaining near-normal glycemia relative to usual care in a home-use study in adults and children with T1D. Secondary Objectives • To assess the impact of the insulin-only configuration of the iLet BP System on quality of life and treatment satisfaction. The study has four major parts: (1) the Test-Run Phase, (2) the RCT Period, (3) the Extension Phase for the UC Arm, and (4) the Transition Phase. These four parts are described below, and detailed in the main part of the protocol. A Test-Run Phase will be conducted to (1) test the functionality of all aspects of the iLet BP System, (2) train the clinical staff on the execution of the clinical protocol, and (3) provide hands-on training with the device prior to initiating the RCT Period. The initial test run will be conducted at one site (MGH) with \~5 participants using the iLet BP system for 4-7 days. If there are no safety or consequential device issues, a test run will be conducted at each of the other 15 sites, with \~2 participants per site using the iLet BP system for 4-7 days. The iLet BP system will use insulin lispro or insulin aspart. Results of this Test-Run Phase will be evaluated for safety prior to beginning the RCT Period as described in section 3.3. The 13-week, parallel-group, multi-center RCT Period is designed to compare the insulin-only iLet BP Group using insulin lispro, insulin aspart, or Fiasp (adults only); and a control group following usual care (UC Group). Upon completion of the RCT Period, the BP Group will enter the 2-4 day Transition Phase and the UC Group will enter the Extension Phase. The UC Group Extension Phase will immediately follow the RCT Period. Participants from the UC Group who complete the primary outcome visit, miss no more than 3 of the maximum possible number of the weekly questionnaires, attend all clinic visits, and follow study procedures for collecting CGM data during the RCT Period, will be given the option to use the iLet BP system for 13 weeks. The visit schedule and procedures for the Extension Phase will be similar to that of the BP Group in the RCT Period. A 2-4 day Transition Phase will be conducted for all participants who complete BP use at the end of the RCT Period (BP Group). Participants will be randomly assigned (1:1) to either transition back to their usual mode of therapy (MDI or pump therapy) based on therapeutic guidance from the iLet BP system or transition back to their usual mode of therapy based on what their own insulin regimens were prior to enrolling in the RCT Period. For those randomized to using their pre-study regimens, the dosing can be adjusted by the investigator to mitigate safety issues but should follow pre-study regimen as closely as possible. An optional ancillary study will be offered to participants who are using the iLet at the time of the 13-week randomized trial visit. This will will assess the safety of utilizing blood glucose measurements instead of CGM measurements as input into the iLet for \~48-60 hours. It will be completed at the end of the RCT for those in the BP Group prior to the Transition Phase. Test-Run Visit and Phone Contact Schedule * Screening Visit - Eligibility assessed, informed consent, point-of-care/local HbA1c, testing and procedures similar to the RCT Screening Visit including psychosocial questionnaires; if eligible, BP system started. o For participants who completed the separate screening protocol, eligibility will be reassessed. Point-of-care/local HbA1c will be obtained if more than 28 days have elapsed. Participants will not need to repeat the psychosocial questionnaires. * Phone contact after 1-2 days * Shut-down visit at the end of the study period 4-7 days RCT Period Visit and Phone Contact Schedule * Screening Visit (which may be completed as part of a separate screening protocol) * Eligibility assessed, informed consent signed, point-of-care/local HbA1c, psychosocial questionnaires completed, blinded Dexcom G6 CGM sensor placed for non Dexcom G6 users. * For baseline data collection, participants using a personal Dexcom G6 who have at least 85% of possible glucose data in last 14 days can skip the blinded CGM wear * Participants using a personal Dexcom G6 with \<85% of data will use their personal Dexcom G6. * For participants who completed the separate screening protocol, eligibility will be reassessed. Point-of-care/local HbA1c will be obtained if more than 28 days have elapsed. Participants will not need to repeat the psychosocial questionnaires or blinded CGM wear. * If the separate screening protocol or Test Run Phase of this protocol was completed or blinded CGM wear is not needed, randomization can proceed immediately. If blinded CGM wear was performed as part of this protocol, randomization visit will occur14-21 days after screening. * Prior to randomization, eligibility will be reassessed and blood drawn for central lab HbA1c * BP study start/UC study start on day of Randomization Visit * Phone contacts after 1-2 days and 7 (±2) days * Visits at 2 weeks (±4 days), 6 weeks (±4 days), 10 weeks (±4 days), and \~13 weeks (91-98 days from randomization): * Participants in the UC Group will wear a blinded Dexcom G6 sensor throughout the entire study unless they are current users of the Dexcom G6 CGM, in which case they will continue to use their own Dexcom G6 CGM. * At the 6-week and 13-week visits, central lab HbA1c determination and psychosocial questionnaires UC Group Extension Phase Visit and Phone Contact Schedule * BP initiation at 13-week visit * Phone contacts after 13 weeks plus 1-2 days and 14 weeks (±2 days) * Visits at 15 weeks (± 4 days), 19 (±4 days), 23 (±4 days), and \~26 weeks (182-189 days): * At the 19-week and 26-week visits, central lab HbA1c determination and psychosocial questionnaires Transition Phase Visit Schedule * Randomization and transition to UC regimen at 13-week visit for RCT BP Group for a period of 2-4 days in duration. * Visit ≤4 days later for end of study Ancillary Study Day 1 (13-week visit of the RCT) - stop CGM, start blinded CGM, start SMBG at least every 2 hours during waking hours and at least once during each overnight for the next 48-60hrs. Day 2: Phone call for safety Day 3: stop iLet, stop blinded CGM, restart unblinded CGM, enter Transition Phase.