The Insulin-Only Bionic Pancreas Pivotal Trial

The Insulin-Only Bionic Pancreas Pivotal Trial: Testing the iLet in Adults and Children With Type 1 Diabetes

This multi-center randomized control trial (RCT) will compare efficacy and safety endpoints using the insulin-only configuration of the iLet Bionic Pancreas (BP) System versus Usual Care (UC) during a 13-week study period. Participants may be enrolled initially into a screening protocol and then transfer into the RCT protocol, or they may enter directly into the RCT protocol. The RCT will be followed by an Extension Phase in which the RCT Usual Care (UC) Group will use the insulin-only configuration of the iLet Bionic Pancreas (BP) System for 3 months. At the completion of use of the BP system in the RCT only, participants will enter a 2-4 day Transition Phase and be randomly assigned 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.

There is an optional ancillary study to assess the safety of utilizing self-monitored blood glucose (SMBG) measurements instead of continuous glucose monitor (CGM) measurements as input into the iLet for ~48-60 hours. The Study is intended to mirror a real-world situation where CGM may not be available for an extended period of time (eg, user runs out of sensors and is awaiting new shipment).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Diabetes Mellitus, Type 1; Type 1 Diabetes
• Intervention / Treatment: Combination product: Bionic Pancreas (BP) with Aspart or Lispro; Combination product: Bionic Pancreas with Fiasp (BPFiasp); Other: Usual Care (UC); Other: BP Guidance Insulin Dosing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 440
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County (Pediatrics)
    • San Diego, California, United States, 92037
      • University of California - San Diego (Adults)
    • Stanford, California, United States, 94305
      • Stanford University (Pediatrics and Adults)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center for Diabetes (Pediatrics and Adults)
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System (Pediatrics)
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic (Pediatrics)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University (Pediatrics)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital - Diabetes Research Center (Peds and Adults)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System (Adults)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University (Adults)
  • New York
    • New York, New York, United States, 10032
      • Naomi Berrie Diabetes Center at Columbia University (Pediatrics)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • University of Noth Carolina- Chapel Hill (Adults)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic (Adults)
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas- Southwestern (Pediatrics and Adults)
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center (Pediatrics)
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington (Adults)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Clinical diagnosis of T1D for at least one year and using insulin for at least 1 year 2. Diabetes managed using the same regimen (either pump or MDI, with or without CGM) for ≥ 3 months

  3. Age ≥ 6 years old

  • Exception: the initial 5-participant test run will be limited to >18 years old

    4. Current use of a CGM, or if not a CGM user, at least 3 blood glucose meter tests daily on average over the last 4 weeks (according to judgment of investigator if meter is not available).

    5. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial

    6. For participants <18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia.

    7. For participants >18 years old who live alone, participant has a relative or acquaintance who lives within 30 minutes of participant and is willing to be contacted to check on participant if study staff feel that participant may be experiencing a medical emergency and can't be reached.

    8. Investigator believes that the participant can safely use the iLet and will follow the protocol

  • The investigator will take into account the participant's HbA1c level, compliance with current diabetes management, and prior acute diabetic complications. For this reason, there is no upper limit on HbA1c specified for eligibility.

    9. If a GLP-1 agonist or pramlintide is being used, participant must be willing to discontinue use while the iLet BP system is being used, including the randomized trial and extension study.

Exclusion Criteria:

• Eligibility may be assessed initially in a separate screening protocol or at a screening visit in the RCT protocol. To be eligible for all phases of the study, a participant must meet all of the following inclusion criteria and none of the exclusion criteria:

Exclusion

1. Unable to provide informed consent (e.g. impaired cognition or judgment)
2. Unable to safely comply with study procedures and reporting requirements (e.g. impairment of vision or dexterity that prevents safe operation of the bionic pancreas, impaired memory)

3. Unable to speak and read English

   • For pediatric participants, both caregivers and participants must be able to speak and read English

4. Plan to change usual diabetes regimen in the next 3 months

   • This would include changing from MDI to pump. pump to MDI, change in insulin automation delivery system, starting a CGM if not previously used, changes in drug therapy specifically for glucose control except for changes in one insulin analog to another.
   • Changes in insulin dose, carb ratio, sensitivity factor and basal rate profile are allowed.
5. Current use of non-FDA approved closed-loop or hybrid closed-loop insulin delivery system
6. Use of Apidra as the pre-study rapid-acting insulin analog and unwilling to switch to lispro or aspart for the duration of the study
7. Known hemoglobinopathy (sickle cell trait is not an exclusion)
8. Current participation in another diabetes-related clinical trial
9. History of cystic fibrosis, pancreatitis, or other pancreatic disease, including pancreatic tumor or insulinoma, or history of complete pancreatectomy
10. Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference
11. Established history of allergy or severe reaction to adhesive or tape that must be used in the study

12. Current use of SGLT2 inhibitors or a sulfonylurea drug (use more than 3 months prior to enrollment is acceptable)

    • If using GLP1 agonist, pramlintide, or metformin drugs must be on a stable dose for 3 months prior to enrollment (and as per inclusion criterion #8, must be willing to discontinue use of GLP-1 agonist or pramlintide while using the iLet BP system during the RCT and the extension phase).

13. Pregnant (positive urine hCG), breast feeding, plan to become pregnant in the next 3 months, or sexually active without use of contraception

14. For adults >18 years old, most recent (must be within the last 2 years) eGFR <30 ml/min OR currently in renal failure on dialysis

    • If no eGFR is available for an adult participant during the last 2 years, one must be obtained to confirm eligibility

15. Presence of a medical condition or use of a medication that, in the judgment of the investigator, clinical protocol chair, or medical monitor, could compromise the results of the study or the safety of the participant. Conditions to be considered by the investigator may include the following:

    • Alcohol or drug abuse
    • Use of prescription drugs that may dull the sensorium, reduce sensitivity to symptoms of hypoglycemia, or hinder decision making during the period of participation in the study
    • Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g. climbing a flight of stairs) despite medical management, or within the last 12 months before screening a history of myocardial infarction, percutaneous coronary intervention, enzymatic lysis of a presumed coronary occlusion, or coronary artery bypass grafting
    • Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV
    • History of TIA or stroke in the last 12 months
    • Untreated or inadequately treated mental illness
    • History of eating disorder within the last 2 years, such as anorexia, bulimia, or diabulemia or omission of insulin to manipulate weight
    • History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
16. Employed by, or having immediate family members employed by Beta Bionics, or being directly involved in conducting the clinical trial, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bionic Pancreas (BP); Some adults and 1/2 peds will be randomized to use the Bionic Pancreas (BP) with lispro or aspart for 13 weeks	Combination product: Bionic Pancreas (BP) with Aspart or Lispro; iLet Bionic Pancreas System, which consists of an integrated infusion pump, touchscreen display, Bluetooth radio, and insulin dosing algorithms, that automatically controls insulin delivery based on glucose values obtained by communicating with a Dexcom G6 sensor using lispro or aspart insulin.; Other Names: iLet
Experimental: Bionic Pancreas with Fiasp (BPFiasp); Some adults will be randomized to use the Bionic Pancreas (BP) with Fiasp for 13 weeks during RCT	Combination product: Bionic Pancreas with Fiasp (BPFiasp); iLet Bionic Pancreas System, which consists of an integrated infusion pump, touchscreen display, Bluetooth radio, and insulin dosing algorithms, that automatically controls Fiasp insulin delivery based on glucose values obtained by communicating with a Dexcom G6 sensor.
Other: Usual Care (UC); Adults and peds will use their own diabetes insulin regimen plus continuous glucose monitoring (CGM) during the RCT	Other: Usual Care (UC); Using pre-study insulin regimen with the Dexcom G6 CGM
Experimental: Transition Phase - BP Guidance; Adults and peds will use their own diabetes insulin regimen plus SMBG and blinded continuous glucose monitoring (CGM) in the Transition phase and use dosing based on guidance from the BP system	Other: Usual Care (UC); Using pre-study insulin regimen with the Dexcom G6 CGM; Other: BP Guidance Insulin Dosing; Pre-study insulin delivery method with SMBG and blinded CGM with dosing guidance by the BP
Other: Transition- Pre-study dosing; Adults and peds will use their own diabetes insulin regimen plus SMBG and blinded continuous glucose monitoring (CGM) in the Transition phase and use dosing based on their pre-study regimen	Other: Usual Care (UC); Using pre-study insulin regimen with the Dexcom G6 CGM
Experimental: Bionic Pancreas Extension; Used by all participants in the EXT study	Combination product: Bionic Pancreas (BP) with Aspart or Lispro; iLet Bionic Pancreas System, which consists of an integrated infusion pump, touchscreen display, Bluetooth radio, and insulin dosing algorithms, that automatically controls insulin delivery based on glucose values obtained by communicating with a Dexcom G6 sensor using lispro or aspart insulin.; Other Names: iLet; Combination product: Bionic Pancreas with Fiasp (BPFiasp); iLet Bionic Pancreas System, which consists of an integrated infusion pump, touchscreen display, Bluetooth radio, and insulin dosing algorithms, that automatically controls Fiasp insulin delivery based on glucose values obtained by communicating with a Dexcom G6 sensor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	The primary outcome is superiority for central lab hemoglobin A1c at 13 weeks. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority for CGM-measured Time <54 mg/dL (Key Secondary Endpoint)	The key secondary endpoint is CGM-measured time <54 mg/dL over 13 weeks	13 weeks
CGM-measured Mean Glucose Level Over 13 Weeks		13 weeks
CGM-measured Percentage Time 70-180 mg/dL Over 13 Weeks		13 weeks
CGM-measured Percentage Time >180 mg/dL Over 13 Weeks		13 weeks
CGM-measured Percentage Time >250 mg/dL Over 13 Weeks		13 weeks
CGM-measured Glucose Standard Deviation (SD) mg/dL Over 13 Weeks		13 weeks
CGM-Measured Percentage Time <70 mg/dL Over 13 Weeks		13 weeks
CGM-measured Percentage Time <54 mg/dL Over 13 Weeks		13 weeks
CGM-Measured Glucose Coefficient of Variation Over 13 Weeks		13 weeks
Other Secondary Efficacy Endpoint: HbA1c <7.0%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c <7.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c <7.0% in Participants With Baseline HbA1c >7.5%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c <7.0% at week 13 in participants with baseline HbA1c >7.5%. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c <7.5%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c <7.5% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c <8.0%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c <8.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c >9.0%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c >9.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c Improvement >0.5%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c improvement >0.5% from baseline to week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c improvement >1.0% from baseline to week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c Relative Improvement >10%	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c relative improvement >10% from baseline to week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0% or HbA1c <7.0% at 13 Weeks	Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c improvement >1.0% from baseline to week 13 or central lab hemoglobin A1c <7.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-140 mg/dL Over 13 Weeks		13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-120 mg/dL Over 13 Weeks		13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <60 mg/dL Over 13 Weeks		13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Area Over the Curve 70 mg/dL Over 13 Weeks	Area over the curve 70 mg/dL over the 13-week RCT period, measured as the mean of the differences between 70 mg/dL and CGM-measured glucose values below 70 mg/dL. For CGM-measured glucose values above 70 mg/dL, a value of 0 is used instead of the difference. For example, suppose a participant has 10 glucose readings of 78, 60, 59, 71, 80, 100, 110, 115, 120, and 118 mg/dL measured every 5 minutes. The distance between each reading below 70 mg/dL and 70 mg/dL is 0, 10, 11, 0, 0, 0, 0, 0, 0, and 0 mg/dL. The total area is 105 mg/dL*min; however, this value is then standardized by dividing by the length of time (50 min), resulting in a final CGM-measured area over the curve 70 mg/dL of 2.1 mg/dL.	13 weeks
Other Secondary Efficacy Endpoint: Low Blood Glucose Index (LBGI)	Other Secondary Efficacy Endpoint: CGM-measured low blood glucose index (LBGI) over 13 weeks. Ranges from 0 to 38.20, with higher values indicating more low CGM-measured glucose values over 13 weeks. Higher values are considered a worse outcome.	13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Hypoglycemic Events	Other Secondary Efficacy Endpoint: CGM-measured hypoglycemic event (at least 15 consecutive minutes with a sensor reading <54 mg/dL) rate over 13 weeks	13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Hyperglycemic Events	Other Secondary Efficacy Endpoint: CGM-measured hyperglycemic event (at least 90 minutes within a 120 minute period with a sensor reading >300 mg/dL) rate over 13 weeks	13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time >300 mg/dL Over 13 Weeks		13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Area Under the Curve 180 mg/dL Over 13 Weeks	Area under the curve 180 mg/dL over the 13-week RCT period, measured as the mean of the differences between 180 mg/dL and CGM-measured glucose values above 180 mg/dL. For CGM-measured glucose values under 180 mg/dL, a value of 0 is used instead of the difference. For example, suppose a participant has 10 glucose readings of 100, 120, 182, 200, 250, 193, 179, 150, 140 and 118 mg/dL measured every 5 minutes. The distance between each reading above 180 mg/dL and 180 mg/dL is 0, 0, 2, 20, 70, 13, 0, 0, 0, and 0 mg/dL. The total area is 525 mg/dL*min; however, this value is then standardized by dividing by the length of time (50 min), resulting in a final CGM-measured area under the curve 180 mg/dL of 10.5 mg/dL.	13 weeks
Other Secondary Efficacy Endpoint: High Blood Glucose Index (HBGI)	Other Secondary Efficacy Endpoint: CGM-measured high blood glucose index (HBGI) over 13 weeks. Ranges from 0 to 57.27, with higher values indicating more high CGM-measured glucose values over 13 weeks. Higher values are considered a worse outcome.	13 weeks
Other Secondary Efficacy Endpoint: Mean of Daily Difference in Mean Glucose	Other Secondary Efficacy Endpoint: CGM-measured mean of daily difference in mean glucose over 13 weeks	13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-180 mg/dL >70% Over 13 Weeks		13 weeks
Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5%	Other Secondary Efficacy Endpoint: CGM-measured percentage time in range 70-180 mg/dL improvement from baseline to 13 weeks ≥5%	13 weeks
Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10%	Other Secondary Efficacy Endpoint: CGM-measured percentage time in range 70-180 mg/dL improvement from baseline to 13 weeks ≥10%	13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <70 mg/dL <4%		13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <54 mg/dL <1%		13 weeks
Other Secondary Efficacy Endpoint: Blood Glucose Risk Index (LBGI + HBGI)	Other Secondary Efficacy Endpoint: CGM-measured Blood Glucose Risk Index (LBGI + HBGI) over 13 weeks. Calculated as Low Blood Glucose Index (LBGI) + High Blood Glucose Index (HBGI). Ranges from 0 to 57.27, with higher values indicating more low or high CGM-measured glucose values over 13 weeks. Higher values are considered a worse outcome. LBGI and HBGI are inversely related: the presence of a high CGM-measured glucose reading removes an opportunity for a low glucose reading to exist and vice versa, therefore a maximum HBGI of 57.27 and a maximum LGBI of 38.20 cannot exist simultaneously. For instance, if a participant had glucose values of only 401 mg/dL, then the participant has no low glucose values, and therefore their HBGI = 57.27 and LBGI = 0. If a participant had only glucose values of 39 mg/dL, then the participant has no high glucose values, and therefore their HBGI = 0 and LBGI = 38.20. Consequently, the maximum blood glucose risk index is 57.27.	13 weeks
Other Secondary Efficacy Endpoint: Improvement in HbA1c > 0.5% Without an Increase in Time < 54 mg/dl by > 0.5% OR Improvement in Time < 54 mg/dl by > 0.5% Without an Increase in HbA1c by > 0.5%	Other Secondary Efficacy Endpoint: Baseline to week 13 improvement in central lab hemoglobin A1c >0.5% without an increase in CGM-measured percentage time <54 mg/dl by >0.5% OR improvement in CGM-measured percentage time <54 mg/dl by >0.5% without an increase in central lab hemoglobin A1c by >0.5%. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks
Other Secondary Efficacy Endpoint: Improvement in Time 70-180 mg/dl by >10% Without an Increase in Time < 54 mg/dl by > 0.5% OR Improvement in Time < 54 mg/dl by > 0.5% Without a Decrease in Time 70-180 mg/dl by > 10%	Other Secondary Efficacy Endpoint: Baseline to 13-week improvement in CGM-measured percentage time 70-180 mg/dL by >10% without an increase in CGM-measured percentage time <54 mg/dL by >0.5% OR improvement in CGM-measured percentage time <54 mg/dL by >0.5% without a decrease in CGM-measured percentage time 70-180 mg/dL by >10%	13 weeks
Other Secondary Efficacy Endpoint: Mean Glucose <154 mg/dL and Time <54 mg/dL <1%	Other Secondary Efficacy Endpoint: CGM-measured mean glucose <154 mg/dL and percentage time <54 mg/dL <1% over 13 weeks	13 weeks
Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL >70% and Time <54 mg/dL <1%	Other Secondary Efficacy Endpoint: CGM-measured percentage time in range 70-180 mg/dL >70% and percentage time <54 mg/dL <1% over 13 weeks	13 weeks
Other Secondary Efficacy Endpoint: Total Daily Insulin (Units/kg)	Other Secondary Efficacy Endpoint: Total daily insulin (units/kg) from week 13 site-reported insulin data for the UC group and iLet pump device data over 13 weeks for the BP-A/L and BP-F groups.	13 weeks
Other Secondary Efficacy Endpoint: Percentage Change in the TDD of Insulin Over the First Two-week Period Relative to the TDD of Insulin in the Last Two-week Period	Other Secondary Efficacy Endpoint: Percentage change in the TDD of insulin over the first two-week period relative to the TDD of insulin in the last two-week period from iLet pump device data over 13 weeks for the BP-A/L and BP-F groups.	Weeks 1-2 and weeks 12-13
Other Secondary Efficacy Endpoint: Body Weight at Week 13		13 weeks
Other Secondary Efficacy Endpoint: Body Mass Index (BMI) at Week 13		13 weeks
Other Secondary Efficacy Endpoint: Mean Participant-reported Number of Hypoglycemic Events Requiring Carbohydrate Treatment Per 24 Hours	Mean participant-reported number of hypoglycemic events requiring carbohydrate treatment per 24 hours, based on the responses to the question, 'How many times in the last 24 hours did you take carbohydrates to treat a low blood sugar?' administered to participants once weekly during the 13-week RCT period.	13 weeks
Other Secondary Efficacy Endpoint: Mean Participant-reported Grams of Carbohydrate Taken Specifically to Prevent or Treat Hypoglycemic Events Per 24 Hours	Mean participant-reported number of hypoglycemic events requiring carbohydrate treatment per 24 hours, based on the responses to the question, 'Estimate the total amount of grams of carbohydrates you were given to treat these low blood sugars', which is a follow-up question to 'How many times in the last 24 hours did you take carbohydrates to treat a low blood sugar?'. Both questions were administered to participants once weekly during the 13-week RCT period.	13 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome Measure: Severe Hypoglycemia Events	Safety Outcome Measure: Severe hypoglycemia (SH) events with cognitive impairment requiring assistance of a third party for treatment.	13 weeks
Safety Outcome Measure: Diabetic Ketoacidosis Events	Safety Outcome Measure: Diabetic ketoacidosis events (DKA) over 13 weeks as defined by the Diabetes Control and Complications Trial: symptoms such as polyuria, polydipsia, nausea, or vomiting; serum ketones >1.5 mmol/L or large/moderate urine ketones; either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15; and treatment provided in a health care facility.	13 weeks
Safety Outcome Measure: Other Serious Adverse Events	Safety Outcome Measure: Serious adverse events excluding SH and DKA	13 weeks
Safety Outcome Measure: Worsening of HbA1c by >0.5%	Safety Outcome Measure: Worsening of central lab hemoglobin A1c from baseline to week 13 by >0.5%. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.	13 weeks

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: Boston University; Massachusetts General Hospital; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Beta Bionics, Inc.
• Investigators: Principal Investigator: R. Paul Wadwa, MD, University of Colorado, Denver; Principal Investigator: Mark Daniels, MD, Children's Hospital of Orange County; Principal Investigator: Fran Cogen, MD, Children's National Health System; Principal Investigator: Keren Zhou, MD, The Cleveland Clinic; Principal Investigator: Andrew Muir, MD, Emory University; Principal Investigator: Davida Kruger, NP, Henry Ford Health System; Principal Investigator: Steven J Russell, MD, Massachusetts General Hospital; Principal Investigator: Robin Goland, MD, Naomi Berrie Center - Columbia University; Principal Investigator: Nelly Mauras, MD, Nemours Children's Health System; Principal Investigator: Jeremy Pettus, MD, UC-San Diego; Principal Investigator: John Buse, MD, University of North Carolina, Chapel Hill; Principal Investigator: Irl Hirsch, MD, University of Washington; Principal Investigator: Jane Lynch, MD, UT Health Science Center - San Antonio; Principal Investigator: Perrin White, MD, University of Texas, Southwestern Medical Center at Dallas; Principal Investigator: Janet McGill, MD, Washington University School of Medicine; Principal Investigator: Jill Weissberg-Benchell, PhD, Lurie Children's Hospital; Study Director: Roy Beck, MD, PhD, Jaeb Center for Health Research; Study Director: Katrina Ruedy, MSPH, Jaeb Center for Health Research; Principal Investigator: Philip Raskin, MD, UT Southwestern; Principal Investigator: Bruce Buckingham, MD, Stanford University

Publications and helpful links

General Publications

• Lynch J, Kanapka LG, Russell SJ, Damiano ER, El-Khatib FH, Ruedy KJ, Balliro C, Calhoun P, Beck RW. The Insulin-Only Bionic Pancreas Pivotal Trial Extension Study: A Multi-Center Single-Arm Evaluation of the Insulin-Only Configuration of the Bionic Pancreas in Adults and Youth with Type 1 Diabetes. Diabetes Technol Ther. 2022 Oct;24(10):726-736. doi: 10.1089/dia.2022.0341.
• Messer LH, Buckingham BA, Cogen F, Daniels M, Forlenza G, Jafri RZ, Mauras N, Muir A, Wadwa RP, White PC, Russell SJ, Damiano ER, El-Khatib FH, Ruedy KJ, Balliro CA, Li Z, Marak MC, Calhoun P, Beck RW. Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial. Diabetes Technol Ther. 2022 Oct;24(10):712-725. doi: 10.1089/dia.2022.0201.pub.
• Mauras N, Damiano ER, El-Khatib FH, Marak MC, Calhoun P, Ruedy KJ, Balliro C, Li Z, Beck RW, Russell SJ. Utility and Safety of Backup Insulin Regimens Generated by the Bionic Pancreas: A Randomized Study. Diabetes Technol Ther. 2023 Jun;25(6):437-441. doi: 10.1089/dia.2022.0461. Epub 2023 Mar 22.
• Li Z, Calhoun P, Ruedy KJ, Beck RW. Concordance of Central Laboratory Hemoglobin A1c Measurements from Capillary Kits Compared to Venous Draws in the Insulin-Only Bionic Pancreas Pivotal Trial. Diabetes Technol Ther. 2023 Jul;25(7):513-515. doi: 10.1089/dia.2023.0094. Epub 2023 May 2.
• Kruger D, Kass A, Lonier J, Pettus J, Raskin P, Salam M, Trikudanathan S, Zhou K, Russell SJ, Damiano ER, El-Khatib FH, Ruedy KJ, Balliro C, Li Z, Marak MC, Calhoun P, Beck RW. A Multicenter Randomized Trial Evaluating the Insulin-Only Configuration of the Bionic Pancreas in Adults with Type 1 Diabetes. Diabetes Technol Ther. 2022 Oct;24(10):697-711. doi: 10.1089/dia.2022.0200.
• Beck RW, Russell SJ, Damiano ER, El-Khatib FH, Ruedy KJ, Balliro C, Li Z, Calhoun P. A Multicenter Randomized Trial Evaluating Fast-Acting Insulin Aspart in the Bionic Pancreas in Adults with Type 1 Diabetes. Diabetes Technol Ther. 2022 Oct;24(10):681-696. doi: 10.1089/dia.2022.0167.
• Bionic Pancreas Research Group; Russell SJ, Beck RW, Damiano ER, El-Khatib FH, Ruedy KJ, Balliro CA, Li Z, Calhoun P, Wadwa RP, Buckingham B, Zhou K, Daniels M, Raskin P, White PC, Lynch J, Pettus J, Hirsch IB, Goland R, Buse JB, Kruger D, Mauras N, Muir A, McGill JB, Cogen F, Weissberg-Benchell J, Sherwood JS, Castellanos LE, Hillard MA, Tuffaha M, Putman MS, Sands MY, Forlenza G, Slover R, Messer LH, Cobry E, Shah VN, Polsky S, Lal R, Ekhlaspour L, Hughes MS, Basina M, Hatipoglu B, Olansky L, Bhangoo A, Forghani N, Kashmiri H, Sutton F, Choudhary A, Penn J, Jafri R, Rayas M, Escaname E, Kerr C, Favela-Prezas R, Boeder S, Trikudanathan S, Williams KM, Leibel N, Kirkman MS, Bergamo K, Klein KR, Dostou JM, Machineni S, Young LA, Diner JC, Bhan A, Jones JK, Benson M, Bird K, Englert K, Permuy J, Cossen K, Felner E, Salam M, Silverstein JM, Adamson S, Cedeno A, Meighan S, Dauber A. Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes. N Engl J Med. 2022 Sep 29;387(13):1161-1172. doi: 10.1056/NEJMoa2205225.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2020
• Primary Completion (Actual): October 30, 2021
• Study Completion (Actual): January 14, 2022

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: December 13, 2019
• First Posted (Actual): December 16, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Artificial Pancreas; Closed-loop Insulin Delivery
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Gastrointestinal Agents; Pancrelipase; Pancreatin
• Other Study ID Numbers: IOBPPT; 1UC4DK108612-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes