The Insulin-Only Bionic Pancreas Pivotal Trial

• ClinicalTrials.gov Identifier: NCT04200313
• Recruitment Status: Active, not recruiting
• First Posted: December 16, 2019
• Last Update Posted: February 9, 2021
• Sponsor: Jaeb Center for Health Research
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Beta Bionics, Inc.; Boston University; Massachusetts General Hospital
• Information provided by (Responsible Party): Jaeb Center for Health Research

Study Description

Brief Summary:

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 System for 3 months. At the completion of use of the BP system (end of RCT for BP Group and end of Extension Phase for UC Group), 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.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus; Type 1 Diabetes; Diabetes Mellitus, Type 1	Device: Bionic Pancreas	Not Applicable

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, and Fiasp [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 with insulin lispro or insulin aspart 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. Upon completion of the Extension Phase, participants will enter the 2-4 day Transition Phase.

A 2-4 day Transition Phase will be conducted for all participants who complete BP use at either the end of the RCT Period (BP Group) or at the end of the Extension Phase (UC 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.

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):

  o 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 BP Group and 26-week visit for Usual Care Group, for a period of 2-4 days in duration.
• Visit ≤4 days later for end of study

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 440 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Insulin-Only Bionic Pancreas Pivotal Trial: Testing the iLet in Adults and Children With Type 1 Diabetes
• Actual Study Start Date: March 31, 2020
• Estimated Primary Completion Date: August 30, 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bionic Pancreas (BP); Adults and peds will use the Bionic Pancreas (BP) with lispro or aspart for 13 weeks	Device: Bionic Pancreas; 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.; Other Name: iLet
Experimental: Bionic Pancreas with Fiasp (BPFiasp); Adults will use the Bionic Pancreas (BP) with Fiasp for 13 weeks	Device: Bionic Pancreas; 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.; Other Name: iLet
No Intervention: Usual Care (UC); Adults and peds will use their own diabetes regimen

Outcome Measures

Primary Outcome Measures :

1. HbA1c [ Time Frame: HbA1c will be taken at baseline, 6 weeks and 13 weeks ]
   Superiority for HbA1c at 13 weeks will be considered the primary endpoint.

Secondary Outcome Measures :

1. CGM time <54mg/dL (key secondary endpoint) [ Time Frame: 13 weeks ]
   based on sensor glucose ata

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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. 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.

    8. 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:

Inclusion

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. 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.

8. 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

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. Renal failure on dialysis or with an eGFR <30mL/min

    • If eGFR is not available within the last 12 months, it must be obtained as part of usual care in order 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

Contacts and Locations

Locations

United States, California

Children's Hospital of Orange County (Pediatrics)

Orange, California, United States, 92868

University of California - San Diego (Adults)

San Diego, California, United States, 92037

Stanford University (Pediatrics and Adults)

Stanford, California, United States, 94305

United States, Colorado

Barbara Davis Center for Diabetes (Pediatrics and Adults)

Aurora, Colorado, United States, 80045

United States, District of Columbia

Children's National Health System (Pediatrics)

Washington, District of Columbia, United States, 20010

United States, Florida

Nemours Children's Clinic (Pediatrics)

Jacksonville, Florida, United States, 32207

United States, Georgia

Emory University (Pediatrics)

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Massachusetts General Hospital - Diabetes Research Center (Peds and Adults)

Boston, Massachusetts, United States, 02114

United States, Michigan

Henry Ford Health System (Adults)

Detroit, Michigan, United States, 48202

United States, Missouri

Washington University (Adults)

Saint Louis, Missouri, United States, 63110

United States, New York

Naomi Berrie Diabetes Center at Columbia University (Pediatrics)

New York, New York, United States, 10032

United States, North Carolina

University of Noth Carolina- Chapel Hill (Adults)

Chapel Hill, North Carolina, United States, 27517

United States, Ohio

Cleveland Clinic (Adults)

Cleveland, Ohio, United States, 44195

United States, Texas

University of Texas- Southwestern (Pediatrics and Adults)

Dallas, Texas, United States, 75390

University of Texas Health Science Center (Pediatrics)

San Antonio, Texas, United States, 78229

United States, Washington

University of Washington (Adults)

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Jaeb Center for Health Research

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Beta Bionics, Inc.

Boston University

Massachusetts General Hospital

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: Betul Hatipoglu, 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: Bruce Buckingham, MD; Stanford University
• 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

  Study Documents (Full-Text)

Documents provided by Jaeb Center for Health Research:

Informed Consent Form: Screening ICF  [PDF] March 13, 2020

Informed Consent Form: Screening Assent  [PDF] November 1, 2019

Informed Consent Form: Test Run ICF  [PDF] October 6, 2020

Informed Consent Form: Test Run Assent  [PDF] August 12, 2020

More Information

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT04200313
• Other Study ID Numbers: IOBPPT; 1UC4DK108612-01 ( U.S. NIH Grant/Contract )
• First Posted: December 16, 2019
• Last Update Posted: February 9, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Jaeb Center for Health Research:

Artificial Pancreas; Closed-loop Insulin Delivery

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Pancrelipase; Gastrointestinal Agents