The Insulin-Only Bionic Pancreas Pivotal Trial

Study Design & Population

Study type: Interventional
Phase: N/A
Interventions: Bionic Pancreas (BP) with Aspart or Lispro (Combination_product); Bionic Pancreas with Fiasp (BPFiasp) (Combination_product); Usual Care (UC) (Other); BP Guidance Insulin Dosing (Other)
Age: Pediatric, Adult, Older Adult · 6+ yrs
Sex: All
Sponsor: Jaeb Center for Health Research
Primary completion: Oct 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY HbA1c	56; 54; 61	<0.001 sig
SECONDARY Non-inferiority for CGM-measured Time <54 mg/dL (Key Secondary Endpoint)	0.33; 0.26; 0.24	<0.001 sig
SECONDARY CGM-measured Mean Glucose Level Over 13 Weeks	164; 155; 181	<0.001 sig
SECONDARY CGM-measured Percentage Time 70-180 mg/dL Over 13 Weeks	65; 71; 54	<0.001 sig
SECONDARY CGM-measured Percentage Time >180 mg/dL Over 13 Weeks	33; 27; 44	<0.001 sig
SECONDARY CGM-measured Percentage Time >250 mg/dL Over 13 Weeks	8.5; 4.8; 14.9	<0.001 sig
SECONDARY CGM-measured Glucose Standard Deviation (SD) mg/dL Over 13 Weeks	60; 52; 67	<0.001 sig
SECONDARY CGM-Measured Percentage Time <70 mg/dL Over 13 Weeks	1.8; 1.7; 1.8	0.51
SECONDARY CGM-measured Percentage Time <54 mg/dL Over 13 Weeks	0.33; 0.26; 0.24	—
SECONDARY CGM-Measured Glucose Coefficient of Variation Over 13 Weeks	36; 33; 37	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c <7.0%	65; 49; 27	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c <7.0% in Participants With Baseline HbA1c >7.5%	15; 18; 2	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c <7.5%	128; 86; 40	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c <8.0%	182; 105; 73	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c >9.0%	1; 1; 13	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c Improvement >0.5%	100; 62; 13	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0%	55; 30; 5	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c Relative Improvement >10%	72; 42; 5	—
SECONDARY Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0% or HbA1c <7.0% at 13 Weeks	108; 66; 30	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-140 mg/dL Over 13 Weeks	39; 43; 33	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-120 mg/dL Over 13 Weeks	23; 25; 21	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <60 mg/dL Over 13 Weeks	0.7; 0.5; 0.6	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Area Over the Curve 70 mg/dL Over 13 Weeks	0.18; 0.15; 0.16	—
SECONDARY Other Secondary Efficacy Endpoint: Low Blood Glucose Index (LBGI)	0.54; 0.55; 0.52	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Hypoglycemic Events	0.68; 0.53; 0.48	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Hyperglycemic Events	0.9; 0.4; 2.1	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Percentage Time >300 mg/dL Over 13 Weeks	2.4; 1.0; 6.0	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Area Under the Curve 180 mg/dL Over 13 Weeks	17.2; 10.8; 26.2	—
SECONDARY Other Secondary Efficacy Endpoint: High Blood Glucose Index (HBGI)	7.4; 5.8; 10.0	—
SECONDARY Other Secondary Efficacy Endpoint: Mean of Daily Difference in Mean Glucose	20; 16; 30	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-180 mg/dL >70% Over 13 Weeks	56; 65; 23	—
SECONDARY Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5%	159; 90; 55	—
SECONDARY Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10%	146; 84; 43	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <70 mg/dL <4%	194; 109; 86	—
SECONDARY Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <54 mg/dL <1%	190; 108; 88	—
SECONDARY Other Secondary Efficacy Endpoint: Blood Glucose Risk Index (LBGI + HBGI)	8.0; 6.3; 10.7	—
SECONDARY 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%	104; 62; 15	—
SECONDARY 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%	120; 74; 25	—
SECONDARY Other Secondary Efficacy Endpoint: Mean Glucose <154 mg/dL and Time <54 mg/dL <1%	46; 51; 17	—
SECONDARY Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL >70% and Time <54 mg/dL <1%	52; 63; 16	—
SECONDARY Other Secondary Efficacy Endpoint: Total Daily Insulin (Units/kg)	0.86; 0.65; 0.81	—
SECONDARY 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	5; 6	—
SECONDARY Other Secondary Efficacy Endpoint: Body Weight at Week 13	69; 84; 70	—
SECONDARY Other Secondary Efficacy Endpoint: Body Mass Index (BMI) at Week 13	25.5; 29.2; 25.2	—
SECONDARY Other Secondary Efficacy Endpoint: Mean Participant-reported Number of Hypoglycemic Events Requiring Carbohydrate Treatment Per 24 Hours	1.0; 0.9; 0.8	—
SECONDARY Other Secondary Efficacy Endpoint: Mean Participant-reported Grams of Carbohydrate Taken Specifically to Prevent or Treat Hypoglycemic Events Per 24 Hours	12.7; 12.6; 12.5	—

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 (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).

Eligibility 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
Age ≥ 6 years old
Exception: the initial 5-participant test run will be limited to >18 years old
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).
Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial
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.
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.
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

Unable to provide informed consent (e.g. impaired cognition or judgment)
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)
Unable to speak and read English
For pediatric participants, both caregivers and participants must be able to speak and read English
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.
Current use of non-FDA approved closed-loop or hybrid closed-loop insulin delivery system
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
Known hemoglobinopathy (sickle cell trait is not an exclusion)
Current participation in another diabetes-related clinical trial
History of cystic fibrosis, pancreatitis, or other pancreatic disease, including pancreatic tumor or insulinoma, or history of complete pancreatectomy
Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference
Established history of allergy or severe reaction to adhesive or tape that must be used in the study
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).
Pregnant (positive urine hCG), breast feeding, plan to become pregnant in the next 3 months, or sexually active without use of contraception
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 a

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