The Insulin-Only Bionic Pancreas Bridging Study

This study will serve as a transitional study, bridging to larger and longer outpatient
pivotal studies using the insulin-only configuration of the bionic pancreas. This study will
be divided into 5 parts including a test-run period, adult randomized control trial, a
pediatric transitional study session and a pediatric randomized control period and a
post-study transition back to usual diabetes care.

Test-Run Period: Prior to beginning the Adult RCT Period, 8 adults ≥ 18 years old with T1D
will participate in the Test-Run Period. The Test-Run Period will consist of an uncontrolled,
7-day pilot study testing the iLet in the insulin-only configuration with the Dexcom G5 CGM,
and the insulin analog that they use for their usual care (either Humalog or Novolog).

Adult RCT Period: After the Test-Run Period is completed the data will be reviewed to verify
safety prior to beginning the Adult RCT Period. The Adult RCT Period will consist of a
multi-center, three-period, random-order, cross-over, feasibility study in 36 adult
participants ≥ 18 years old with T1D. Insulin therapy for each participant will be
administered (i) using the iLet in the insulin-only configuration the Dexcom G5 CGM, and the
insulin analog that they use for their usual care (either Humalog or Novolog), (ii) in
another period using the iLet in the insulin-only configuration with faster insulin aspart
(Fiasp) in (iii) in a third period using the participant's own usual care (UC),. All three
experimental periods will be followed by round-the-clock, remote, telemetric monitoring for
hyperglycemia (> 300 mg/dl for ≥ 90 minutes) and hypoglycemia (< 50 mg/dl for ≥ 15 minutes).
Half the subjects will manage their diabetes with MDI and the other half with insulin pumps
in their UC. An implantable Eversense CGM will also be placed in half the study participants
for a CGM comparison.

Pediatric Transitional Study Session: Prior to beginning the Pediatric RCT Period, 20
pediatric participants will take part in the Pediatric Transitional Study Session to assess
the efficacy, safety, and reliability of the insulin-only configuration of the bionic
pancreas in regulating glycemia in pediatric subjects in a more supervised setting prior to
beginning the true outpatient study. The Pediatric Transitional Study Session will consist of
a two-period, random-order, cross-over, pilot study in 20 pediatric participants 6-17 years
old with T1D Insulin therapy for each participant will be administered (i) in one period
using the iLet in the insulin-only configuration with the Dexcom G5 CGM, and the insulin
analog that they use for their usual care (either Humalog or Novolog), and (ii) in the other
period using the participant's own usual care (UC). Both experimental periods will be
followed by round-the-clock, remote, telemetric monitoring for hyperglycemia (> 300 mg/dl for
≥ 90 minutes) and hypoglycemia (< 50 mg/dl for ≥ 15 minutes). The two experimental periods
will each span 5 days, including 4 nights (e.g. Monday-Friday). A washout period of ~ 3 days
in duration will separate the two experimental periods of the Pediatric Transitional Study
Session. All 20 pediatric participants in the Pediatric Transitional Study Session will use
insulin pump therapy for their usual diabetes management.

Pediatric RCT Period: The Pediatric Transitional Study Session will be completed and the data
will be reviewed to verify safety prior to beginning the Pediatric RCT Period. The Pediatric
RCT Period will consist of a multi-center, two-period, random-order, cross-over, feasibility
study in 20 pediatric participants 6-17 years old with T1D Insulin therapy for each
participant will be administered (i) in one period using the iLet in the insulin-only
configuration with the Dexcom G5 CGM, and the insulin analog that they use for their usual
care (either Humalog or Novolog), and (ii) in the other period using the participant's own
usual care (UC), Both experimental periods will be followed by round-the-clock, remote,
telemetric monitoring for hyperglycemia (> 300 mg/dl for ≥ 90 minutes) and hypoglycemia (< 50
mg/dl for ≥ 15 minutes). The two experimental periods will each have a duration of 7 days. A
washout period of approximately 5-9 days in duration will separate the two experimental
periods of the Pediatric RCT. Half of the subjects will be on MDI therapy for their usual
diabetes management; the remaining half will use insulin pump therapy.

Post-Study Transition to Usual Diabetes Management: For 48 hours after the last period of the
RCT Period in both adults and pediatric participants is completed, there will be a small
Post-Study Transition period. Adult and pediatric participants who complete the RCT Period on
an intervention period will transition to their usual care (CSII or MDI) regimen following
the recommendations of the bionic pancreas for 48 hours.

Inclusion Criteria:

1. Clinical diagnosis of type 1 diabetes for at least one year and using insulin for at
least 1 year

2. Diabetes managed using an insulin pump for ≥ 3 months or with multiple daily
injections (approximately 1/2 of participants should use a pump and approximately 1/2
should use MDI)

3. Age ≥18 years (for Test-Run Period and Adult RCT Period); >6 years, up to 17 years
(for Pediatric Transitional Study and Pediatric RCT Period)

• There is no upper age limit in the Adult RCT Period (instead the exclusion criteria
are used to restrict the participants to those healthy enough to participate in the
trial)

4. HbA1c level <11.0%

• A point of care or local lab measurement is used to assess eligibility for
screening.

5. At least 3 SMBG meter tests daily on average or use of a CGM and 2 or more SMBG meter
tests daily on average by history

6. For females, not currently known to be pregnant

• If female, sexually active, and at risk for pregnancy, must agree to use a highly
effective form of contraception to prevent pregnancy while a participant in the study.
A negative urine pregnancy test will be required for all women who are post-menarche
and pre-menopause who are not surgically sterile. Participants who become pregnant
will be discontinued from the study.

7. An understanding of and willingness to follow the protocol and sign the informed
consent and assent where applicable

8. Pediatric Transitional Study Session and Adult Test Run only: an adult (≥ 18 years of
age) willing to serve as an emergency contact person throughout the study

Exclusion Criteria:

-The presence of any of the following is an exclusion for the study:

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 BP, impaired
memory)

3. Unable to speak and read English

4. Currently using for the first time a real-time CGM for < 1 month (Individuals who have
been using CGM for 1 or more months are eligible)

5. Current use of non-FDA approved closed-loop or hybrid closed-loop insulin delivery
system

6. Current use of insulin glulisine (Apidra) as part of usual diabetes home regimen

7. Current off-label use of faster-acting insulin aspart (Fiasp) in CSII therapy as part
of usual diabetes home regimen

8. Current participation in another diabetes-related clinical trial that, in the judgment
of the principal investigator, will compromise the results of this study or the safety
of the participant

9. Pregnant (positive urine HCG), breast feeding, plan to become pregnant in the next 12
months, or sexually active and at risk for pregnancy without use of contraception

10. Current alcohol abuse (intake averaging >4 drinks daily in last 30 days) or other
substance abuse (use within the last 3 months of controlled substances other than
marijuana without a prescription)

11. Unwilling or unable or to avoid use of drugs that may dull the sensorium, reduce
sensitivity to symptoms of hypoglycemia, or hinder decision making during the period
of participation in the study (use of benzodiazepines or narcotics, even if by
prescription, may be excluded according to the judgment of the principal investigator)

12. Stage 4 renal failure (eGFR <30) or Stage 5 renal failure on dialysis (hemodialysis or
peritoneal dialysis)

13. History of cystic fibrosis, pancreatitis, or other pancreatic disease, including
pancreatic tumor or insulinoma, or history of complete pancreatectomy

14. Coronary artery disease that is not stable with medical management, including unstable
angina, angina that prevents moderate exercise (e.g. exercise of intensity up to 6
METS) 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

15. Abnormal EKG consistent with increased risk of malignant arrhythmia including, but not
limited to, evidence of active ischemia, proximal LAD critical stenosis (Wellen's
sign), or prolonged QT interval (> 440 ms). Other EKG findings, including stable Q
waves, are not grounds for exclusion as long as the participant is not excluded
according to other criteria. A reassuring evaluation by a cardiologist after an
abnormal EKG finding may allow participation.

• EKG is only required for participants ≥50 years old or with diabetes duration ≥20
years

16. For participants < 50 years of age and < 20 years since diagnosis: History of
prolonged QT interval, malignant arrhythmia, or congenital heart disease

17. Congestive heart failure with New York Heart Association (NYHA) Functional
Classification III or IV

18. History of TIA or stroke in the last 12 months

19. Recent history of diabetic ketoacidosis (DKA) or severe hypoglycemia in the last 6
months. Severe hypoglycemia is defined as an event that required assistance of another
person due to altered consciousness, and required another person to actively
administer carbohydrate, glucagon, or other resuscitative actions. This means that the
participant was impaired cognitively to the point that he/she was unable to treat
himself/herself, was unable to verbalize his/ her needs, was incoherent, disoriented,
and/or combative, or experienced seizure or coma.

20. History of more than 1 episode of DKA requiring hospitalization in the last 2 years

21. History of more than 1 episode of severe hypoglycemia in the last year.

22. Untreated or inadequately treated mental illness (indicators would include symptoms
such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the
last year), or treatment with anti-psychotic medications that are known to affect
glucose regulation.

23. Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be
susceptible to RF interference

24. Unable or unwilling to completely avoid acetaminophen for duration of study

25. Established history of allergy or severe reaction to adhesive or tape that must be
used in the study

26. History of eating disorder within the last 2 years, such as anorexia, bulimia, or
diabulemia or omission of insulin to manipulate weight

27. Current or planned use of SGLT2 inhibitors (prior use more than 3 months prior to
enrollment is acceptable; SGLT2 inhibitors should not be initiated during the trial)

28. If using GLP1, pramlintide, or metformin must be on a stable dose for 3 months prior
to enrollment (these agents should not be initiated during the trial)

29. Required use of 2 or more steroid bursts in the 6 months prior to the trial

30. History of intentional, inappropriate administration of insulin leading to severe
hypoglycemia requiring treatment

31. Any factors that, in the opinion of the site principal investigator or clinical
protocol chair, would interfere with the safe completion of the study, including
medical conditions that may require hospitalization during the trial