The Bihormonal iLet Bionic Pancreas Feasibility Study

Trial end date:
Target enrollment:
Participant gender:
Our objective is to evaluate the function of the bihormonal configuration of the ILet bionic pancreas delivering dasiglucagon when compared to the insulin-only configuration of the ILet bionic pancreas in a home-use study in adults with type 1 diabetes.
Phase 2/Phase 3
Accepts Healthy Volunteers?
Lead Sponsor:
Massachusetts General Hospital
Beta Bionics, Inc.
Zealand Pharma
Glucagon-Like Peptide 1
Insulin, Globin Zinc
Inclusion Criteria:

1. Age ≥ 18 years and have had clinical type 1 diabetes for at least one year

2. Diabetes managed using an insulin pump for ≥ 3 months

3. Prescription medication regimen stable for > 1 month (except for medications that will
not affect the safety of the participant and are not expected to affect any outcome of
the study, in the judgement of the principal investigator)

4. Willing to wear one Dexcom CGM sensor, and up to two steel cannula infusion sets (6 mm
Contact Detach) and change infusion sets frequently (if the subject is known not to
tolerate steel infusion sets then a plastic set may be used)

5. Have used a CGM for at least one cumulative month over the last 24 months

6. Willing to stay within a 250-mile radius of the designated base throughout the study.
Air travel is not permitted.

7. Informed consent obtained before any trial-related activities

8. Have a designated contact (an adult ≥ 18 years of age) willing to serve as an
emergency contact for them throughout the study.

Exclusion Criteria:

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 iLet, impaired
memory, unable to speak and read English)

3. Current participation in another clinical trial with administration of investigational

4. 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

5. Previous exposure to dasiglucagon (otherwise known as ZP4207)

6. Pregnant (positive urine HCG), breast feeding, plan to become pregnant in the next 12
months, or sexually active without use of contraception

1. Subjects must use acceptable contraception for the two weeks prior to the study,
throughout the study and for the two weeks following the study.

2. Acceptable contraception methods include:Oral contraceptive pills (OCP),
Intrauterine Device (IUD, hormonal or copper), Male condoms, Female condoms,
Diaphragm or cervical cap with spermicide, Contraceptive patch (such as
OrthoEvra), Contraceptive implant (such as Implanon, Nexplanon), Vaginal ring
(such as Nuvaring), Progestin shot (such as Depo-Provera), Male partner with a
vasectomy proven to be effective by semen analysis

7. 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)

8. 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)

9. Renal failure on dialysis

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

11. 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

12. 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.

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

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

15. History of liver disease that is expected to interfere with the anti-hypoglycemic
action of glucagon (e.g. liver failure or cirrhosis). Other liver disease (e.g. active
hepatitis, steatosis, active biliary disease, any tumor of the liver, hemochromatosis,
glycogen storage disease) may exclude the subject if it causes significant compromise
to liver function or may do so in an unpredictable fashion.

16. Personal history of pheochromocytoma, MEN 2A, MEN 2B, neurofibromatosis, or von
Hippel-Lindau disease

a.Fractionated metanephrines will be tested to rule out pheochromocytoma in patients
with symptoms that could be related to a catecholamine secreting tumor, including
those with: Episodic or treatment refractory (requiring 4 or more medications to
achieve normotension) hypertension, Paroxyms of tachycardia, pallor or headache

17. History of adrenal disease or tumor that has not undergone characterization for
endocrine function

18. Hypertension with systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100
mm Hg despite treatment

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 adverse reaction to glucagon (including allergy) besides nausea or vomiting

27. History of severe hypersensitivity to milk proteins or lactose

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

29. 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)

30. 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)

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

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

33. 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