Bionic Pancreas: A Randomized Trial of the Insulin-only Bionic Pancreas in Cystic Fibrosis Related Diabetes (H-55979)

Description: This multi-center randomized controlled trial (RCT) will compare efficacy and safety endpoints using the insulin-only configuration of the iLet Bionic Pancreas System (BP) versus a control group using their usual care insulin delivery method and continuous glucose monitoring (CGM) during a 13-week study period in individuals ≥14 years old with cystic fibrosis-related diabetes (CFRD). After 13 weeks, participants will continue in a 13-week Extension Phase in which the BP group will continue to use the BP system and the Usual Care group will initiate use of the BP system.

Study Goal(s)

Primary Objective

• To compare the efficacy and safety of the BP relative to usual care (which includes CGM) in a 13-week randomized trial in individuals ≥ 14 years old with CFRD.

Secondary Objectives

• To assess the sustainability of BP use, efficacy, and safety over an additional 13 weeks after the end of the RCT in an extension phase
• To assess the efficacy and safety of BP use after initiation of the BP for 13 weeks in the RCT usual care group comparing the 13-week BP use period with the preceding 13-week usual care period.
• To assess the impact of use of the BP on patient reported outcomes

Eligibility Criteria

To be eligible, a participant must meet all of the following inclusion criteria and none of the exclusion criteria:

Inclusion

1. Age ≥ 14 years old at time of signing informed consent
2. Able to provide informed consent (and assent for participants <18 years old)
3. Clinical diagnosis of CFRD treated with insulin for ≥3 months prior to screening
4. Using the same insulin regimen for ≥1 month prior to screening and collection of baseline CGM data, with no plans to change regimen during the study: either multiple daily injections of insulin (MDI), basal-only without bolus insulin, an insulin pump without automation, or an automated insulin delivery (AID) system other than the BP (which is an exclusion)
5. Total daily insulin dose must be ≥0.1 units/kg 
6. Able to speak and read English sufficient to understand the pump user interface and provide written materials for safe operation of the BP
   • For pediatric participants, this applies to both the participant and caregiver
7. For participants <18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia. 
8. 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.
9. No use of a non-insulin glucose-lowering medication, except metformin, that is not approved for use in T1D within 3 months prior to signing informed consent and willing to not use any such medications during the course of the trial. Note: such drugs cannot be used even if prescribed for weight loss rather than glucose-lowering.
10. If not currently using a rapid-acting insulin that is approved for use in the iLet pump, willing and able to obtain an approved insulin when using the BP.
11. Participant has commercial glucagon available for treatment of severe hypoglycemia or will obtain it prior to randomization
12. No plans for trips of more than 14 consecutive days outside the United States during the period of study participation
13. 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 (there is no upper limit for eligibility), compliance with current diabetes management, prior acute diabetic complications, cognitive ability, and general medical condition. For this reason, there is no upper limit on HbA1c specified for eligibility.

Exclusion

1. Current use of the BP or a non-FDA approved AID system
2. Known hemoglobinopathy (sickle cell trait is not an exclusion)
3. Current participation in another diabetes-related interventional trial
4. Established history of allergy or severe reaction to adhesive or tape that must be used in the study
5. Pregnant (positive urine hCG), breast feeding, plan to become pregnant in the next 7 months, or sexually active without use of contraception 
6. Current use of hydroxyurea or unable to avoid hydroxyurea use during the study (interferes with accuracy of Dexcom sensor)
7. Have started or stopped a CFTR modulator in the 4 weeks prior to screening.
8. Anticipated lung or liver transplant (on transplant list)
9. Lung or liver transplant within one year prior to screening
   • If rejection episode has occurred in prior 8 weeks, individual is excluded.
   • If individual has already received a lung or liver transplant, doses of corticosteroids and/or calcineurin inhibitors must be stable for one month prior to enrollment and are not expected to change significantly over the course of the study
10. Acute pulmonary exacerbation or hospitalization within the 4 weeks prior to screening or treatment with IV antibiotics in the 4 weeks prior to screening. 
11. History of a complete pancreatectomy
12. Currently using enteral tube feedings for nutritional support
13. 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
    • Severe liver disease such as end-stage cirrhosis
    • Renal failure requiring dialysis or known eGFR <30
    • Untreated or inadequately treated mental illness 
    • History of untreated or inadequately treated eating disorder within the last 2 years, such as anorexia, bulimia, or diabulimia or omission of insulin to manipulate weight
    • History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
14. 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

Investigator(s):
Principal, Co-investigators:
PI: Lina Merjaneh, M.D.
Co-investigators: Daniel Desalvo M.D., Fadel Ruiz, M.D.

Supported by:
Institutions, Hospitals, Awards, etc.: 
The Cystic Fibrosis Foundation

Contact: 
Lina Merjaneh, email: lxmerjan@texaschildrens.org
Pavel Tuekam, email: OrnellaPavel.TuekamMeko@bcm.edu