Clinical trial NCT06449677: Bionic Pancreas in CFRD
Official title: A Randomized Trial of the Insulin-only Bionic Pancreas in Cystic Fibrosis Related Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cystic Fibrosis-related Diabetes
Keywords: Cystic fibrosis-related diabetes (CFRD)
iLet bionic pancreas
Automated insulin delivery
Continuous glucose monitoring
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: Massachusetts General Hospital
name: Beta Bionics, Inc.
First posted: 2024-06-10
Enrollment: 150
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 13-week RCT followed by a 13-week Extension Phase in which all participants use the iLet BP System
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

   * Sweat chloride equal to or greater than 60 mmol/liter by quantitative pilocarpine iontophoresis test (QPIT) (when not taking a cystic fibrosis transmembrane conductance regulator (CFTR) modulator)
   * Two well-characterized mutations in the CFTR gene
4. Clinical diagnosis of CFRD, defined as a person with CF and diabetes mellitus, treated with insulin for ≥3 months prior to screening
5. 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)
6. Total daily insulin dose must be ≥0.1 units/kg
7. 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
8. For participants \<18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia. A designated care partner must be willing to be linked to the participant's Dexcom Follow application with location sharing on.
9. 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 cannot be reached. A designated care partner must be willing to be linked to the participant's Dexcom Follow application with location sharing on.
10. 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.
11. If not currently using a rapid-acting insulin that is approved for use in the iLet pump, willing and able to switch to an approved insulin when using the BP.
12. Participant has commercial glucagon available for treatment of severe hypoglycemia or will obtain it prior to randomization
13. Willing to authorize the study team to contact the participant's primary physician to inform them about their participation in this study.
14. Enrolled in the Cystic Fibrosis Foundation Patient Registry (participants may enroll in the Registry at the time of enrollment if not already enrolled).
15. No plans for trips of more than 14 consecutive days outside the United States during the period of study participation
16. 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 an AID system not FDA approved for T1D
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 and can become pregnant but not using 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.

   • Modifications of the dosing of a CFTR modulator is acceptable
8. Anticipated lung or liver transplant (on transplant list)
9. Lung or liver transplant within one year prior to screening. If they have had a transplant more than a year ago, but they:

   * Have had a rejection episode occur in prior 8 weeks, individual is excluded.
   * Their doses of corticosteroids and/or calcineurin inhibitors have not been stable for one month prior to enrollment and/or is expected to change significantly over the course of the study, individual is excluded.
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, or hinder decision-making during the period of participation in the study such has opioids or short-acting benzodiazepines
    * 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.

Primary outcomes:
measure: CGM-measured Time In Target Range of 70-180 mg/dL (TIR)
timeFrame: 13 weeks
Secondary outcomes:
measure: CGM-measured Time In Range <54 mg/dL
timeFrame: 13 weeks
Other outcomes:
measure: CGM-measured Mean Glucose
timeFrame: 13 weeks
measure: CGM-measured Time In Range >180 mg/dL
timeFrame: 13 weeks
measure: CGM-measured Time In Range >250 mg/dL
timeFrame: 13 weeks
measure: HbA1c At 13 Weeks
timeFrame: 13 weeks
measure: Glucose Variability Measured With the Standard Deviation (SD)
timeFrame: 13 weeks
measure: CGM-measured Time In Range <70 mg/dL
timeFrame: 13 weeks
measure: Glucose Variability With the Coefficient of Variation (CV)
timeFrame: 13 weeks
measure: HbA1c <7.0% At 13 Weeks
timeFrame: 13 weeks
measure: HbA1c <7.0% At 13 Weeks In Participants With Baseline HbA1c >7.5%
timeFrame: 13 weeks
measure: HbA1c <8.0% At 13 Weeks
timeFrame: 13 weeks
measure: HbA1c Improvement From Baseline To 13 Weeks >0.5%
timeFrame: 13 weeks
measure: HbA1c Improvement From Baseline To 13 Weeks >1.0%
timeFrame: 13 weeks
measure: HbA1c Improvement From Baseline To 13 Weeks >1.0% Or HbA1c <7.0% At 13 Weeks
timeFrame: 13 weeks
measure: CGM-measured Time In Tight Range (TITR) 70-140 mg/dL
timeFrame: 13 weeks
measure: CGM-measured Area Over the Curve (70 mg/dL)
timeFrame: 13 weeks
measure: CGM-measured Low Sensor Glucose Events
timeFrame: 13 weeks
measure: CGM-measured Prolonged High Sensor Glucose Events
timeFrame: 13 weeks
measure: CGM-measured Time >300 mg/dL
timeFrame: 13 weeks
measure: CGM-measured Area Under the Curve (180 mg/dL)
timeFrame: 13 weeks
measure: CGM-measured TIR >70%
timeFrame: 13 weeks
measure: CGM-measured TIR Improvement From Baseline To 13 Weeks ≥5%
timeFrame: 13 weeks
measure: CGM-measured TIR Improvement From Baseline To 13 Weeks ≥10%
timeFrame: 13 weeks
measure: CGM-measured Time <70 mg/dL <4%
timeFrame: 13 weeks
measure: CGM-measured Time <54 mg/dL <1%
timeFrame: 13 weeks
measure: CGM-measured TIR >70% and Time <54 mg/dL <1%
timeFrame: 13 weeks
measure: CGM-measured Improvement In TIR By >10% Without An Increase In Time <54 mg/dL By >0.5%
timeFrame: 13 weeks
measure: Type 1 Diabetes Distress Scale (T1-DDS)
timeFrame: Screening, 13 weeks
measure: Problem Areas In Diabetes - Teens (PAID-T) and Parents of Teens (P-PAID-T)
timeFrame: Screening, 13 weeks
measure: Hypoglycemia Confidence Scale (≥18)
timeFrame: Screening, 13 weeks
measure: INSPIRE Survey (Insulin Delivery Systems: Perceptions, Ideas, Reflections, and Expectations)
timeFrame: Screening, 13 weeks
measure: Fear of Hypoglycemia Survey (HFS-II) - Total Score, 2 Subscales and 4 Factor Scores
timeFrame: Screening, 13 weeks
measure: The EuroQol 5 Dimension 5 Level (EQ-5D-5L)
timeFrame: Screening, 13 weeks
measure: World Health Organization Well-being Index (WHO-5)
timeFrame: Screening, 13 weeks
measure: Perceived Benefits and Burdens of AID Systems
timeFrame: Screening, 13 weeks
measure: Total Daily Insulin (Units/kg)
timeFrame: 13 weeks
measure: Percentage of Total Insulin Delivered Via Basal
timeFrame: 13 weeks
measure: Percentage of Total Insulin Delivered Via Bolus
timeFrame: 13 weeks
measure: Weight
timeFrame: 13 weeks
measure: Body Mass Index (BMI)
timeFrame: 13 weeks
measure: Number of Severe Hypoglycemia (SH) Events and SH Event Rate Per 100 person-years
timeFrame: 13 weeks
measure: Number of Diabetes Ketoacidosis (DKA) Events and DKA Event Rate Per 100 person-years
timeFrame: 13 weeks
measure: Number of Other Serious Adverse Events (SAEs other than SH events and DKA events)
timeFrame: 13 weeks
measure: Number of Unanticipated Adverse Device Effects (UADE)
timeFrame: 13 weeks
measure: Number of Infusion Set Failures
timeFrame: 13 weeks
measure: Other Device Malfunctions/Device Issues
timeFrame: 13 weeks
Locations:
city: Aurora
country: United States
facility: University of Colorado-Barbara Davis Center for Diabetes
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia-Center for Diabetes Technology
state: Virginia
Study officials:
affiliation: Massachusetts General Hospital
name: Melissa Putman, MD
role: STUDY_CHAIR
affiliation: Jaeb Center for Health Research
name: Colleen Bauza, PhD, MPH
role: STUDY_DIRECTOR
References: