Bionic Pancreas in CFRD

Cystic Fibrosis-related Diabetes Clinical Trial

Official title:

A Randomized Trial of the Insulin-only Bionic Pancreas in Cystic Fibrosis Related Diabetes

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06449677
• Other study ID #: BPCFRD
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: March 2026

Study information

• Verified date: June 2024
• Source: Jaeb Center for Health Research
• Contact: Colleen Bauza, PhD, MPH
• Phone: 813-975-8690
• Email: cbauza[@]jaeb.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: March 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis-related Diabetes
• Fibrosis

Intervention

Device:
• iLet Bionic Pancreas System (BP)
The iLet Bionic Pancreas System (BP) consists of an integrated infusion pump, touchscreen display, Bluetooth radio, and insulin dosing algorithms, that automatically controls insulin delivery based on glucose values obtained by communicating with a CGM sensor.
• Usual Care (UC)
Usual Care consists in the participant existing insulin therapy (prior to enrollment) in conjunction with a study CGM. Existing insulin therapies are defined as multiple daily injections of insulin (MDI) or use of an insulin pump.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	Beta Bionics, Inc., Cystic Fibrosis Foundation, Massachusetts General Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CGM-measured Mean Glucose	Average glucose value measured by CGM	13 weeks
Other	CGM-measured Time In Range >180 mg/dL	CGM-measured time in range >180 mg/dL	13 weeks
Other	CGM-measured Time In Range >250 mg/dL	CGM-measured time in range >250 mg/dL	13 weeks
Other	HbA1c At 13 Weeks	HbA1c at 13 weeks	13 weeks
Other	Glucose Variability Measured With the Standard Deviation (SD)	Glucose variability measured with the standard deviation (SD)	13 weeks
Other	CGM-measured Time In Range <70 mg/dL	CGM-measured time in range <70 mg/dL	13 weeks
Other	Glucose Variability With the Coefficient of Variation (CV)	Glucose variability with the coefficient of variation (CV)	13 weeks
Other	HbA1c <7.0% At 13 Weeks	HbA1c <7.0% at 13 weeks	13 weeks
Other	HbA1c <7.0% At 13 Weeks In Participants With Baseline HbA1c >7.5%	HbA1c <7.0% at 13 weeks in participants with baseline HbA1c >7.5%	13 weeks
Other	HbA1c <8.0% At 13 Weeks	HbA1c <8.0% at 13 weeks	13 weeks
Other	HbA1c Improvement From Baseline To 13 Weeks >0.5%	HbA1c improvement from baseline to 13 weeks >0.5%	13 weeks
Other	HbA1c Improvement From Baseline To 13 Weeks >1.0%	HbA1c improvement from baseline to 13 weeks >1.0%	13 weeks
Other	HbA1c Improvement From Baseline To 13 Weeks >1.0% Or HbA1c <7.0% At 13 Weeks	HbA1c improvement from baseline to 13 weeks >1.0% or HbA1c <7.0% at 13 weeks	13 weeks
Other	CGM-measured Time In Tight Range (TITR) 70-140 mg/dL	CGM-measured time in tight range (TITR) 70-140 mg/dL	13 weeks
Other	CGM-measured Area Over the Curve (70 mg/dL)	CGM-measured area over the curve (70 mg/dL)	13 weeks
Other	CGM-measured Low Sensor Glucose Events	CGM-measured low sensor glucose events	13 weeks
Other	CGM-measured Prolonged High Sensor Glucose Events	CGM-measured prolonged high sensor glucose events	13 weeks
Other	CGM-measured Time >300 mg/dL	CGM-measured time >300 mg/dL	13 weeks
Other	CGM-measured Area Under the Curve (180 mg/dL)	CGM-measured area under the curve (180 mg/dL)	13 weeks
Other	CGM-measured TIR >70%	CGM-measured TIR >70%	13 weeks
Other	CGM-measured TIR Improvement From Baseline To 13 Weeks =5%	CGM-measured TIR improvement from baseline to 13 weeks =5%	13 weeks
Other	CGM-measured TIR Improvement From Baseline To 13 Weeks =10%	CGM-measured TIR improvement from baseline to 13 weeks =10%	13 weeks
Other	CGM-measured Time <70 mg/dL <4%	CGM-measured time <70 mg/dL <4%	13 weeks
Other	CGM-measured Time <54 mg/dL <1%	CGM-measured time <54 mg/dL <1%	13 weeks
Other	CGM-measured TIR >70% and Time <54 mg/dL <1%	CGM-measured TIR >70% and time <54 mg/dL <1%	13 weeks
Other	CGM-measured Improvement In TIR By >10% Without An Increase In Time <54 mg/dL By >0.5%	CGM-measured improvement in TIR by >10% without an increase in time <54 mg/dL by >0.5%	13 weeks
Other	Type 1 Diabetes Distress Scale (T1-DDS)	The T1-DDS is to evaluate diabetes-related emotional distress in type 1 diabetic patients. The scale consists of 17 items, contains 4 domains (emotional burden subscale, physician-related subscale, regimen-related distress subscale, and diabetes-related interpersonal distress). Each item is rated on a 6-point Likert scale from 1 (no problem) to 6 (serious problem). Patients with higher scores are considered with more distress	Screening, 13 weeks
Other	Problem Areas In Diabetes - Teens (PAID-T) and Parents of Teens (P-PAID-T)	The PAID-T and P-PAID-T questionnaires consist of 26 items that are scored on a 6-point Likert scale from 1-2 (not a problem) to 5-6 (serious problem). The derived total score (26 questions) ranges between 26 and 156, where high scores represent a higher burden	Screening, 13 weeks
Other	Hypoglycemia Confidence Scale (=18)	A person-reported outcome measure (PROM) that examines the degree to which people with diabetes feel able, secure, and comfortable regarding their ability to stay safe from hypoglycemic-related problems (9-item scale with 4 choices that range from 1 (Not Confident At All) to 4 (Very Confident)). The total score can range from 1 to 4, with a higher score indicating a better outcome	Screening, 13 weeks
Other	INSPIRE Survey (Insulin Delivery Systems: Perceptions, Ideas, Reflections, and Expectations)	INSPIRE 5-point Likert scale from strongly agree to strongly disagree, along with an N/A option	Screening, 13 weeks
Other	Fear of Hypoglycemia Survey (HFS-II) - Total Score, 2 Subscales and 4 Factor Scores	Fear of Hypoglycemia Survey (HFS-II) - total score, 2 subscales and 4 factor scores: Behavior (avoidance, maintain high BG), Worry (helplessness, social consequences)	Screening, 13 weeks
Other	The EuroQol 5 Dimension 5 Level (EQ-5D-5L)	The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical appraisal. The EQ-5D evaluates 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) using a 5-level severity scale from 1 (no problems) to 5 (extreme problems), and is converted to a single summary index by applying a formula that essentially attaches weight to each of the levels in each dimension. The visual analogue score (VAS) evaluates the health condition assessed by patients to producae a quantitive measure of health outcome that reflects the patient's own judgement on a range from "the worst health you can imagine" to "the best health you can imagine"	Screening, 13 weeks
Other	World Health Organization Well-being Index (WHO-5)	WHO-5 is a 5-item questionnaire of the World Health Organization that measures health related quality of life. Each item is scored on a scale of 0 (at no time) to 5 (all the time). Higher scores indicate greater well-being	Screening, 13 weeks
Other	Perceived Benefits and Burdens of AID Systems	A 35-item survey that assesses user expectations of a hybrid closed loop AID system using a 5-point Likert scale from "strongly disagree" to "strongly agree"	Screening, 13 weeks
Other	Total Daily Insulin (Units/kg)	Total daily insulin (Units/kg)	13 weeks
Other	Percentage of Total Insulin Delivered Via Basal	Percentage of total insulin delivered via basal	13 weeks
Other	Percentage of Total Insulin Delivered Via Bolus	Percentage of total insulin delivered via bolus	13 weeks
Other	Weight	Weight	13 weeks
Other	Body Mass Index (BMI)	Body Mass Index (BMI)	13 weeks
Other	Number of Severe Hypoglycemia (SH) Events and SH Event Rate Per 100 person-years	Number of Severe Hypoglycemia (SH) events and SH event rate per 100 person-years	13 weeks
Other	Number of Diabetes Ketoacidosis (DKA) Events and DKA Event Rate Per 100 person-years	Number of Diabetes Ketoacidosis (DKA) events and DKA event rate per 100 person-years	13 weeks
Other	Number of Other Serious Adverse Events (SAEs other than SH events and DKA events)	Number of Other Serious Adverse Events (SAEs other than SH events and DKA events)	13 weeks
Other	Number of Unanticipated Adverse Device Effects (UADE)	Number of Unanticipated Adverse Device Effects (UADE)	13 weeks
Other	Number of Infusion Set Failures	Number of infusion set failures	13 weeks
Other	Other Device Malfunctions/Device Issues	Number of other malfunctions/issues related to the study device	13 weeks
Primary	CGM-measured Time In Target Range of 70-180 mg/dL (TIR)	CGM-measured time in target range of 70-180 mg/dL (TIR)	13 weeks
Secondary	CGM-measured Time In Range <54 mg/dL	CGM-measured time in range <54 mg/dL	13 weeks