Pivotal Omnipod Horizon™ Automated Glucose Control System

• ClinicalTrials.gov Identifier: NCT04196140
• Recruitment Status: Active, not recruiting
• First Posted: December 12, 2019
• Last Update Posted: April 15, 2021
• Sponsor: Insulet Corporation
• Information provided by (Responsible Party): Insulet Corporation

Tracking Information

• First Submitted Date: December 5, 2019
• First Posted Date: December 12, 2019
• Last Update Posted Date: April 15, 2021
• Actual Study Start Date: December 30, 2019
• Actual Primary Completion Date: September 22, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 11, 2020)

• Incidence rate of severe hypoglycemia (events per person months) [ Time Frame: Phase 2 hybrid closed-loop (94 days) ]
  Measure of serious device-related adverse events
• Incidence rate of diabetic ketoacidosis (DKA) (events per person months) [ Time Frame: Phase 2 hybrid closed-loop (94 days) ]
  Measure of serious device-related adverse events
• Glycated hemoglobin (A1C) [ Time Frame: 6 weeks continuous Phase 2 participation compared to baseline ]
  Measures device effectiveness
• Time in range 70-180 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) compared to Phase 1 standard therapy (14 days) ]
  Measures device effectiveness

Original Primary Outcome Measures (submitted: December 10, 2019)

• Incidence rate of severe hypoglycemia (events per person months) [ Time Frame: hybrid closed-loop (91 days) ]
  Measure of serious device-related adverse events
• Incidence rate of diabetic ketoacidosis (DKA) (events per person months) [ Time Frame: hybrid closed-loop (91 days) ]
  Measure of serious device-related adverse events
• End of study glycated hemoglobin (A1C) compared to baseline A1C [ Time Frame: Screening visit compared to end of study visit (Day-30 to Day 91) ]
  Measures device effectiveness
• Time in range 70-180 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) ]
  Measures device effectiveness

Current Secondary Outcome Measures (submitted: June 11, 2020)

• percent of time >180 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) compared to Phase 1 standard therapy (14 days) ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time <70 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) compared to Phase 1 standard therapy (14 days) ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• Glycated hemoglobin (A1C) [ Time Frame: at least 6 weeks and at least 8 weeks of continuous Phase 2 participation, end of Phase 2 (94 days), 6 months (180 days) and end of Phase 3 (270 days) ]
  Measures device effectiveness
• Mean glucose [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time in range 70-180 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time in range 70-140 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time >180 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time ≥ 250 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time ≥ 300 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time < 70 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time < 54 mg/dL [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• Standard deviation [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)-measured glucose variability with the standard deviation (SD)
• Coefficient of variation [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)-measured glucose variability with the coefficient of variation (CV)
• Percentage of time in hybrid closed-loop as proportion of overall device usage time [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 (270 days) ]
  Measure of system usage
• Glucose management indicator (GMI) based on overall mean glucose [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days) ]
  Measurement of glucose management using overall glucose averages
• Total daily insulin (TDI) (units) [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily insulin (TDI) (units/kg) [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily basal insulin (units) [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily basal insulin (units/kg) [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily bolus insulin (units) [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily bolus insulin (units/kg) [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days) ]
  Measure of insulin requirements
• Body Mass Index (BMI) (kg/m2) [ Time Frame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to baseline ]
  Measure of change in weight

Original Secondary Outcome Measures (submitted: December 10, 2019)

• percent of time >180 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time <70 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• Mean glucose [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time in range 70-180 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time in range 70-140 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time >180 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time ≥ 250 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time ≥ 300 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time < 70 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time < 54 mg/dL [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• Standard deviation [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)-measured glucose variability with the standard deviation (SD)
• Coefficient of variation [ Time Frame: hybrid closed-loop (91 days) compared to standard therapy (14 days) during the day, overnight, and overall ]
  Glucose metric from study continuous glucose monitoring system (CGM)-measured glucose variability with the coefficient of variation (CV)
• Percentage of time in hybrid closed-loop as proportion of overall device usage time [ Time Frame: hybrid closed-loop (91 days) ]
  Measure of system usage
• Glucose management indicator (GMI) based on overall mean glucose [ Time Frame: hybrid closed-loop (91 days) compared to the standard therapy (14 days) ]
  Measurement of glucose management using overall glucose averages
• Total daily insulin (TDI) (units) [ Time Frame: hybrid closed-loop (91 days) compared to the standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily insulin (TDI) (units/kg) [ Time Frame: hybrid closed-loop (91 days) compared to the standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily basal insulin (units) [ Time Frame: hybrid closed-loop (91 days) compared to the standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily basal insulin (units/kg) [ Time Frame: hybrid closed-loop (91 days) compared to the standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily bolus insulin (units) [ Time Frame: hybrid closed-loop (91 days) compared to the standard therapy (14 days) ]
  Measure of insulin requirements
• Total daily bolus insulin (units/kg) [ Time Frame: hybrid closed-loop (91 days) compared to the standard therapy (14 days) ]
  Measure of insulin requirements
• Change from baseline in body mass index (BMI) (kg/m2) to end of study [ Time Frame: Screening visit compared to end of study visit (Day-30 to Day 91) ]
  Measure of change in weight
• Proportion of subjects demonstrating improvement in A1c from baseline at end of study [ Time Frame: Screening visit compared to end of study visit (Day-30 to Day 91) ]
  Measure of change in glucose control

Current Other Pre-specified Outcome Measures (submitted: April 12, 2021)

• Incidence rate of hypoglycemia (<70 mg/dL confirmed by BG) [ Time Frame: HypoProtect compared to standard Omnipod 5 system use (3-day exercise challenge) ]
  Measure of device safety
• Average number of hypoglycemic events (<70 mg/dL confirmed by BG) [ Time Frame: HypoProtect compared to Automated Mode (3-day exercise challenge) ]
  Measure of device effectiveness
• Area under the curve (AUC) less than 70 mg/dL (based on CGM value) [ Time Frame: HypoProtect compared to Automated Mode (3-day exercise challenge) ]
  Measure of device effectiveness
• Minimum continuous glucose monitor value (nadir glucose) [ Time Frame: HypoProtect compared to Automated Mode (3-day exercise challenge) ]
  Measure of device effectiveness
• Area under the curve (AUC) greater than 180 mg/dL (based on CGM value) [ Time Frame: HypoProtect compared to Automated Mode (3-day exercise challenge) ]
  Measure of device effectiveness
• Mean absolute decrease in glucose (based on CGM value, from start of exercise to nadir glucose) [ Time Frame: HypoProtect compared to Automated Mode (3-day exercise challenge) ]
  Measure of device effectiveness
• Carbohydrates consumed during exercise (grams) [ Time Frame: HypoProtect compared to Automated Mode (3-day exercise challenge) ]
  Measure of device effectiveness
• Mean glucose [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Glucose metric from study continuous glucose monitoring system (CGM)
• percent of time in range 70-180 mg/dL [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Measure of device effectiveness
• percent of time > 180 mg/dL [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Measure of device effectiveness
• percent of time ≥ 250 mg/dL [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Measure of device effectiveness
• percent of time ≥ 300 mg/dL [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Measure of device effectiveness
• percent of time < 70 mg/dL [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Measure of device effectiveness
• percent of time < 54 mg/dL [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Measure of device effectiveness
• Standard deviations [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Glucose metric from study continuous glucose monitoring system (CGM)-measured glucose variability with the standard deviation (SD)
• Coefficient of variation [ Time Frame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise ]
  Glucose metric from study continuous glucose monitoring system (CGM)-measured glucose variability with the coefficient of variation (CV)

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pivotal Omnipod Horizon™ Automated Glucose Control System
• Official Title: Evaluating the Safety and Effectiveness of the Omnipod Horizon™ Automated Glucose Control System in Patients With Type 1 Diabetes
• Brief Summary: Subjects will undergo a 14-day outpatient, standard therapy phase during which sensor and insulin data will be collected. This will be followed by a 94-day (13-week) hybrid closed-loop phase conducted in an outpatient setting and an optional 12-month extension phase.

Detailed Description

The study schedule will consist of a standard therapy data collection phase followed by a hybrid closed-loop phase.

Subjects will undergo a 14-day outpatient, standard therapy phase during which sensor and insulin data will be collected. Subjects, or their caregivers, will manage their diabetes at home per their usual routine using the study continuous glucose monitoring system (CGM) and remain on current multiple daily injections (MDI) or pump therapy. This will be followed by a 94-day (13-week) hybrid closed-loop phase, conducted in an outpatient setting where subjects, or their caregivers, will manage their diabetes at home using the Omnipod Horizon™ Automated Glucose Control System. After completing the 94-day hybrid closed-loop phase, subjects will have the option to continue using the system for an additional 12 months.

During the hybrid closed-loop phase, there will be supervised exercise challenges. A subset of subjects will participate in 5-days of supervised Meal and Exercise challenges. A subset of subjects will participate in 3-days of supervised HypoProtect Exercise challenges.

The hybrid closed-loop phase will begin on Study Day 1.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This is a single-arm, multi-center, prospective clinical study.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Type 1 Diabetes Mellitus

Intervention

Device: Omnipod Horizon™ Automated Glucose Control System

The Omnipod Horizon™ Automated Glucose Control System will provide automated insulin delivery

Study Arms

Experimental: Treatment

All subjects wearing the Omnipod Horizon™ Automated Glucose Control System using the closed-loop algorithm.

Intervention: Device: Omnipod Horizon™ Automated Glucose Control System

Publications *

• Polonsky WH, Hood KK, Levy CJ, MacLeish SA, Hirsch IB, Brown SA, Bode BW, Carlson AL, Shah VN, Weinstock RS, Bhargava A, Jones TC, Aleppo G, Mehta SN, Laffel LM, Forlenza GP, Sherr JL, Huyett LM, Vienneau TE, Ly TT; Omnipod 5 Research Group. How introduction of automated insulin delivery systems may influence psychosocial outcomes in adults with type 1 diabetes: Findings from the first investigation with the Omnipod(R) 5 System. Diabetes Res Clin Pract. 2022 Aug;190:109998. doi: 10.1016/j.diabres.2022.109998. Epub 2022 Jul 16.
• Brown SA, Forlenza GP, Bode BW, Pinsker JE, Levy CJ, Criego AB, Hansen DW, Hirsch IB, Carlson AL, Bergenstal RM, Sherr JL, Mehta SN, Laffel LM, Shah VN, Bhargava A, Weinstock RS, MacLeish SA, DeSalvo DJ, Jones TC, Aleppo G, Buckingham BA, Ly TT; Omnipod 5 Research Group. Multicenter Trial of a Tubeless, On-Body Automated Insulin Delivery System With Customizable Glycemic Targets in Pediatric and Adult Participants With Type 1 Diabetes. Diabetes Care. 2021 Jul;44(7):1630-1640. doi: 10.2337/dc21-0172. Epub 2021 Jun 7.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 11, 2020): 235
• Original Estimated Enrollment (submitted: December 10, 2019): 240
• Estimated Study Completion Date: December 2021
• Actual Primary Completion Date: September 22, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age at time of consent/assent 6-70 years
2. Subjects aged < 18 years must be living with parent/legal guardian
3. Diagnosed with type 1 diabetes for at least 6 months. Diagnosis is based on investigator's clinical judgment
4. Deemed appropriate for pump therapy per investigator's assessment taking into account previous history of severe hypoglycemic and hyperglycemic events, and other comorbidities
5. Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol
6. Willing to use only the following types of insulin during the study: Humalog, Novolog, Admelog or Apidra during the study
7. Must be willing to travel to and participate in meal and exercise challenges during 5-days of the hybrid closed-loop phase
8. Willing to wear the system continuously throughout the study
9. A1C <10% at screening visit
10. Must be willing to use the Dexcom App on the Omnipod Horizon™ Personal Diabetes Manager (PDM) as the sole source of Dexcom data (with the exception of the Dexcom Follow App) during the hybrid closed-loop phase
11. Subjects scoring ≥ 4 on the Clarke Questionnaire must agree to have an overnight companion, defined as someone who resides in the same home or building as the study subject and who can be available overnight
12. Able to read and speak English fluently
13. Willing and able to sign the Informed Consent Form (ICF) and/or has a parent/guardian willing and able to sign the ICF. Assent will be obtained from pediatric and adolescent subjects aged < 18 years per State requirements.

Exclusion Criteria:

1. A medical condition, which in the opinion of the investigator, would put the subject at an unacceptable safety risk
2. History of severe hypoglycemia in the past 6 months
3. History of DKA in the past 6 months, unrelated to an intercurrent illness, infusion set failure or initial diagnosis
4. Diagnosed with sickle cell disease
5. Diagnosed with hemophilia or any other bleeding disorders
6. Plans to receive blood transfusion over the course of the study
7. Currently diagnosed with anorexia nervosa or bulimia
8. Acute or chronic kidney disease (e.g. estimated GFR < 45) or currently on hemodialysis
9. History of adrenal insufficiency
10. Has taken oral or injectable steroids within the past 8-weeks or plans to take oral or injectable steroids during the course of the study
11. Unable to tolerate adhesive tape or has any unresolved skin condition in the area of sensor or pump placement
12. Plans to use insulin other than U-100 insulin intended for use in the study device during the course of the study
13. Use of non-insulin anti-diabetic medication other than metformin (e.g. GLP1 agonist, SGLT2 inhibitor, DPP-4 inhibitor, pramlintide)
14. Current or known history of coronary artery disease that is not stable with medical management, including unstable angina, or angina that prevents moderate exercise despite medical management, or a history of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting within the previous 12-months.
15. For subjects >50 years old or with diabetes duration >20 years, abnormal electrocardiogram consistent with increased risk of arrhythmia, ischemia, or prolonged QTc interval (> 450 ms)
16. Thyroid Stimulating Hormone (TSH) is outside of normal range with clinical signs of hypothyroidism or hyperthyroidism
17. Pregnant or lactating, or is a woman of childbearing potential and not on acceptable form of birth control (acceptable includes abstinence, condoms, oral/injectable contraceptives, IUD or implant)
18. Participation in another clinical study using an investigational drug or device other than the Omnipod Horizon™ Automated Glucose Control System within the preceding 30-days or intends to participate during the study period
19. Unable to follow clinical protocol for the duration of the study or is otherwise deemed unacceptable to participate in the study per the investigator's clinical judgment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04196140
• Other Study ID Numbers: Horizon™ Pivotal Study
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Insulet Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Insulet Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Bruce Buckingham, MD; Stanford University
• Study Chair: Sue Brown, MD; University of Virginia

• PRS Account: Insulet Corporation
• Verification Date: April 2021