Pivotal Omnipod Horizon™ Automated Glucose Control System

Study Overview
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Brief Summary
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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
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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.

Official Title
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Evaluating the Safety and Effectiveness of the Omnipod Horizon™ Automated Glucose Control System in Patients With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: Omnipod Horizon™ Automated Glucose Control System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at time of consent/assent 6-70 years Subjects aged < 18 years must be living with parent/legal guardian Diagnosed with type 1 diabetes for at least 6 months. Diagnosis is based on investigator's clinical judgment Deemed appropriate for pump therapy per investigator's assessment taking into account previous history of severe hypoglycemic and hyperglycemic events, and other comorbidities Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol Willing to use only the following types of insulin during the study: Humalog, Novolog, Admelog or Apidra during the study Must be willing to travel to and participate in meal and exercise challenges during 5-days of the hybrid closed-loop phase Willing to wear the system continuously throughout the study A1C <10% at screening visit 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 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 Able to read and speak English fluently 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: A medical condition, which in the opinion of the investigator, would put the subject at an unacceptable safety risk History of severe hypoglycemia in the past 6 months History of DKA in the past 6 months, unrelated to an intercurrent illness, infusion set failure or initial diagnosis Diagnosed with sickle cell disease Diagnosed with hemophilia or any other bleeding disorders Plans to receive blood transfusion over the course of the study Currently diagnosed with anorexia nervosa or bulimia Acute or chronic kidney disease (e.g. estimated GFR < 45) or currently on hemodialysis History of adrenal insufficiency 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 Unable to tolerate adhesive tape or has any unresolved skin condition in the area of sensor or pump placement Plans to use insulin other than U-100 insulin intended for use in the study device during the course of the study Use of non-insulin anti-diabetic medication other than metformin (e.g. GLP1 agonist, SGLT2 inhibitor, DPP-4 inhibitor, pramlintide) 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. 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) Thyroid Stimulating Hormone (TSH) is outside of normal range with clinical signs of hypothyroidism or hyperthyroidism 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) 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 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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single-arm, multi-center, prospective clinical study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All subjects wearing the Omnipod Horizon™ Automated Glucose Control System using the closed-loop algorithm. | Device: Omnipod Horizon™ Automated Glucose Control System<br>* The Omnipod Horizon™ Automated Glucose Control System will provide automated insulin delivery<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Omnipod, T1D