Multi-center Trial in Adult and Pediatric Patients With Type 1 Diabetes Using Hybrid Closed Loop System and Control at Home

Multi-center, Randomized, Parallel, Adaptive, Controlled Trial in Adult and Pediatric Patients With Type 1 Diabetes Using Hybrid Closed Loop System and Control (CSII, MDI and SAP) at Home

The purpose of this study is to evaluate the safety and effectiveness of the Hybrid Closed Loop system (HCL) in adult and pediatric patients with type 1 diabetes in the home setting. A diverse population of patients with type 1 diabetes will be studied. The study population will have a large range for duration of diabetes and glycemic control, as measured by glycosylated hemoglobin (A1C). They will be enrolled in the study regardless of their prior diabetes regimen, including using Multiple Daily Injections (MDI), Continuous Subcutaneous Insulin Infusion (CSII) or Sensor-Augmented Pump therapy (SAP)

This is a 6 month, multi-center, randomized, parallel, adaptive study in type 1 diabetes with a 6 month continuation period. The study will have three periods, per Cohort:

1. Run-in Period: The run-in period can be up to 60 days during which time a blinded CGM sensor will be worn for two weeks.
2. Study Period: There will be a 6 month randomized study period with two arms: The HCL system and Control. The primary and secondary endpoints will be evaluated during this period only.
3. Continuation Period: There will be a 6 month continuation period during which time all subjects will use the HCL system with Auto Mode. Only the safety endpoint will be evaluated during this period.

Up to 1500 subjects will be enrolled in order to have 1000 subjects complete the study. Up to 70 investigational Centers in the US, Europe, Canada, Australia and New Zealand will be enrolled.

Inclusion Criteria

1. Subject is age 2-80 years at time of screening

   1. US, Canada, Australia and New Zealand: Subjects 2-80 years of age will be allowed to enroll in the post approval study.
   2. Europe: Only subjects ≥7 years of age are allowed to enroll in the post-market study.

2. Subjects who are 2-21 years are determined by the investigator to have the appropriate, requisite support (family, caregiver or social network) to successfully participate in this study

3. Subject must have a minimum daily insulin requirement (Total Daily Dose) of equal to or greater than 8 units/day

4. Subjects who are determined by the investigator to be psychologically sound in order to successfully participate in this study

5. Subject has been diagnosed with type 1 diabetes for at least three months Note: Determination of classification for diabetes will be based on American Diabetes Association Clinical Practice Guidelines accounting for several patient characteristics such as: age of onset, patient's weight or BMI, history of diabetic ketoacidosis, history of therapy management, if available in the medical records.

6. Subject must be on one of the following management therapies:

   1. Multiple daily injections defined by use of rapid analogue with meals and approved long acting analogue (e.g. detemir or glargine) with or without CGM
   2. Insulin pump therapy with or without CGM

7. Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily

8. Subject is willing to perform required study procedures

9. Subject is willing to wear the system continuously throughout the study for at least 80% of the time.

10. Subject is willing to upload data at least weekly from the study pump/meter, must have Internet access and a computer system that meets the requirements for uploading the study pump/meter for data collection

11. Subject must be willing to use the study glucose meter system (i.e. along with study meter strips).

12. If subject has celiac disease, it has been adequately treated as determined by the investigator

13. Subject with the diagnosis of myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure, ventricular rhythm disturbances or thromboembolic disease, within 1 year of screening, will be included in the study with the consent of the Investigator

14. Subject is willing to take one of the following insulins and can financially afford to use either of the 2 insulin preparations throughout the course of the study (i.e. co-payments for insulin with insurance or able to pay full amount)

    1. Humalog® (insulin lispro injection)
    2. NovoLog® (insulin aspart)

Exclusion Criteria:

1. Subject participated in any Closed Loop study in the past.
2. Subject is unable to tolerate tape adhesive in the area of sensor placement
3. Subject has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, rash, Staphylococcus infection) or area of infusion set placement
4. Women of child-bearing potential who have a positive pregnancy test at screening or plan to become pregnant during the course of the study
5. Subject is being treated for hyperthyroidism at time of screening
6. Subject has an abnormality (out of reference range) in thyroid-stimulating hormone (TSH) at time of screening visit. TSH is not required for subjects 2-13 years of age.
7. Subject has taken any oral, injectable, or IV glucocorticoids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV glucocorticoids during the course of the study.
8. Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks
9. Subject is currently abusing illicit drugs or marijuana
10. Subject is currently abusing prescription drugs
11. Subject is currently abusing alcohol
12. Subject is using pramlintide (Symlin), SGLT2 inhibitors, GLP agonists, biguanides, DPP-4 inhibitors or sulfonylureas at time of screening
13. Subject is using hydroxyurea at the time of screening or plans to use it during the study
14. Subject has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator
15. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
16. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation
17. Subject diagnosed with current moderate to severe eating disorder such as anorexia or bulimia
18. Subject has been diagnosed with chronic kidney disease requiring dialysis or resulting in chronic anemia
19. Subjects who are currently being actively treated for cancer.
20. Subject who is designated as a research staff member for this study