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

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:

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.

3. Continuation Period: There will be a 6 month continuation period during which time all
subjects will use the HCL system with Auto Mode.

Up to 1500 subjects will be enrolled in order to have 1120 subjects complete the study. Up to
70 investigational Centers in the US, Europe and Canada will be enrolled.

Inclusion Criteria

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

1. US and Canada: Subjects 2-6 years of age will be allowed to enroll in the post
approval study, once DMC has reviewed data from 10 subjects age 2-4 years who
have completed participation in the study period of the CEP302 study and has
given approval to enroll

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

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 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

14. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell
transfusion or erythropoietin within 3 months prior to time of screening

15. Subject plans to receive red blood cell transfusion or erythropoietin over the course
of study participation

16. Subject diagnosed with current moderate to severe eating disorder such as anorexia or
bulimia

17. Subject has been diagnosed with chronic kidney disease requiring dialysis or resulting
in chronic anemia

18. Subjects who are currently being actively treated for cancer.

19. Subject who is designated as a research staff member for this study