Safety Evaluation of the Hybrid Closed Loop (HCL) System in Pediatric Subjects With Type 1 Diabetes

The study will proceed as follows:

Run-in Period - General:

A total of up to 200 subjects (age 2-13) will be enrolled at up to 15 investigational centers (14 in the US, 1 EMEA) in order to reach 120 subjects who will complete the HCL study.

Study Period - At Home:

Following the two week run-in period using the Study Pump (670G), all subjects (age 2-13) will participate in a 3-month study period.

Study Period - Hotel Study Subjects (age 7-13) will participate in a Hotel study (6 days, 5 nights), with the remainder of the study period to be spent at home. Subjects 2-6 years of age are not required to participate in a hotel study. Instead, they will participate in an out-of-home study for 5 consecutive days, 4-6 hours per day.

Continued Access Program Subjects will be given the opportunity to extend use of their study devices for a period of up to 3 years . If subjects choose to participate in the continuation period, they will retain the study devices at the end of study period visit or receive them back in the event they have been returned to study staff already.

Inclusion criteria

General Inclusion Criteria

• Subject is age 2-13 years at time of screening
• Subject has a clinical diagnosis of type 1 diabetes for 1 year or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis
• Subject age 2-6 years has a clinical diagnosis of type 1 diabetes for 3 months or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis

Study-specific inclusion criteria

• Subject must have a minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 8 units
• Subjects 7-13: Subjects and their parent(s)/guardian(s) are willing to participate in an overnight visit at the end of the run-in period.
• Subject 7-13 years of age and their parent(s)/guardian(s) are willing to participate in a hotel study for the specified duration of hotel stay.
• Subject 2-6 years of age and their parent(s)/guardian(s) are willing to participate in an extended visit during the study period to perform Frequent Sample Testing.
• Subject must have companion 18 years or older who will sleep in the same dwelling place every night during the study period. This requirement may be verified by subject report at screening visit.
• Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily
• Subject is willing to perform required sensor calibrations
• Subject is willing to wear the system continuously throughout the study
• Subject has a Glycosylated hemoglobin (A1C) value less than 10.0% (as processed by Central Lab) at time of screening visit Note: All HbA1C blood specimens will be sent to and tested by a NGSP certified Central Laboratory. A1C testing must follow National Glycohemoglobin Standardization Program (NGSP) standards.
• Subject has TSH in the normal range OR if the TSH is out of normal reference range the Free T3 is below or within the lab's reference range and Free T4 is within the normal reference range.
• Subject 7 -13 years of age has had pump therapy for greater than 6 months prior to screening (with or without CGM experience)
• Subject 2-6 years of age has had pump therapy for greater than 90 days prior to screening (with or without CGM experience)
• Subjects and their parent(s)/guardian(s) are willing to upload data from the study pump; must have Internet access and a computer system that meets the requirements for uploading the study pump
• If subject has celiac disease, it has been adequately treated as determined by the investigator
• Subjects and their parent(s)/guardian(s) are willing to take one of the following insulins and can financially support the use of 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)

• Humalog® (insulin lispro injection)
• NovoLog® (insulin aspart)
• Subjects and their parent(s)/guardian(s)/companions must be able to speak and be literate in English as verified by the investigator

Exclusion criteria

• Subject has a history of 2 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to screening:

• Medical assistance (i.e. Paramedics, Emergency Room ( ER) or Hospitalization)
• Coma
• Seizures
• Subject is unable to tolerate tape adhesive in the area of sensor placement
• Subject has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection)
• Females who are sexually active and able to conceive will be excluded if they are not using an effective method of contraception and do not agree to continue using an effective method of contraception for the duration of the study as determined by investigator.
• Subject has a cardiovascular condition which the investigator determines should exclude the subject, i.e. ventricular rhythm disturbance, hypertrophic cardiomyopathy
• Subject is being treated for hyperthyroidism at time of screening
• Subject has diagnosis of adrenal insufficiency
• Subject 7-13 years of age has had DKA in the 6 months prior to screening visit.
• Subject 2-6 years of age has had DKA in the 3 months prior to screening visit
• Subject has taken any oral, injectable, or intravenous (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
• 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
• Subject 7-13 years of age has been hospitalized or has visited the ER in the 6 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes
• Subject 2-6 years of age has been hospitalized or has visited the ER in the 3 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes
• Subject is currently abusing illicit drugs
• Subject is currently abusing marijuana.
• Subject is currently abusing prescription drugs
• Subject is currently abusing alcohol
• Subject is using pramlintide (Symlin), DPP-4 inhibitor, liraglutide (Victoza or other GLP-1 agonists), metformin, canagliflozin (Invokana or other SGLT2 inhibitors) at time of screening
• 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
• Subject has elective surgery planned that requires general anesthesia during the course of the study
• Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
• Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation
• Subject diagnosed with current eating disorder such as anorexia or bulimia
• Subject has been diagnosed with chronic kidney disease that results in chronic anemia
• Subject has a hematocrit that is below the normal reference range of lab used.
• Subject is on dialysis
• Subject has serum creatinine of >2 mg/dL.