ADvanced Hybrid Closed Loop Study in Adult Population With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study evaluate the safety and efficacy of the Advanced Hybrid Closed Loop (AHCL) system in sub-optimally controlled patients with T1D, in comparison with Multiple Daily Injection (MDI) therapy with Flash Glucose Monitoring (FGM) or Continuous Glucose Monitoring (CGM). Patient with a diagnosis of Type 1 diabetes currently under MDI+ FGM or MDI+ CGM therapy will be enrolled.

Detailed Description
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This study is a pre-market, multi-center, prospective, open label, adaptative, randomized controlled trial in insulin-requiring adult subjects with type 1 diabetes on MDI therapy. The study will have three period: Run-in Phase: The Run-in period is of 4 weeks (and can be extended for 2 additional ones) during which time a blinded CGM sensor will be worn for two weeks. Study Phase: There will be a 6 months randomized study period with two arms: Treatment Arm (AHCL) and the Control Arm. Continuation Phase: There will be a 6 months continuation phase during which time all the subjects will use the AHCL system. Approximately 124 subjects will be enrolled in the study up to 20 investigational centers in EMEA.

Official Title
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ADvanced Hybrid Closed Loop Study in Adult Population With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: MDI
* Device: AHCL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is age ≥ 18 years old at time of screening Subject has a clinical diagnosis of Type 1 diabetes for ≥ 2 years prior to screening as determined via source documentation On MDI therapy (defined as ≥ 3 insulin injections per day and/or a basal/bolus regimen) ≥ 2 years prior to screening Subject has been followed and treated by the investigator at this investigational site for at least 3 months prior to screening and subject has already undergone local educational therapeutic programs. Subject is using: Flash Glucose Monitoring (FGM) for ≥ 3 months with a daily average number of scans ≥ 5 over and with sensor readings > 70% of time over the previous month prior to screening (based on sensor usage from the download summary report of the FGM system over 30 days prior to screening) Or Continuous Glucose Monitoring (CGM) for ≥ 3 months with a frequency of sensor use ≥ 70% of the time over the previous month prior to screening (based on download summary report from the CGM system over 30 days prior to screening). Subject has a glycosylated hemoglobin (HbA1c) ≥ 8.0% (64 mmol/mol) at time of screening visit (as processed by a Central Lab). Subject is willing to take or switch to one of the following insulins: Humalog™ (insulin lispro injection) NovoLog™ (insulin aspart) Subject must have a minimum daily insulin requirement (Total Daily Dose) of ≥ 8 units and a maximum of 250 units. Subject is willing to upload data from the study pump and meter, must have Internet access and a compatible computer system that meets the requirements for uploading the study pump data at home. Subject is willing and able to sign and date informed consent, comply with all study procedures and wear all study devices, as required during the study. Exclusion Criteria: Subject has untreated Addison's disease, thyroid disorder, growth hormone deficiency, hypopituitarism or definite gastroparesis, per investigator judgment. Subject is using pramlintide, DPP-4 inhibitor, GLP-1 agonists/mimetics, metformin, SGLT2 inhibitors at time of screening. Subject has had renal failure defined by creatinine clearance <30 ml/min, as assessed by local lab test ≤ 12 months before screening or performed at screening at local lab, as defined by the creatinine-based Cockcroft or MDRD equations. Subject is planning to switch from FGM to CGM therapy during the 6 months study phase. Note: Subject randomized to Control Arm should remain on their current FGM or CGM therapy during the study phase and will be switched to AHCL during the continuation phase. Subject has a history of hearing or vision impairment hindering perception of glucose display and alarms, or otherwise incapable of using the study devices, per investigator judgment. Women of child-bearing potential who have a positive pregnancy test at screening or plan to become pregnant during the course of the study. 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, per investigator judgment. Subject has any unresolved adverse skin conditions in the area of sensor placement (e.g. psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection). Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or device in the last 2 weeks before enrollment into this study, as per investigator judgment. Subject is currently abusing illicit drugs, marijuana, alcohol or prescription drugs (other than nicotine), per investigator judgment. Subject has any other disease or condition that may preclude the patient from participating in the study, per investigator judgment. Subject is legally incompetent, illiterate or vulnerable person. Research staff involved with the study.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There will be 2 Cohort for this study: Cohort A: Subjects on MDI + FGM will be randomized into: Treatment Arm (AHCL) and Control Arm (MDI+ FGM) Cohort B: Subjects on MDI + Real-Time CGM will be randomized into: Treatment Arm (AHCL) and Control Arm (MDI+ CGM) (exploratory analysis)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm<br>The Control Arm will use individual subject's current diabetes therapy (MDI+FGM or MDI+CGM) for 6 months during the Study Phase. During the Continuation Phase of 6 months Control Arm will start using the Advance Hybrid Close Loop (AHCL) MiniMed™ 670G system version 4.0 | Other: MDI<br>* Subject continues their standard Multiple Daily Injections therapy with FGM or RT-CGM<br>Device: AHCL<br>* Subject starts using the Advance Hybrid Close Loop (AHCL) MiniMed™ 670G system version 4.0. Starting time depends on which Arm the subject is assigned to: if the subject is assigned to the Treatment Arm, then the intervention starts after the RUN-IN period. If the subject is assigned to the Control Arm the intervention will start after 6 months from the date of the enrollment.<br>|
| Experimental: Treatment Arm<br>The Treatment Arm will use the Advance Hybrid Close Loop (AHCL) MiniMed™ 670G system version 4.0 for 6 months during the Study Phase and other 6 months during the Continuation Phase. | Device: AHCL<br>* Subject starts using the Advance Hybrid Close Loop (AHCL) MiniMed™ 670G system version 4.0. Starting time depends on which Arm the subject is assigned to: if the subject is assigned to the Treatment Arm, then the intervention starts after the RUN-IN period. If the subject is assigned to the Control Arm the intervention will start after 6 months from the date of the enrollment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c 6 Months Change Between AHCL and MDI | The difference in the mean HbA1c change (6 months - baseline) between the AHCL and the MDI + FGM arm will be evaluated (Cohort A). | Baseline and end of 6-month study phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TIR Between 70-180 mg/dL | % Time spent within range with sensor glucose (SG) between 70 - 180 mg/dL (3.9-10.0 mmol/L). The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A). | 6 months study phase | 
| Time in Hyperglycemic Range | % Time spent in hyperglycemic range with SG > 180 mg/dL (> 10.0 mmol/L). The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A). | 6 months study phase | 
| Hypoglycemic Events | Number of biochemical hypoglycemic events< 54 mg/dL (3.0 mmol/L) (defined as sensor values < 54 mg/dL (3.0 mmol/L) per 15 consecutive minutes (Danne, 2017). When the time between two successive events is less than 30 minutes, they will be combined and counted as one event. The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A) | 6 months study phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Hybrid Closed Loop, Multiple Daily Injections, Flash Glucose Monitoring, Continuous Glucose Monitoring