Children, Only, Diabetes type1
Conditions
Brief summary
The purpose of this study is to demonstrate the safety and performance of the MiniMed™ 780G system in pediatric subjects (2-6 years old) with type 1 diabetes in a home setting. The objective of this study is to evaluate the safety and performance of the MiniMed™ 780G system in Auto Mode firstly in comparison to the MiniMed™ 780G system in Manual Mode with Suspend before low activated (currently available standard therapy) and secondly in comparison to the new MiniMed™ 780G BLE 2.0 system with DS5 sensor in Auto Mode among pediatric population (2-6 years old).
Detailed description
CIP342 study is a pre-market, prospective, open-label, multi-center, randomized crossover trial in paediatric subjects (2-6 years old) with type 1 diabetes. The study consists of a run-in phase, a study phase and a continuation phase. Run-in Phase: The purpose of the run-in phase (2 to 4 weeks) is to train subject's parent(s)/legal guardian(s) on the MiniMed 780G system in Manual Mode with Suspend before low (SBL) activated and to collect 2 weeks of baseline data. At the end of Run-in Phase, subjects will be randomized into one of two sequences (A or B). The MiniMed 780G system is composed by the MiniMed 780G pump used with Guardian 4 Sensor (G4S) and Guardian Transmitter 4. Study Phase: * Sequence A: subjects will use the Advanced Hybrid Closed Loop (AHCL) therapy (MiniMed 780G system in Auto Mode) for 12 weeks (Treatment). The washout phase of 2 weeks will be followed by a 12-week phase where subjects will use predictive low-glucose suspend (780G system in Manual Mode with SBL activated) (Control). * Sequence B: subjects will continue to use predictive low-glucose suspend (MiniMed 780G system in Manual Mode with SBL activated) (Control). After a washout phase of 2 weeks, subjects will use Advanced Hybrid Closed Loop (AHCL) therapy (MiniMed 780G system in Auto Mode) for 12 weeks (Treatment). During washout period all the subjects will use MiniMed 780G system in Manual Mode with SBL activated. At the end of Study Phase, subjects will start Continuation Phase that is divided in two periods. Continuation Phase: * Period 1: enrolled subjects will enter the continuation phase period 1 and will use MiniMed 780G system in Auto Mode for 18 weeks +/- 6 weeks. * Period 2: At the end of the continuation phase period 1, subjects will be randomized into 2 arms (A2 and B2). This second randomization is completely independent from the first one in the Study Phase. Arm A2: Subjects will start using the MiniMed 780G BLE 2.0 system (treatment) for 12 weeks. The MiniMed 780G BLE 2.0 system is composed by the MiniMed 780 BLE 2.0 and Disposable Sensor labeled (DS5) Arm B2: Subjects will continue to use MiniMed™ 780G system in Auto Mode for 12 weeks.
Interventions
DEVICEMiniMed 780G Auto Mode with G4S sensor
MiniMed™ 780G system in Auto Mode with G4S sensor.
DEVICEMiniMed 780G Manual Mode with G4S sensor
MiniMed™ 780G system in Manual Mode.
DEVICEMiniMed 780G Auto Mode with DS5 sensor
MiniMed 780G Auto Mode with DS5 sensor
Sponsors
Medtronic Diabetes
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Run-in Phase: training on the MiniMed 780G system in Manual Mode with SBL activated to collect 2 weeks of baseline data. Study Phase: Sequence A: subjects MiniMed 780G system in Auto Mode for 12 weeks (Treatment). The washout phase of 2 weeks will be followed by a 12-week phase where subjects will use 780G system in Manual Mode with SBL activated (Control). Sequence B: subjects 780G system in Manual Mode with SBL activated (Control). After a washout phase of 2 weeks, subjects will use t MiniMed 780G system in Auto Mode for 12 weeks (Treatment). Continuation Phase: Period 1: subjects will use MiniMed 780G system in Auto Mode for 18 weeks +/- 6 weeks. Period 2: Arm A2: subjects will start using the MiniMed 780G BLE 2.0 system (treatment) for 12 weeks (Treatment). Arm B2: subjects will continue to use MiniMed™ 780G system in Auto Mode for 12 weeks (Control).
Eligibility
Sex/Gender
ALL
Age
2 Years to 6 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 2 - 6 years at time of screening 2. Has a clinical diagnosis of type 1 diabetes for ≥ 6 months prior to screening as determined via medical record or source documentation by an individual qualified to make a medical diagnosis 3. Is on MDI therapy or CSII with or without CGM prior to screening 4. Has a glycosylated hemoglobin (HbA1c) \< 11% (97 mmol/mol) at time of screening visit as processed by a Local Lab 5. Is using or willing to switch to one of the following commercialized available insulins: Humalog (insulin lispro injection) and NovoLog (insulin aspart). 6. Must have a minimum daily insulin requirement (Total Daily Dose) of ≥ 6 units 7. Parent(s)/legal guardian(s) willing to upload data from the pump system, must have Internet access, a compatible computer or mobile phone that meets the requirements for uploading the study pump data at home. 8. Is living with one or more parent(s)/legal guardian(s) knowledgeable about emergency procedures for severe hypoglycemia and able to contact emergency services and study staff. 9. Investigator has confidence that the parent(s)/legal guardian(s) can successfully operate all study devices and is capable of adhering to the protocol 10. Subject and parent(s)/legal guardian(s) willingness to participate in all training sessions as directed by study staff. 11. Subject's parent/legal guardian must be willing and able to provide written informed consent.
Exclusion criteria
1. Has Addison's disease, growth hormone deficiency, coeliac disease, hypopituitarism or definite gastroparesis, untreated thyroid disorder, or poorly controlled asthma, per investigator judgment. 2. Is using any anti-diabetic medication other than insulin at the time of screening or plan of using during the study (e.g. pramlintide, DPP-4 inhibitor, GLP-1, agonists/mimetics, metformin, SGLT2 inhibitors). 3. 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. 4. Has had renal failure defined by creatinine clearance \<30 ml/min, as assessed by local lab test ≤6 months before screening or performed at screening at local lab, as defined by the creatinine-based Cockcroft, CKD-EPI or MDRD equations. 5. Has any unresolved adverse skin conditions in the area of sensor placement (e.g. psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection). 6. Is under Control IQ or CamAPS FX or other advanced hybrid closed loop therapy (e.g. DIY, MiniMed 780G) in the previous 3 months before enrollment. Note: For the continuation phase only, subjects using MiniMed 780G can be enrolled. 7. 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. 8. Has any other disease or condition that may preclude the patient from participating in the study, per investigator judgment. 9. History of \>1 DKA event not related to illness or initial diagnosis in the last 3 months. 10. Parent(s)/legal guardian(s) are part of research staff involved with the study. 11. Parent(s)/legal guardian(s) are illiterate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Phase Primary Endpoint: Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test | 12 weeks for each cross-over period | The primary endpoint is the between-treatment difference in the percentage of time that the sensor glucose measurement is in the target range, 70 to 180 mg/dL (3.9-10.0 mmol/L), non-inferiority test. |
| Continuation Phase Primary Endpoint: Mean HbA1c (%) - Non-inferiority Test | The outcome was measured at the end of the 12-week continuation phase period 2 | The primary endpoint for continuation phase is the between-treatment difference in the mean HbA1c (%) at the end of 12-week continuation phase period 2. The endpoint will be assessed for non-inferiority with an absolute margin of 0.4% HbA1c. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Phase Secondary Endpoint 3 - Mean HbA1c (%) - Superiority Test. | The outcome was measured at the end of each 12 week cross-over period | Between-treatment difference in mean HbA1c at the end of each 12-week cross-over period, superiority test. |
| Continuation Phase Secondary Endpoint 1- Mean HbA1c (%) - Superiority Test | The outcome was measured at the end of the 12-week continuation phase period 2 | Between-treatment difference in Mean HbA1c at the end of the 12-week continuation phase period 2, superiority test. |
| Study Phase Secondary Endpoint 1- Mean HbA1c (%) - Non-inferiority Test | The outcome was measured at the end of each 12 week cross-over period | Between-treatment difference in mean HbA1c at the end of each 12-week cross-over period, non-inferiority test. |
| Continuation Phase Secondary Endpoint 3- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test | 12 weeks of continuation phase period 2 | Between-treatment difference in % Time spent in target range (70 to 180 mg/dL \[3.9-10.0 mmol/L\]) during the end 12-week continuation phase period 2, superiority test. |
| Continuation Phase Secondary Endpoint 2- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test | 12 weeks of continuation phase period 2 | Between-treatment difference in % Time spent in target range (70 to 180 mg/dL \[3.9-10.0 mmol/L\]) during the end 12-week continuation phase period 2, non-inferiority test |
| Study Phase Secondary Endpoint 2 - Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test | 12 weeks for each cross-over period | Between-treatment difference in % Time spent in target range (70 to 180 mg/dL \[3.9-10.0 mmol/L\]), during each 12 week cross-over period, superiority test. |
Countries
Finland, Italy, Slovenia, United Kingdom
Participant flow
Recruitment details
101 subjects signed the informed consent and were assessed for enrollment. Out of them, 3 screening failures due to the following inclusion criteria not met: Investigator has confidence that the parent(s)/ legal guardian(s) can successfully operate all study devices and is capable of adhering to the protocol discontinued the study before starting the run-in phase.
Pre-assignment details
Run-in period
Participants by arm
| Arm | Count |
|---|---|
| Study Phase - Sequence A Subjects used the MiniMed 780G (with G4S sensor) system in Auto Mode for 12 weeks (Treatment), followed by 2 weeks of washout period where the system was used in Manual Mode with SBL activated (Control).
After the washout period the subjects used the MiniMed 780G (with G4S sensor) system in Manual Mode with SBL activated (Control).
MiniMed 780G Auto Mode with G4S sensor: MiniMed™ 780G system in Auto Mode with G4S sensor.
MiniMed 780G Manual Mode with G4S sensor: MiniMed™ 780G system in Manual Mode. | 50 |
| Study Phase - Sequence B Subjects used the MiniMed 780G (with G4S sensor) system in Manual Mode with SBL activated for 12 weeks (Control), followed by 2 weeks of washout period where the system was used in Manual Mode with SBL activated (Control).
After the washout period the subjects used the MiniMed 780G (with G4S sensor) system in Auto Mode (Treatment).
MiniMed 780G Auto Mode with G4S sensor: MiniMed™ 780G system in Auto Mode with G4S sensor.
MiniMed 780G Manual Mode with G4S sensor: MiniMed™ 780G system in Manual Mode. | 48 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Continuation Phase Period 1 | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Continuation Phase Period 1 | Death | 1 | 0 | 0 | 0 | 0 |
| Continuation Phase Period 1 | Physician Decision | 1 | 0 | 0 | 0 | 0 |
| Continuation Phase Period 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
| Continuation Phase Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
| Pre Run-In | Screening failure | 3 | 0 | 0 | 0 | 0 |
| Study Phase Period 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
| Study Phase Period 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Study Phase - Sequence B | Total | Study Phase - Sequence A |
|---|---|---|---|
| Age, Continuous | 4.84 years STANDARD_DEVIATION 1.234 | 4.72 years STANDARD_DEVIATION 1.156 | 4.61 years STANDARD_DEVIATION 1.076 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Finland | 15 participants | 27 participants | 12 participants |
| Region of Enrollment Italy | 12 participants | 25 participants | 13 participants |
| Region of Enrollment Slovenia | 10 participants | 20 participants | 10 participants |
| Region of Enrollment United Kingdom | 11 participants | 26 participants | 15 participants |
| Sex: Female, Male Female | 25 Participants | 48 Participants | 23 Participants |
| Sex: Female, Male Male | 23 Participants | 50 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 98 | 0 / 98 | 0 / 97 | 0 / 97 | 1 / 95 | 0 / 45 | 0 / 46 |
| other Total, other adverse events | 18 / 98 | 45 / 98 | 11 / 97 | 39 / 97 | 37 / 95 | 11 / 45 | 17 / 46 |
| serious Total, serious adverse events | 1 / 98 | 5 / 98 | 1 / 97 | 2 / 97 | 4 / 95 | 1 / 45 | 2 / 46 |
Outcome results
Primary
Continuation Phase Primary Endpoint: Mean HbA1c (%) - Non-inferiority Test
The primary endpoint for continuation phase is the between-treatment difference in the mean HbA1c (%) at the end of 12-week continuation phase period 2. The endpoint will be assessed for non-inferiority with an absolute margin of 0.4% HbA1c.
Time frame: The outcome was measured at the end of the 12-week continuation phase period 2
Population: The number of subjects with endpoint measurements available at the end of the continuation phase period 2 were 38 out of 45 and 42 out of 46 for arm A2 and arm B2, respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Continuation Phase Primary Endpoint: Mean HbA1c (%) - Non-inferiority Test | 7.30 % of hba1c | Standard Deviation 0.529 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Continuation Phase Primary Endpoint: Mean HbA1c (%) - Non-inferiority Test | 7.24 % of hba1c | Standard Deviation 0.643 |
95% CI: [-0.03, 0.31]Regression, Linear
Primary
Study Phase Primary Endpoint: Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test
The primary endpoint is the between-treatment difference in the percentage of time that the sensor glucose measurement is in the target range, 70 to 180 mg/dL (3.9-10.0 mmol/L), non-inferiority test.
Time frame: 12 weeks for each cross-over period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Study Phase Primary Endpoint: Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test | 68.34 percentage of time | Standard Deviation 6.922 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Study Phase Primary Endpoint: Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test | 58.34 percentage of time | Standard Deviation 12.455 |
95% CI: [8.04, 11.72]Mixed Models Analysis
Secondary
Continuation Phase Secondary Endpoint 1- Mean HbA1c (%) - Superiority Test
Between-treatment difference in Mean HbA1c at the end of the 12-week continuation phase period 2, superiority test.
Time frame: The outcome was measured at the end of the 12-week continuation phase period 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Continuation Phase Secondary Endpoint 1- Mean HbA1c (%) - Superiority Test | 7.30 % of hba1c | Standard Deviation 0.529 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Continuation Phase Secondary Endpoint 1- Mean HbA1c (%) - Superiority Test | 7.24 % of hba1c | Standard Deviation 0.643 |
p-value: 0.109795% CI: [-0.03, 0.31]Regression, Linear
Secondary
Continuation Phase Secondary Endpoint 2- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test
Between-treatment difference in % Time spent in target range (70 to 180 mg/dL \[3.9-10.0 mmol/L\]) during the end 12-week continuation phase period 2, non-inferiority test
Time frame: 12 weeks of continuation phase period 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Continuation Phase Secondary Endpoint 2- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test | 69.7 percentage of time | Standard Deviation 7.728 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Continuation Phase Secondary Endpoint 2- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Non-inferiority Test | 68.8 percentage of time | Standard Deviation 8.615 |
95% CI: [-0.04, 2.38]Regression, Linear
Secondary
Continuation Phase Secondary Endpoint 3- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test
Between-treatment difference in % Time spent in target range (70 to 180 mg/dL \[3.9-10.0 mmol/L\]) during the end 12-week continuation phase period 2, superiority test.
Time frame: 12 weeks of continuation phase period 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Continuation Phase Secondary Endpoint 3- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test | 69.66 percentage of time | Standard Deviation 7.734 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Continuation Phase Secondary Endpoint 3- Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test | 68.86 percentage of time | Standard Deviation 8.615 |
p-value: 0.058195% CI: [-0.04, 2.38]Regression, Linear
Secondary
Study Phase Secondary Endpoint 1- Mean HbA1c (%) - Non-inferiority Test
Between-treatment difference in mean HbA1c at the end of each 12-week cross-over period, non-inferiority test.
Time frame: The outcome was measured at the end of each 12 week cross-over period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Study Phase Secondary Endpoint 1- Mean HbA1c (%) - Non-inferiority Test | 7.00 % of hba1c | Standard Deviation 0.533 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Study Phase Secondary Endpoint 1- Mean HbA1c (%) - Non-inferiority Test | 7.61 % of hba1c | Standard Deviation 0.906 |
95% CI: [-0.76, -0.46]Mixed Models Analysis
Secondary
Study Phase Secondary Endpoint 2 - Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test
Between-treatment difference in % Time spent in target range (70 to 180 mg/dL \[3.9-10.0 mmol/L\]), during each 12 week cross-over period, superiority test.
Time frame: 12 weeks for each cross-over period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Study Phase Secondary Endpoint 2 - Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test | 68.34 percentage of time | Standard Deviation 6.922 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Study Phase Secondary Endpoint 2 - Percentage of Time in Range (TIR 70 to 180 mg/dL [3.9-10.0 mmol/L]) - Superiority Test | 58.34 percentage of time | Standard Deviation 12.455 |
p-value: <0.000195% CI: [8.04, 11.72]Mixed Models Analysis
Secondary
Study Phase Secondary Endpoint 3 - Mean HbA1c (%) - Superiority Test.
Between-treatment difference in mean HbA1c at the end of each 12-week cross-over period, superiority test.
Time frame: The outcome was measured at the end of each 12 week cross-over period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MiniMed 780G (With G4S Sensor) System in Auto Mode | Study Phase Secondary Endpoint 3 - Mean HbA1c (%) - Superiority Test. | 7.00 % of hba1c | Standard Deviation 0.533 |
| MiniMed 780G (With G4S Sensor) System in Manual Mode + SBL | Study Phase Secondary Endpoint 3 - Mean HbA1c (%) - Superiority Test. | 7.61 % of hba1c | Standard Deviation 0.906 |
p-value: <0.000195% CI: [-0.76, -0.46]Mixed Models Analysis