Pen-Administered Low-Dose Dasiglucagon for Prevention and Treatment of Hypoglycemia in People With Type 1 Diabetes

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to evaluate the efficacy, safety and feasibility of outpatient-utilization of low-dose dasiglucagon administered via a multi-dose reusable pen injector in preventing and treating mild hypoglycemia in insulin pump-treated people with type 1 diabetes.

Detailed Description
-----------------
A randomized, open-label, two-arm, two-week crossover study will be conducted to assess the study objectives. The study will enroll 24 participants with insulin pump-treated type 1 diabetes. Upon study enrollment, participants will complete two consecutive 2-week periods - a 'usual care' period and 'dasiglucagon' period. During the 'usual care' period, participants will manage episodes of manifest or impending hypoglycemia as usual, e.g. through carbohydrate consumption or manual insulin pump suspension. During the 'dasiglucagon' period, participants will use pen-administered low-dose dasiglucagon to treat or prevent episodes of hypoglycemia.

Official Title
-----------------
Pen-Administered Low-Dose Dasiglucagon for Prevention and Treatment of Hypoglycemia in People With Type 1 Diabetes: A Randomized, Open-Label, Two-Period Crossover Outpatient Study

Conditions
-----------------
Type 1 Diabetes, Hypoglycemia

Intervention / Treatment
-----------------
* Drug: Dasiglucagon


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years T1D ≥ 2 years Use of insulin pump therapy (without sensor-augmented insulin suspension/adjustment functionality) ≥ 6 months Use of CGM (real-time or intermittently scanned) ≥ 3 months and ≥ 70% during the previous 14 days HbA1c ≤ 70 mmol/l (8.5%) Performs aerobic exercise on a regular basis (≥ 2 times per week; self-reported) and desires to exercise per American Diabetes Association guidelines (150 minutes per week) during the study. Use of carbohydrate counting and bolus calculator (self-reported) Sensor glucose level < 3.9 mmol/l on ≥ 4/14 previous days assessed by CGM data Exclusion Criteria: Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period and within 30 days prior to study start Known or suspected allergies to glucagon or related products History of hypersensitivity or allergic reaction to dasiglucagon or any of the excipients Patients with pheochromocytoma or insulinoma Hypoglycemia unawareness Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods Inability to understand the individual information and to give informed consent Current participation in another clinical trial that, in the judgment of the investigator, will compromise the results of the study or the safety of the subject Concomitant medical or psychological conditions identified through review of medical history, physical examination and clinical laboratory analysis that, according to the investigator's assessment, makes the individual unsuitable for study participation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A Randomized, Open-Label, Two-Period, Two-Week Crossover Outpatient Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual care<br>During the 'usual care' period, participants will manage episodes of manifest or impending hypoglycemia as usual, e.g. through carbohydrate consumption or manual insulin pump suspension. | |
| Experimental: Dasiglucagon<br>During the 'dasiglucagon' period, participants will use pen-administered low-dose (80 µg) dasiglucagon to treat or prevent episodes of hypoglycemia. | Drug: Dasiglucagon<br>* Abdominal s.c. administration using a multi-dose reusable pen injector<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in percentage of time in range between the two study periods | Sensor glucose level ≥ 3.9 mmol/l and ≤ 10.0 mmol/l | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in percentage of time in hypoglycemia between the two study periods | Sensor glucose level < 3.9 mmol/l | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference in percentage of time in hyperglycemia between the two study periods | Sensor glucose level > 10 mmol/l | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference in coefficient of variation (%) between the two study periods |  | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference between successful cases (%) of hypoglycemia treatment between the two study periods | Initial sensor glucose level ≥ 2.2 mmol/l and ≤ 3.9 mmol/l AND sensor glucose level > 3.9 mmol/l 30 minutes post-treatment | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference in successful cases (%) of hypoglycemia treatment without subsequent hyperglycemia [sensor glucose level > 10 mmol/l during the first two hours post-treatment] between the two study periods | Initial sensor glucose level ≥ 2.2 mmol/l and ≤ 3.9 mmol/l AND sensor glucose level > 3.9 mmol/l 30 minutes post-treatment AND sensor glucose level ≤ 10 mmol/l during the first two hours post-treatment | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference in successful cases (%) of hypoglycemia prevention between the two study periods | Initial sensor glucose level > 3.9 mmol/l AND sensor glucose level < 3.9 for ≤ 15 consecutive minutes during the first two hours post-treatment | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference in time from hypoglycemia treatment to euglycemia between the two study periods | Minutes from initial sensor glucose level ≥ 2.2 mmol/l and ≤ 3.9 mmol/l to sensor glucose level ≥ 3.9 mmol/l | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Incidence rate of supplement carbohydrate administration during the first hour following dasiglucagon administration |  | 2-week 'dasiglucagon' period | 
| Difference between the average daily carbohydrate intake between the two study periods | Registered on the insulin pump | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference between the average total daily insulin dose between the two study periods |  | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Difference in the number and intensity of episodes with nausea, headache, stomach-ache, palpitations and injection site pain between the two study periods | Intensity: mild/moderate/severe | 2-week 'usual care' period and 2-week 'dasiglucagon' period | 
| Percentage of participants scoring a favorable outcome on the patient-reported outcome questionnaire | Scoring likely OR very likely on a four-point Likert scale | At the end-of-study visit (estimated week 6) | 
| Percentage of participants with treatment-induced or treatment-boosted anti-dasiglucagon antibodies |  | Measured 4 weeks after the 'dasiglucagon' period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 1 Diabetes, Hypoglycemia, Dasiglucagon