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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Type 1 Diabetes
• Intervention / Treatment: Drug: Dasiglucagon

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Steno Diabetes Center Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Usual care; 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; During the 'dasiglucagon' period, participants will use pen-administered low-dose (80 µg) dasiglucagon to treat or prevent episodes of hypoglycemia.	Drug: Dasiglucagon; Abdominal s.c. administration using a multi-dose reusable pen injector

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

Other Outcome Measures

Outcome Measure	Time Frame
Number of device failures/malfunctions	2-week 'dasiglucagon' period

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Investigators: Principal Investigator: Christian Laugesen, MD, Steno Diabetes Center Copenhagen

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 27, 2021
• Primary Completion (ACTUAL): December 30, 2021
• Study Completion (ACTUAL): January 28, 2022

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (ACTUAL): February 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 5, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Hypoglycemia; Type 1 Diabetes; Dasiglucagon
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: 77119; H-21000002 (OTHER: Regional Scientific Ethics Committee); 2020-005745-16 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No