Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
Study Details
Study Description
Brief Summary
The objective of the trial is to evaluate the efficacy of dasiglucagon administered as a subcutaneous (SC) infusion in reducing hypoglycemia in children with CHI.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Standard of Care + dasiglucagon 8 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care |
Drug: dasiglucagon
Glucagon analog
Other Names:
Other: Standard of Care
Standard of care according to site and/or country
|
| Other: Standard of Care 4 weeks of standard of care + 4 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care |
Drug: dasiglucagon
Glucagon analog
Other Names:
Other: Standard of Care
Standard of care according to site and/or country
|
Outcome Measures
Primary Outcome Measures
- Hypoglycemia events [Weeks 2-4]
Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
Secondary Outcome Measures
- Fasting tolerance [Baseline to week 4]
Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continous glucose monitorting reading <70 mg/dL [3.9 mmol/L])
- Gastric carbohydrates administered to treat hypoglycemia [Week 2-4]
Total amount of gastric carbohydrates adminstered via nasogastric tube or gastrostomy per week to treat hypoglycemia
- Time in range [Week 2-4]
Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continous glucose monitoring
- Clinically significant hypoglycemia events [Week 2-4]
Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), as detected my self-measured plasma glucose
- Gastric carbohydrates administrations to treat hypoglycemia [Week 2-4]
Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia
- Extent of hypoglycemia [Week 2-4]
Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitorting
- Nightly gastric carbohydrates administered [Week 2-4]
Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week
- Gastric carbohydrates administered [Week 2-4]
Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week
- Time in hypoglycemia [Week 2-4]
Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
- Rate of hypoglycemic episodes [Week 2-4]
Rate of hypoglycemic episodes, defined as number of episodes <70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continous glucose monitoring
- Time in hypoglycemia in treatment period 2 [Week 6-8]
Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
- Gastric carbohydrates administrations to treat hypoglycemia in treatment period 2 [Week 6-8]
Average weekly number of gastric carbohydrate administrations via nasogastric tube or gastrostomy to treat hypoglycemia
- Hypoglycemic events in treatment period 2 [Week 6-8]
Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
- Clinically significant hypoglycemia events in treatment period 2 [Week 6-8]
Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), for 15 minutes or more as measured by continous glucose monitorting (CGM)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Established and documented diagnosis of CHI based on standard of care
-
Experiencing ≥3 events of hypoglycemia per week (PG <70 mg/dL [<3.9 mmol/L]) according to the investigator's evaluation
-
Previously undergone near-total pancreatectomy or being treated with a non-surgical approach, having been evaluated as not eligible for pancreatic surgery
-
If somatostatin analogues or sirolimus are used, the therapy should be well established as judged by the investigator, especially when considering their biological half-life
Exclusion Criteria:
-
Previous administration of dasiglucagon
-
Known or suspected allergy to the trial drug or related products
-
Previous participation (randomization) in this trial
-
Circulatory instability requiring supportive medication
-
Requires exogenous insulin
-
Body weight of <4 kg (8.8 lbs.)
-
Documented HbA1c ≥7% subsequent to near-total pancreatectomy and within 6 months prior to screening
-
Known or suspected presence of significant central nervous system disease/injury such that in the investigator's opinion will affect trial participation
-
Use of systemic corticosteroids, e.g., hydrocortisone >20 mg/m2 body surface area or equivalent in the 5 days before screening
-
Use of anti-inflammatory biological agents, or other immune modulating agents in the 3 months prior to screening
-
Any clinically significant abnormality identified on echocardiogram that in the opinion of the investigator would affect the patient's ability to participate in the trial
-
Any recognized clotting or bleeding disorders
-
Has participated in an interventional clinical trial (investigational or marketed product) within 3 months of screening or 5 half-lives of the drug under investigation (whichever comes first), or plans to participate in another clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Colorado | Aurora | Colorado | United States | 13123 |
| 2 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 3 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 4 | University Hospital Düsseldorf, Department of Pediatrics | Düsseldorf | Germany | 40225 | |
| 5 | Otto von Guericke University Magdeburg, Department of Pediatrics | Magdeburg | Germany | 39120 | |
| 6 | Hadassah Medical Center | Jerusalem | Israel | 9765422 | |
| 7 | NHS Greater Glasgow and Clyde | Glasgow | United Kingdom | ||
| 8 | Alder Hey Children'sHospital NHS Foundation Trust | Liverpool | United Kingdom | ||
| 9 | Great Osmond Street Hospital for Children NHS Foundation Trust | London | United Kingdom | ||
| 10 | Central Manchester University Hospital NHS Foundation Trust | Manchester | United Kingdom |
Sponsors and Collaborators
- Zealand Pharma
Investigators
- Study Director: Benedikte Bandak, Zealand Pharma
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZP4207-17109