Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism

Congenital Hyperinsulinism Clinical Trial

Official title:

A Randomized Trial in 2 Parts: Double-Blind, Placebo-Controlled, Crossover Part 1 and Open-label Part 2, Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04172441
• Other study ID #: ZP4207-17103
• Secondary ID: 2017-004545-24
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 22, 2020
• Est. completion date: March 7, 2022

Study information

• Verified date: March 2023
• Source: Zealand Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of the trial is to evaluate the efficacy of dasiglucagon in reducing glucose requirements in children with persistent congenital hyperinsulinism (CHI) requiring continuous intravenous (IV) glucose administration to prevent/manage hypoglycemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 7, 2022
• Est. primary completion date: March 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Days to 364 Days

Eligibility

Inclusion Criteria:

• CHI diagnosis established based on the following:

1. Hyperinsulinemia: plasma insulin above the limit of detection of the assay documented during an event of hypoglycemia, and/or

2. Hypofattyacidemia: plasma free fatty acid <1.7 mmol/L, and/or

3. Hypoketonemia: Beta-hydroxybutyrate <1.8 mmol/L, and/or

4. Glycemic response: an increase in PG of >30 mg/dL (1.7 mmol/L) after 1 mg IV or intramuscular (IM) glucagon administration

• Male or female, age =7 days and <12 months at screening
• Body weight of =2.0 kg (4.4 lbs.)
• Continuous IV glucose requirement to prevent hypoglycemia

Exclusion Criteria:

• Is suspected of having a transient form of CHI (e.g., transient hyperinsulinism due to maternal diabetes or perinatal stress)
• Was born preterm below 34 weeks of gestational age
• Presence of hypertension or hypotension, including circulatory instability requiring supportive medication or presence of pheochromocytoma
• Known or suspected presence of severe brain damage
• Evidence of metabolic, endocrine, or syndromic causes of hypoglycemia not due to hyperinsulinism
• Use of systemic corticosteroids, e.g., hydrocortisone >20 mg/m2 body surface area or equivalent within 5 days before screening
• Prior use of lanreotide, sirolimus (mechanistic target of rapamycin (mTOR) inhibitors), anti inflammatory biological agents, or other immune modulating agents. Prior use of octreotide is allowed after a minimum of 48 hour washout before randomization.
• Any clinically significant abnormality identified on echocardiogram that in the opinion of the investigator would affect the subject's ability to participate in the trial
• Any recognized clotting or bleeding disorder
• The use of prescription or non-prescription medications known to cause QT prolongation

Related Conditions & MeSH terms

• Congenital Hyperinsulinism
• Hyperinsulinism
• Nesidioblastosis

Intervention

Drug:
• dasiglucagon
Glucagon analogue
• Placebo
Placebo for dasiglucagon

Locations

Country	Name	City	State
Germany	University Children's Hospital	Düsseldorf
Germany	University Hospital, Magdeburg	Magdeburg
Israel	Hadassah Medical Center	Jerusalem
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Zealand Pharma

Countries where clinical trial is conducted

United States,  Germany,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean intravenous glucose infusion rate	Mean intravenous glucose infusion rate in the last 12 hours of each treatment period during the crossover part of the trial (dasiglucagon or placebo administration)	36-48 hours after initiation of trial drug
Secondary	Carbohydrates administered	Total amount (g) of carbohydrates administered during the crossover part of the trial (dasiglucagon or placebo administration) per day	0-48 hours after initiation of trial drug
Secondary	Carbohydrates administered	Mean intravenous glucose infusion rate for each 48-hour treatment period during the crossover part of the trial (dasiglucagon or placebo administration)	0-48 hours after initiation of trial drug
Secondary	Carbohydrates administered	Mean intravenous glucose infusion rate below 10 mg/kg/min in the last 12 hours of each treatment period during the crossover part of the trial (yes/no) (dasiglucagon or placebo administration)	36-48 hours after initiation of trial drug
Secondary	Time to complete weaning off intravenous glucose	Time to complete weaning off intravenous glucose administration during part 2	Day 5-25
Secondary	Hypoglycemia event rate in part 2	Hypoglycemia event rate, defined as number of hypoglycemic events (PG <70 mg/dL or 3.9 mmol/L), as detected by self-monitored plasma glucose	Day 5-25
Secondary	Clinically significant hypoglycemia events in part 2	Clinically significant hypoglycemia event rate, defined as number of events <54 mg/dL (3.0 mmol/L), as detected by self-monitored plasma glucose	Day 5-25
Secondary	Time to actual hospital discharge	Time (days) from start of part 2 until the patient is discharged from the hospital	Day 5-25
Secondary	Time to pancreatic surgery	Time (days) to pancreatic surgery (sub-total or total pancreatectomy)	Day 5-25
Secondary	Carbohydrates administered	Total amount (g) of carbohydrates administered (regardless of the route) per day	Day 5-25
Secondary	Carbohydrates administered intravenously	Amount (g) of carbohydrates administered via IV glucose infusion or bolus (not as part of total parental nutrition)	Day 5-25
Secondary	Carbohydrates administered parenterally	Amount (g) of carbohydrates administered as part of total parenteral nutrition	Day 5-25
Secondary	Carbohydrates administered orally	Amount (g) of carbohydrates administered via oral route	Day 5-25
Secondary	Carbohydrates administered via gastric feed	Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy	Day 5-25
Secondary	Time in range in part 2	Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continuous glucose monitoring	Day 5-25
Secondary	Time in hypoglycemia in part 2	Percent time in hypoglycemia (<70 mg/dL or 3.9 mmol/L) as measured by continuous glucose monitoring	Day 5-25
Secondary	Time in clinically significant hypoglycemia in part 2	Percent time in clinically significant hypoglycemia (<54 mg/dL or 3.0 mmol/L) as measured by continuous glucose monitoring	Day 5-25
Secondary	Hypoglycemia episodes in part 2	Rate of hypoglycemia episodes, defined as number of episodes <70 mg/dL (3.9 mmol/L) for 15 min or more, as measured by continuous glucose monitoring	Day 5-25
Secondary	Clinically significant hypoglycemia episodes in part 2	Rate of clinically significant hypoglycemia episodes, defined as number of episodes <54 mg/dL (3.0 mmol/L) for 15 min or more, as measured by continuous glucose monitoring	Day 5-25
Secondary	Extent of hypoglycemia in part 2	Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring	Day 5-25
Secondary	Extent of clinically significant hypoglycemia in part 2	Extent of clinically significant hypoglycemia (area over the glucose curve [AOCglucose] below 54 mg/dL [3.0 mmol/L]) as measured by continuous glucose monitoring	Day 5-25
Secondary	Time in hyperglycemia in part 2	Percent time in hyperglycemia (>180 mg/dL or 10.0 mmol/L), as measured by continuous glucose monitoring	Day 5-25