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

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

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.

Study Overview

• Status: Completed
• Conditions: Congenital Hyperinsulinism
• Intervention / Treatment: Drug: Placebo; Drug: dasiglucagon

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Düsseldorf, Germany, 40225
    • University Children's Hospital
  • Magdeburg, Germany, 39120
    • University Hospital, Magdeburg
• Israel
  • Jerusalem, Israel, 9765422
    • Hadassah Medical Center
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 11 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dasiglucagon first then placebo; 48 hours of dasiglucagon subcutaneous (sc) infusion starting at 10 µg/hour with crossover to 48 hours placebo sc infusion (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).	Drug: Placebo; Placebo for dasiglucagon; Drug: dasiglucagon; Glucagon analogue; Other Names: ZP4207
Experimental: placebo first then dasiglucagon; 48 hours of placebo sc infusion with crossover to 48 hours dasiglucagon sc infusion starting at 10 µg/hour (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).	Drug: Placebo; Placebo for dasiglucagon; Drug: dasiglucagon; Glucagon analogue; Other Names: ZP4207

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Time to complete weaning off intravenous glucose	Time to complete weaning off intravenous glucose administration during part 2	Day 5-25
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
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
Time to actual hospital discharge	Time (days) from start of part 2 until the patient is discharged from the hospital	Day 5-25
Time to pancreatic surgery	Time (days) to pancreatic surgery (sub-total or total pancreatectomy)	Day 5-25
Carbohydrates administered	Total amount (g) of carbohydrates administered (regardless of the route) per day	Day 5-25
Carbohydrates administered intravenously	Amount (g) of carbohydrates administered via IV glucose infusion or bolus (not as part of total parental nutrition)	Day 5-25
Carbohydrates administered parenterally	Amount (g) of carbohydrates administered as part of total parenteral nutrition	Day 5-25
Carbohydrates administered orally	Amount (g) of carbohydrates administered via oral route	Day 5-25
Carbohydrates administered via gastric feed	Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy	Day 5-25
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Zealand Pharma

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2020
• Primary Completion (Actual): March 7, 2022
• Study Completion (Actual): March 7, 2022

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Hypoglycemia; Hyperinsulinism; Congenital Hyperinsulinism; Nesidioblastosis
• Other Study ID Numbers: ZP4207-17103; 2017-004545-24 (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: Yes
• Studies a U.S. FDA-regulated device product: No