Clinical trial NCT04172441: Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Congenital Hyperinsulinism
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
First posted: 2019-11-21
Enrollment: 12
Sex: ALL
Minimum age (years): 7
Maximum age (years): 364
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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 plasma glucose (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/m\^2 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

Primary outcomes:
measure: Mean Intravenous Glucose Infusion Rate
timeFrame: Hours 36-48 after initiation of trial drug (Part 1)
Secondary outcomes:
measure: Carbohydrates Administered
timeFrame: 0 to 48 hours after initiation of trial drug
measure: Mean Intravenous Glucose Infusion Rate
timeFrame: 48 hours after initiation of trial drug (Part 1)
measure: Mean Intravenous Glucose Infusion Rate Below 10 mg/kg/Minute
timeFrame: Hours 36-48 after initiation of trial drug (Part 1)
measure: Time to Complete Weaning Off Intravenous Glucose
timeFrame: Days 5 to 25 (Part 2)
measure: Hypoglycemia Event Rate in Part 2
timeFrame: Days 5 to 25
measure: Clinically Significant Hypoglycemia Events in Part 2
timeFrame: Days 5 to 25
measure: Time to Actual Hospital Discharge
timeFrame: Days 5 to 25
measure: Time to Pancreatic Surgery
timeFrame: Days 5 to 25
measure: Carbohydrates Administered
timeFrame: Days 5 to 25
measure: Carbohydrates Administered Intravenously
timeFrame: Days 5 to 25
measure: Carbohydrates Administered Parenterally
timeFrame: Days 5 to 25
measure: Carbohydrates Administered Orally
timeFrame: Days 5 to 25
measure: Carbohydrates Administered Via Gastric Feed
timeFrame: Days 5 to 25
measure: Time in Range in Part 2
timeFrame: Days 5 to 25
measure: Time in Hypoglycemia in Part 2
timeFrame: Days 5 to 25
measure: Time in Clinically Significant Hypoglycemia in Part 2
timeFrame: Days 5 to 25
measure: Hypoglycemia Episodes in Part 2
timeFrame: Days 5 to 25
measure: Clinically Significant Hypoglycemia Episodes in Part 2
timeFrame: Days 5 to 25
measure: Extent of Hypoglycemia in Part 2
timeFrame: Days 5 to 25
measure: Extent of Clinically Significant Hypoglycemia in Part 2
timeFrame: Days 5 to 25
measure: Time in Hyperglycemia in Part 2
timeFrame: Days 5 to 25
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Düsseldorf
country: Germany
facility: University Children's Hospital
city: Magdeburg
country: Germany
facility: University Hospital, Magdeburg
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
Study officials:
affiliation: Zealand Pharma
name: Jelena Ivkovic, MD
role: STUDY_DIRECTOR
References: