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

Zealand Pharma12 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Congenital Hyperinsulinism

Interventions

dasiglucagonDRUG

Glucagon analogue

PlaceboDRUG

Placebo for dasiglucagon

Eligibility

Sex: ALLMin age: 7 DaysMax age: 364 Days

Medical Language ↔ Plain English

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

Locations (6)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

University Children's Hospital

Düsseldorf, Germany

University Hospital, Magdeburg

Magdeburg, Germany

Outcomes

Primary Outcomes

Mean Intravenous Glucose Infusion Rate

Mean intravenous (IV) glucose infusion rate (GIR) in the last 12 hours of each treatment period during Part 1, the crossover part of the trial (dasiglucagon or placebo administration).

Time frame: Hours 36-48 after initiation of trial drug (Part 1)

Secondary Outcomes

Carbohydrates Administered

Total amount (g) of carbohydrates administered during the crossover part of the trial (dasiglucagon or placebo administration) per day.

Time frame: 0 to 48 hours after initiation of trial drug

Mean Intravenous Glucose Infusion Rate

Mean IV GIR for each 48-hour treatment period during Part 1, the crossover part of the trial (dasiglucagon or placebo administration).

Time frame: 48 hours after initiation of trial drug (Part 1)

Mean Intravenous Glucose Infusion Rate Below 10 mg/kg/Minute

Mean IV GIR below 10 mg/kg/minute in the last 12 hours of each treatment period during Part 1, the crossover part of the trial (dasiglucagon or placebo administration) (yes/no)

Time frame: Hours 36-48 after initiation of trial drug (Part 1)

Time to Complete Weaning Off Intravenous Glucose

Time in days to complete weaning off IV glucose administration during Part 2, defined as the first point in time when the patient had been off IV glucose administration for at least 12 hours.

Time frame: Days 5 to 25 (Part 2)

Hypoglycemia Event Rate in Part 2

Hypoglycemia event rate, defined as number of hypoglycemic events when PG was \<70 mg/dL (or 3.9 mmol/L), as detected by self-monitored plasma glucose.

Time frame: Days 5 to 25

Data from ClinicalTrials.gov

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Hadassah Medical Center

Jerusalem, Israel

Manchester University NHS Foundation Trust

Manchester, United Kingdom

Clinically Significant Hypoglycemia Events in Part 2

Clinically significant hypoglycemia event rate, defined as number of events when PG was \<54 mg/dL (3.0 mmol/L), as detected by self-monitored plasma glucose.

Time frame: Days 5 to 25

Time to Actual Hospital Discharge

Time in days to actual hospital discharge defined as the time from first exposure to the study drug in Part 2 to discharge from hospital.

Time frame: Days 5 to 25

Time to Pancreatic Surgery

Time (days) to pancreatic surgery (sub-total or total pancreatectomy with a cutoff of ≥95%).

Time frame: Days 5 to 25

Carbohydrates Administered

Total amount (g) of carbohydrates administered (regardless of the route) per day.

Time frame: Days 5 to 25

Carbohydrates Administered Intravenously

Amount (g) of carbohydrates administered via IV glucose infusion or bolus or total parenteral nutrition. This secondary endpoint was intended to account only for carbohydrates administered via IV glucose infusion or bolus. It was not possible to differentiate between carbohydrates administered via IV glucose infusion or bolus and carbohydrates administered as being, or not being, part of total parenteral nutrition from the collected data. This endpoint was expanded to include both.

Time frame: Days 5 to 25

Carbohydrates Administered Parenterally

Amount (g) of carbohydrates administered as part of total parenteral nutrition.

Time frame: Days 5 to 25

Carbohydrates Administered Orally

Amount (g) of carbohydrates administered via oral route.

Time frame: Days 5 to 25

Carbohydrates Administered Via Gastric Feed

Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy.

Time frame: Days 5 to 25

Time in Range in Part 2

Percent time in range (PG between 70 to 180 mg/dL \[3.9-10.0 mmol/L\]) as measured by continuous glucose monitoring.

Time frame: Days 5 to 25

Time in Hypoglycemia in Part 2

Percent time in hypoglycemia (when PG was \<70 mg/dL \[or 3.9 mmol/L\]) as measured by continuous glucose monitoring.

Time frame: Days 5 to 25

Time in Clinically Significant Hypoglycemia in Part 2

Percent time in clinically significant hypoglycemia (when PG was \<54 mg/dL \[or 3.0 mmol/L\]) as measured by continuous glucose monitoring.

Time frame: Days 5 to 25

Hypoglycemia Episodes in Part 2

Rate of hypoglycemia episodes, defined as number of episodes per week when PG was \<70 mg/dL (3.9 mmol/L) for 15 minutes or more, as measured by continuous glucose monitoring.

Time frame: Days 5 to 25

Clinically Significant Hypoglycemia Episodes in Part 2

Rate of clinically significant hypoglycemia episodes, defined as number of episodes per week when was \<54 mg/dL (3.0 mmol/L) for 15 minutes or more, as measured by continuous glucose monitoring.

Time frame: Days 5 to 25

Extent of Hypoglycemia in Part 2

Extent of hypoglycemia (defined as the area over the glucose curve \[AOCglucose\] below 70 mg/dL \[3.9 mmol/L\]) as measured by continuous glucose monitoring.

Time frame: Days 5 to 25

Extent of Clinically Significant Hypoglycemia in Part 2

Extent of clinically significant hypoglycemia (defined as the area over the glucose curve \[AOCglucose\] below 54 mg/dL \[3.0 mmol/L\]) as measured by continuous glucose monitoring, divided by the total duration in hours of continuous glucose monitoring.

Time frame: Days 5 to 25

Time in Hyperglycemia in Part 2

Percent time in hyperglycemia (when PG was \>180 mg/dL \[10.0 mmol/L\]), as measured by continuous glucose monitoring.

Time frame: Days 5 to 25