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

Zealand Pharma

Status and phase: Completed; Phase 3; Phase 2

Conditions: Congenital Hyperinsulinism

Treatments: Drug: Placebo; Drug: dasiglucagon

Study type: Interventional

Funder types: Industry

Identifiers

NCT04172441

2017-004545-24 (EudraCT Number)

ZP4207-17103

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 7 to 364 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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12 participants in 2 patient groups

dasiglucagon first then placebo

Experimental group

Description:

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).

Treatment:

Drug: dasiglucagon

Drug: Placebo

placebo first then dasiglucagon

Experimental group

Description:

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).

Treatment:

Drug: dasiglucagon

Drug: Placebo