Children with congenital hyperinsulinism MedDRA version: 20.0 Level: PT Classification code 10061211 Term: Hyperinsulinism System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Dasiglucagon
Product Code: ZP4207
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Dasiglucagon
CAS Number: 1544300-84-6
Current Sponsor code: ZP4207
Concentration unit:
Sponsors
Zealand Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. CHI diagnosis established based on the following: a. Hyperinsulinemia: plasma insulin above the limit of detection of the assay documented during an event of hypoglycemia, and/or b. Hypofattyacidemia: plasma free fatty acid 30 mg/dL (1.7 mmol/L) after 1 mg IV or IM glucagon administration 2. Male or female, age =7 days and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Is suspected of having a transient form of CHI (e.g., transient hyperinsulinism due to maternal diabetes or perinatal stress) 2. Was born preterm below 34 weeks of gestational age 3. Presence of hypertension or hypotension, including circulatory instability requiring supportive medication or presence of pheochromocytoma 4. Known or suspected presence of severe brain damage 5. Evidence of metabolic, endocrine, or syndromic causes of hypoglycemia not due to hyperinsulinism 6. Use of systemic corticosteroids, e.g., hydrocortisone >20 mg/m2 body surface area or equivalent within 5 days before screening 7. 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. 8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 X the upper limit of normal (ULN), or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 adjusted by a pediatric formula (e.g., Schwartz formula) 9. 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 10. Known history of laboratory test results obtained before screening that show presence of HIV, hepatitis B surface antigen, hepatitis C antibody, or hepatitis A immunoglobulin M 11. Any recognized clotting or bleeding disorder 12. Previous administration of dasiglucagon (previously referred to as ZP4207) 13. Known or suspected allergy to the trial drug or related products 14. Previous participation (randomization) in the clinical program (Trials ZP4207-17103 or -17109) 15. Has participated in an interventional clinical trial (investigational or marketed product) within 30 days of screening, or plans to participate in another clinical trial, except for 18F-Dopa PET CT/MRI investigation (where performed as a part of a research trial), which is allowed for diagnosis of focal CHI. 16. The use of prescription or non-prescription medications known to cause QT prolongation. A screened patient will not be randomized if: 1. Mean IV glucose requirement is <10 mg/kg/min to maintain glycemia above 70 mg/dL (3.9 mmol/L) during the previous 24 hours prior to randomization 2. Use of glucagon within 24 hours before randomization. 3. Use of additional enteral glucose within 24 hours before randomization. Patients should be transitioned to IV glucose infusions only at least 24 hours before randomization. 4. Is not sufficiently clinically stable on IV GIR only (± diazoxide, as applicable), in the opinion of the investigator, to undergo the placebo-controlled randomized Part 1 of the trial (2x48 hours).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of dasiglucagon in reducing glucose requirements in children with persistent CHI requiring continuous IV glucose administration to prevent/manage hypoglycemia.;Secondary Objective: To evaluate the safety and tolerability of dasiglucagon administered as a subcutaneous (SC) infusion in patients with CHI;Primary end point(s): Part 1 (Day 1 to 4) - Mean IV GIR in the last 12 hours of each treatment period during Part 1 (dasiglucagon or placebo administration);Timepoint(s) of evaluation of this end point: Period from 36h to 48 h and from 84h to 96h after the start of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 (Day 1 to 4, for each 48-hour treatment period) 1. Total amount (g) of carbohydrates administered (regardless of the route) per day. Part 1 (Day 1 to 4, for each 48-hour treatment period) • Mean IV GIR for each 48-hour treatment period during Part 1 (dasiglucagon or placebo administration) • Mean IV GIR below 10 mg/kg/min in the last 12 hours of each treatment period during Part 1 (yes/no) (dasiglucagon or placebo administration) Part 2 (Day 5 to 25, assessed from the start of treatment in part 2) • Time to complete weaning off IV GIR. • Hypoglycemia event rate, defined as number of hypoglycemic events (PG 180 mg/dL or 10.0 mmol/L).;Timepoint(s) of evaluation of this end point: - Continously during each 48 hour period of Part 1 (day 1-2 and day 3-4) - Continously from day 5 to 25 of Part 2 | — |
Countries
Germany, Israel, United Kingdom, United States
Contacts
Public ContactClinical Trial Manager
Zealand Pharma A/S
Outcome results
None listed