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

• ClinicalTrials.gov Identifier: NCT04172441
• Recruitment Status: Completed
• First Posted: November 21, 2019
• Last Update Posted: March 15, 2023
• Sponsor: Zealand Pharma
• Information provided by (Responsible Party): Zealand Pharma

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Congenital Hyperinsulinism	Drug: dasiglucagon; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 22, 2020
• Actual Primary Completion Date: March 7, 2022
• Actual Study Completion Date: March 7, 2022

Arms and Interventions

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: dasiglucagon; Glucagon analogue; Other Name: ZP4207; Drug: Placebo; Placebo for dasiglucagon
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: dasiglucagon; Glucagon analogue; Other Name: ZP4207; Drug: Placebo; Placebo for dasiglucagon

Outcome Measures

Primary Outcome Measures :

1. Mean intravenous glucose infusion rate [ Time Frame: 36-48 hours after initiation of trial drug ]
   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)

Secondary Outcome Measures :

1. Carbohydrates administered [ Time Frame: 0-48 hours after initiation of trial drug ]
   Total amount (g) of carbohydrates administered during the crossover part of the trial (dasiglucagon or placebo administration) per day
2. Carbohydrates administered [ Time Frame: 0-48 hours after initiation of trial drug ]
   Mean intravenous glucose infusion rate for each 48-hour treatment period during the crossover part of the trial (dasiglucagon or placebo administration)
3. Carbohydrates administered [ Time Frame: 36-48 hours after initiation of trial drug ]
   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)
4. Time to complete weaning off intravenous glucose [ Time Frame: Day 5-25 ]
   Time to complete weaning off intravenous glucose administration during part 2
5. Hypoglycemia event rate in part 2 [ Time Frame: Day 5-25 ]
   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
6. Clinically significant hypoglycemia events in part 2 [ Time Frame: Day 5-25 ]
   Clinically significant hypoglycemia event rate, defined as number of events <54 mg/dL (3.0 mmol/L), as detected by self-monitored plasma glucose
7. Time to actual hospital discharge [ Time Frame: Day 5-25 ]
   Time (days) from start of part 2 until the patient is discharged from the hospital
8. Time to pancreatic surgery [ Time Frame: Day 5-25 ]
   Time (days) to pancreatic surgery (sub-total or total pancreatectomy)
9. Carbohydrates administered [ Time Frame: Day 5-25 ]
   Total amount (g) of carbohydrates administered (regardless of the route) per day
10. Carbohydrates administered intravenously [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via IV glucose infusion or bolus (not as part of total parental nutrition)
11. Carbohydrates administered parenterally [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered as part of total parenteral nutrition
12. Carbohydrates administered orally [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via oral route
13. Carbohydrates administered via gastric feed [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy
14. Time in range in part 2 [ Time Frame: Day 5-25 ]
    Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continuous glucose monitoring
15. Time in hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    Percent time in hypoglycemia (<70 mg/dL or 3.9 mmol/L) as measured by continuous glucose monitoring
16. Time in clinically significant hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    Percent time in clinically significant hypoglycemia (<54 mg/dL or 3.0 mmol/L) as measured by continuous glucose monitoring
17. Hypoglycemia episodes in part 2 [ Time Frame: Day 5-25 ]
    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
18. Clinically significant hypoglycemia episodes in part 2 [ Time Frame: Day 5-25 ]
    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
19. Extent of hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring
20. Extent of clinically significant hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    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
21. Time in hyperglycemia in part 2 [ Time Frame: Day 5-25 ]
    Percent time in hyperglycemia (>180 mg/dL or 10.0 mmol/L), as measured by continuous glucose monitoring

Eligibility Criteria

• Ages Eligible for Study: 7 Days to 364 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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

Contacts and Locations

Locations

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Cook Children's Medical Center

Fort Worth, Texas, United States, 76104

Germany

University Children's Hospital

Düsseldorf, Germany, 40225

University Hospital, Magdeburg

Magdeburg, Germany, 39120

Israel

Hadassah Medical Center

Jerusalem, Israel, 9765422

United Kingdom

Manchester University NHS Foundation Trust

Manchester, United Kingdom, M13 9WL

Sponsors and Collaborators

Zealand Pharma

Investigators

• Study Director: Jelena Ivkovic, MD; Zealand Pharma

More Information

• Responsible Party: Zealand Pharma
• ClinicalTrials.gov Identifier: NCT04172441
• Other Study ID Numbers: ZP4207-17103; 2017-004545-24 ( EudraCT Number )
• First Posted: November 21, 2019
• Last Update Posted: March 15, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Congenital Hyperinsulinism; Nesidioblastosis; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Hypoglycemia