A Two-Period Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism

November 23, 2023 updated by: Zealand Pharma

A Two-Period, Open-label Trial Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism

The objective of the trial is to evaluate the efficacy and safety of dasiglucagon administered as a subcutaneous (SC) infusion in reducing hypoglycemia in children with CHI.

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Düsseldorf, Germany, 40225
        • University Hospital Düsseldorf, Department of Pediatrics
      • Magdeburg, Germany, 39120
        • Otto von Guericke University Magdeburg, Department of Pediatrics
      • Jerusalem, Israel, 9765422
        • Hadassah medical Center
      • Glasgow, United Kingdom
        • NHS Greater Glasgow and Clyde
      • Liverpool, United Kingdom
        • Alder Hey Children'sHospital NHS Foundation Trust
      • London, United Kingdom
        • Great Osmond Street Hospital for Children NHS Foundation Trust
      • Manchester, United Kingdom
        • Central Manchester University Hospital NHS Foundation Trust
    • Colorado
      • Aurora, Colorado, United States, 13123
        • Children's Hospital of Colorado
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 12 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Established and documented diagnosis of CHI based on standard of care
  • Experiencing ≥3 events of hypoglycemia per week (plasma glucose [PG] <70 mg/dL [<3.9 mmol/L]) according to the investigator's evaluation
  • Previously undergone near-total pancreatectomy or being treated with a non-surgical approach, having been evaluated as not eligible for pancreatic surgery
  • If somatostatin analogues or sirolimus are used, the therapy should be well established as judged by the investigator, especially when considering their biological half-life

Exclusion Criteria:

  • Previous administration of dasiglucagon
  • Known or suspected allergy to the trial drug or related products
  • Previous participation (randomization) in this trial
  • Circulatory instability requiring supportive medication or presence of pheochromocytoma
  • Requires exogenous insulin
  • Body weight of <4 kg (8.8 lbs.)
  • Documented HbA1c ≥7% subsequent to near-total pancreatectomy and within 6 months prior to screening
  • Known or suspected presence of significant central nervous system disease/injury such that in the investigator's opinion will affect trial participation
  • Use of systemic corticosteroids, e.g., hydrocortisone >20 mg/m2 body surface area or equivalent in the 5 days before screening
  • Use of anti-inflammatory biological agents, or other immune modulating agents in the 3 months prior to screening
  • Any clinically significant abnormality identified on echocardiogram that in the opinion of the investigator would affect the patient's ability to participate in the trial
  • Any recognized clotting or bleeding disorders
  • Has participated in an interventional clinical trial (investigational or marketed product) within 3 months of screening or 5 half-lives of the drug under investigation (whichever comes first), or plans to participate in another clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Standard of Care + dasiglucagon
4 weeks (Treatment Period 1) + 4 weeks (Treatment Period 2) of dasiglucagon treatment as an SC infusion starting at 10 µg/hr on top of standard of care
Standard of care according to site and/or country
Glucagon analog
Other Names:
  • ZP4207
Other: Standard of Care Only
4 weeks (Treatment Period 1) of standard of care only + 4 weeks (Treatment Period 2) of dasiglucagon treatment as an SC infusion starting at 10 µg/hr on top of standard of care
Standard of care according to site and/or country
Glucagon analog
Other Names:
  • ZP4207

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hypoglycemia Episode Rate
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Hypoglycemia episode rate, defined as average weekly number of hypoglycemic episodes (PG <70 mg/dL [3.9 mmol/L]) during Weeks 2-4 as detected by self-monitored plasma glucose (SMPG). The Week 2-4 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 2-week baseline period.
Baseline, Week 2-4 (Treatment Period 1)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase in Fasting Tolerance
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continuous glucose monitoring reading <70 mg/dL [3.9 mmol/L]), or the time the test ended if a continuous 15-minute CGM reading <70 mg/dL was not reached. The change from Baseline to the End of Treatment Period 1 (Week 4) is also provided. The Baseline value is the value recorded at the Screening visit.
Baseline, Week 2-4 (Treatment Period 1)
Percent Time in Range 70-180 mg/dL
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) during Weeks 2-4 as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly percent time in range 70-180 mg/dL across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value was calculated as the average percent time in range during the 14 days before randomization.
Baseline, Week 2-4 (Treatment Period 1)
Clinically Significant Hypoglycemia Episode Rates
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Clinically significant hypoglycemia episode rates during Weeks 2-4, defined as average weekly number of clinically significant hypoglycemic episodes (PG <54 mg/dL [3.0 mmol/L]), as detected by SMPG. The Week 2-4 value is the average weekly clinically significant hypoglycemia episode rate across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of clinically significant hypoglycemic episodes during the 2-week baseline period.
Baseline, Week 2-4 (Treatment Period 1)
Total Amount of Gastric Carbohydrates Administered to Treat Hypoglycemia
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week to treat hypoglycemia. The Week 2-4 value is the average weekly total amount of gastric carbohydrates across the last 3 weeks of treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value recorded during the 2-week Baseline period.
Baseline, Week 2-4 (Treatment Period 1)
Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia, calculated as the number of times gastric carbohydrates were administered to treat hypoglycemia per week. The Week 2-4 value is the average weekly rate of gastric carbohydrate administrations across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value recorded during the 2-week Baseline period.
Baseline, Week 2-4 (Treatment Period 1)
Extent of Hypoglycemia
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) and below 54 mg/dL [3.0 mmol/L] as measured by continuous glucose monitoring. The extent of hypoglycemia was defined as the AOCglucose under the threshold divided by total duration in hours of CGM measurement. A reduction in this measure indicates a benefit. The Week 2-4 value is the average weekly extent of hypoglycemia below 70 mg/dL and below 54 mg/dL across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value assessed during the 14 days before randomization.
Baseline, Week 2-4 (Treatment Period 1)
Amount of Nightly Gastric Carbohydrates Administered
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week. The change from Baseline is also provided for each week. The Baseline value is the value recorded during the 2-week Baseline period.
Baseline, Week 2-4 (Treatment Period 1)
Total Amount of Gastric Carbohydrates Administered
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Total amount of gastric carbohydrates administered (regardless of whether this was to treat hypoglycemia or not) via nasogastric tube or gastrostomy per week. The Week 2-4 value is the average amount of gastric carbohydrates administered via nasogastric tube or gastrostomy across the last 3 weeks of the treatment period. The change from baseline to Week 2-4 is also provided. The baseline value is the value recorded during the 2-week baseline period.
Baseline, Week 2-4 (Treatment Period 1)
Percent Time in Hypoglycemia
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Percent time in hypoglycemia (PG <70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly percent of time in hypoglycemia across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the value assessed during the 14 days before randomization.
Baseline, Week 2-4 (Treatment Period 1)
Rate of Hypoglycemic Episodes
Time Frame: Baseline, Week 2-4 (Treatment Period 1)
Rate of hypoglycemic episodes, defined as number of episodes with PG <70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continuous glucose monitoring. The Week 2-4 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 2-4 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 14 days before randomization.
Baseline, Week 2-4 (Treatment Period 1)
Percent Time in Hypoglycemia in Treatment Period 2
Time Frame: Baseline, Week 6-8 (Treatment Period 2)
Percent time in hypoglycemia (PG <70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring. The Week 6-8 value is the average weekly percent of time in hypoglycemia across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the value assessed during the 14 days before randomization.
Baseline, Week 6-8 (Treatment Period 2)
Rate of Gastric Carbohydrates Administrations to Treat Hypoglycemia in Treatment Period 2
Time Frame: Baseline, Week 6-8 (Treatment Period 2)
Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia, calculated as the number of times gastric carbohydrates were administered to treat hypoglycemia per week. The Week 6-8 value is the average weekly rate of gastric carbohydrate administrations across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the value recorded during the 2-week Baseline period.
Baseline, Week 6-8 (Treatment Period 2)
Rate of Hypoglycemic Episodes in Treatment Period 2
Time Frame: Baseline, Week 6-8 (Treatment Period 2)
Hypoglycemia episode rate, defined as average weekly number of hypoglycemic episodes (PG <70 mg/dL [3.9 mmol/L]) as detected by SMPG. The Week 6-8 value is the average weekly number of hypoglycemic episodes across the last 3 weeks of the treatment period. The change from Baseline to Week 6-8 is also provided. The Baseline value is the average weekly number of hypoglycemic episodes during the 2-week baseline period.
Baseline, Week 6-8 (Treatment Period 2)
Rate of Clinically Significant Hypoglycemia Episodes in Treatment Period 2
Time Frame: Baseline, Week 6-8 (Treatment Period 2)
Change from Baseline to Week 6-8 in the clinically significant (CS) hypoglycemia episode rate in treatment period 2, defined as the average weekly number of episodes <54 mg/dL (3.0 mmol/L), for 15 minutes or more, as measured by continuous glucose monitoring (CGM). The Week 6-8 value is the average weekly CS hypoglycemia episode rate across the last 3 weeks of the treatment period. The Baseline value is the average weekly number of CS hypoglycemic episodes during the 14 days before randomization.
Baseline, Week 6-8 (Treatment Period 2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Charlotte Teglman Schioeler, Zealand Pharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2019

Primary Completion (Actual)

August 31, 2020

Study Completion (Actual)

October 5, 2020

Study Registration Dates

First Submitted

December 13, 2018

First Submitted That Met QC Criteria

December 13, 2018

First Posted (Actual)

December 17, 2018

Study Record Updates

Last Update Posted (Actual)

December 13, 2023

Last Update Submitted That Met QC Criteria

November 23, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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