Back to resultsOpen-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
Primary Purpose
Congenital Hyperinsulinism
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
dasiglucagon
Standard of Care
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Hyperinsulinism
Eligibility Criteria
Inclusion Criteria:
- Established and documented diagnosis of CHI based on standard of care
- Experiencing ≥3 events of hypoglycemia per week (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
- 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.
Sites / Locations
- Children's Hospital of Colorado
- Children's Hospital of Philadelphia
- Cook Children's Medical Center
- University Hospital Düsseldorf, Department of Pediatrics
- Otto von Guericke University Magdeburg, Department of Pediatrics
- Hadassah Medical Center
- NHS Greater Glasgow and Clyde
- Alder Hey Children'sHospital NHS Foundation Trust
- Great Osmond Street Hospital for Children NHS Foundation Trust
- Central Manchester University Hospital NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Standard of Care + dasiglucagon
Standard of Care
Arm Description
8 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care
4 weeks of standard of care + 4 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care
Outcomes
Primary Outcome Measures
Hypoglycemia events
Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
Secondary Outcome Measures
Fasting tolerance
Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continous glucose monitorting reading <70 mg/dL [3.9 mmol/L])
Gastric carbohydrates administered to treat hypoglycemia
Total amount of gastric carbohydrates adminstered via nasogastric tube or gastrostomy per week to treat hypoglycemia
Time in range
Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continous glucose monitoring
Clinically significant hypoglycemia events
Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), as detected my self-measured plasma glucose
Gastric carbohydrates administrations to treat hypoglycemia
Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia
Extent of hypoglycemia
Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitorting
Nightly gastric carbohydrates administered
Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week
Gastric carbohydrates administered
Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week
Time in hypoglycemia
Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
Rate of hypoglycemic episodes
Rate of hypoglycemic episodes, defined as number of episodes <70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continous glucose monitoring
Time in hypoglycemia in treatment period 2
Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
Gastric carbohydrates administrations to treat hypoglycemia in treatment period 2
Average weekly number of gastric carbohydrate administrations via nasogastric tube or gastrostomy to treat hypoglycemia
Hypoglycemic events in treatment period 2
Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
Clinically significant hypoglycemia events in treatment period 2
Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), for 15 minutes or more as measured by continous glucose monitorting (CGM)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03777176
Brief Title
Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
Official Title
A Two-Period, Open-label Trial Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
March 4, 2019 (Actual)
Primary Completion Date
September 8, 2020 (Actual)
Study Completion Date
October 5, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand Pharma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective of the trial is to evaluate the efficacy of dasiglucagon administered as a subcutaneous (SC) infusion in reducing hypoglycemia in children with CHI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Hyperinsulinism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard of Care + dasiglucagon
Arm Type
Experimental
Arm Description
8 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care
Arm Title
Standard of Care
Arm Type
Other
Arm Description
4 weeks of standard of care + 4 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care
Intervention Type
Drug
Intervention Name(s)
dasiglucagon
Other Intervention Name(s)
ZP4207
Intervention Description
Glucagon analog
Intervention Type
Other
Intervention Name(s)
Standard of Care
Intervention Description
Standard of care according to site and/or country
Primary Outcome Measure Information:
Title
Hypoglycemia events
Description
Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
Time Frame
Weeks 2-4
Secondary Outcome Measure Information:
Title
Fasting tolerance
Description
Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continous glucose monitorting reading <70 mg/dL [3.9 mmol/L])
Time Frame
Baseline to week 4
Title
Gastric carbohydrates administered to treat hypoglycemia
Description
Total amount of gastric carbohydrates adminstered via nasogastric tube or gastrostomy per week to treat hypoglycemia
Time Frame
Week 2-4
Title
Time in range
Description
Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continous glucose monitoring
Time Frame
Week 2-4
Title
Clinically significant hypoglycemia events
Description
Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), as detected my self-measured plasma glucose
Time Frame
Week 2-4
Title
Gastric carbohydrates administrations to treat hypoglycemia
Description
Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia
Time Frame
Week 2-4
Title
Extent of hypoglycemia
Description
Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitorting
Time Frame
Week 2-4
Title
Nightly gastric carbohydrates administered
Description
Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week
Time Frame
Week 2-4
Title
Gastric carbohydrates administered
Description
Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week
Time Frame
Week 2-4
Title
Time in hypoglycemia
Description
Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
Time Frame
Week 2-4
Title
Rate of hypoglycemic episodes
Description
Rate of hypoglycemic episodes, defined as number of episodes <70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continous glucose monitoring
Time Frame
Week 2-4
Title
Time in hypoglycemia in treatment period 2
Description
Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
Time Frame
Week 6-8
Title
Gastric carbohydrates administrations to treat hypoglycemia in treatment period 2
Description
Average weekly number of gastric carbohydrate administrations via nasogastric tube or gastrostomy to treat hypoglycemia
Time Frame
Week 6-8
Title
Hypoglycemic events in treatment period 2
Description
Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
Time Frame
Week 6-8
Title
Clinically significant hypoglycemia events in treatment period 2
Description
Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), for 15 minutes or more as measured by continous glucose monitorting (CGM)
Time Frame
Week 6-8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Established and documented diagnosis of CHI based on standard of care
Experiencing ≥3 events of hypoglycemia per week (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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benedikte Bandak
Organizational Affiliation
Zealand Pharma
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
13123
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
University Hospital Düsseldorf, Department of Pediatrics
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Otto von Guericke University Magdeburg, Department of Pediatrics
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
9765422
Country
Israel
Facility Name
NHS Greater Glasgow and Clyde
City
Glasgow
Country
United Kingdom
Facility Name
Alder Hey Children'sHospital NHS Foundation Trust
City
Liverpool
Country
United Kingdom
Facility Name
Great Osmond Street Hospital for Children NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
Central Manchester University Hospital NHS Foundation Trust
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
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