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

Study Overview
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Brief Summary
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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.

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

Conditions
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Congenital Hyperinsulinism

Intervention / Treatment
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* Drug: Dasiglucagon
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard of Care + dasiglucagon<br>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 | Drug: Dasiglucagon<br>* Glucagon analog<br>* Other names: ZP4207;Other: Standard of Care<br>* Standard of care according to site and/or country<br>|
| Other: Standard of Care Only<br>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 | Drug: Dasiglucagon<br>* Glucagon analog<br>* Other names: ZP4207;Other: Standard of Care<br>* Standard of care according to site and/or country<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia Episode Rate | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) |