Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon in Children With Congenital Hyperinsulinism

Study Overview
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Brief Summary
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This is an open-label, multinational, multicenter, long-term safety and efficacy extension trial in patients with Congenital Hyperinsulinism (CHI) who completed either ZP4207-17103 or ZP4207-17109 (defined as lead-in trials). The primary objective is to evaluate the long-term safety of dasiglucagon administered as subcutaneous (SC) infusion in children with CHI.

Official Title
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An Extension Trial Evaluating the Long-term Safety and Efficacy 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed treatment in either Trial ZP4207-17103 or ZP4207-17109 Expected to continue to have a positive benefit-risk assessment for treatment with dasiglucagon (based on considerations of glycemic effect, tolerability, and nature and frequency of adverse events experienced in the lead-in trial) Exclusion Criteria: The patient developed any conditions prohibited by the lead-in trial, requires medication prohibited by the lead-in trial, or has other new complications that preclude participation in the investigator's opinion.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 13 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasiglucagon open-label<br>Dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care | Drug: dasiglucagon<br>* Glucagon analog<br>* Other names: ZP4207;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of adverse events occurring up to Month 1, Month 1 to Month 3 and in each 3-month period for the first year; subsequent years will have longer periods assigned for analysis | Baseline through treatment completion, up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of gastric carbohydrates administered to treat hypoglycemia | Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week to treat hypoglycemia | Baseline through treatment completion, up to 3 years | 
| Nasogastric (NG) tube or gastrostomy removal | Time to removal of NG tube or gastrostomy | Baseline through treatment completion, up to 3 years | 
| Pancreatic surgery | Time to pancreatic surgery (sub-total or total pancreatectomy) | Baseline through treatment completion, up to 3 years | 
| Time in hypoglycemia | Continuous glucose monitoring (CGM) percent time <70 mg/dL (3.9 mmol/L) | Baseline through treatment completion, up to 3 years | 
| Hypoglycemia episodes | Rate of CGM-detected hypoglycemia episodes <70 mg/dL (3.9 mmol/L) for 15 minutes or more | Baseline through treatment completion, up to 3 years | 
| Clinically significant episodes of hypoglycemia | Rate of clinically significant CGM-detected hypoglycemia episodes <54 mg/dL (3.0 mmol/L) for 15 minutes or more | Baseline through treatment completion, up to 3 years | 
| Gastric carbohydrate administrations | Number of gastric carbohydrate administrations (nasogastric tube or gastrostomy) to treat hypoglycemia | Baseline through treatment completion, up to 3 years | 
| Nightly gastric carbohydrate administrations | Number of nightly (midnight to 6 am) gastric carbohydrate administrations (nasogastric tube or gastrostomy) to treat hypoglycemia | Baseline through treatment completion, up to 3 years | 
| 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 monitoring (CGM) | Baseline through treatment completion, up to 3 years | 
| Extent of clinically significant hypoglycemia | Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 54 mg/dL [3.0 mmol/L]) as measured by continous glucose monitoring (CGM) | Baseline through treatment completion, up to 3 years | 
| Diazoxide dose | Reduction in diazoxide dose in mg/kg body weight/day from start of lead-in trial | Baseline through treatment completion, up to 3 years | 
| Somatostatin analog dose | Reduction in somatostatin analog dose from start of lead-in trial | Baseline through treatment completion, up to 3 years | 
| Prescribed amount of continuous gastric carbohydrate administration | Change in total amount of prescribed continuous gastric carbohydrate administration from start of lead-in trial (g/day) | Baseline through treatment completion, up to 3 years | 
| Prescribed duration of continuous gastric carbohydrate administration | Change in prescribed duration of infusion of continuous gastric carbohydrate administration from start of lead-in trial (h/day) | Baseline through treatment completion, up to 3 years | 
| Prescribed duration of nightly continuous gastric carbohydrate administration | Change in prescribed duration of infusion of nightly (8 pm - 8 am) continuous gastric carbohydrate administration from start of lead-in trial (h/day) | Baseline through treatment completion, up to 3 years |