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

Primary Purpose

Congenital Hyperinsulinism

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

dasiglucagon

Placebo

About this trial

This is an interventional treatment trial for Congenital Hyperinsulinism

Eligibility Criteria

7 Days - 364 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Children's Hospital of Philadelphia
Cook Children's Medical Center
University Children's Hospital
University Hospital, Magdeburg
Hadassah Medical Center
Manchester University NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

dasiglucagon first then placebo

placebo first then dasiglucagon

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Mean intravenous glucose infusion rate

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

Carbohydrates administered

Total amount (g) of carbohydrates administered during the crossover part of the trial (dasiglucagon or placebo administration) per day

Carbohydrates administered

Mean intravenous glucose infusion rate for each 48-hour treatment period during the crossover part of the trial (dasiglucagon or placebo administration)

Carbohydrates administered

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)

Time to complete weaning off intravenous glucose

Time to complete weaning off intravenous glucose administration during part 2

Hypoglycemia event rate in part 2

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

Clinically significant hypoglycemia events in part 2

Clinically significant hypoglycemia event rate, defined as number of events <54 mg/dL (3.0 mmol/L), as detected by self-monitored plasma glucose

Time to actual hospital discharge

Time (days) from start of part 2 until the patient is discharged from the hospital

Time to pancreatic surgery

Time (days) to pancreatic surgery (sub-total or total pancreatectomy)

Carbohydrates administered

Total amount (g) of carbohydrates administered (regardless of the route) per day

Carbohydrates administered intravenously

Amount (g) of carbohydrates administered via IV glucose infusion or bolus (not as part of total parental nutrition)

Carbohydrates administered parenterally

Amount (g) of carbohydrates administered as part of total parenteral nutrition

Carbohydrates administered orally

Amount (g) of carbohydrates administered via oral route

Carbohydrates administered via gastric feed

Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy

Time in range in part 2

Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continuous glucose monitoring

Time in hypoglycemia in part 2

Percent time in hypoglycemia (<70 mg/dL or 3.9 mmol/L) as measured by continuous glucose monitoring

Time in clinically significant hypoglycemia in part 2

Percent time in clinically significant hypoglycemia (<54 mg/dL or 3.0 mmol/L) as measured by continuous glucose monitoring

Hypoglycemia episodes in part 2

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

Clinically significant hypoglycemia episodes in part 2

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

Extent of hypoglycemia in part 2

Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring

Extent of clinically significant hypoglycemia in part 2

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

Time in hyperglycemia in part 2

Percent time in hyperglycemia (>180 mg/dL or 10.0 mmol/L), as measured by continuous glucose monitoring

Full Information

NCT ID

NCT04172441

First Posted

November 18, 2019

Last Updated

March 13, 2023

Sponsor

Zealand Pharma

1. Study Identification

Unique Protocol Identification Number

NCT04172441

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

June 22, 2020 (Actual)

Primary Completion Date

March 7, 2022 (Actual)

Study Completion Date

March 7, 2022 (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

Data Monitoring Committee

Yes

5. 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.

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 2, Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

dasiglucagon first then placebo

Arm Type

Experimental

Arm Description

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).

Arm Title

placebo first then dasiglucagon

Arm Type

Experimental

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

dasiglucagon

Other Intervention Name(s)

ZP4207

Intervention Description

Glucagon analogue

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo for dasiglucagon

Primary Outcome Measure Information:

Title

Mean intravenous glucose infusion rate

Description

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)

Time Frame

36-48 hours after initiation of trial drug

Secondary Outcome Measure Information:

Title

Carbohydrates administered

Description

Total amount (g) of carbohydrates administered during the crossover part of the trial (dasiglucagon or placebo administration) per day

Time Frame

0-48 hours after initiation of trial drug

Title

Carbohydrates administered

Description

Mean intravenous glucose infusion rate for each 48-hour treatment period during the crossover part of the trial (dasiglucagon or placebo administration)

Time Frame

0-48 hours after initiation of trial drug

Title

Carbohydrates administered

Description

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)

Time Frame

36-48 hours after initiation of trial drug

Title

Time to complete weaning off intravenous glucose

Description

Time to complete weaning off intravenous glucose administration during part 2

Time Frame

Day 5-25

Title

Hypoglycemia event rate in part 2

Description

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

Time Frame

Day 5-25

Title

Clinically significant hypoglycemia events in part 2

Description

Clinically significant hypoglycemia event rate, defined as number of events <54 mg/dL (3.0 mmol/L), as detected by self-monitored plasma glucose

Time Frame

Day 5-25

Title

Time to actual hospital discharge

Description

Time (days) from start of part 2 until the patient is discharged from the hospital

Time Frame

Day 5-25

Title

Time to pancreatic surgery

Description

Time (days) to pancreatic surgery (sub-total or total pancreatectomy)

Time Frame

Day 5-25

Title

Carbohydrates administered

Description

Total amount (g) of carbohydrates administered (regardless of the route) per day

Time Frame

Day 5-25

Title

Carbohydrates administered intravenously

Description

Amount (g) of carbohydrates administered via IV glucose infusion or bolus (not as part of total parental nutrition)

Time Frame

Day 5-25

Title

Carbohydrates administered parenterally

Description

Amount (g) of carbohydrates administered as part of total parenteral nutrition

Time Frame

Day 5-25

Title

Carbohydrates administered orally

Description

Amount (g) of carbohydrates administered via oral route

Time Frame

Day 5-25

Title

Carbohydrates administered via gastric feed

Description

Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy

Time Frame

Day 5-25

Title

Time in range in part 2

Description

Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continuous glucose monitoring

Time Frame

Day 5-25

Title

Time in hypoglycemia in part 2

Description

Percent time in hypoglycemia (<70 mg/dL or 3.9 mmol/L) as measured by continuous glucose monitoring

Time Frame

Day 5-25

Title

Time in clinically significant hypoglycemia in part 2

Description

Percent time in clinically significant hypoglycemia (<54 mg/dL or 3.0 mmol/L) as measured by continuous glucose monitoring

Time Frame

Day 5-25

Title

Hypoglycemia episodes in part 2

Description

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

Time Frame

Day 5-25

Title

Clinically significant hypoglycemia episodes in part 2

Description

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

Time Frame

Day 5-25

Title

Extent of hypoglycemia in part 2

Description

Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring

Time Frame

Day 5-25

Title

Extent of clinically significant hypoglycemia in part 2

Description

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

Time Frame

Day 5-25

Title

Time in hyperglycemia in part 2

Description

Percent time in hyperglycemia (>180 mg/dL or 10.0 mmol/L), as measured by continuous glucose monitoring

Time Frame

Day 5-25

10. Eligibility

Sex

All

Minimum Age & Unit of Time

7 Days

Maximum Age & Unit of Time

364 Days

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: CHI diagnosis established based on the following: Hyperinsulinemia: plasma insulin above the limit of detection of the assay documented during an event of hypoglycemia, and/or Hypofattyacidemia: plasma free fatty acid <1.7 mmol/L, and/or Hypoketonemia: Beta-hydroxybutyrate <1.8 mmol/L, and/or 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jelena Ivkovic, MD

Organizational Affiliation

Zealand Pharma

Official's Role

Study Director

Facility Information:

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 Children's Hospital

City

Düsseldorf

ZIP/Postal Code

40225

Country

Germany

Facility Name

University Hospital, Magdeburg

City

Magdeburg

ZIP/Postal Code

39120

Country

Germany

Facility Name

Hadassah Medical Center

City

Jerusalem

ZIP/Postal Code

9765422

Country

Israel

Facility Name

Manchester University NHS Foundation Trust

City

Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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