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

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ClinicalTrials.gov Identifier: NCT04172441
Recruitment Status : Recruiting
First Posted : November 21, 2019
Last Update Posted : April 8, 2021
Sponsor:
Information provided by (Responsible Party):
Zealand Pharma

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.

Condition or disease Intervention/treatment Phase
Congenital Hyperinsulinism Drug: dasiglucagon Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : June 22, 2020
Estimated Primary Completion Date : September 22, 2021
Estimated Study Completion Date : October 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: dasiglucagon first then placebo
48 hours of dasiglucagon sc infusion starting at 10 µg/hr with crossover to 48 hours placebo sc infusion (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).
Drug: dasiglucagon
Glucagon analog
Other Name: ZP4207

Drug: Placebo
Placebo for dasiglucagon

Experimental: placebo first then dasiglucagon
48 hours of placebo sc infusion with crossover to 48 hours dasiglucagon sc infusion starting at 10 µg/hr (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).
Drug: dasiglucagon
Glucagon analog
Other Name: ZP4207

Drug: Placebo
Placebo for dasiglucagon




Primary Outcome Measures :
  1. Mean intravenous glucose infusion rate [ Time Frame: 36-48 hours after initiation of trial drug ]
    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 :
  1. Carbohydrates administered [ Time Frame: 0-48 hours after initiation of trial drug ]
    Total amount (g) of carbohydrates administered during the crossover part of the trial (dasiglucagon or placebo administration)

  2. Hypoglycemia events [ Time Frame: 0-48 hours after initiation of trial drug ]
    Hypoglycemia event rate, defined as number of hypoglycemic events (plasma glucose (PG) <70 mg/dL or 3.9 mmol/L), as detected by self-monitored plasma glucose during the crossover part of the trial (dasiglucagon or placebo administration)

  3. Time in range [ Time Frame: 0-48 hours after initiation of trial drug ]
    Percent time in plasma glucose range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continuous glucose monitoring during the crossover part of the trial (dasiglucagon or placebo administration)

  4. Clinically significant hypoglycemia events [ Time Frame: 0-48 hours after initiation of trial drug ]
    Clinically significant hypoglycemia event rate, defined as number of events <54 mg/dL (3.0 mmol/L), as detected by self-monitored plasma glucose during the crossover part of the trial (dasiglucagon or placebo administration)

  5. Time in hypoglycemia [ Time Frame: 0-48 hours after initiation of trial drug ]
    Percent time in hypoglycemia (<70 mg/dL or 3.9 mmol/L) as measured by continuous glucose monitoring during the crossover part of the trial (dasiglucagon or placebo administration)

  6. Clinically significant hypoglycemia episodes [ Time Frame: 0-48 hours after initiation of trial drug ]
    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 during the crossover part of the trial (dasiglucagon or placebo administration)

  7. Extent of hypoglycemia [ Time Frame: 0-48 hours after initiation of trial drug ]
    Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring during the crossover part of the trial (dasiglucagon or placebo administration)

  8. Extent of clinically significant hypoglycemia [ Time Frame: 0-48 hours after initiation of trial drug ]
    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 during the crossover part of the trial (dasiglucagon or placebo administration)

  9. Time to complete weaning off intravenous glucose [ Time Frame: Day 5-25 ]
    Time to complete weaning off intravenous glucose administration during part 2

  10. Hypoglycemia event rate in part 2 [ Time Frame: Day 5-25 ]
    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

  11. Clinically significant hypoglycemia events in part 2 [ Time Frame: Day 5-25 ]
    Clinically significant hypoglycemia event rate, defined as number of events <54 mg/dL (3.0 mmol/L), as detected by self-monitored plasma glucose

  12. Time to actual hospital discharge [ Time Frame: Day 5-25 ]
    The time from start of part 2 until the patient is discharged from the hospital

  13. Time to pancreatic surgery [ Time Frame: Day 5-25 ]
    Time to pancreatic surgery (sub-total or total pancreatectomy)

  14. Carbohydrates administered intravenously [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via intravenous glucose infusion

  15. Carbohydrates administered parenteral [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered as part of total parenteral nutrition

  16. Carbohydrates administered orally [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via oral route

  17. Carbohydrates administered via gastric feed [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy

  18. Time in range in part 2 [ Time Frame: Day 5-25 ]
    Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continuous glucose monitoring

  19. Time in hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    Percent time in hypoglycemia (<70 mg/dL or 3.9 mmol/L) as measured by continuous glucose monitoring

  20. Clinically significant hypoglycemia episodes in part 2 [ Time Frame: Day 5-25 ]
    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

  21. Extent of hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continuous glucose monitoring

  22. Extent of clinically significant hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    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



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Ages Eligible for Study:   up to 364 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04172441


Contacts
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Contact: Charlotte T Schiøler, MSc +4550603722 cts@zealandpharma.com

Locations
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United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Cook Children's Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Germany
University Children's Hospital Recruiting
Düsseldorf, Germany, 40225
University Hospital, Magdeburg Recruiting
Magdeburg, Germany, 39120
Israel
Hadassah Medical Center Recruiting
Jerusalem, Israel, 9765422
United Kingdom
Manchester University NHS Foundation Trust Recruiting
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Zealand Pharma
Investigators
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Study Director: Benedikte Bandak, MSc Zealand Pharma
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Responsible Party: Zealand Pharma
ClinicalTrials.gov Identifier: NCT04172441    
Other Study ID Numbers: ZP4207-17103
First Posted: November 21, 2019    Key Record Dates
Last Update Posted: April 8, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Congenital Hyperinsulinism
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Hypoglycemia