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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04172441
Recruitment Status : Completed
First Posted : November 21, 2019
Last Update Posted : October 3, 2022
Sponsor:
Information provided by (Responsible Party):
Zealand Pharma

Tracking Information
First Submitted Date  ICMJE November 18, 2019
First Posted Date  ICMJE November 21, 2019
Last Update Posted Date October 3, 2022
Actual Study Start Date  ICMJE June 22, 2020
Actual Primary Completion Date March 7, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2019)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2021)
  • 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) per day
  • Carbohydrates administered [ Time Frame: 0-48 hours after initiation of trial drug ]
    Mean intravenous glucose infusion rate for each 48-hour treatment period during the crossover part of the trial (dasiglucagon or placebo administration)
  • Carbohydrates administered [ Time Frame: 36-48 hours after initiation of trial drug ]
    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 Frame: Day 5-25 ]
    Time to complete weaning off intravenous glucose administration during part 2
  • 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
  • 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
  • Time to actual hospital discharge [ Time Frame: Day 5-25 ]
    Time (days) from start of part 2 until the patient is discharged from the hospital
  • Time to pancreatic surgery [ Time Frame: Day 5-25 ]
    Time (days) to pancreatic surgery (sub-total or total pancreatectomy)
  • Carbohydrates administered [ Time Frame: Day 5-25 ]
    Total amount (g) of carbohydrates administered (regardless of the route) per day
  • Carbohydrates administered intravenously [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via IV glucose infusion or bolus (not as part of total parental nutrition)
  • Carbohydrates administered parenterally [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered as part of total parenteral nutrition
  • Carbohydrates administered orally [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via oral route
  • Carbohydrates administered via gastric feed [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy
  • 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
  • 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
  • Time in clinically significant hypoglycemia in part 2 [ Time Frame: Day 5-25 ]
    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 [ Time Frame: Day 5-25 ]
    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 [ 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
  • 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
  • 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
  • Time in hyperglycemia in part 2 [ Time Frame: Day 5-25 ]
    Percent time in hyperglycemia (>180 mg/dL or 10.0 mmol/L), as measured by continuous glucose monitoring
Original Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2019)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Time to complete weaning off intravenous glucose [ Time Frame: Day 5-25 ]
    Time to complete weaning off intravenous glucose administration during part 2
  • 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
  • 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
  • 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
  • Time to pancreatic surgery [ Time Frame: Day 5-25 ]
    Time to pancreatic surgery (sub-total or total pancreatectomy)
  • Carbohydrates administered intravenously [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via intravenous glucose infusion
  • Carbohydrates administered parenteral [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered as part of total parenteral nutrition
  • Carbohydrates administered orally [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via oral route
  • Carbohydrates administered via gastric feed [ Time Frame: Day 5-25 ]
    Amount (g) of carbohydrates administered via nasogastric tube or gastrostomy
  • 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
  • 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
  • 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
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Congenital Hyperinsulinism
Intervention  ICMJE
  • Drug: dasiglucagon
    Glucagon analog
    Other Name: ZP4207
  • Drug: Placebo
    Placebo for dasiglucagon
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: dasiglucagon
    • Drug: Placebo
  • 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).
    Interventions:
    • Drug: dasiglucagon
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 18, 2019)
12
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 7, 2022
Actual Primary Completion Date March 7, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Days to 364 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Israel,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04172441
Other Study ID Numbers  ICMJE ZP4207-17103
2017-004545-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Zealand Pharma
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Zealand Pharma
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jelena Ivkovic, MD Zealand Pharma
PRS Account Zealand Pharma
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP