<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03777176</url>
  </required_header>
  <id_info>
    <org_study_id>ZP4207-17109</org_study_id>
    <nct_id>NCT03777176</nct_id>
  </id_info>
  <brief_title>Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism</brief_title>
  <official_title>A Two-Period, Open-label Trial Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zealand Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zealand Pharma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the trial is to evaluate the efficacy of dasiglucagon administered as a&#xD;
      subcutaneous (SC) infusion in reducing hypoglycemia in children with CHI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 4, 2019</start_date>
  <completion_date type="Actual">October 5, 2020</completion_date>
  <primary_completion_date type="Actual">September 8, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hypoglycemia events</measure>
    <time_frame>Weeks 2-4</time_frame>
    <description>Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG &lt;70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fasting tolerance</measure>
    <time_frame>Baseline to week 4</time_frame>
    <description>Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continous glucose monitorting reading &lt;70 mg/dL [3.9 mmol/L])</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastric carbohydrates administered to treat hypoglycemia</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Total amount of gastric carbohydrates adminstered via nasogastric tube or gastrostomy per week to treat hypoglycemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in range</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continous glucose monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinically significant hypoglycemia events</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Clinically significant hypoglycemia event rates, defined as average weekly number of events &lt;54 mg/dL (3.0 mmol/L), as detected my self-measured plasma glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastric carbohydrates administrations to treat hypoglycemia</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extent of hypoglycemia</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitorting</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nightly gastric carbohydrates administered</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastric carbohydrates administered</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in hypoglycemia</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Percent time in hypoglycemia (&lt;70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of hypoglycemic episodes</measure>
    <time_frame>Week 2-4</time_frame>
    <description>Rate of hypoglycemic episodes, defined as number of episodes &lt;70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continous glucose monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in hypoglycemia in treatment period 2</measure>
    <time_frame>Week 6-8</time_frame>
    <description>Percent time in hypoglycemia (&lt;70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastric carbohydrates administrations to treat hypoglycemia in treatment period 2</measure>
    <time_frame>Week 6-8</time_frame>
    <description>Average weekly number of gastric carbohydrate administrations via nasogastric tube or gastrostomy to treat hypoglycemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypoglycemic events in treatment period 2</measure>
    <time_frame>Week 6-8</time_frame>
    <description>Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG &lt;70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinically significant hypoglycemia events in treatment period 2</measure>
    <time_frame>Week 6-8</time_frame>
    <description>Clinically significant hypoglycemia event rates, defined as average weekly number of events &lt;54 mg/dL (3.0 mmol/L), for 15 minutes or more as measured by continous glucose monitorting (CGM)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Congenital Hyperinsulinism</condition>
  <arm_group>
    <arm_group_label>Standard of Care + dasiglucagon</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>4 weeks of standard of care + 4 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dasiglucagon</intervention_name>
    <description>Glucagon analog</description>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_label>Standard of Care + dasiglucagon</arm_group_label>
    <other_name>ZP4207</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard of care according to site and/or country</description>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_label>Standard of Care + dasiglucagon</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Established and documented diagnosis of CHI based on standard of care&#xD;
&#xD;
          -  Experiencing ≥3 events of hypoglycemia per week (PG &lt;70 mg/dL [&lt;3.9 mmol/L]) according&#xD;
             to the investigator's evaluation&#xD;
&#xD;
          -  Previously undergone near-total pancreatectomy or being treated with a non-surgical&#xD;
             approach, having been evaluated as not eligible for pancreatic surgery&#xD;
&#xD;
          -  If somatostatin analogues or sirolimus are used, the therapy should be well&#xD;
             established as judged by the investigator, especially when considering their&#xD;
             biological half-life&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous administration of dasiglucagon&#xD;
&#xD;
          -  Known or suspected allergy to the trial drug or related products&#xD;
&#xD;
          -  Previous participation (randomization) in this trial&#xD;
&#xD;
          -  Circulatory instability requiring supportive medication&#xD;
&#xD;
          -  Requires exogenous insulin&#xD;
&#xD;
          -  Body weight of &lt;4 kg (8.8 lbs.)&#xD;
&#xD;
          -  Documented HbA1c ≥7% subsequent to near-total pancreatectomy and within 6 months prior&#xD;
             to screening&#xD;
&#xD;
          -  Known or suspected presence of significant central nervous system disease/injury such&#xD;
             that in the investigator's opinion will affect trial participation&#xD;
&#xD;
          -  Use of systemic corticosteroids, e.g., hydrocortisone &gt;20 mg/m2 body surface area or&#xD;
             equivalent in the 5 days before screening&#xD;
&#xD;
          -  Use of anti-inflammatory biological agents, or other immune modulating agents in the 3&#xD;
             months prior to screening&#xD;
&#xD;
          -  Any clinically significant abnormality identified on echocardiogram that in the&#xD;
             opinion of the investigator would affect the patient's ability to participate in the&#xD;
             trial&#xD;
&#xD;
          -  Any recognized clotting or bleeding disorders&#xD;
&#xD;
          -  Has participated in an interventional clinical trial (investigational or marketed&#xD;
             product) within 3 months of screening or 5 half-lives of the drug under investigation&#xD;
             (whichever comes first), or plans to participate in another clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Months</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Benedikte Bandak</last_name>
    <role>Study Director</role>
    <affiliation>Zealand Pharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>13123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cook Children's Medical Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Düsseldorf, Department of Pediatrics</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Otto von Guericke University Magdeburg, Department of Pediatrics</name>
      <address>
        <city>Magdeburg</city>
        <zip>39120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <zip>9765422</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Greater Glasgow and Clyde</name>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alder Hey Children'sHospital NHS Foundation Trust</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Osmond Street Hospital for Children NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Manchester University Hospital NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Israel</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <disposition_first_submitted>September 2, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>September 2, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 9, 2021</disposition_first_posted>
  <last_update_submitted>January 31, 2023</last_update_submitted>
  <last_update_submitted_qc>January 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Congenital Hyperinsulinism</mesh_term>
    <mesh_term>Nesidioblastosis</mesh_term>
    <mesh_term>Hyperinsulinism</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 1, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03777176
org study id: ZP4207-17109
nct id: NCT03777176
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The objective of the trial is to evaluate the efficacy of dasiglucagon administered as a
      subcutaneous (SC) infusion in reducing hypoglycemia in children with CHI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hypoglycemia events
time frame: Weeks 2-4
description: Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
measure: Fasting tolerance
time frame: Baseline to week 4
description: Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute continous glucose monitorting reading <70 mg/dL [3.9 mmol/L])
measure: Gastric carbohydrates administered to treat hypoglycemia
time frame: Week 2-4
description: Total amount of gastric carbohydrates adminstered via nasogastric tube or gastrostomy per week to treat hypoglycemia
measure: Time in range
time frame: Week 2-4
description: Percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) as measured by continous glucose monitoring
measure: Clinically significant hypoglycemia events
time frame: Week 2-4
description: Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), as detected my self-measured plasma glucose
measure: Gastric carbohydrates administrations to treat hypoglycemia
time frame: Week 2-4
description: Rate of gastric carbohydrate administrations via nasogastric tube or gastrostomy per week to treat hypoglycemia
measure: Extent of hypoglycemia
time frame: Week 2-4
description: Extent of hypoglycemia (area over the glucose curve [AOCglucose] below 70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitorting
measure: Nightly gastric carbohydrates administered
time frame: Week 2-4
description: Amount of nightly (midnight to 6 am) gastric carbohydrates administered via nasogastric tube or gastrostomy per week
measure: Gastric carbohydrates administered
time frame: Week 2-4
description: Total amount of gastric carbohydrates administered via nasogastric tube or gastrostomy per week
measure: Time in hypoglycemia
time frame: Week 2-4
description: Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
measure: Rate of hypoglycemic episodes
time frame: Week 2-4
description: Rate of hypoglycemic episodes, defined as number of episodes <70 mg/dL (3.9 mmol/L) for 15 minutes or more per week, as measured by continous glucose monitoring
measure: Time in hypoglycemia in treatment period 2
time frame: Week 6-8
description: Percent time in hypoglycemia (<70 mg/dL [3.9 mmol/L]) as measured by continous glucose monitoring
measure: Gastric carbohydrates administrations to treat hypoglycemia in treatment period 2
time frame: Week 6-8
description: Average weekly number of gastric carbohydrate administrations via nasogastric tube or gastrostomy to treat hypoglycemia
measure: Hypoglycemic events in treatment period 2
time frame: Week 6-8
description: Hypoglycemia event rate, defined as average weekly number of hypoglycemic events (PG <70 mg/dL [3.9 mmol/L]) as detected by self-monitored plasma glucose
measure: Clinically significant hypoglycemia events in treatment period 2
time frame: Week 6-8
description: Clinically significant hypoglycemia event rates, defined as average weekly number of events <54 mg/dL (3.0 mmol/L), for 15 minutes or more as measured by continous glucose monitorting (CGM)
arm group label: Standard of Care + dasiglucagon
arm group type: Experimental
description: 8 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care
arm group label: Standard of Care
arm group type: Other
description: 4 weeks of standard of care + 4 weeks of dasiglucagon treatment as sc infusion starting at 10 µg/hr on top of standard of care
intervention type: Drug
intervention name: dasiglucagon
description: Glucagon analog
arm group label: Standard of Care
arm group label: Standard of Care + dasiglucagon
other name: ZP4207
intervention type: Other
intervention name: Standard of Care
description: Standard of care according to site and/or country
arm group label: Standard of Care
arm group label: Standard of Care + dasiglucagon
criteria: 
gender: All
minimum age: 3 Months
maximum age: 12 Years
healthy volunteers: No
last name: Benedikte Bandak
role: Study Director
affiliation: Zealand Pharma
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Israel
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Congenital Hyperinsulinism
mesh term: Nesidioblastosis
mesh term: Hyperinsulinism
sharing ipd: No
submitted: September 1, 2023