<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/NCT03782636</url>
  </required_header>
  <id_info>
    <org_study_id>13341</org_study_id>
    <nct_id>NCT03782636</nct_id>
  </id_info>
  <brief_title>Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)</brief_title>
  <acronym>ITAD</acronym>
  <official_title>Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oxford Clinical Trials Research Unit (OCTRU)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centre for Statistics in Medicine, Oxford</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Juvenile Diabetes Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wellcome</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to see if a drug called aldesleukin, can preserve insulin&#xD;
      production in children and young adults recently diagnosed with type 1 diabetes.&#xD;
&#xD;
      One group will receive aldesleukin and the other a placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators know that the longer people with diabetes can produce their own insulin, the&#xD;
      better it is for the control of their blood glucose levels and long-term complications.&#xD;
&#xD;
      People get type 1 diabetes because their immune system, the part of the body, which helps&#xD;
      fight infections, mistakenly attacks and destroys the beta cells in the pancreas that produce&#xD;
      insulin. As the immune system destroys these insulin-producing cells, the body's own ability&#xD;
      to produce insulin decreases and diabetes develops.&#xD;
&#xD;
      At diagnosis, there are usually a small number of beta cells (10-20%) left in the pancreas,&#xD;
      which still produce small amounts of insulin. This is called 'beta cell function' and it is&#xD;
      assessed by measuring C-peptide, which is a protein made by the pancreas when insulin is&#xD;
      produced. Most people with type 1 diabetes eventually stop producing insulin themselves, this&#xD;
      may occur rapidly in a few months, or more slowly over several years.&#xD;
&#xD;
      New treatments preserving insulin production could improve management of diabetes. This could&#xD;
      be done by using drugs acting on cells of the immune system. In type 1 diabetes, there is an&#xD;
      imbalance between cells of the immune system, and there is evidence that one protein produced&#xD;
      by our body, called Interleukin-2, could help in resetting the balance between those cells.&#xD;
      It is important to start this treatment soon after diagnosis because this when there is the&#xD;
      best chance of saving the beta cells still left in the pancreas.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 28, 2019</start_date>
  <completion_date type="Anticipated">September 2022</completion_date>
  <primary_completion_date type="Anticipated">April 2022</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Differences in slopes of DBS (Dried Blood Spot) C-peptide over the 6 month-treatment period between the active and placebo groups.</measure>
    <time_frame>Weekly DBS C-peptide collected during the 6-month treatment period, and then monthly during the 6 months of follow-up</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Treg, Teff and NK56bright cell frequencies and phenotypes from baseline</measure>
    <time_frame>At baseline and then1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (reported reactions using CTCAE grading v5.0)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Assessment of the most commonly reported reactions to low- or high-dose aldesleukin, namely influenza-like syndrome, skin reaction, diarrhoea, nausea using CTCAE grading v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (temperature in celsius)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Vital signs - temperature in celsius</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (weight, in kilograms)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Vital signs - weight, in kilograms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (blood pressure: systolic/diastolic)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Vital signs - blood pressure: systolic/diastolic</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (heart rate: bpm)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Vital signs - heart rate: bpm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (AST, ALT, ALP, GGT units per liter (U/L)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Abnormal laboratory parameters liver function (AST, ALT, ALP, GGT units per liter (U/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit total bilirubin - milligrams per deciliter (mg/dL)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Abnormal laboratory parameters liver function total bilirubin - milligrams per deciliter (mg/dL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (urea and creatinine - mmol/L)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Abnormal laboratory parameters kidney function (urea and creatinine - mmol/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed at each visit (full blood count - 109/L)</measure>
    <time_frame>At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
    <description>Abnormal laboratory parameters full blood count - 109/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the absolute numbers of T, B and NK (Natural Killer) cells.</measure>
    <time_frame>At baseline and then, 1, 2 , 3, 6 and 12 months from the beginning of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HbA1c and daily insulin requirements during the trial period.</measure>
    <time_frame>HbA1c - At baseline and then 3,6 and 12 months Insulin dose data -Baseline and then 1, 2, 3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Type1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Aldesleukin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultra-low dose aldesleukin injected subcutaneously, at a dose of 0.2 x 106 IU/m2 twice-weekly , three days apart, for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo sc, at a similar dose (expressed in ml) to the active drug</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aldesleukin</intervention_name>
    <description>PROLEUKIN® 18 x 106 IU&#xD;
Powder for solution for injection or infusion</description>
    <arm_group_label>Aldesleukin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>sterile diluent used for the aldesleukin preparation and 5% glucose</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have given written informed consent to participate or assent with parental consent&#xD;
&#xD;
          2. Be aged 6-18 years&#xD;
&#xD;
          3. Be diagnosed with T1D (Type 1 Diabetes) (at least one autoantibody positive),&#xD;
             requiring insulin treatment&#xD;
&#xD;
          4. Be within 6 weeks from diagnosis of T1D (at screening)&#xD;
&#xD;
          5. Have a random C-peptide &gt; 200 pmol/l&#xD;
&#xD;
          6. Normal full blood count&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-type 1 diabetes (type 2 or monogenic diabetes) and secondary diabetes&#xD;
&#xD;
          2. Pre-existing autoimmune disease (excluding type 1 diabetes)&#xD;
&#xD;
          3. Hypersensitivity to aldesleukin or any of the excipients&#xD;
&#xD;
          4. History of severe cardiac disease (NYHA Class III or IV)&#xD;
&#xD;
          5. History of malignancy within the past 5 years (with the exception of adequately&#xD;
             treated basal or squamous cell carcinoma or cervical carcinoma in situ)&#xD;
&#xD;
          6. Clinically significant abnormal laboratory values (out of range and associated with&#xD;
             clinical symptoms or signs) in haematology, biochemistry, thyroid, liver and kidney&#xD;
             function&#xD;
&#xD;
          7. Pre-existing severe major organ dysfunction or seizure disorders&#xD;
&#xD;
          8. Participation in another clinical trial (CTIMP) within 4 months prior to screening&#xD;
&#xD;
          9. Females who are pregnant, lactating or intend to get pregnant during the study&#xD;
&#xD;
         10. Females of childbearing potential who are unwilling or unable to comply with&#xD;
             contraceptive advice and regular pregnancy testing throughout the trial&#xD;
&#xD;
         11. Sexually active males who are unwilling or unable to comply with contraceptive advice&#xD;
&#xD;
         12. Current use of immunosuppressive agents or steroids&#xD;
&#xD;
         13. Current treatment with hepatotoxic, nephrotoxic, myelotoxic, or cardiotoxic products&#xD;
&#xD;
         14. Active clinical infections - participants can be recruited after a minimum period of&#xD;
             48 h after last day of feeling unwell or last day of antibiotic/anti-viral treatment&#xD;
&#xD;
         15. Any medical history or clinically relevant abnormality that is deemed by the principal&#xD;
             investigator and/or medical monitor to make the participant ineligible for inclusion&#xD;
             because of a safety concern&#xD;
&#xD;
         16. Children with compliance problems (families where the local investigators consider&#xD;
             that problems with compliance may be an issue)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Johnson, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oxford Children's Hospital</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bristol Royal Hospital for Children</name>
      <address>
        <city>Bristol</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Great North Children's Hospital</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham Children's Hospital</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>September 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>December 15, 2021</last_update_submitted>
  <last_update_submitted_qc>December 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2021</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>Diabetes Mellitus</mesh_term>
    <mesh_term>Autoimmune Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aldesleukin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03782636
org study id: 13341
nct id: NCT03782636
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The main purpose of this study is to see if a drug called aldesleukin, can preserve insulin
      production in children and young adults recently diagnosed with type 1 diabetes.

      One group will receive aldesleukin and the other a placebo.
Investigators know that the longer people with diabetes can produce their own insulin, the
      better it is for the control of their blood glucose levels and long-term complications.

      People get type 1 diabetes because their immune system, the part of the body, which helps
      fight infections, mistakenly attacks and destroys the beta cells in the pancreas that produce
      insulin. As the immune system destroys these insulin-producing cells, the body's own ability
      to produce insulin decreases and diabetes develops.

      At diagnosis, there are usually a small number of beta cells (10-20%) left in the pancreas,
      which still produce small amounts of insulin. This is called 'beta cell function' and it is
      assessed by measuring C-peptide, which is a protein made by the pancreas when insulin is
      produced. Most people with type 1 diabetes eventually stop producing insulin themselves, this
      may occur rapidly in a few months, or more slowly over several years.

      New treatments preserving insulin production could improve management of diabetes. This could
      be done by using drugs acting on cells of the immune system. In type 1 diabetes, there is an
      imbalance between cells of the immune system, and there is evidence that one protein produced
      by our body, called Interleukin-2, could help in resetting the balance between those cells.
      It is important to start this treatment soon after diagnosis because this when there is the
      best chance of saving the beta cells still left in the pancreas.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Differences in slopes of DBS (Dried Blood Spot) C-peptide over the 6 month-treatment period between the active and placebo groups.
time frame: Weekly DBS C-peptide collected during the 6-month treatment period, and then monthly during the 6 months of follow-up
measure: Change in Treg, Teff and NK56bright cell frequencies and phenotypes from baseline
time frame: At baseline and then1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (reported reactions using CTCAE grading v5.0)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Assessment of the most commonly reported reactions to low- or high-dose aldesleukin, namely influenza-like syndrome, skin reaction, diarrhoea, nausea using CTCAE grading v5.0
measure: Safety will be assessed at each visit (temperature in celsius)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Vital signs - temperature in celsius
measure: Safety will be assessed at each visit (weight, in kilograms)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Vital signs - weight, in kilograms
measure: Safety will be assessed at each visit (blood pressure: systolic/diastolic)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Vital signs - blood pressure: systolic/diastolic
measure: Safety will be assessed at each visit (heart rate: bpm)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Vital signs - heart rate: bpm
measure: Safety will be assessed at each visit (AST, ALT, ALP, GGT units per liter (U/L)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Abnormal laboratory parameters liver function (AST, ALT, ALP, GGT units per liter (U/L)
measure: Safety will be assessed at each visit total bilirubin - milligrams per deciliter (mg/dL)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Abnormal laboratory parameters liver function total bilirubin - milligrams per deciliter (mg/dL)
measure: Safety will be assessed at each visit (urea and creatinine - mmol/L)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Abnormal laboratory parameters kidney function (urea and creatinine - mmol/L)
measure: Safety will be assessed at each visit (full blood count - 109/L)
time frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
description: Abnormal laboratory parameters full blood count - 109/L
measure: Changes in the absolute numbers of T, B and NK (Natural Killer) cells.
time frame: At baseline and then, 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Change in HbA1c and daily insulin requirements during the trial period.
time frame: HbA1c - At baseline and then 3,6 and 12 months Insulin dose data -Baseline and then 1, 2, 3, 6 and 12 months
arm group label: Aldesleukin
arm group type: Experimental
description: Ultra-low dose aldesleukin injected subcutaneously, at a dose of 0.2 x 106 IU/m2 twice-weekly , three days apart, for 6 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo sc, at a similar dose (expressed in ml) to the active drug
intervention type: Drug
intervention name: Aldesleukin
description: PROLEUKIN® 18 x 106 IU
Powder for solution for injection or infusion
arm group label: Aldesleukin
intervention type: Other
intervention name: Placebo
description: sterile diluent used for the aldesleukin preparation and 5% glucose
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: No
last name: Paul Johnson, Professor
role: Principal Investigator
affiliation: University of Oxford
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Autoimmune Diseases
mesh term: Aldesleukin
sharing ipd: Undecided