<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/NCT03837093</url>
  </required_header>
  <id_info>
    <org_study_id>APHP180274</org_study_id>
    <secondary_id>2018-004123-37</secondary_id>
    <secondary_id>MEDAECNAT-2018-11-0048</secondary_id>
    <secondary_id>2-17-33</secondary_id>
    <nct_id>NCT03837093</nct_id>
  </id_info>
  <brief_title>Low-dose IL-2 to the Kinetics of Regulatory T-cell in Healthy Volunteers</brief_title>
  <acronym>HEALTHIL-2</acronym>
  <official_title>A Study of the Dose-response Relationship of Low-dose IL-2 to the Kinetics of Regulatory T-cell Response in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Iltoo Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and the dose-response relationship of&#xD;
      ILT-101 to blood Tregs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the healthy physiological state, there is homeostasis between regulatory T cells (Tregs)&#xD;
      and effector T cells (Teffs) which is deregulated in autoimmune diseases (AID).&#xD;
&#xD;
      The existence of an AID indicates a lack of Tregs. Our team has discovered that low-dose&#xD;
      interleukin-2 (ld-IL2) activates and specifically increases Tregs in humans and thus may&#xD;
      improve AID. Exploiting this potential requires i) to better target the dose with the best&#xD;
      benefit / risk ratio and also ii) to better understand the mechanism of action of this&#xD;
      molecule through clinical trials of ld-IL2 in progress, including in type 1 diabetes,&#xD;
      multiple sclerosis and systemic lupus erythematosus. During these clinical trials, a very&#xD;
      thorough immunological follow-up is carried out in order to discover biomarkers of treatment&#xD;
      efficacy. Exploitation of these results will benefit both the cross-analysis of the effects&#xD;
      of IL-2 in these 3 diseases with distinct pathophysiologies, but also very importantly a&#xD;
      comparison with the effects of ld-IL2 at the healthy volunteer. These analyzes should make it&#xD;
      possible to define the most effective dose of IL-2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 6, 2019</start_date>
  <completion_date type="Actual">November 6, 2021</completion_date>
  <primary_completion_date type="Actual">March 3, 2021</primary_completion_date>
  <phase>Phase 1</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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Variation of Tregs(in (expressed in % of CD4 and total)</measure>
    <time_frame>from Day 1 to Day 5</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC corresponding to the évolution of residual values of tregs/CD4+</measure>
    <time_frame>Day 5 to Day 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>numbers of different circulating immune populations</measure>
    <time_frame>baseline to Day 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>levels of serum cytokine(pg)</measure>
    <time_frame>from baseline to Day 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>levels of serum chemokine</measure>
    <time_frame>from baseline to Day 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composition of the intestinal microbiota</measure>
    <time_frame>from baseline to Day 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events, anti IL-2 autoantibodies</measure>
    <time_frame>from baseline to Day 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>levels of serum anti-IL-2 autoantibodies</measure>
    <time_frame>from baseline to Day 60</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>dose A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ILT-101</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dose B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ILT-101</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dose C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ILT-101</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dose D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ILT-101</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dose E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ILT-101</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ILT101</intervention_name>
    <description>Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks</description>
    <arm_group_label>dose A</arm_group_label>
    <arm_group_label>dose B</arm_group_label>
    <arm_group_label>dose C</arm_group_label>
    <arm_group_label>dose D</arm_group_label>
    <arm_group_label>dose E</arm_group_label>
    <other_name>low-dose IL-2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Without any chronic diseases diagnosed (including allergies);&#xD;
&#xD;
          -  Effective contraception&gt; 2 weeks before the first administration of the experimental&#xD;
             drug or its placebo and β-hCG negative at the verification of the selection criteria;&#xD;
&#xD;
          -  Affiliated to a social security system;&#xD;
&#xD;
          -  Free, informed and written consent, signed by the subject and the investigator, before&#xD;
             any action required by the research.&#xD;
&#xD;
          -  Not taking any treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject in a period of exclusion of participation in other biomedical research;&#xD;
&#xD;
          -  Participation in another research ≤ 1 month and during the study except for research&#xD;
             Transimmunom (Non-interventional research involving the human person);&#xD;
&#xD;
          -  known antecedents of autoimmune diseases;&#xD;
&#xD;
          -  Hypersensitivity to any of the excipients of the investigational drug (mannitol,&#xD;
             sodium laurilsulfate, monosodium phosphate dihydrate, disodium phosphate dihydrate);&#xD;
&#xD;
          -  Evolutionary infection requiring treatment;&#xD;
&#xD;
          -  Viral infection and benign infection less than 2 months old;&#xD;
&#xD;
          -  Venous capital not allowing blood samples;&#xD;
&#xD;
          -  Pregnant or lactating women;&#xD;
&#xD;
          -  Men and women of childbearing potential without effective contraception during the&#xD;
             study;&#xD;
&#xD;
          -  Live attenuated virus vaccination in the month prior to inclusion or during the study;&#xD;
&#xD;
          -  Surgical intervention ≤ 2 months or planned during the study;&#xD;
&#xD;
          -  Psychiatric pathology or drug addiction that may impair ability to comply with&#xD;
             protocol requirements or give informed consent;&#xD;
&#xD;
          -  Presence or history of cancer that has not been cured for less than 5 years, except in&#xD;
             situ cervical cancer, or basocellular cancer;&#xD;
&#xD;
          -  Subject under a legal protection measure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Klatzmann, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Investigation Center in Biotherapy et immunology Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris l'hopital 75013 Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roberta Lorenzon, MD</last_name>
    <role>Study Director</role>
    <affiliation>Clinical Investigation Center Paris Est Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Investigation Center Paris Est Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>December 10, 2021</last_update_submitted>
  <last_update_submitted_qc>December 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Low dose of IL-2</keyword>
  <keyword>Healthy volunteers</keyword>
  <keyword>Kinetic study</keyword>
  <!-- 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/NCT03837093
org study id: APHP180274
secondary id: 2018-004123-37
secondary id: MEDAECNAT-2018-11-0048
secondary id: 2-17-33
nct id: NCT03837093
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the safety and the dose-response relationship of
      ILT-101 to blood Tregs.
In the healthy physiological state, there is homeostasis between regulatory T cells (Tregs)
      and effector T cells (Teffs) which is deregulated in autoimmune diseases (AID).

      The existence of an AID indicates a lack of Tregs. Our team has discovered that low-dose
      interleukin-2 (ld-IL2) activates and specifically increases Tregs in humans and thus may
      improve AID. Exploiting this potential requires i) to better target the dose with the best
      benefit / risk ratio and also ii) to better understand the mechanism of action of this
      molecule through clinical trials of ld-IL2 in progress, including in type 1 diabetes,
      multiple sclerosis and systemic lupus erythematosus. During these clinical trials, a very
      thorough immunological follow-up is carried out in order to discover biomarkers of treatment
      efficacy. Exploitation of these results will benefit both the cross-analysis of the effects
      of IL-2 in these 3 diseases with distinct pathophysiologies, but also very importantly a
      comparison with the effects of ld-IL2 at the healthy volunteer. These analyzes should make it
      possible to define the most effective dose of IL-2.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Variation of Tregs(in (expressed in % of CD4 and total)
time frame: from Day 1 to Day 5
measure: AUC corresponding to the évolution of residual values of tregs/CD4+
time frame: Day 5 to Day 60
measure: numbers of different circulating immune populations
time frame: baseline to Day 60
measure: levels of serum cytokine(pg)
time frame: from baseline to Day 60
measure: levels of serum chemokine
time frame: from baseline to Day 60
measure: composition of the intestinal microbiota
time frame: from baseline to Day 60
measure: adverse events, anti IL-2 autoantibodies
time frame: from baseline to Day 60
measure: levels of serum anti-IL-2 autoantibodies
time frame: from baseline to Day 60
arm group label: dose A
arm group type: Experimental
description: ILT-101
arm group label: dose B
arm group type: Experimental
description: ILT-101
arm group label: dose C
arm group type: Experimental
description: ILT-101
arm group label: dose D
arm group type: Experimental
description: ILT-101
arm group label: dose E
arm group type: Experimental
description: ILT-101
arm group label: Placebo
arm group type: Experimental
intervention type: Drug
intervention name: ILT101
description: Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks
arm group label: dose A
arm group label: dose B
arm group label: dose C
arm group label: dose D
arm group label: dose E
other name: low-dose IL-2
intervention type: Drug
intervention name: Placebo
description: Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Klatzmann, MD
role: Principal Investigator
affiliation: Investigation Center in Biotherapy et immunology Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris l'hopital 75013 Paris
last name: Roberta Lorenzon, MD
role: Study Director
affiliation: Clinical Investigation Center Paris Est Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris
facility: 
country: France
responsible party type: Sponsor