<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/NCT04429334</url>
  </required_header>
  <id_info>
    <org_study_id>MOT-C-204</org_study_id>
    <nct_id>NCT04429334</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Nangibotide in Patients With COVID-19 Receiving Ventilatory Support</brief_title>
  <acronym>ESSENTIAL</acronym>
  <official_title>Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients With ventiLatory Support (ESSENTIAL) A Randomized, Double-blind, Placebo-controlled Study With Adaptive Features</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Inotrem</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Inotrem</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>
      This is a randomized, double-blind, placebo-controlled, in which one dose of nangibotide will&#xD;
      be tested versus placebo.&#xD;
&#xD;
      All patients with a diagnosis of COVID-19, and a requirement for respiratory support will be&#xD;
      considered for study participation. The applicable local requirements for informed consent&#xD;
      will be followed. Where permissible, an emergency consent procedure will be followed for&#xD;
      patients unable to provide consent by themselves. All potential study patients will receive&#xD;
      standard of care treatment throughout the study. Patients will receive a continuous&#xD;
      intravenous (i.v.) infusion of nangibotide at 1.0 mg/kg/h or a matching placebo. Treatment&#xD;
      with study drug must be initiated as early as possible but no later than 48 hours after the&#xD;
      initiation of ventilatory support (Patients will be treated for 5 days or until discharge&#xD;
      from critical care, whichever is sooner). Follow-up visits will be performed on days 8 and&#xD;
      14. The end of study visit is at day 28. A further follow up visit will be undertaken on day&#xD;
      60.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ESSENTIAL was a randomized, double-blind, placebo-controlled trial, in which one dose of&#xD;
      nangibotide was tested versus placebo. It took place in 14 sites in France and Belgium. The&#xD;
      study was overseen by an independent Data Monitoring Committee (DMC).&#xD;
&#xD;
      The study was divided into two parts running sequentially without unblinding. Part 1&#xD;
      evaluated safety and tolerability study and included 60 patients, randomized in a 2:1 ratio&#xD;
      of nangibotide to placebo. Part 2 included all recruited patients with an initially planned&#xD;
      sample size of 370 patients, randomized in a 1:1 ratio of nangibotide to placebo.&#xD;
&#xD;
      All patients or their legally authorised representatives provided written informed consent&#xD;
      or, in relevant countries, an independent physician, confirmed patient eligibility for&#xD;
      enrolment in the trial.&#xD;
&#xD;
      Patients received a continuous intravenous infusion of nangibotide at 1.0 mg/kg/h or a&#xD;
      matching placebo for 5 days (or until discharge from ICU, whichever was sooner). The&#xD;
      treatment was in addition to standard of care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 23, 2020</start_date>
  <completion_date type="Actual">June 22, 2022</completion_date>
  <primary_completion_date type="Actual">May 20, 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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events until day 28</measure>
    <time_frame>28 days</time_frame>
    <description>Part 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Status (7-point Ordinal Scale) assessed at Day 28</measure>
    <time_frame>28 days</time_frame>
    <description>Part 2</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">220</enrollment>
  <condition>COVID19</condition>
  <arm_group>
    <arm_group_label>nangibotide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Continuous infusion of experimental agent for up to 120 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Continuous infusion of matched placebo for up to 120 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nangibotide</intervention_name>
    <description>nangibotide 1.0 mg/kg/h</description>
    <arm_group_label>nangibotide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>matching placebo</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provided informed consent (emergency consent according to local regulations where&#xD;
             approved)&#xD;
&#xD;
          2. Age 18 to 75 years (inclusive)&#xD;
&#xD;
          3. Admitted to an intensive care unit&#xD;
&#xD;
          4. Treatment with High Flow Nasal Oxygen, non-invasive ventilation or invasive mechanical&#xD;
             ventilation for acute respiratory failure caused by COVID-19 for less than 48 hours&#xD;
&#xD;
          5. A PaO2:FiO2 ratio of &lt;200mmHg (&lt;26.7kPa) with a FiO2 ≥0.6&#xD;
&#xD;
          6. Confirmed laboratory diagnosis of COVID-19 within 7 days of meeting screening criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known pregnancy (positive urine or serum pregnancy test)&#xD;
&#xD;
          2. Ongoing treatment with an immunomodulatory agent not included in the standard of care&#xD;
             for COVID-19 (including participation in clinical trials of such agents)&quot;.&#xD;
&#xD;
          3. Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg&#xD;
&#xD;
          4. Anticipated transfer to another hospital, which is not a study site within 72 hours&#xD;
&#xD;
          5. Expected to die within 6 months of treatment due to underlying chronic disease&#xD;
&#xD;
          6. Limitations of care in place during current hospital admission&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Jacques Garaud, MD</last_name>
    <role>Study Chair</role>
    <affiliation>INOTREM SA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinique universitaire Saint-Luc</name>
      <address>
        <city>Brussels</city>
        <zip>B-1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis Oost-Limburg</name>
      <address>
        <city>Genk</city>
        <zip>3600</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier Victor Dupouy</name>
      <address>
        <city>Argenteuil</city>
        <zip>95107</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Germont et Gauthier</name>
      <address>
        <city>Bethune</city>
        <zip>62400</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dijon - Bourgogne - Hôpital François Mitterrand</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHD Site la Roche sur Yon, les Oudairies</name>
      <address>
        <city>La Roche sur Yon</city>
        <zip>85 925</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier le Manas</name>
      <address>
        <city>Le Mans</city>
        <zip>72037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Dupuytren</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier de Melun</name>
      <address>
        <city>Melun</city>
        <zip>77000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Eloi CHU Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Réanimation Médicale, Hôpital Central</name>
      <address>
        <city>Nancy</city>
        <zip>54000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Dieu - CHU Nanates</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Civil - Nouvel Hôpital civil</name>
      <address>
        <city>Strasbourg</city>
        <zip>67091</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU - Hôpital Bretonneau</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Franch-Comté Site Trevenans</name>
      <address>
        <city>Trevenans</city>
        <zip>90400</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 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>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nangibotide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04429334
org study id: MOT-C-204
nct id: NCT04429334
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, double-blind, placebo-controlled, in which one dose of nangibotide will
      be tested versus placebo.

      All patients with a diagnosis of COVID-19, and a requirement for respiratory support will be
      considered for study participation. The applicable local requirements for informed consent
      will be followed. Where permissible, an emergency consent procedure will be followed for
      patients unable to provide consent by themselves. All potential study patients will receive
      standard of care treatment throughout the study. Patients will receive a continuous
      intravenous (i.v.) infusion of nangibotide at 1.0 mg/kg/h or a matching placebo. Treatment
      with study drug must be initiated as early as possible but no later than 48 hours after the
      initiation of ventilatory support (Patients will be treated for 5 days or until discharge
      from critical care, whichever is sooner). Follow-up visits will be performed on days 8 and
      14. The end of study visit is at day 28. A further follow up visit will be undertaken on day
      60.
ESSENTIAL was a randomized, double-blind, placebo-controlled trial, in which one dose of
      nangibotide was tested versus placebo. It took place in 14 sites in France and Belgium. The
      study was overseen by an independent Data Monitoring Committee (DMC).

      The study was divided into two parts running sequentially without unblinding. Part 1
      evaluated safety and tolerability study and included 60 patients, randomized in a 2:1 ratio
      of nangibotide to placebo. Part 2 included all recruited patients with an initially planned
      sample size of 370 patients, randomized in a 1:1 ratio of nangibotide to placebo.

      All patients or their legally authorised representatives provided written informed consent
      or, in relevant countries, an independent physician, confirmed patient eligibility for
      enrolment in the trial.

      Patients received a continuous intravenous infusion of nangibotide at 1.0 mg/kg/h or a
      matching placebo for 5 days (or until discharge from ICU, whichever was sooner). The
      treatment was in addition to standard of care.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of adverse events until day 28
time frame: 28 days
description: Part 1
measure: Clinical Status (7-point Ordinal Scale) assessed at Day 28
time frame: 28 days
description: Part 2
arm group label: nangibotide
arm group type: Experimental
description: Continuous infusion of experimental agent for up to 120 hours
arm group label: placebo
arm group type: Placebo Comparator
description: Continuous infusion of matched placebo for up to 120 hours
intervention type: Drug
intervention name: nangibotide
description: nangibotide 1.0 mg/kg/h
arm group label: nangibotide
intervention type: Drug
intervention name: placebo
description: matching placebo
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jean-Jacques Garaud, MD
role: Study Chair
affiliation: INOTREM SA
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Nangibotide
sharing ipd: No