<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/NCT04475588</url>
  </required_header>
  <id_info>
    <org_study_id>ITOLI-C19-02-I-00</org_study_id>
    <nct_id>NCT04475588</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Itolizumab in COVID-19 Complications</brief_title>
  <official_title>A Multi-Centre, Open Label, Two Arm Randomized, Phase 2 Trial to Study the Efficacy and Safety of Itolizumab in COVID-19 Complications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biocon Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biocon Limited</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized, Parallel Group, Active Controlled Trial&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Multi-Centric, Open label, Two Arm Randomized, Phase 2 Study.&#xD;
&#xD;
      All eligible patients entering into the study will be randomized in 2:1 ratio to receive the&#xD;
      treatment A (Best supportive care + Itolizumab) / B (Best supportive care) respectively. Each&#xD;
      patient will undergo the treatment based on their assigned treatment for a month along with&#xD;
      battery of tests that includes, but not limited to, cytokines and chemokine, along with&#xD;
      recording of TLC; DLC, ANC, ALC; Platelet count; S. creatinine; T.Bilirubin; morning Vitals&#xD;
      -pulse, BP, RR; Temperature, PaO2/FiO2, MAP, GCS.&#xD;
&#xD;
      As Itolizumab is an investigational drug, the benefit to COVID-19 patients experiencing&#xD;
      complications such as Cytokine Release Syndrome is not known. However, findings from this&#xD;
      study may be beneficial to the society at a large at the National and International Level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Actual">July 7, 2020</completion_date>
  <primary_completion_date type="Actual">July 7, 2020</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>One-month Mortality Rate Between the Two Arms</measure>
    <time_frame>One-month</time_frame>
    <description>1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2</measure>
    <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
    <description>Stable SpO2: Defined as number of patients with absence of increase in FiO2 to maintain SpO2 ≥ 92% Improvement of SpO2: Defined as number of patients with decrease in FiO2 to maintain SpO2 &gt; 92%</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV)</measure>
    <time_frame>Day 30</time_frame>
    <description>Number of patients needing Intubation/IMV post treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reduction in Proportion of Patients on Non-invasive Ventilation</measure>
    <time_frame>Baseline (Day 1), Day 7, Day 14 Day 21 &amp; Day 30</time_frame>
    <description>Reduction in proportion of Patients on Non-invasive Ventilation: defined as number of patient improved and shifted to Face mask, Nasal cannula, non-rebreather mask or off oxygen over time</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2</measure>
    <time_frame>Day 7, Day14, Day 21 &amp; Day30</time_frame>
    <description>Stable PaO2: Defined as number of patients with up to 10% change in PaO2/FiO2 ratio from baseline.&#xD;
Improvement of PaO2: Defined as number of patients with &gt; 10% improvement in PaO2/FiO2 ratio from baseline (including patients weaned off oxygen).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reduction in Proportion of Patients- Invasive Mechanical Ventilation</measure>
    <time_frame>Day7, Day14, Day21 &amp; Day 30</time_frame>
    <description>Patient improved from invasive ventilation over time from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reduction in Proportion of Patients-High Flow Nasal Oxygen</measure>
    <time_frame>Day7 ,Day 14 ,Day 21, Day 30</time_frame>
    <description>Patient improved from High Flow Nasal Oxygen over time from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Change From Baseline in Ferritin</measure>
    <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
    <description>Mean Change from Baseline in Ferritin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Change From Baseline in LDH</measure>
    <time_frame>Day 7, Day14, Day 21 and Day 30.</time_frame>
    <description>Mean Change from Baseline in LDH</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Change From Baseline in CRP (C-reactive Protein)</measure>
    <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
    <description>Mean Change from Baseline in CRP</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Change From Baseline D-Dimer</measure>
    <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline of Absolute Lymphocyte Count</measure>
    <time_frame>day 7, day 14 ,day 21 &amp; day 30</time_frame>
    <description>Mean change From baseline in Lymphocyte count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers (IL-6, TNF-a)</measure>
    <time_frame>Pre and Post 1st dose; Pre and Post 2nd dose</time_frame>
    <description>Mean values of Pre and Post 1st and 2nd dose are shown</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean PaO2 (Partial Pressure of Oxygen) / FiO2 (Fraction of Inspired Oxygen, FiO2) Ratio (or P/F Ratio)</measure>
    <time_frame>Baseline, Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
    <description>Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and Percentage of Patients With Radiological Response</measure>
    <time_frame>up to Day 30</time_frame>
    <description>Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <condition>Cytokine Release Syndrome</condition>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Arm A - Itolizumab + BSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B - Best supportive care (BSC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itolizumab IV infusion</intervention_name>
    <description>First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B</description>
    <arm_group_label>Arm A - Itolizumab + BSC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Best supportive care (BSC)</intervention_name>
    <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
    <arm_group_label>Arm A - Itolizumab + BSC</arm_group_label>
    <arm_group_label>Arm B - Best supportive care (BSC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Male or female adults above 18 years (not tested in children yet)&#xD;
&#xD;
          2. Informed consent for participation in the study&#xD;
&#xD;
          3. Virological diagnosis of SARS-CoV2 infection (PCR)&#xD;
&#xD;
          4. Hospitalized due to clinical/instrumental diagnosis of COVID-19 infection&#xD;
&#xD;
          5. Oxygen saturation at rest in ambient air ≤94%&#xD;
&#xD;
          6. Patients who are in moderate to severe ARDS as defined by PaO2/Fio2 ratio of &lt; 200&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Known severe allergic reactions to monoclonal antibodies&#xD;
&#xD;
          2. Active tuberculosis (TB) infection&#xD;
&#xD;
          3. History of inadequately treated tuberculosis or latent tuberculosis&#xD;
&#xD;
          4. In the opinion of the investigator,progression to death is highly probable,&#xD;
             irrespective of the provision of treatments&#xD;
&#xD;
          5. Have received oral anti-rejection or immune-suppressive drugs within the past 6 months&#xD;
&#xD;
          6. Participating in other drug clinical trials (participation in COVID-19 anti-viral&#xD;
             trials may be permitted if approved by Medical Monitor)&#xD;
&#xD;
          7. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination&#xD;
&#xD;
          8. Patients with known history of Hepatitis B, Hepatitis C or HIV&#xD;
&#xD;
          9. Absolute Neutrophils count (ANC) &lt;1000 / mm3&#xD;
&#xD;
         10. Platelets &lt;50,000 / mm3&#xD;
&#xD;
         11. Absolute Lymphocyte count (ALC): &lt;500/mm3&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Topiwala National Medical College &amp; B. Y. L. Nair Charitable Hospital,</name>
      <address>
        <city>Mumbai</city>
        <zip>400008</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seth GS Medical College and KEM Hospital</name>
      <address>
        <city>Mumbai</city>
        <zip>400012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital</name>
      <address>
        <city>New Delhi</city>
        <zip>110002</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>All India Institute Of Medical Sciences</name>
      <address>
        <city>New Delhi</city>
        <zip>110029</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <results_first_submitted>August 2, 2020</results_first_submitted>
  <results_first_submitted_qc>May 17, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 20, 2021</results_first_posted>
  <last_update_submitted>June 10, 2021</last_update_submitted>
  <last_update_submitted_qc>June 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 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>COVID-19</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Cytokine Release Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT04475588/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT04475588/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm A - Itolizumab + BSC</title>
          <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
        </group>
        <group group_id="P2">
          <title>Arm B - Best Supportive Care (BSC)</title>
          <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22">Stated in protocol apriori, patient not completing 1st infusion were not evaluable &amp; were replaced.</participants>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm A - Itolizumab + BSC</title>
          <description>IItolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
        </group>
        <group group_id="B2">
          <title>Arm B - Best Supportive Care (BSC)</title>
          <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.55" spread="12.49"/>
                    <measurement group_id="B2" value="48.30" spread="14.62"/>
                    <measurement group_id="B3" value="49.13" spread="13.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>India</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>One-month Mortality Rate Between the Two Arms</title>
        <description>1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30</description>
        <time_frame>One-month</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>One-month Mortality Rate Between the Two Arms</title>
          <description>1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2</title>
        <description>Stable SpO2: Defined as number of patients with absence of increase in FiO2 to maintain SpO2 ≥ 92% Improvement of SpO2: Defined as number of patients with decrease in FiO2 to maintain SpO2 &gt; 92%</description>
        <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
        <population>Patients improved/ weaned off O2, the observation was carried forward</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2</title>
          <description>Stable SpO2: Defined as number of patients with absence of increase in FiO2 to maintain SpO2 ≥ 92% Improvement of SpO2: Defined as number of patients with decrease in FiO2 to maintain SpO2 &gt; 92%</description>
          <population>Patients improved/ weaned off O2, the observation was carried forward</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV)</title>
        <description>Number of patients needing Intubation/IMV post treatment</description>
        <time_frame>Day 30</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH,Steroids,Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV)</title>
          <description>Number of patients needing Intubation/IMV post treatment</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Reduction in Proportion of Patients on Non-invasive Ventilation</title>
        <description>Reduction in proportion of Patients on Non-invasive Ventilation: defined as number of patient improved and shifted to Face mask, Nasal cannula, non-rebreather mask or off oxygen over time</description>
        <time_frame>Baseline (Day 1), Day 7, Day 14 Day 21 &amp; Day 30</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Reduction in Proportion of Patients on Non-invasive Ventilation</title>
          <description>Reduction in proportion of Patients on Non-invasive Ventilation: defined as number of patient improved and shifted to Face mask, Nasal cannula, non-rebreather mask or off oxygen over time</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2</title>
        <description>Stable PaO2: Defined as number of patients with up to 10% change in PaO2/FiO2 ratio from baseline.&#xD;
Improvement of PaO2: Defined as number of patients with &gt; 10% improvement in PaO2/FiO2 ratio from baseline (including patients weaned off oxygen).</description>
        <time_frame>Day 7, Day14, Day 21 &amp; Day30</time_frame>
        <population>Patients improved/ weaned off O2, the observation was carried forward.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2</title>
          <description>Stable PaO2: Defined as number of patients with up to 10% change in PaO2/FiO2 ratio from baseline.&#xD;
Improvement of PaO2: Defined as number of patients with &gt; 10% improvement in PaO2/FiO2 ratio from baseline (including patients weaned off oxygen).</description>
          <population>Patients improved/ weaned off O2, the observation was carried forward.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Reduction in Proportion of Patients- Invasive Mechanical Ventilation</title>
        <description>Patient improved from invasive ventilation over time from baseline.</description>
        <time_frame>Day7, Day14, Day21 &amp; Day 30</time_frame>
        <population>There were no patients on invasive mechanical ventilation at baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Reduction in Proportion of Patients- Invasive Mechanical Ventilation</title>
          <description>Patient improved from invasive ventilation over time from baseline.</description>
          <population>There were no patients on invasive mechanical ventilation at baseline</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Reduction in Proportion of Patients-High Flow Nasal Oxygen</title>
        <description>Patient improved from High Flow Nasal Oxygen over time from baseline.</description>
        <time_frame>Day7 ,Day 14 ,Day 21, Day 30</time_frame>
        <population>There were no patients on High Flow Nasal Oxygen at baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Reduction in Proportion of Patients-High Flow Nasal Oxygen</title>
          <description>Patient improved from High Flow Nasal Oxygen over time from baseline.</description>
          <population>There were no patients on High Flow Nasal Oxygen at baseline</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in Ferritin</title>
        <description>Mean Change from Baseline in Ferritin</description>
        <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
        <population>only &quot;observed values&quot; were used.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Ferritin</title>
          <description>Mean Change from Baseline in Ferritin</description>
          <population>only &quot;observed values&quot; were used.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-117.8" spread="1477.0"/>
                    <measurement group_id="O2" value="-87.05" spread="140.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-713.9" spread="693.68"/>
                    <measurement group_id="O2" value="-209.6" spread="177.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-780.9" spread="630.61"/>
                    <measurement group_id="O2" value="4238" spread="8319.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-479.3" spread="620.95"/>
                    <measurement group_id="O2" value="-234.4" spread="405.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in LDH</title>
        <description>Mean Change from Baseline in LDH</description>
        <time_frame>Day 7, Day14, Day 21 and Day 30.</time_frame>
        <population>Only &quot;observed values&quot; were used.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in LDH</title>
          <description>Mean Change from Baseline in LDH</description>
          <population>Only &quot;observed values&quot; were used.</population>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-134" spread="174.67"/>
                    <measurement group_id="O2" value="-44.29" spread="176.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-195.8" spread="291.94"/>
                    <measurement group_id="O2" value="-195.2" spread="119.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-308.1" spread="202.76"/>
                    <measurement group_id="O2" value="155.3" spread="736.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-212.7" spread="188.48"/>
                    <measurement group_id="O2" value="-97" spread="89.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in CRP (C-reactive Protein)</title>
        <description>Mean Change from Baseline in CRP</description>
        <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
        <population>Only &quot;observed values&quot; were used.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in CRP (C-reactive Protein)</title>
          <description>Mean Change from Baseline in CRP</description>
          <population>Only &quot;observed values&quot; were used.</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-61.69" spread="81.86"/>
                    <measurement group_id="O2" value="-103.6" spread="87.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-81.65" spread="74.71"/>
                    <measurement group_id="O2" value="-107.2" spread="104.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-90.99" spread="81.97"/>
                    <measurement group_id="O2" value="-127.5" spread="124.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-103.2" spread="100.53"/>
                    <measurement group_id="O2" value="-127.6" spread="59.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline D-Dimer</title>
        <time_frame>Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
        <population>Only &quot;observed values&quot; were used.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline D-Dimer</title>
          <population>Only &quot;observed values&quot; were used.</population>
          <units>µg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.43" spread="6.31"/>
                    <measurement group_id="O2" value="2.30" spread="6.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.45" spread="6.39"/>
                    <measurement group_id="O2" value="-0.68" spread="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.35" spread="6.13"/>
                    <measurement group_id="O2" value="8.54" spread="14.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.63" spread="2.43"/>
                    <measurement group_id="O2" value="-0.35" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline of Absolute Lymphocyte Count</title>
        <description>Mean change From baseline in Lymphocyte count</description>
        <time_frame>day 7, day 14 ,day 21 &amp; day 30</time_frame>
        <population>Only &quot;observed values&quot; were used.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline of Absolute Lymphocyte Count</title>
          <description>Mean change From baseline in Lymphocyte count</description>
          <population>Only &quot;observed values&quot; were used.</population>
          <units>cells/mm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119.95" spread="478.63"/>
                    <measurement group_id="O2" value="45.88" spread="762.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="421.25" spread="569.71"/>
                    <measurement group_id="O2" value="142.60" spread="731.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="701.55" spread="625.34"/>
                    <measurement group_id="O2" value="10.00" spread="930.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="719.75" spread="1004.0"/>
                    <measurement group_id="O2" value="85.00" spread="601.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biomarkers (IL-6, TNF-a)</title>
        <description>Mean values of Pre and Post 1st and 2nd dose are shown</description>
        <time_frame>Pre and Post 1st dose; Pre and Post 2nd dose</time_frame>
        <population>Only &quot;observed values&quot; were used.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Biomarkers (IL-6, TNF-a)</title>
          <description>Mean values of Pre and Post 1st and 2nd dose are shown</description>
          <population>Only &quot;observed values&quot; were used.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IL-6 (Pre 1st Dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="159.09" spread="293.0"/>
                    <measurement group_id="O2" value="162.16" spread="185.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6 (Post 1st Dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.98" spread="52.9"/>
                    <measurement group_id="O2" value="211.52" spread="297.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6 (Pre 2nd Dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="311.3" spread="660.4"/>
                    <measurement group_id="O2" value="310.4" spread="528.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6 (Post 2nd Dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.0" spread="245.6"/>
                    <measurement group_id="O2" value="316.8" spread="373.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-a (Pre 1st Dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.64" spread="72.9"/>
                    <measurement group_id="O2" value="11.26" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-a (Post 1st Dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.87" spread="12.3"/>
                    <measurement group_id="O2" value="39.19" spread="104.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-a (Pre 2nd Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.0" spread="109.5"/>
                    <measurement group_id="O2" value="107.8" spread="175.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-a (Post 2nd Dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.1" spread="140.2"/>
                    <measurement group_id="O2" value="185.0" spread="275.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean PaO2 (Partial Pressure of Oxygen) / FiO2 (Fraction of Inspired Oxygen, FiO2) Ratio (or P/F Ratio)</title>
        <description>Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)</description>
        <time_frame>Baseline, Day 7, Day 14, Day 21 &amp; Day 30</time_frame>
        <population>Only &quot;observed values&quot; were used.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Mean PaO2 (Partial Pressure of Oxygen) / FiO2 (Fraction of Inspired Oxygen, FiO2) Ratio (or P/F Ratio)</title>
          <description>Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)</description>
          <population>Only &quot;observed values&quot; were used.</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline/Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126.57" spread="38.31"/>
                    <measurement group_id="O2" value="114.05" spread="30.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="203.50" spread="95.51"/>
                    <measurement group_id="O2" value="184.53" spread="95.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="283.43" spread="104.26"/>
                    <measurement group_id="O2" value="338.40" spread="42.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="350.25" spread="70.36"/>
                    <measurement group_id="O2" value="398.33" spread="24.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30/EOS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="397.67" spread="15.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number and Percentage of Patients With Radiological Response</title>
        <description>Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment</description>
        <time_frame>up to Day 30</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A - Itolizumab + BSC</title>
            <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
          <group group_id="O2">
            <title>Arm B - Best Supportive Care (BSC)</title>
            <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
          </group>
        </group_list>
        <measure>
          <title>Number and Percentage of Patients With Radiological Response</title>
          <description>Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm A - Itolizumab + BSC</title>
          <description>Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.&#xD;
BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
        </group>
        <group group_id="E2">
          <title>Arm B - Best Supportive Care (BSC)</title>
          <description>Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion due to underlying hypothyroidism</sub_title>
                <description>Unrelated event in Arm A</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <description>Outcome death, in Arm B</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <description>Related event in Arm A</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <description>Patient had Infusion Reaction, did not complete initial dose. Event resolved same day. Per protocol, patient not completing first infusion were not evaluable &amp; were replaced. Patient recovered &amp; was discharged 2-wks later.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <description>Outcome was death, in Arm B</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Acute Respiratory Distress Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <description>1 Pt. had chills did not complete initial dose. Event resolved same day. Per protocol pt. not completing 1 dose were not evaluable &amp; replaced. Pt had COVID19 complications, death 9 days later, deemed not related to drug. Stated in all cause mortality</description>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fibrin D dimer increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Low density lipoprotein increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Non-high-density lipoprotein cholesterol increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to current pandemic situation few datapoints not available for ptxs who got discharged earlier basis clinical status &amp; bed shortage. As time to discharge was influenced by load on the hospital it was not an evaluable parameter after the trial.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Subramanian Loganathan</name_or_title>
      <organization>Biocon Biologics India Limited</organization>
      <phone>0802808 ext 5466</phone>
      <email>subramanian.l101@biocon.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04475588
org study id: ITOLI-C19-02-I-00
nct id: NCT04475588
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Randomized, Parallel Group, Active Controlled Trial
This is a Multi-Centric, Open label, Two Arm Randomized, Phase 2 Study.

      All eligible patients entering into the study will be randomized in 2:1 ratio to receive the
      treatment A (Best supportive care + Itolizumab) / B (Best supportive care) respectively. Each
      patient will undergo the treatment based on their assigned treatment for a month along with
      battery of tests that includes, but not limited to, cytokines and chemokine, along with
      recording of TLC; DLC, ANC, ALC; Platelet count; S. creatinine; T.Bilirubin; morning Vitals
      -pulse, BP, RR; Temperature, PaO2/FiO2, MAP, GCS.

      As Itolizumab is an investigational drug, the benefit to COVID-19 patients experiencing
      complications such as Cytokine Release Syndrome is not known. However, findings from this
      study may be beneficial to the society at a large at the National and International Level.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: One-month Mortality Rate Between the Two Arms
time frame: One-month
description: 1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30
measure: Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2
time frame: Day 7, Day 14, Day 21 & Day 30
description: Stable SpO2: Defined as number of patients with absence of increase in FiO2 to maintain SpO2 ≥ 92% Improvement of SpO2: Defined as number of patients with decrease in FiO2 to maintain SpO2 > 92%
measure: Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV)
time frame: Day 30
description: Number of patients needing Intubation/IMV post treatment
measure: Reduction in Proportion of Patients on Non-invasive Ventilation
time frame: Baseline (Day 1), Day 7, Day 14 Day 21 & Day 30
description: Reduction in proportion of Patients on Non-invasive Ventilation: defined as number of patient improved and shifted to Face mask, Nasal cannula, non-rebreather mask or off oxygen over time
measure: Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2
time frame: Day 7, Day14, Day 21 & Day30
description: Stable PaO2: Defined as number of patients with up to 10% change in PaO2/FiO2 ratio from baseline.
Improvement of PaO2: Defined as number of patients with > 10% improvement in PaO2/FiO2 ratio from baseline (including patients weaned off oxygen).
measure: Reduction in Proportion of Patients- Invasive Mechanical Ventilation
time frame: Day7, Day14, Day21 & Day 30
description: Patient improved from invasive ventilation over time from baseline.
measure: Reduction in Proportion of Patients-High Flow Nasal Oxygen
time frame: Day7 ,Day 14 ,Day 21, Day 30
description: Patient improved from High Flow Nasal Oxygen over time from baseline.
measure: Mean Change From Baseline in Ferritin
time frame: Day 7, Day 14, Day 21 & Day 30
description: Mean Change from Baseline in Ferritin
measure: Mean Change From Baseline in LDH
time frame: Day 7, Day14, Day 21 and Day 30.
description: Mean Change from Baseline in LDH
measure: Mean Change From Baseline in CRP (C-reactive Protein)
time frame: Day 7, Day 14, Day 21 & Day 30
description: Mean Change from Baseline in CRP
measure: Mean Change From Baseline D-Dimer
time frame: Day 7, Day 14, Day 21 & Day 30
measure: Mean Change From Baseline of Absolute Lymphocyte Count
time frame: day 7, day 14 ,day 21 & day 30
description: Mean change From baseline in Lymphocyte count
measure: Biomarkers (IL-6, TNF-a)
time frame: Pre and Post 1st dose; Pre and Post 2nd dose
description: Mean values of Pre and Post 1st and 2nd dose are shown
measure: Mean PaO2 (Partial Pressure of Oxygen) / FiO2 (Fraction of Inspired Oxygen, FiO2) Ratio (or P/F Ratio)
time frame: Baseline, Day 7, Day 14, Day 21 & Day 30
description: Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)
measure: Number and Percentage of Patients With Radiological Response
time frame: up to Day 30
description: Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment
arm group label: Arm A - Itolizumab + BSC
arm group type: Experimental
arm group label: Arm B - Best supportive care (BSC)
arm group type: Active Comparator
intervention type: Drug
intervention name: Itolizumab IV infusion
description: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks.
BSC: similar to Arm B
arm group label: Arm A - Itolizumab + BSC
intervention type: Drug
intervention name: Best supportive care (BSC)
description: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
arm group label: Arm A - Itolizumab + BSC
arm group label: Arm B - Best supportive care (BSC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: India
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
mesh term: Cytokine Release Syndrome
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to current pandemic situation few datapoints not available for ptxs who got discharged earlier basis clinical status & bed shortage. As time to discharge was influenced by load on the hospital it was not an evaluable parameter after the trial.
point of contact: 