<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/NCT04435184</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00249874</org_study_id>
    <nct_id>NCT04435184</nct_id>
  </id_info>
  <brief_title>Crizanlizumab for Treating COVID-19 Vasculopathy</brief_title>
  <acronym>CRITICAL</acronym>
  <official_title>Crizanlizumab for Treating COVID-19 Vasculopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Socar Research SA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial is to test the efficacy and safety of crizanlizumab in patients&#xD;
      hospitalized with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infection with severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) causes&#xD;
      coronavirus disease 2019 (COVID-19). The clinical course of COVID-19 is variable, and some&#xD;
      patients develop severe pneumonia, multi-organ failure, and shock.&#xD;
&#xD;
      Severe COVID-19 is characterized by a hyper-inflammatory and hyper-thrombotic state. We&#xD;
      propose that this state is caused by viral injury of the vascular endothelium, leading to&#xD;
      endothelial release of von Willebrand Factor (VWF) and P-selectin, which in turn drive&#xD;
      thrombosis and vascular inflammation.&#xD;
&#xD;
      Crizanlizumab is a monoclonal antibody that targets P-selectin. Crizanlizumab can decrease&#xD;
      inflammation by binding to P-selectin, blocking leucocyte and platelet adherence to the&#xD;
      vessel wall.&#xD;
&#xD;
      We now plan to test the safety and efficacy of crizanlizumab in decreasing biomarkers of&#xD;
      inflammation and thrombosis in a placebo-controlled, double-blind randomized clinical trial&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 9, 2020</start_date>
  <completion_date type="Actual">January 4, 2021</completion_date>
  <primary_completion_date type="Actual">November 28, 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>
    <intervention_model_description>Double-blind, placebo-controlled, randomized interventional trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Soluble P-selectin Level</measure>
    <time_frame>Day 3 after randomization or day of hospital discharge, whichever is earlier</time_frame>
    <description>Level of soluble P-selectin in ng/mL.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Soluble P-selectin Level</measure>
    <time_frame>Day 7 after randomization</time_frame>
    <description>Level of soluble P-selectin in ng/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Soluble P-selectin Level</measure>
    <time_frame>Day 14 after randomization</time_frame>
    <description>Level of soluble P-selectin in ng/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>D-dimer Level</measure>
    <time_frame>Day 3 after randomization</time_frame>
    <description>Level of D-dimer in mg/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>D-dimer Level</measure>
    <time_frame>Day 7 after randomization</time_frame>
    <description>Level of D-dimer in mg/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>D-dimer Level</measure>
    <time_frame>Day 14 after randomization</time_frame>
    <description>Level of D-dimer in mg/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VWF Level</measure>
    <time_frame>Day 3 after randomization</time_frame>
    <description>Level of von Willebrand Factor (VWF) antigen in IU/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VWF Level</measure>
    <time_frame>Day 7 after randomization</time_frame>
    <description>Level of VWF antigen in IU/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VWF Level</measure>
    <time_frame>Day 14 after randomization</time_frame>
    <description>Level of VWF antigen in IU/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRP Level</measure>
    <time_frame>Day 3 after randomization</time_frame>
    <description>Level of C-reactive protein (CRP) in mg/dL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRP Level</measure>
    <time_frame>Day 7 after randomization</time_frame>
    <description>Level of C-reactive protein (CRP) in mg/dL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRP Level</measure>
    <time_frame>Day 14 after randomization</time_frame>
    <description>Level of C-reactive protein (CRP) in mg/dL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials</measure>
    <time_frame>Days 3, 7 and 14 after randomization</time_frame>
    <description>Change in the clinical status over 14 days as measured by an ordinal scale that is the first assessment of the clinical status on a given study day. The scale is as follows:&#xD;
0 = Uninfected; no viral RNA detected&#xD;
= Ambulatory; asymptomatic; viral RNA detected&#xD;
= Ambulatory; symptomatic; independent&#xD;
= Ambulatory; symptomatic; assistance needed&#xD;
= Hospitalized; no oxygen therapy&#xD;
= Hospitalized; oxygen by mask or nasal prongs&#xD;
= Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow&#xD;
= Hospitalized; intubation and mechanical ventilation, partial pressure of oxygen / fraction of inspired oxygen (pO2/FIO2) ≥ 150 or oxygen saturation / FIO2 (SpO2/FIO2) ≥ 200&#xD;
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 &lt; 150 or SpO2/FIO2 &lt; 200 or vasopressors&#xD;
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 &lt; 150 or SpO2/FIO2 &lt; 200 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO)&#xD;
= Dead</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Hospital Discharge</measure>
    <time_frame>Up to 30 days after randomization</time_frame>
    <description>Time (days) to hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Crizanlizumab as Assessed by Adverse Events</measure>
    <time_frame>Up to day 14 after randomization</time_frame>
    <description>Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Crizanlizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Saline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.9% saline 100 ml IV once.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Crizanlizumab</intervention_name>
    <description>Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
    <arm_group_label>Crizanlizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>0.9% saline</intervention_name>
    <description>0.9% saline 100 ml IV once.</description>
    <arm_group_label>Placebo Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing to provide written informed consent&#xD;
&#xD;
          2. Willing to comply with all study procedures and be available for the duration of the&#xD;
             study&#xD;
&#xD;
          3. Male or female ≥ 18 years of age&#xD;
&#xD;
          4. SARS-CoV-2 infection (COVID-19) within the past 10 d documented by laboratory test&#xD;
             (nucleic acid test (NAT) or reverse transcriptase-polymerase chain reaction (RT-PCR))&#xD;
&#xD;
          5. Currently hospitalized&#xD;
&#xD;
          6. Symptoms of acute respiratory infection (at least one of the following: cough, fever &gt;&#xD;
             37.5°C, dyspnea, sore throat, anosmia),&#xD;
&#xD;
          7. Radiographic evidence of pulmonary infiltrates&#xD;
&#xD;
          8. Requiring supplemental oxygen or the peripheral capillary oxygenation saturation&#xD;
             (SpO2) &lt; 94% on room air at screening&#xD;
&#xD;
          9. Elevated D-Dimer &gt; 0.49 mg/L&#xD;
&#xD;
         10. Negative pregnancy test for females of childbearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of home oxygen at baseline&#xD;
&#xD;
          2. Current use of mechanical ventilation&#xD;
&#xD;
          3. Inability to provide consent&#xD;
&#xD;
          4. Do not intubate status&#xD;
&#xD;
          5. Prisoner or incarcerated&#xD;
&#xD;
          6. Pregnancy or Breast Feeding&#xD;
&#xD;
          7. Participation in other interventional therapy trials for COVID-19.&#xD;
&#xD;
          8. International normalized ratio (INR) &gt; 3 or activated partial thromboplastin time&#xD;
             (aPTT) &gt; 60&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charles J Lowenstein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439. doi: 10.1056/NEJMoa1611770. Epub 2016 Dec 3.</citation>
    <PMID>27959701</PMID>
  </reference>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <results_first_submitted>November 3, 2021</results_first_submitted>
  <results_first_submitted_qc>November 3, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 9, 2021</results_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>coronavirus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 14, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT04435184/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>From July 15, 2020 through November 27, 2020, 583 patients were screened at 3 hospitals within the Johns Hopkins Health System. A total of 54 patients who fulfilled study entry criteria were randomized to receive crizanlizumab (n = 27) or placebo (n = 27).</recruitment_details>
      <pre_assignment_details>Out of the 27 assigned to receive crizanlizumab, 2 did not receive crizanlizumab because of early discharge or early intubation. Out of the 27 assigned to receive placebo, 2 did not receive placebo because of early discharge or withdrawn consent.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Crizanlizumab</title>
          <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Saline</title>
          <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>follow-up blood draws missing</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline characteristics data was collected for the 42 participants who completed the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Crizanlizumab</title>
          <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Saline</title>
          <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</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="22"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="42"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="58" spread="17.7"/>
                    <measurement group_id="B2" value="54.6" spread="13.4"/>
                    <measurement group_id="B3" value="56.2" spread="15.5"/>
                  </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="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Soluble P-selectin Level</title>
        <description>Level of soluble P-selectin in ng/mL.</description>
        <time_frame>Day 3 after randomization or day of hospital discharge, whichever is earlier</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>Soluble P-selectin Level</title>
          <description>Level of soluble P-selectin in ng/mL.</description>
          <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="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" spread="7"/>
                    <measurement group_id="O2" value="39" spread="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Soluble P-selectin Level</title>
        <description>Level of soluble P-selectin in ng/mL.</description>
        <time_frame>Day 7 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>Soluble P-selectin Level</title>
          <description>Level of soluble P-selectin in ng/mL.</description>
          <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="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" spread="8"/>
                    <measurement group_id="O2" value="48" spread="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Soluble P-selectin Level</title>
        <description>Level of soluble P-selectin in ng/mL.</description>
        <time_frame>Day 14 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>Soluble P-selectin Level</title>
          <description>Level of soluble P-selectin in ng/mL.</description>
          <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="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" spread="10"/>
                    <measurement group_id="O2" value="48" spread="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>D-dimer Level</title>
        <description>Level of D-dimer in mg/L.</description>
        <time_frame>Day 3 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>D-dimer Level</title>
          <description>Level of D-dimer in mg/L.</description>
          <units>mg/L</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" lower_limit="0.7" upper_limit="2.8"/>
                    <measurement group_id="O2" value="0.7" lower_limit="0.5" upper_limit="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>D-dimer Level</title>
        <description>Level of D-dimer in mg/L.</description>
        <time_frame>Day 7 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>D-dimer Level</title>
          <description>Level of D-dimer in mg/L.</description>
          <units>mg/L</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" lower_limit="0.6" upper_limit="2.0"/>
                    <measurement group_id="O2" value="0.7" lower_limit="0.5" upper_limit="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>D-dimer Level</title>
        <description>Level of D-dimer in mg/L.</description>
        <time_frame>Day 14 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>D-dimer Level</title>
          <description>Level of D-dimer in mg/L.</description>
          <units>mg/L</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" lower_limit="0.5" upper_limit="1.9"/>
                    <measurement group_id="O2" value="0.7" lower_limit="0.5" upper_limit="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>VWF Level</title>
        <description>Level of von Willebrand Factor (VWF) antigen in IU/mL.</description>
        <time_frame>Day 3 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>VWF Level</title>
          <description>Level of von Willebrand Factor (VWF) antigen in IU/mL.</description>
          <units>IU/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" lower_limit="1.9" upper_limit="4.9"/>
                    <measurement group_id="O2" value="2.8" lower_limit="1.7" upper_limit="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>VWF Level</title>
        <description>Level of VWF antigen in IU/mL.</description>
        <time_frame>Day 7 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>VWF Level</title>
          <description>Level of VWF antigen in IU/mL.</description>
          <units>IU/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9" lower_limit="2.5" upper_limit="5.9"/>
                    <measurement group_id="O2" value="3.6" lower_limit="2.1" upper_limit="6.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>VWF Level</title>
        <description>Level of VWF antigen in IU/mL.</description>
        <time_frame>Day 14 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>VWF Level</title>
          <description>Level of VWF antigen in IU/mL.</description>
          <units>IU/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" lower_limit="1.9" upper_limit="4.2"/>
                    <measurement group_id="O2" value="4.6" lower_limit="2.6" upper_limit="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CRP Level</title>
        <description>Level of C-reactive protein (CRP) in mg/dL.</description>
        <time_frame>Day 3 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>CRP Level</title>
          <description>Level of C-reactive protein (CRP) in mg/dL.</description>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" lower_limit="2.1" upper_limit="5.6"/>
                    <measurement group_id="O2" value="4.5" lower_limit="1.2" upper_limit="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CRP Level</title>
        <description>Level of C-reactive protein (CRP) in mg/dL.</description>
        <time_frame>Day 7 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>CRP Level</title>
          <description>Level of C-reactive protein (CRP) in mg/dL.</description>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="1.1" upper_limit="4.9"/>
                    <measurement group_id="O2" value="2.1" lower_limit="0.6" upper_limit="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CRP Level</title>
        <description>Level of C-reactive protein (CRP) in mg/dL.</description>
        <time_frame>Day 14 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>CRP Level</title>
          <description>Level of C-reactive protein (CRP) in mg/dL.</description>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" lower_limit="1.1" upper_limit="5.1"/>
                    <measurement group_id="O2" value="1.3" lower_limit="0.6" upper_limit="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials</title>
        <description>Change in the clinical status over 14 days as measured by an ordinal scale that is the first assessment of the clinical status on a given study day. The scale is as follows:&#xD;
0 = Uninfected; no viral RNA detected&#xD;
= Ambulatory; asymptomatic; viral RNA detected&#xD;
= Ambulatory; symptomatic; independent&#xD;
= Ambulatory; symptomatic; assistance needed&#xD;
= Hospitalized; no oxygen therapy&#xD;
= Hospitalized; oxygen by mask or nasal prongs&#xD;
= Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow&#xD;
= Hospitalized; intubation and mechanical ventilation, partial pressure of oxygen / fraction of inspired oxygen (pO2/FIO2) ≥ 150 or oxygen saturation / FIO2 (SpO2/FIO2) ≥ 200&#xD;
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 &lt; 150 or SpO2/FIO2 &lt; 200 or vasopressors&#xD;
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 &lt; 150 or SpO2/FIO2 &lt; 200 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO)&#xD;
= Dead</description>
        <time_frame>Days 3, 7 and 14 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials</title>
          <description>Change in the clinical status over 14 days as measured by an ordinal scale that is the first assessment of the clinical status on a given study day. The scale is as follows:&#xD;
0 = Uninfected; no viral RNA detected&#xD;
= Ambulatory; asymptomatic; viral RNA detected&#xD;
= Ambulatory; symptomatic; independent&#xD;
= Ambulatory; symptomatic; assistance needed&#xD;
= Hospitalized; no oxygen therapy&#xD;
= Hospitalized; oxygen by mask or nasal prongs&#xD;
= Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow&#xD;
= Hospitalized; intubation and mechanical ventilation, partial pressure of oxygen / fraction of inspired oxygen (pO2/FIO2) ≥ 150 or oxygen saturation / FIO2 (SpO2/FIO2) ≥ 200&#xD;
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 &lt; 150 or SpO2/FIO2 &lt; 200 or vasopressors&#xD;
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 &lt; 150 or SpO2/FIO2 &lt; 200 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO)&#xD;
= Dead</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="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>WHO Clinical Status: Day 3</title>
              <category_list>
                <category>
                  <title>&lt;/= 3 (discharged)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>9</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>10</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WHO Clinical Status: Day 7</title>
              <category_list>
                <category>
                  <title>&lt;/= 3 (discharged)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>9</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>10</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WHO Clinical Status: Day 14</title>
              <category_list>
                <category>
                  <title>&lt;/= 3 (discharged)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>9</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>10</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Hospital Discharge</title>
        <description>Time (days) to hospital discharge</description>
        <time_frame>Up to 30 days after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Hospital Discharge</title>
          <description>Time (days) to hospital discharge</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="4.4"/>
                    <measurement group_id="O2" value="6.2" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety of Crizanlizumab as Assessed by Adverse Events</title>
        <description>Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.</description>
        <time_frame>Up to day 14 after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Crizanlizumab</title>
            <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Saline</title>
            <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety of Crizanlizumab as Assessed by Adverse Events</title>
          <description>Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.</description>
          <units>total adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                  </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>Crizanlizumab</title>
          <description>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.&#xD;
Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Saline</title>
          <description>0.9% saline 100 ml IV once.&#xD;
0.9% saline: 0.9% saline 100 ml IV once.</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="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>multi-organ failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="7" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Altered mental status</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Dark and Infrequent Urination</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Venous thrombembolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </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>
    <point_of_contact>
      <name_or_title>Dr. Charles Lowenstein</name_or_title>
      <organization>Johns Hopkins University - Baltimore, MD</organization>
      <phone>4105020391</phone>
      <email>clowens1@jhmi.edu</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/NCT04435184
org study id: IRB00249874
nct id: NCT04435184
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this trial is to test the efficacy and safety of crizanlizumab in patients
      hospitalized with COVID-19.
Infection with severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) causes
      coronavirus disease 2019 (COVID-19). The clinical course of COVID-19 is variable, and some
      patients develop severe pneumonia, multi-organ failure, and shock.

      Severe COVID-19 is characterized by a hyper-inflammatory and hyper-thrombotic state. We
      propose that this state is caused by viral injury of the vascular endothelium, leading to
      endothelial release of von Willebrand Factor (VWF) and P-selectin, which in turn drive
      thrombosis and vascular inflammation.

      Crizanlizumab is a monoclonal antibody that targets P-selectin. Crizanlizumab can decrease
      inflammation by binding to P-selectin, blocking leucocyte and platelet adherence to the
      vessel wall.

      We now plan to test the safety and efficacy of crizanlizumab in decreasing biomarkers of
      inflammation and thrombosis in a placebo-controlled, double-blind randomized clinical trial
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double-blind, placebo-controlled, randomized interventional trial.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Soluble P-selectin Level
time frame: Day 3 after randomization or day of hospital discharge, whichever is earlier
description: Level of soluble P-selectin in ng/mL.
measure: Soluble P-selectin Level
time frame: Day 7 after randomization
description: Level of soluble P-selectin in ng/mL.
measure: Soluble P-selectin Level
time frame: Day 14 after randomization
description: Level of soluble P-selectin in ng/mL.
measure: D-dimer Level
time frame: Day 3 after randomization
description: Level of D-dimer in mg/L.
measure: D-dimer Level
time frame: Day 7 after randomization
description: Level of D-dimer in mg/L.
measure: D-dimer Level
time frame: Day 14 after randomization
description: Level of D-dimer in mg/L.
measure: VWF Level
time frame: Day 3 after randomization
description: Level of von Willebrand Factor (VWF) antigen in IU/mL.
measure: VWF Level
time frame: Day 7 after randomization
description: Level of VWF antigen in IU/mL.
measure: VWF Level
time frame: Day 14 after randomization
description: Level of VWF antigen in IU/mL.
measure: CRP Level
time frame: Day 3 after randomization
description: Level of C-reactive protein (CRP) in mg/dL.
measure: CRP Level
time frame: Day 7 after randomization
description: Level of C-reactive protein (CRP) in mg/dL.
measure: CRP Level
time frame: Day 14 after randomization
description: Level of C-reactive protein (CRP) in mg/dL.
measure: Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials
time frame: Days 3, 7 and 14 after randomization
description: Change in the clinical status over 14 days as measured by an ordinal scale that is the first assessment of the clinical status on a given study day. The scale is as follows:
0 = Uninfected; no viral RNA detected
= Ambulatory; asymptomatic; viral RNA detected
= Ambulatory; symptomatic; independent
= Ambulatory; symptomatic; assistance needed
= Hospitalized; no oxygen therapy
= Hospitalized; oxygen by mask or nasal prongs
= Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow
= Hospitalized; intubation and mechanical ventilation, partial pressure of oxygen / fraction of inspired oxygen (pO2/FIO2) ≥ 150 or oxygen saturation / FIO2 (SpO2/FIO2) ≥ 200
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 < 150 or SpO2/FIO2 < 200 or vasopressors
= Hospitalized; intubation and mechanical ventilation, pO2/FIO2 < 150 or SpO2/FIO2 < 200 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO)
= Dead
measure: Time to Hospital Discharge
time frame: Up to 30 days after randomization
description: Time (days) to hospital discharge
measure: Safety of Crizanlizumab as Assessed by Adverse Events
time frame: Up to day 14 after randomization
description: Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.
arm group label: Crizanlizumab
arm group type: Experimental
description: Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.
arm group label: Placebo Saline
arm group type: Active Comparator
description: 0.9% saline 100 ml IV once.
intervention type: Drug
intervention name: Crizanlizumab
description: Crizanlizumab 5.0 mg/kg in 100 ml IV once.
arm group label: Crizanlizumab
intervention type: Other
intervention name: 0.9% saline
description: 0.9% saline 100 ml IV once.
arm group label: Placebo Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charles J Lowenstein, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
country: United States
citation: Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439. doi: 10.1056/NEJMoa1611770. Epub 2016 Dec 3.
PMID: 27959701
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 