<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/NCT04409509</url>
  </required_header>
  <id_info>
    <org_study_id>CSL312_COVID-19</org_study_id>
    <nct_id>NCT04409509</nct_id>
  </id_info>
  <brief_title>Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)</brief_title>
  <official_title>A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CSL Behring</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CSL Behring</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled,&#xD;
      parallel group study to assess the safety and efficacy of CSL312 administered intravenously,&#xD;
      in combination with standard of care (SOC) treatment, in patients with Coronavirus disease&#xD;
      2019 (COVID 19)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">January 12, 2021</completion_date>
  <primary_completion_date type="Actual">January 12, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation</measure>
    <time_frame>From randomization to Day 28</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants With Death From All Causes</measure>
    <time_frame>From randomization to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants With Tracheal Intubation</measure>
    <time_frame>From randomization to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale</measure>
    <time_frame>From randomization to Day 28</time_frame>
    <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID</measure>
    <time_frame>From randomization to Day 28</time_frame>
    <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Within Each of the Categories of the NIAID at End of Study</measure>
    <time_frame>Day 28</time_frame>
    <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants Within Each of the Categories of the NIAID at End of Study</measure>
    <time_frame>Day 28</time_frame>
    <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)</measure>
    <time_frame>From randomization to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)</measure>
    <time_frame>From randomization to Day 28</time_frame>
    <description>None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)</measure>
    <time_frame>From randomization to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score</measure>
    <time_frame>From randomization to Day 28</time_frame>
    <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in SOFA Total Score</measure>
    <time_frame>From randomization to Day 28</time_frame>
    <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Individual Components of SOFA Score</measure>
    <time_frame>From randomization to Day 28</time_frame>
    <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Hospital Stay</measure>
    <time_frame>From randomization to Day 28 (+/- 2 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Adverse Events (AEs)</measure>
    <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants Experiencing AEs</measure>
    <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Serious Adverse Events (SAEs)</measure>
    <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants Experiencing SAEs</measure>
    <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events of Special Interest (AESIs)</measure>
    <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants With AESIs</measure>
    <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-CSL312 Antibodies</measure>
    <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of CSL312</measure>
    <time_frame>Up to 28 days after CSL312 administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) of CSL312</measure>
    <time_frame>Up to 28 days after CSL312 administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312</measure>
    <time_frame>Up to 28 days after CSL312 administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-life (T1/2) of CSL312</measure>
    <time_frame>Up to 28 days after CSL312 administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">124</enrollment>
  <condition>Coronavirus Disease 2019 (COVID-19)</condition>
  <arm_group>
    <arm_group_label>CSL312</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>CSL312 diluent administered intravenously</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody</intervention_name>
    <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
    <arm_group_label>CSL312</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>CSL312 diluent administered intravenously</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection as&#xD;
             determined using a molecular diagnostic test (reverse transcription polymerase chain&#xD;
             reaction [RT-PCR] or equivalent) approved by regulatory authorities (including Food&#xD;
             and Drug Administration or Brazilian Health Regulatory Agency) or allowed under an&#xD;
             emergency use authorization within 14 days before Screening. If a false negative&#xD;
             result is suspected, the SARS-CoV-2 test may be repeated within the Screening Period.&#xD;
&#xD;
          -  Chest CT scan or X ray results confirming interstitial pneumonia&#xD;
&#xD;
          -  Severe COVID 19 disease as evidenced by ≥ 1 of the following criteria at Screening&#xD;
             including within 24 hours before Screening:&#xD;
&#xD;
               -  Respiratory frequency &gt; 30 breaths per minute&#xD;
&#xD;
               -  SpO2 ≤ 93% on room air&#xD;
&#xD;
               -  Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen&#xD;
                  (PaO2/FiO2) &lt; 300&#xD;
&#xD;
               -  Ratio of Arterial oxygen saturation to fraction of inspired oxygen (SaO2/FiO2&#xD;
                  ratio) &lt; 218 (if PaO2/FiO2 ratio is not available)&#xD;
&#xD;
               -  Radiographic lung infiltrates &gt; 50%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently enrolled, planning to enroll, or participated, within the last 30 days, in a&#xD;
             clinical study requiring administration of an IP, including expanded access or&#xD;
             compassionate use with the only exception being administration of convalescent plasma.&#xD;
             Administration of IP is permitted only if an emergency use authorization has been&#xD;
             granted (eg, remdesivir). Additionally, off label use of approved drugs (eg, anti IL&#xD;
             6/anti IL 6R) is also permitted.&#xD;
&#xD;
          -  Pregnant or breastfeeding (female subjects)&#xD;
&#xD;
          -  Intubated and require mechanical ventilation (including ECMO) at the time of&#xD;
             randomization&#xD;
&#xD;
          -  In the opinion of the investigator, the subject is expected to be intubated in the&#xD;
             first 24 hours after IMP administration&#xD;
&#xD;
          -  Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order&#xD;
&#xD;
          -  In the opinion of the investigator, not expected to survive for &gt; 48 hours after&#xD;
             admission&#xD;
&#xD;
          -  Presence of any of the following comorbid conditions prior to randomization and prior&#xD;
             to SARS CoV 2 infection:&#xD;
&#xD;
               -  Severe heart failure (New York Heart Association Class IV)&#xD;
&#xD;
               -  End stage renal disease (Stage ≥ 4) or need for renal replacement therapy&#xD;
&#xD;
               -  Biopsy confirmed cirrhosis, portal hypertension, or hepatic encephalopathy&#xD;
&#xD;
               -  Malignancy (Stage IV)&#xD;
&#xD;
               -  Chronic lung disease requiring the use of oxygen at home&#xD;
&#xD;
               -  Active tuberculosis disease&#xD;
&#xD;
          -  Active bleeding or a current clinically significant coagulopathy (eg, international&#xD;
             normalized ratio [INR] &gt; 1.5) or clinically significant risk for bleeding (eg, recent&#xD;
             intracranial hemorrhage or bleeding peptic ulcer within the last 4 weeks)&#xD;
&#xD;
          -  History of venous thrombosis, myocardial infarction or cerebrovascular event within 3&#xD;
             months, or a prothrombotic disorder (eg, antithrombin III, protein C or protein S&#xD;
             deficiency)&#xD;
&#xD;
          -  Known or suspected Grade 3 or 4 infusion-related reaction or hypersensitivity (per&#xD;
             Common Terminology Criteria for Adverse Events [CTCAE]) to monoclonal antibody&#xD;
             therapy, or hypersensitivity to the IMP or any excipients of the IMP&#xD;
&#xD;
          -  Currently receiving a therapy not permitted during the study.&#xD;
&#xD;
          -  Female subject of childbearing potential or fertile male subject either not using or&#xD;
             not willing to use an acceptable method of contraception to avoid pregnancy during the&#xD;
             study and for 90 days after receipt of the last dose of IMP&#xD;
&#xD;
          -  Any clinical or laboratory abnormality or other underlying conditions (eg,&#xD;
             psychological disorders, substance abuse) that would render the subject unsuitable for&#xD;
             participation in the study, in the opinion of the investigator&#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>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>CSL Behring</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nova Clinical Research, LLC</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theia Clinical Research, LLC</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33707</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MercyOne North Iowa Medical Center</name>
      <address>
        <city>Mason City</city>
        <state>Iowa</state>
        <zip>50401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northeast Iowa Medical Education Foundation</name>
      <address>
        <city>Waterloo</city>
        <state>Iowa</state>
        <zip>50702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Hospital and Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Name Hospital</name>
      <address>
        <city>Teaneck</city>
        <state>New Jersey</state>
        <zip>07666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inspira Health Center Vineland</name>
      <address>
        <city>Vineland</city>
        <state>New Jersey</state>
        <zip>08360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sisters of Charity Hospital/ St. Joseph's Campus</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Institute for Clinical Research</name>
      <address>
        <city>Fayetteville</city>
        <state>North Carolina</state>
        <zip>28304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monument Health Clinical Research</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PharmaTex Research</name>
      <address>
        <city>Amarillo</city>
        <state>Texas</state>
        <zip>79109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Health Science Center, McGovern Medical School</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Alexandria Hospital</name>
      <address>
        <city>Alexandria</city>
        <state>Virginia</state>
        <zip>22304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <results_first_submitted>December 23, 2021</results_first_submitted>
  <results_first_submitted_qc>January 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">January 24, 2022</results_first_posted>
  <last_update_submitted>January 20, 2022</last_update_submitted>
  <last_update_submitted_qc>January 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prevention of respiratory failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.&#xD;
Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.&#xD;
If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.</ipd_time_frame>
    <ipd_access_criteria>Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.&#xD;
An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.&#xD;
The requesting party must execute an appropriate data sharing agreement before IPD will be made available.</ipd_access_criteria>
  </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>September 16, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT04409509/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>August 28, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT04409509/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
        </group>
        <group group_id="P2">
          <title>CSL312</title>
          <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="61"/>
                <participants group_id="P2" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Failure to meet randomization requirement</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with study drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Randomized by mistake</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
        </group>
        <group group_id="B2">
          <title>CSL312</title>
          <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</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="61"/>
            <count group_id="B2" value="63"/>
            <count group_id="B3" value="124"/>
          </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="33"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="59"/>
                  </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="62.2" spread="12.74"/>
                    <measurement group_id="B2" value="62.7" spread="14.61"/>
                    <measurement group_id="B3" value="62.5" spread="13.67"/>
                  </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="20"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="93"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="12"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation</title>
        <time_frame>From randomization to Day 28</time_frame>
        <population>Intent-to-treat Analysis Set (ITT) comprises all subjects who were randomly assigned to treatment and who were assigned randomization numbers.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation</title>
          <population>Intent-to-treat Analysis Set (ITT) comprises all subjects who were randomly assigned to treatment and who were assigned randomization numbers.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.2"/>
                    <measurement group_id="O2" value="22.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants With Death From All Causes</title>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants With Death From All Causes</title>
          <population>ITT</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.0"/>
                    <measurement group_id="O2" value="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants With Tracheal Intubation</title>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants With Tracheal Intubation</title>
          <population>ITT</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.6"/>
                    <measurement group_id="O2" value="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale</title>
        <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale</title>
          <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
          <population>ITT</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID</title>
        <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID</title>
          <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
          <population>ITT</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.1"/>
                    <measurement group_id="O2" value="66.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Within Each of the Categories of the NIAID at End of Study</title>
        <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
        <time_frame>Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Within Each of the Categories of the NIAID at End of Study</title>
          <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
          <population>ITT</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, on Invasive Mechanical Ventilation or ECMO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, Requiring Supplemental Oxygen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care</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>Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care</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>Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hospitalized, no Limitations on Activities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Done</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants Within Each of the Categories of the NIAID at End of Study</title>
        <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
        <time_frame>Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants Within Each of the Categories of the NIAID at End of Study</title>
          <description>The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.</description>
          <population>ITT</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.0"/>
                    <measurement group_id="O2" value="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, on Invasive Mechanical Ventilation or ECMO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3"/>
                    <measurement group_id="O2" value="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, Requiring Supplemental Oxygen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care</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>Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care</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>Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.0"/>
                    <measurement group_id="O2" value="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hospitalized, no Limitations on Activities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.0"/>
                    <measurement group_id="O2" value="41.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Done</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.2"/>
                    <measurement group_id="O2" value="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)</title>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)</title>
          <population>ITT</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.4"/>
                    <measurement group_id="O2" value="19.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)</title>
        <description>None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.</description>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT. None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)</title>
          <description>None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.</description>
          <population>ITT. None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <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>Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)</title>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)</title>
          <population>ITT</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.0"/>
                    <measurement group_id="O2" value="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score</title>
        <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT. Participants with missing values were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score</title>
          <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
          <population>ITT. Participants with missing values were not included in the analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="1.54"/>
                    <measurement group_id="O2" value="0.1" spread="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in SOFA Total Score</title>
        <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT. Participants with missing values were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in SOFA Total Score</title>
          <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
          <population>ITT. Participants with missing values were not included in the analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="1.77"/>
                    <measurement group_id="O2" value="-1.3" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Individual Components of SOFA Score</title>
        <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
        <time_frame>From randomization to Day 28</time_frame>
        <population>ITT. Participants with missing values were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Individual Components of SOFA Score</title>
          <description>The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.</description>
          <population>ITT. Participants with missing values were not included in the analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Respiration Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="1.32"/>
                    <measurement group_id="O2" value="-1.2" spread="1.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Coagulation Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.42"/>
                    <measurement group_id="O2" value="0.4" spread="1.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Liver Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.22"/>
                    <measurement group_id="O2" value="0.0" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cardiovascular Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="1.65"/>
                    <measurement group_id="O2" value="0.5" spread="1.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Central Nervous System Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.00"/>
                    <measurement group_id="O2" value="0.0" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Renal Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="0.93"/>
                    <measurement group_id="O2" value="0.5" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Hospital Stay</title>
        <time_frame>From randomization to Day 28 (+/- 2 days)</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Hospital Stay</title>
          <population>ITT</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.00" lower_limit="0" upper_limit="29"/>
                    <measurement group_id="O2" value="6.50" lower_limit="0" upper_limit="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Adverse Events (AEs)</title>
        <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
        <population>The Safety Analysis Set (SA) comprises all subjects in the ITT Analysis Set who receive any amount of CSL312 or placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Adverse Events (AEs)</title>
          <population>The Safety Analysis Set (SA) comprises all subjects in the ITT Analysis Set who receive any amount of CSL312 or placebo.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants Experiencing AEs</title>
        <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
        <population>SA</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants Experiencing AEs</title>
          <population>SA</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.8"/>
                    <measurement group_id="O2" value="60.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Serious Adverse Events (SAEs)</title>
        <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
        <population>SA</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Serious Adverse Events (SAEs)</title>
          <population>SA</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants Experiencing SAEs</title>
        <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
        <population>SA</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants Experiencing SAEs</title>
          <population>SA</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.2"/>
                    <measurement group_id="O2" value="34.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events of Special Interest (AESIs)</title>
        <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
        <population>SA</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events of Special Interest (AESIs)</title>
          <population>SA</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants With AESIs</title>
        <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
        <population>SA</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants With AESIs</title>
          <population>SA</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.2"/>
                    <measurement group_id="O2" value="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Anti-CSL312 Antibodies</title>
        <time_frame>Up to 28 days after CSL312 or placebo administration</time_frame>
        <population>The pharmacodynamic (PD) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for analysis of biomarkers.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
          </group>
          <group group_id="O2">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-CSL312 Antibodies</title>
          <population>The pharmacodynamic (PD) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for analysis of biomarkers.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration (Cmax) of CSL312</title>
        <time_frame>Up to 28 days after CSL312 administration</time_frame>
        <population>The pharmacokinetic (PK) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for CSL312 concentration measurement.</population>
        <group_list>
          <group group_id="O1">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of CSL312</title>
          <population>The pharmacokinetic (PK) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for CSL312 concentration measurement.</population>
          <units>ug/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="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="147.335" spread="77.1286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration (Tmax) of CSL312</title>
        <time_frame>Up to 28 days after CSL312 administration</time_frame>
        <population>PK</population>
        <group_list>
          <group group_id="O1">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax) of CSL312</title>
          <population>PK</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.667" lower_limit="0.28" upper_limit="139.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312</title>
        <time_frame>Up to 28 days after CSL312 administration</time_frame>
        <population>PK</population>
        <group_list>
          <group group_id="O1">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312</title>
          <population>PK</population>
          <units>h*ug/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="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15806.644" spread="9393.6295"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-life (T1/2) of CSL312</title>
        <time_frame>Up to 28 days after CSL312 administration</time_frame>
        <population>PK. Participants with missing values were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>CSL312</title>
            <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life (T1/2) of CSL312</title>
          <population>PK. Participants with missing values were not included in the analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="226.165" spread="102.6690"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 28 days per participant after CSL312 or placebo administration</time_frame>
      <desc>All-Cause mortality uses ITT set and treatment emergent adverse events uses the safety analysis set.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>CSL312 diluent administered intravenously&#xD;
Placebo: CSL312 diluent administered intravenously</description>
        </group>
        <group group_id="E2">
          <title>CSL312</title>
          <description>Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously&#xD;
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</default_vocab>
        <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="11" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Disseminated intravascular coagulation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Enterobacter bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Enterobacter pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Pneumonia escherichia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Pneumonia streptococcal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Brain hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Cerebellar infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Haemorrhagic stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Arterial thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Peripheral artery thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Venous thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.1</default_vocab>
        <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="21" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Fibrin D dimer increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
              </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 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>Study Director</name_or_title>
      <organization>CSL Behring</organization>
      <phone>610-878-4000</phone>
      <email>clinicaltrials@cslbehring.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/NCT04409509
org study id: CSL312_COVID-19
nct id: NCT04409509
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled,
      parallel group study to assess the safety and efficacy of CSL312 administered intravenously,
      in combination with standard of care (SOC) treatment, in patients with Coronavirus disease
      2019 (COVID 19)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation
time frame: From randomization to Day 28
measure: Percent of Participants With Death From All Causes
time frame: From randomization to Day 28
measure: Percent of Participants With Tracheal Intubation
time frame: From randomization to Day 28
measure: Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale
time frame: From randomization to Day 28
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
measure: Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID
time frame: From randomization to Day 28
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
measure: Number of Participants Within Each of the Categories of the NIAID at End of Study
time frame: Day 28
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
measure: Percent of Participants Within Each of the Categories of the NIAID at End of Study
time frame: Day 28
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
measure: Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
time frame: From randomization to Day 28
measure: Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)
time frame: From randomization to Day 28
description: None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.
measure: Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)
time frame: From randomization to Day 28
measure: Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score
time frame: From randomization to Day 28
description: The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
measure: Change From Baseline in SOFA Total Score
time frame: From randomization to Day 28
description: The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
measure: Change From Baseline in the Individual Components of SOFA Score
time frame: From randomization to Day 28
description: The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
measure: Length of Hospital Stay
time frame: From randomization to Day 28 (+/- 2 days)
measure: Number of Participants Experiencing Adverse Events (AEs)
time frame: Up to 28 days after CSL312 or placebo administration
measure: Percent of Participants Experiencing AEs
time frame: Up to 28 days after CSL312 or placebo administration
measure: Number of Participants Experiencing Serious Adverse Events (SAEs)
time frame: Up to 28 days after CSL312 or placebo administration
measure: Percent of Participants Experiencing SAEs
time frame: Up to 28 days after CSL312 or placebo administration
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
time frame: Up to 28 days after CSL312 or placebo administration
measure: Percent of Participants With AESIs
time frame: Up to 28 days after CSL312 or placebo administration
measure: Number of Participants With Anti-CSL312 Antibodies
time frame: Up to 28 days after CSL312 or placebo administration
measure: Maximum Plasma Concentration (Cmax) of CSL312
time frame: Up to 28 days after CSL312 administration
measure: Time to Maximum Plasma Concentration (Tmax) of CSL312
time frame: Up to 28 days after CSL312 administration
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312
time frame: Up to 28 days after CSL312 administration
measure: Terminal Half-life (T1/2) of CSL312
time frame: Up to 28 days after CSL312 administration
arm group label: CSL312
arm group type: Experimental
description: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
arm group label: Placebo
arm group type: Placebo Comparator
description: CSL312 diluent administered intravenously
intervention type: Biological
intervention name: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
description: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
arm group label: CSL312
intervention type: Drug
intervention name: Placebo
description: CSL312 diluent administered intravenously
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: CSL Behring
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Antibodies
mesh term: Antibodies, Monoclonal
sharing ipd: Yes
ipd description: CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.
If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
ipd access criteria: Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.
An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.
The requesting party must execute an appropriate data sharing agreement before IPD will be made available.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 