<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/NCT04402060</url>
  </required_header>
  <id_info>
    <org_study_id>APL9-COV-201</org_study_id>
    <nct_id>NCT04402060</nct_id>
  </id_info>
  <brief_title>A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19</brief_title>
  <official_title>A Randomized, Double-Blinded, Vehicle-Controlled, Multicenter, Parallel-Group Study of APL-9 in Mild to Moderate Acute Respiratory Distress Syndrome Due to COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Apellis Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Apellis Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and effectiveness of APL-9 in adults with&#xD;
      mild to moderate ARDS (acute respiratory distress syndrome) caused by COVID-19 who are&#xD;
      hospitalized and require supplemental oxygen therapy with or without mechanical ventilation.&#xD;
&#xD;
      It is thought that COVID-19 activates the complement system, part of the immune system that&#xD;
      responds to infection or tissue damage, and increases inflammation in the lungs. APL-9 has&#xD;
      been designed to inhibit or block activation of part of the complement pathway, and&#xD;
      potentially reduce inflammation in the lungs.&#xD;
&#xD;
      Part 1 of the study is open-label to evaluate safety; all participants will receive APL-9&#xD;
      plus standard of care. Part 2 of the study is double-blind, randomized; participants will&#xD;
      receive either APL-9 or the vehicle-control plus standard of care.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 28, 2020</start_date>
  <completion_date type="Actual">February 13, 2021</completion_date>
  <primary_completion_date type="Actual">February 13, 2021</primary_completion_date>
  <phase>Phase 1/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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs</measure>
    <time_frame>From the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58</time_frame>
    <description>TEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hospital Length of Stay</measure>
    <time_frame>Part 2: Day 1 up to Day 58</time_frame>
    <description>Hospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days])</time_frame>
    <description>Overall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time</measure>
    <time_frame>Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)</time_frame>
    <description>The SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Duration of Mechanical Ventilation</measure>
    <time_frame>Part 2: Day 1 up to Day 58</time_frame>
    <description>Total duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Duration of Oxygen Therapy</measure>
    <time_frame>Part 2: Day 1 up to Day 58</time_frame>
    <description>Total duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of APL-9 Over Time</measure>
    <time_frame>Part 1: Day 1 (pre- and post-dose) and Days 3, 5 and 7 (including EOT visit); Part 2: Day 1 (pre- and post-dose) and Days 3, 5, 7, 11, 15 and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC)</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6)</measure>
    <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
    <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>COVID</condition>
  <condition>Covid-19</condition>
  <condition>Coronavirus</condition>
  <condition>Coronavirus Infection</condition>
  <condition>Severe Acute Respiratory Syndrome</condition>
  <condition>Severe Acute Respiratory Syndrome Coronavirus 2</condition>
  <condition>Sars-CoV2</condition>
  <condition>Ards</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>180 mg APL-9 IV plus SOC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Isotonic saline plus SOC</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>APL-9</intervention_name>
    <description>Complement (C3) Inhibitor</description>
    <arm_group_label>180 mg APL-9 IV plus SOC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Vehicle Control</intervention_name>
    <description>Normal saline of equal volume to active arm</description>
    <arm_group_label>Isotonic saline plus SOC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be at least 18 years of age at time of informed consent&#xD;
&#xD;
          -  Diagnosis of active SARS CoV 2 infection using viral RNA or viral antigen within 7&#xD;
             days of screening&#xD;
&#xD;
          -  Respiratory failure requiring oxygen supplementation or either invasive or noninvasive&#xD;
             mechanical ventilation with PaO2/FiO2 ratio &gt;100 mm Hg. Respiratory failure cannot be&#xD;
             fully explained by cardiac failure or fluid overload.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with immune checkpoint inhibitors, or other immunomodulators within 3 months&#xD;
             prior to study enrollment (however, treatment with convalescent plasma, steroids, IL-6&#xD;
             inhibitors, and antiviral agents is NOT excluded)&#xD;
&#xD;
          -  Active bacterial, fungal, or parasitic infection&#xD;
&#xD;
          -  History of neuromuscular degenerative disease (eg, amyotrophic lateral sclerosis,&#xD;
             Duchenne muscular dystrophy, or multiple sclerosis)&#xD;
&#xD;
          -  Current participation in an interventional clincial trial&#xD;
&#xD;
          -  Subjects who have, at screening, been on mechanical ventilation for &gt;7 days Have&#xD;
             evidence of kidney and liver failure at screening&#xD;
&#xD;
          -  Have a hereditary complement deficiency&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of California at San Francisco - Fresno</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Pacific Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Medical Center Beaches</name>
      <address>
        <city>Jacksonville Beach</city>
        <state>Florida</state>
        <zip>32250</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westchester General Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>40241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University, Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lutheran Health Physicians</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Women's and Children's Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Audobon Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge Medical Trials</name>
      <address>
        <city>Alexandria</city>
        <state>Louisiana</state>
        <zip>71301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Providence Hospital</name>
      <address>
        <city>Southfield</city>
        <state>Michigan</state>
        <zip>48075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers University - Robert Wood Johnson Medical School</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University at Buffalo</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas A&amp;M College of Medicine - Scott and White</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Angelina Caron</name>
      <address>
        <city>Campina Grande Do Sul</city>
        <state>Paraná</state>
        <zip>83430-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irmandade da Santa Casa de Misericordia de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90020-090</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital São Lucas da PUCRS</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>91530-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Estadual Mario Covas</name>
      <address>
        <city>Santo André</city>
        <state>Sao Paulo</state>
        <zip>09190-615</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CEMEC - Centro Multidisciplinar de Estudos Clinicos LTDA EPP</name>
      <address>
        <city>São Bernardo Do Campo</city>
        <state>Sao Paulo</state>
        <zip>0917-090</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Alemao Oswaldo Cruz</name>
      <address>
        <city>São Paulo</city>
        <state>Sao Paulo</state>
        <zip>01323-020</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Marcelina</name>
      <address>
        <city>São Paulo</city>
        <state>Sao Paulo</state>
        <zip>08270-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP</name>
      <address>
        <city>Botucatu</city>
        <state>São Paulo</state>
        <zip>18618-686</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <results_first_submitted>January 4, 2022</results_first_submitted>
  <results_first_submitted_qc>March 21, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 23, 2022</results_first_posted>
  <last_update_submitted>March 21, 2022</last_update_submitted>
  <last_update_submitted_qc>March 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <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>November 9, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT04402060/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>May 11, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT04402060/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a randomized, double-blind, vehicle-controlled, multicenter, parallel-group Phase 1/2 study (with an initial open-label period) evaluating the safety and efficacy of APL-9 versus (vs) vehicle control as an add-on therapy to standard of care (SoC) in subjects who had respiratory failure, including mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).</recruitment_details>
      <pre_assignment_details>The study was conducted in 2 parts: Subjects in Part 1 received open-label APL-9 from Day 1 through Day 7 or resolution of ARDS. Subjects in Part 2 were randomly assigned 1:1 to blinded treatment with either APL-9 or vehicle control from Day 1 through Day 7 or up to and including Day 21, discontinuation of respiratory support or hospital discharge, whichever occurred latest. Extended treatment beyond Day 7 in Part 2 required certain criteria to be met and was at discretion of the Investigator.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1: APL-9</title>
          <description>Subjects received an initial intravenous (IV) infusion of 180 milligram (mg) APL-9 in 50 milliliter (mL) of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2] ratio &gt;300 millimeter [mm] of mercury [Hg]), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
        <group group_id="P2">
          <title>Part 2: APL-9</title>
          <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
        <group group_id="P3">
          <title>Part 2: Control</title>
          <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="34"/>
                <participants group_id="P3" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Treatment</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="33"/>
                <participants group_id="P3" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="18"/>
                <participants group_id="P3" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="7"/>
              </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="0"/>
                <participants group_id="P3" count="1"/>
              </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="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor Request</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received.</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1: APL-9</title>
          <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
        <group group_id="B2">
          <title>Part 2: APL-9</title>
          <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
        <group group_id="B3">
          <title>Part 2: Control</title>
          <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
        <group group_id="B4">
          <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="6"/>
            <count group_id="B2" value="33"/>
            <count group_id="B3" value="32"/>
            <count group_id="B4" value="71"/>
          </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="32"/>
                  </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="3"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="38"/>
                  </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="2"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian/Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black/African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian/Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unspecified</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs</title>
        <description>TEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.</description>
        <time_frame>From the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58</time_frame>
        <population>The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs</title>
          <description>TEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.</description>
          <population>The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="23"/>
                    <measurement group_id="O3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospital Length of Stay</title>
        <description>Hospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.</description>
        <time_frame>Part 2: Day 1 up to Day 58</time_frame>
        <population>The full analysis set (FAS) included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Hospital Length of Stay</title>
          <description>Hospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.</description>
          <population>The full analysis set (FAS) included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.5" lower_limit="8.0" upper_limit="47.0"/>
                    <measurement group_id="O2" value="15.5" lower_limit="9.0" upper_limit="30.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [&lt;65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% confidence interval (CI) was based on the Wald method.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.82</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.98</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.63</ci_lower_limit>
            <ci_upper_limit>1.51</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.</description>
        <time_frame>Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days])</time_frame>
        <population>The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.</description>
          <population>The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="27.0" upper_limit="NA">The upper CI and median were not calculable due to insufficient events.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">The lower and upper CIs and median were not calculable due to insufficient events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [&lt;65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.36</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.62</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.77</ci_lower_limit>
            <ci_upper_limit>3.40</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time</title>
        <description>The SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.</description>
        <time_frame>Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)</time_frame>
        <population>The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. Only subjects with values at both Baseline and the specified visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: APL-9 Plus SoC</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. Follow-up safety assessments were collected 30 days following the last dose of study treatment (with a +7-day window). All subjects received SoC independent of their randomization.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Vehicle Control Plus SoC</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. Follow-up safety assessments were collected 30 days following the last dose of study treatment (with a +7-day window). All subjects received SoC independent of their randomization.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time</title>
          <description>The SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.</description>
          <population>The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. Only subjects with values at both Baseline and the specified visit were 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="31"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change to Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="2.17"/>
                    <measurement group_id="O2" value="1.2" spread="2.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change to Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="3.00"/>
                    <measurement group_id="O2" value="0.6" spread="2.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change to Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="3.97"/>
                    <measurement group_id="O2" value="0.9" spread="3.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change to Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" spread="2.08"/>
                    <measurement group_id="O2" value="0.2" spread="5.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change to Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="2.83"/>
                    <measurement group_id="O2" value="-1.0" spread="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change to EOT</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="3.56"/>
                    <measurement group_id="O2" value="0.6" spread="3.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Duration of Mechanical Ventilation</title>
        <description>Total duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.</description>
        <time_frame>Part 2: Day 1 up to Day 58</time_frame>
        <population>The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Duration of Mechanical Ventilation</title>
          <description>Total duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.</description>
          <population>The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0" lower_limit="NA" upper_limit="NA">The lower and upper CIs were not calculable due to insufficient events.</measurement>
                    <measurement group_id="O2" value="8.5" lower_limit="7.0" upper_limit="NA">The upper CI was not calculable due to insufficient events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [&lt;65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.09</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.01</ci_lower_limit>
            <ci_upper_limit>0.51</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Duration of Oxygen Therapy</title>
        <description>Total duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.</description>
        <time_frame>Part 2: Day 1 up to Day 58</time_frame>
        <population>The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Duration of Oxygen Therapy</title>
          <description>Total duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.</description>
          <population>The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" lower_limit="5.0" upper_limit="47.0"/>
                    <measurement group_id="O2" value="8.0" lower_limit="7.0" upper_limit="NA">The upper CI was not calculable due to insufficient events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [&lt;65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.93</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.09</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.69</ci_lower_limit>
            <ci_upper_limit>1.72</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Concentration of APL-9 Over Time</title>
        <description>To evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.</description>
        <time_frame>Part 1: Day 1 (pre- and post-dose) and Days 3, 5 and 7 (including EOT visit); Part 2: Day 1 (pre- and post-dose) and Days 3, 5, 7, 11, 15 and EOT visit (up to Day 21)</time_frame>
        <population>The PK set included all subjects in the safety set and for whom at least 1 PK sample was evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Concentration of APL-9 Over Time</title>
          <description>To evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.</description>
          <population>The PK set included all subjects in the safety set and for whom at least 1 PK sample was evaluable.</population>
          <units>micrograms (μg)/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1, Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="30"/>
                    <count group_id="O3" value="30"/>
                  </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="3.9" spread="11.72"/>
                    <measurement group_id="O3" value="0.0" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1, 10 mins</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="29"/>
                    <count group_id="O3" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.1" spread="14.00"/>
                    <measurement group_id="O2" value="77.7" spread="168.78"/>
                    <measurement group_id="O3" value="2.6" spread="13.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1, 2 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="26"/>
                    <count group_id="O3" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.2" spread="14.21"/>
                    <measurement group_id="O2" value="54.1" spread="17.28"/>
                    <measurement group_id="O3" value="2.2" spread="12.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="23"/>
                    <count group_id="O3" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.0" spread="11.03"/>
                    <measurement group_id="O2" value="87.7" spread="31.87"/>
                    <measurement group_id="O3" value="5.0" spread="24.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="18"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.5" spread="8.14"/>
                    <measurement group_id="O2" value="103.7" spread="21.95"/>
                    <measurement group_id="O3" value="2.3" spread="10.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116.0" spread="2.83"/>
                    <measurement group_id="O2" value="121.6" spread="28.71"/>
                    <measurement group_id="O3" value="2.3" spread="8.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="115.3" spread="24.54"/>
                    <measurement group_id="O3" value="2.6" spread="5.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="2"/>
                    <count group_id="O3" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="133.4" spread="60.25"/>
                    <measurement group_id="O3" value="2.4" spread="3.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>EOT</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="21"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.5" spread="16.21"/>
                    <measurement group_id="O2" value="95.0" spread="34.19"/>
                    <measurement group_id="O3" value="0.0" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4</title>
        <description>To evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4</title>
          <description>To evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>mg/deciliter (dL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>C3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.0" spread="11.17"/>
                    <measurement group_id="O2" value="91.4" spread="64.00"/>
                    <measurement group_id="O3" value="2.1" spread="35.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="19.30"/>
                    <measurement group_id="O2" value="-3.9" spread="16.34"/>
                    <measurement group_id="O3" value="0.2" spread="15.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC)</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Note: C5a was only measured in Part 2 because this biomarker was added in APL9-COV-201 Protocol Amendment 2 which was after the last subject in Part 1 finished the last study dose. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC)</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Note: C5a was only measured in Part 2 because this biomarker was added in APL9-COV-201 Protocol Amendment 2 which was after the last subject in Part 1 finished the last study dose. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>nanograms (ng)/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>C3a</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-69.6" spread="16.35"/>
                    <measurement group_id="O2" value="-357.6" spread="785.69"/>
                    <measurement group_id="O3" value="-4.0" spread="240.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C4a</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-337.7" spread="371.70"/>
                    <measurement group_id="O2" value="-1560.8" spread="4821.35"/>
                    <measurement group_id="O3" value="-87.0" spread="1028.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C5a</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-6.9" spread="14.88"/>
                    <measurement group_id="O3" value="-3.9" spread="9.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TCC</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-143.1" spread="87.41"/>
                    <measurement group_id="O2" value="-127.4" spread="121.90"/>
                    <measurement group_id="O3" value="-12.2" spread="337.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>μg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="0.13"/>
                    <measurement group_id="O2" value="-0.9" spread="0.74"/>
                    <measurement group_id="O3" value="-0.1" spread="1.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>Units (U)/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="3"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-157.7" spread="26.84"/>
                    <measurement group_id="O2" value="-84.3" spread="44.51"/>
                    <measurement group_id="O3" value="-2.3" spread="43.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>% of reticulocytes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="10325.4" spread="20649.77"/>
                    <measurement group_id="O3" value="23929.1" spread="87585.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>10^9 cells/liter (L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="0.0" spread="NA">Standard deviation was not calculated due to only 1 subject analyzed</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-464.6" spread="427.86"/>
                    <measurement group_id="O2" value="-135.2" spread="186.90"/>
                    <measurement group_id="O3" value="-106.1" spread="205.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>D-dimer</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-783.8" spread="607.57"/>
                    <measurement group_id="O2" value="217.2" spread="1218.54"/>
                    <measurement group_id="O3" value="907.9" spread="2986.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ferritin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-133.6" spread="80.80"/>
                    <measurement group_id="O2" value="-53.1" spread="650.97"/>
                    <measurement group_id="O3" value="-19.3" spread="694.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Haptoglobin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="7"/>
                    <count group_id="O3" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-5435.4" spread="7571.18"/>
                    <measurement group_id="O3" value="-4554.0" spread="7756.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fibrinogen</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="14"/>
                    <count group_id="O3" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-147.3" spread="170.55"/>
                    <measurement group_id="O2" value="3995.1" spread="15113.49"/>
                    <measurement group_id="O3" value="-1348.2" spread="9726.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.0" spread="8.67"/>
                    <measurement group_id="O2" value="6.4" spread="41.21"/>
                    <measurement group_id="O3" value="-3.1" spread="18.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6)</title>
        <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.</description>
        <time_frame>Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)</time_frame>
        <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: APL-9</title>
            <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Control</title>
            <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6)</title>
          <description>To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.</description>
          <population>The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.</population>
          <units>picograms/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="0"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TNFα</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="19.6" spread="62.24"/>
                    <measurement group_id="O3" value="10.4" spread="73.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1β</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-0.6" spread="7.15"/>
                    <measurement group_id="O3" value="-8.1" spread="22.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="203.6" spread="602.54"/>
                    <measurement group_id="O3" value="71.3" spread="499.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58.</time_frame>
      <desc>The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part 1: APL-9</title>
          <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio &gt;300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
        <group group_id="E2">
          <title>Part 2: APL-9</title>
          <description>Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions</description>
        </group>
        <group group_id="E3">
          <title>Part 2: Control</title>
          <description>Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (23.0)</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="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pulseless electrical activity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Right ventricular dilatation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Cardiac valve vegetation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Fungaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumonia pseudomonal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pseudomonas infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood pH decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Glomerular filtration rate decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </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" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </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" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Distributive shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Embolism venous</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (23.0)</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="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood loss anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Heparin-induced thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Neutrophilia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Cardiogenic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Lice infestation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Nosocomial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumonia staphylococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Vulvovaginal mycotic infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Tissue injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Vascular access complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Fibrin D dimer increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Serum ferritin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Anion gap increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Antibiotic level below therapeutic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood pH increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood phosphorus decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood sodium decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood sodium increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Brain natriuretic peptide increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Drug trough level</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Electrocardiogram ST segment elevation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Eosinophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Haematocrit decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Monocyte count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Neutrophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Platelet count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Procalcitonin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Troponin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Alkalosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Calcium deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Metabolic alkalosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Toxic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hallucination, visual</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </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" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Azotaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Oliguria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Bronchial secretion retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hypercapnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumomediastinum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Respiratory acidosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Respiratory disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Dermatitis diaper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Subcutaneous emphysema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Distributive shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Poor peripheral circulation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Venous thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="32"/>
              </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>Apellis Clinical Trial Information Line</name_or_title>
      <organization>Apellis Pharmaceuticals, Inc</organization>
      <phone>1-833-284-6361</phone>
      <email>clinicaltrials@apellis.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/NCT04402060
org study id: APL9-COV-201
nct id: NCT04402060
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety and effectiveness of APL-9 in adults with
      mild to moderate ARDS (acute respiratory distress syndrome) caused by COVID-19 who are
      hospitalized and require supplemental oxygen therapy with or without mechanical ventilation.

      It is thought that COVID-19 activates the complement system, part of the immune system that
      responds to infection or tissue damage, and increases inflammation in the lungs. APL-9 has
      been designed to inhibit or block activation of part of the complement pathway, and
      potentially reduce inflammation in the lungs.

      Part 1 of the study is open-label to evaluate safety; all participants will receive APL-9
      plus standard of care. Part 2 of the study is double-blind, randomized; participants will
      receive either APL-9 or the vehicle-control plus standard of care.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
time frame: From the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58
description: TEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.
measure: Hospital Length of Stay
time frame: Part 2: Day 1 up to Day 58
description: Hospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.
measure: Overall Survival
time frame: Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days])
description: Overall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.
measure: Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time
time frame: Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)
description: The SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.
measure: Total Duration of Mechanical Ventilation
time frame: Part 2: Day 1 up to Day 58
description: Total duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.
measure: Total Duration of Oxygen Therapy
time frame: Part 2: Day 1 up to Day 58
description: Total duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.
measure: Serum Concentration of APL-9 Over Time
time frame: Part 1: Day 1 (pre- and post-dose) and Days 3, 5 and 7 (including EOT visit); Part 2: Day 1 (pre- and post-dose) and Days 3, 5, 7, 11, 15 and EOT visit (up to Day 21)
description: To evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4
time frame: Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC)
time frame: Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb
time frame: Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.
measure: Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.
measure: Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6)
time frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
description: To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.
arm group label: 180 mg APL-9 IV plus SOC
arm group type: Experimental
arm group label: Isotonic saline plus SOC
arm group type: Placebo Comparator
intervention type: Drug
intervention name: APL-9
description: Complement (C3) Inhibitor
arm group label: 180 mg APL-9 IV plus SOC
intervention type: Other
intervention name: Vehicle Control
description: Normal saline of equal volume to active arm
arm group label: Isotonic saline plus SOC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Brazil
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
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