<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/NCT04463004</url>
  </required_header>
  <id_info>
    <org_study_id>HM20019145</org_study_id>
    <nct_id>NCT04463004</nct_id>
  </id_info>
  <brief_title>Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation</brief_title>
  <official_title>Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kiniksa Pharmaceuticals, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled&#xD;
      study is to demonstrate that early treatment with mavrilimumab prevents progression of&#xD;
      respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological&#xD;
      features of hyper-inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective, Phase 2, multi-center, blinded randomized placebo-controlled study is&#xD;
      designed to demonstrate that early treatment with mavrilimumab prevents progression of&#xD;
      respiratory failure in patients with severe Covid-19 pneumonia and clinical and biological&#xD;
      features of hyper-inflammation.&#xD;
&#xD;
      The study population includes patients who have severe pneumonia, defined as hospitalization&#xD;
      due to Covid-19 with abnormal chest imaging and SpO2 &lt;92% on room air or requirement for&#xD;
      supplemental oxygen.&#xD;
&#xD;
      Enrollment: The study will be performed in approximately 4 months total, starting from the&#xD;
      first patient enrolled with enrollment expected to complete within 2 months.&#xD;
&#xD;
      Follow-up period: The follow-up period is 60 days for each patient enrolled.&#xD;
&#xD;
      A total of 60 patients will be randomized using a 1:1 allocation ratio: 30 subjects will&#xD;
      receive mavrilimumab, and 30 subjects will receive placebo infusion. The investigator,&#xD;
      clinical team, and subject will be blinded to treatment assignment.&#xD;
&#xD;
      Participants will be identified by regular review of hospitalized COVID19 patients to&#xD;
      evaluate for inclusion and exclusion criteria. Participants will then be approached in the&#xD;
      standard manner by study investigator and coordinator/research nurse.&#xD;
&#xD;
      Research interventions will take place in the hospital in accordance with privacy standards.&#xD;
&#xD;
      The study team is informed on all study procedures and requirements with daily meetings and&#xD;
      the opportunity to continuously update through secure channels.&#xD;
&#xD;
      In this multicenter consortium, each participating site will have their own IND for patients&#xD;
      enrolled at their site. Data collection, data analysis, and randomization scheme will be&#xD;
      performed by one site, Cleveland Clinic C5 Research.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2, 2020</start_date>
  <completion_date type="Actual">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">November 30, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Subjects Alive and Off of Oxygen at Day 14</measure>
    <time_frame>14 days</time_frame>
    <description>Number of subjects alive and off of oxygen</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects Alive and Without Respiratory Failure at 28 Days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of subjects alive and without respiratory failure</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>COVID-19</condition>
  <condition>Sars-CoV2</condition>
  <condition>Pneumonia</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mavrilimumab</intervention_name>
    <description>Treatment infusion</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>KPL-301</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebo infusion</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent must be obtained before any assessment is performed&#xD;
&#xD;
          2. Documented COVID19 pneumonia defined as positive SARS-CoV2 test AND abnormalities/&#xD;
             infiltrates on chest x-ray or computed tomography AND active fever or documented fever&#xD;
             within 24-48 hours or ongoing anti-pyretic use to suppress fever&#xD;
&#xD;
          3. Hypoxia (Room air SpO2 &lt;92% or requirement for supplemental oxygen)&#xD;
&#xD;
          4. Increased serum inflammatory marker (CRP &gt; 5 mg/dL)&#xD;
&#xD;
          5. Severity of disease warrants inpatient hospitalization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Onset of COVID-19 symptoms &gt;14 days&#xD;
&#xD;
          2. Age &lt; 18 years-old&#xD;
&#xD;
          3. Hospitalized &gt;7 days&#xD;
&#xD;
          4. Mechanically ventilated&#xD;
&#xD;
          5. Serious concomitant illness which in the opinion of the investigator precludes the&#xD;
             patient from enrolling in the trial, including (but not limited to):&#xD;
&#xD;
               -  History of immunodeficiency (congenital or acquired)&#xD;
&#xD;
               -  Neutropenia (absolute neutrophil count &lt;1,500/mm3)&#xD;
&#xD;
               -  History of solid-organ or bone marrow transplant&#xD;
&#xD;
               -  History of current systemic autoimmune or autoinflammatory disease(s) requiring&#xD;
                  systemic immune-modulating drugs&#xD;
&#xD;
               -  History of myeloproliferative disorder or active malignancy receiving cytotoxic&#xD;
                  chemotherapy&#xD;
&#xD;
               -  Pre-existing severe pulmonary disease (i.e. steroid dependent asthma, COPD on&#xD;
                  home oxygen, or other restrictive/obstructive lung disease requiring home oxygen)&#xD;
&#xD;
               -  Pre-existing severe left ventricular systolic dysfunction (i.e. LVEF &lt;35%)&#xD;
&#xD;
               -  Known or suspected active tuberculosis (TB), latent TB, or history of&#xD;
                  incompletely treated TB or at high risk for latent TB (from exposure or prior&#xD;
                  incarceration)&#xD;
&#xD;
               -  History of active or latent viral hepatitis (i.e. Hepatitis B or C)&#xD;
&#xD;
               -  Concomitant uncontrolled systemic bacterial or fungal infection&#xD;
&#xD;
               -  Concomitant viral infection other than COVID-19 (e.g. Influenza, other&#xD;
                  respiratory viruses)&#xD;
&#xD;
               -  History of chronic liver disease with portal hypertension&#xD;
&#xD;
               -  History of end-stage renal disease on chronic renal replacement therapy&#xD;
&#xD;
          6. Recent treatment with cell-depleting biological therapies (e.g., anti-CD20) within 12&#xD;
             months, cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF],&#xD;
             anakinra, anti-Interleukin [IL]-6 receptor [e.g. tocilizumab], or abatacept) within 8&#xD;
             weeks (or 5 half-lives, whichever is longer), treatment with alkylating agents within&#xD;
             12 weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, or&#xD;
             mycophenolate mofetil (MMF) within 4 weeks&#xD;
&#xD;
          7. Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks&#xD;
&#xD;
          8. Chronic or recent corticosteroid use &gt; 10 mg/day&#xD;
&#xD;
          9. Pregnant. Breast-feeding women are eligible with the decision to continue or&#xD;
             discontinue breast-feeding during therapy taking into account the risk of infant&#xD;
             exposure, the benefits of breast-feeding to the infant, and benefits of treatment to&#xD;
             the mother&#xD;
&#xD;
         10. Enrolled in another investigational study using immunosuppressive therapy&#xD;
&#xD;
         11. Known hypersensitivity to mavrilimumab or any of its excipients&#xD;
&#xD;
         12. In the opinion of the investigator, unable to comply with the requirements to&#xD;
             participate in the study&#xD;
&#xD;
         13. Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unless they are using highly effective methods of contraception&#xD;
             during dosing of investigational drug. Such methods include:&#xD;
&#xD;
               -  Total abstinence (when this is in line with the preferred and usual lifestyle of&#xD;
                  the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,&#xD;
                  post-ovulation methods) and withdrawal are not acceptable methods of&#xD;
                  contraception&#xD;
&#xD;
               -  Female sterilization (have had surgical bilateral oophorectomy with or without&#xD;
                  hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks&#xD;
                  before taking study treatment. In case of oophorectomy alone, only when the&#xD;
                  reproductive status of the woman has been confirmed by follow up hormone level&#xD;
                  assessment&#xD;
&#xD;
               -  Male sterilization (at least 6 months prior to screening). For female subjects on&#xD;
                  the study, the vasectomized male partner should be the sole partner for that&#xD;
                  subject&#xD;
&#xD;
               -  Use of oral, (estrogen and progesterone), injected or implanted hormonal methods&#xD;
                  of contraception or placement of an intrauterine device (IUD) or intrauterine&#xD;
                  system (IUS), or other forms of hormonal contraception that have comparable&#xD;
                  efficacy (failure rate &lt;1%), for example hormone vaginal ring or transdermal&#xD;
                  hormone contraception&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antonio Abbate, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <results_first_submitted>August 4, 2021</results_first_submitted>
  <results_first_submitted_qc>August 4, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 11, 2021</results_first_posted>
  <last_update_submitted>August 4, 2021</last_update_submitted>
  <last_update_submitted_qc>August 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mavrilimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 25, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT04463004/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Intervention</title>
          <description>Treatment infusion&#xD;
Mavrilimumab: Treatment infusion</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>Placebo infusion&#xD;
Placebos: Placebo infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intervention</title>
          <description>Treatment infusion&#xD;
Mavrilimumab: Treatment infusion</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Placebo infusion&#xD;
Placebos: Placebo infusion</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="2"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55" spread="0"/>
                    <measurement group_id="B2" value="59" spread="0"/>
                    <measurement group_id="B3" value="57" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Subjects Alive and Off of Oxygen at Day 14</title>
        <description>Number of subjects alive and off of oxygen</description>
        <time_frame>14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Treatment infusion&#xD;
Mavrilimumab: Treatment infusion</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Placebo infusion&#xD;
Placebos: Placebo infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Alive and Off of Oxygen at Day 14</title>
          <description>Number of subjects alive and off of oxygen</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects Alive and Without Respiratory Failure at 28 Days</title>
        <description>Number of subjects alive and without respiratory failure</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Treatment infusion&#xD;
Mavrilimumab: Treatment infusion</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Placebo infusion&#xD;
Placebos: Placebo infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects Alive and Without Respiratory Failure at 28 Days</title>
          <description>Number of subjects alive and without respiratory failure</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>60 days</time_frame>
      <desc>Daily assessment and chart review with routine labs while in patient,&#xD;
Virtual telehealth assessment on day 14, 21, 28 and 60.</desc>
      <group_list>
        <group group_id="E1">
          <title>Intervention</title>
          <description>Treatment infusion&#xD;
Mavrilimumab: Treatment infusion</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Placebo infusion&#xD;
Placebos: Placebo infusion</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Antonio Abbate, MD, PhD</name_or_title>
      <organization>Virginia Commonwealth University</organization>
      <phone>804-628-1215</phone>
      <email>antonio.abbate@vcuhealth.org</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/NCT04463004
org study id: HM20019145
nct id: NCT04463004
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled
      study is to demonstrate that early treatment with mavrilimumab prevents progression of
      respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological
      features of hyper-inflammation.
This prospective, Phase 2, multi-center, blinded randomized placebo-controlled study is
      designed to demonstrate that early treatment with mavrilimumab prevents progression of
      respiratory failure in patients with severe Covid-19 pneumonia and clinical and biological
      features of hyper-inflammation.

      The study population includes patients who have severe pneumonia, defined as hospitalization
      due to Covid-19 with abnormal chest imaging and SpO2 <92% on room air or requirement for
      supplemental oxygen.

      Enrollment: The study will be performed in approximately 4 months total, starting from the
      first patient enrolled with enrollment expected to complete within 2 months.

      Follow-up period: The follow-up period is 60 days for each patient enrolled.

      A total of 60 patients will be randomized using a 1:1 allocation ratio: 30 subjects will
      receive mavrilimumab, and 30 subjects will receive placebo infusion. The investigator,
      clinical team, and subject will be blinded to treatment assignment.

      Participants will be identified by regular review of hospitalized COVID19 patients to
      evaluate for inclusion and exclusion criteria. Participants will then be approached in the
      standard manner by study investigator and coordinator/research nurse.

      Research interventions will take place in the hospital in accordance with privacy standards.

      The study team is informed on all study procedures and requirements with daily meetings and
      the opportunity to continuously update through secure channels.

      In this multicenter consortium, each participating site will have their own IND for patients
      enrolled at their site. Data collection, data analysis, and randomization scheme will be
      performed by one site, Cleveland Clinic C5 Research.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of Subjects Alive and Off of Oxygen at Day 14
time frame: 14 days
description: Number of subjects alive and off of oxygen
measure: Number of Subjects Alive and Without Respiratory Failure at 28 Days
time frame: 28 days
description: Number of subjects alive and without respiratory failure
arm group label: Intervention
arm group type: Active Comparator
description: Treatment infusion
arm group label: Control
arm group type: Placebo Comparator
description: Placebo infusion
intervention type: Drug
intervention name: Mavrilimumab
description: Treatment infusion
arm group label: Intervention
other name: KPL-301
intervention type: Drug
intervention name: Placebos
description: Placebo infusion
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antonio Abbate, MD, PhD
role: Principal Investigator
affiliation: Virginia Commonwealth University
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Respiratory Insufficiency
mesh term: Inflammation
mesh term: Mavrilimumab
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 