<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/NCT04447469</url>
  </required_header>
  <id_info>
    <org_study_id>KPL-301-C203</org_study_id>
    <nct_id>NCT04447469</nct_id>
  </id_info>
  <brief_title>Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation</brief_title>
  <official_title>A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kiniksa Pharmaceuticals, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kiniksa Pharmaceuticals, Ltd.</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>
      Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development&#xD;
      phases (Phase 2 and Phase 3).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Phase 2 portion of the study will evaluate the efficacy and safety of 2 dose levels of&#xD;
      mavrilimumab relative to placebo (standard of care) in participants who have tested positive&#xD;
      for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with x-ray/computed&#xD;
      tomography (CT) evidence of bilateral pneumonia and active or recent signs of&#xD;
      hyperinflammation (fever or clinical laboratory results indicative of hyper-inflammation).&#xD;
      The Phase 3 portion is intended to confirm Phase 2 efficacy and safety findings. In both&#xD;
      Phase 2 and Phase 3, participants will be enrolled into 2 cohorts: Cohort 1 will include&#xD;
      non-intubated, hospitalized participants who require supplemental oxygen to maintain oxygen&#xD;
      saturation (SpO2) ≥ 92% (ie, &quot;non-ventilated&quot; participants); Cohort 2 will include&#xD;
      hospitalized participants for whom mechanical ventilation was recently initiated (ie,&#xD;
      &quot;ventilated&quot; participants). Following Screening, enrolled participants in each cohort will be&#xD;
      randomized 1:1:1 to receive one of 2 mavrilimumab dose levels, or placebo as a single&#xD;
      intravenous (IV) infusion (Day 1). Participants will undergo primary study assessments&#xD;
      through Day 29 and will be followed for safety through Day 90.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Actual">January 14, 2022</completion_date>
  <primary_completion_date type="Actual">November 12, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cohort 1: Proportion of subjects alive and free of mechanical ventilation at Day 29</measure>
    <time_frame>Day 29</time_frame>
    <description>Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Mechanical ventilation status will be evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Subjects whose clinical outcome has met a NIAID score of 2 will be considered as using mechanical ventilation.&#xD;
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2: Mortality rate at Day 29</measure>
    <time_frame>Day 29</time_frame>
    <description>Mortality rate is defined as the proportion of subjects who have died by Day 29.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cohort 1: Mortality rate at Day 29</measure>
    <time_frame>By Day 29</time_frame>
    <description>Mortality rate is defined as the proportion of participants who die.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 1: Ventilation-free survival by Day 29</measure>
    <time_frame>By Day 29</time_frame>
    <description>Defined as time from randomization to ventilation or death; subjects still alive will be censored at Day 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 1: Overall survival by Day 29</measure>
    <time_frame>Day 29</time_frame>
    <description>Defined as time from randomization to death; subjects still alive will be censored at Day 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Time to 1-point clinical improvement by Day 29</measure>
    <time_frame>By Day 29</time_frame>
    <description>Defined as time from randomization to a 1-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever comes first. Subjects who die before Day 29 will be censored at Day 30.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">815</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>10 mg/kg (Cohort 1)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>6 mg/kg (Cohort 1)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Cohort 1)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Non-mechanically ventilated participants administered placebo as a single IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10 mg/kg (Cohort 2)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>6 mg/kg (Cohort 2)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Cohort 2)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Mechanically ventilated participants administered placebo as a single IV infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mavrilimumab</intervention_name>
    <description>anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])</description>
    <arm_group_label>10 mg/kg (Cohort 1)</arm_group_label>
    <arm_group_label>10 mg/kg (Cohort 2)</arm_group_label>
    <arm_group_label>6 mg/kg (Cohort 1)</arm_group_label>
    <arm_group_label>6 mg/kg (Cohort 2)</arm_group_label>
    <other_name>(KPL-301; CAM3001)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>matching placebo</description>
    <arm_group_label>Placebo (Cohort 1)</arm_group_label>
    <arm_group_label>Placebo (Cohort 2)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Subject (or legally authorized representative) is able and willing to provide informed&#xD;
             consent, which includes compliance with study requirements and restrictions listed in&#xD;
             the consent form. Consent must be performed per institutional regulations.&#xD;
&#xD;
          -  Age of ≥ 18 years&#xD;
&#xD;
          -  Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization&#xD;
&#xD;
          -  Hospitalized for SARS-CoV-2 (2019-nCoV)&#xD;
&#xD;
          -  Bilateral pneumonia on chest x-ray or computed tomography&#xD;
&#xD;
          -  Clinical laboratory results indicative of hyper-inflammation within 7 days prior to&#xD;
             randomization&#xD;
&#xD;
          -  Cohort 1: Receiving any form of non-invasive ventilation OR oxygenation to maintain&#xD;
             SpO2 ≥ 92% and non-mechanically ventilated (examples include nasal cannula, face mask,&#xD;
             venturi mask, high-flow nasal cannula, or non-invasive positive pressure ventilation)&#xD;
&#xD;
          -  Cohort 2: Recently ventilated with mechanical ventilation beginning within 48 hours&#xD;
             prior to randomization&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Onset of COVID-19 symptoms &gt; 14 days prior to randomization&#xD;
&#xD;
          -  Hospitalized &gt; 7 days prior to randomization&#xD;
&#xD;
          -  Need for invasive mechanical ventilation (Only for Cohort 1)&#xD;
&#xD;
          -  Need for ECMO&#xD;
&#xD;
          -  Serious prior or concomitant illness that in the opinion of the Investigator precludes&#xD;
             the subject from enrolling in the trial&#xD;
&#xD;
          -  Recent treatment with cell-depleting biological therapies (eg, anti-CD20) within 12&#xD;
             months, non-cell-depleting biological therapies (such as anti-tumor necrosis factor&#xD;
             [TNF], anakinra, anti-IL-6 receptor [eg, tocilizumab], or abatacept) within 8 weeks&#xD;
             (or 5 half-lives, whichever is longer), treatment with alkylating agents within 12&#xD;
             weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, mycophenolate&#xD;
             mofetil (MMF), or other immunosuppressant (except for corticosteroids) within 4 weeks&#xD;
             prior to randomization. Medications that become standard of care for COVID-19 and/or&#xD;
             receive emergency use authorization may be allowed after discussion with the medical&#xD;
             monitor.&#xD;
&#xD;
          -  If subject is receiving or has received hydroxychloroquine within 3 months prior to&#xD;
             screening visit, a corrected QT interval by Federicia method (QTcF) on Screening&#xD;
             electrocardiogram (ECG) ≥500ms is exclusionary. If subject has a pacemaker, this&#xD;
             criterion does not apply.&#xD;
&#xD;
          -  Enrolled in another investigational study of a medical intervention within 30 days&#xD;
             prior to randomization. Participation in open label trials involving investigational&#xD;
             treatments for COVID-19 may be allowed upon approval by the Sponsor.&#xD;
&#xD;
          -  Life expectancy less than 48 hours, in the opinion of the Investigator&#xD;
&#xD;
          -  Known human immunodeficiency virus infection (regardless of immunological status),&#xD;
             known hepatitis B virus surface antigen positivity and/or anti-hepatitis C virus&#xD;
             positivity&#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>UCLA Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SHARP Health Care</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Affinity Health</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60644</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulane University School of Medicine</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allina Health System</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Clinic Hospitalists</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bryn Mawr Hospital</name>
      <address>
        <city>Bryn Mawr</city>
        <state>Pennsylvania</state>
        <zip>19010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Sciences</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Cardio Pulmonar</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <zip>40170-130</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Luxemburgo - Associação Mário Penna</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <zip>30380-472</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CPCLIN - Centro de Pesquisas Clínicas</name>
      <address>
        <city>Natal</city>
        <state>Rio Grande Do Norte</state>
        <zip>59025-050</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Bruno Born</name>
      <address>
        <city>Lajeado</city>
        <state>Rio Grande Do Sul</state>
        <zip>95900-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPECLIN - Unidade de Pesquisa Clínica</name>
      <address>
        <city>Botucatu</city>
        <state>Sao Paulo</state>
        <zip>18618-686</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IPECC - Instituto de Pesquisa Clínica de Campinas</name>
      <address>
        <city>Campinas</city>
        <state>Sao Paulo</state>
        <zip>13060-080</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo</name>
      <address>
        <city>Ribeirão Preto</city>
        <state>São Paulo</state>
        <zip>65470-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Adventista de Belem</name>
      <address>
        <city>Belém</city>
        <zip>66093-904</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará</name>
      <address>
        <city>Fortaleza</city>
        <zip>60192-340</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundação Faculdade Regional de Medicina de São José do Rio Preto</name>
      <address>
        <city>São José</city>
        <zip>15090-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Alemão Oswaldo Cruz</name>
      <address>
        <city>São Paulo</city>
        <zip>01323-020</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Las Condes</name>
      <address>
        <city>Santiago</city>
        <zip>7550000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universidad de Chile</name>
      <address>
        <city>Santiago</city>
        <zip>8380456</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nacional Alberto Sabogal Sologuren</name>
      <address>
        <city>Bellavista</city>
        <zip>07011</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Essalud - Hospital de Emergencias Grau</name>
      <address>
        <city>Lima Cercado</city>
        <zip>15082</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nacional Cayetano Heredia</name>
      <address>
        <city>San Martín De Porres</city>
        <zip>15102</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Providencia</name>
      <address>
        <city>San Miguel</city>
        <zip>15088</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cape Town - Lung Institute</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7700</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IATROS International</name>
      <address>
        <city>Bloemfontein</city>
        <zip>9301</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tiervlei Trial Center</name>
      <address>
        <city>Cape Town</city>
        <zip>7530</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TASK Eden</name>
      <address>
        <city>George</city>
        <zip>6529</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Into Research - Little Company of Mary Medical Center</name>
      <address>
        <city>Pretoria</city>
        <zip>0181</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limpopo Clinical Research Initiative</name>
      <address>
        <city>Rustenburg</city>
        <zip>0299</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Chile</country>
    <country>Peru</country>
    <country>South Africa</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <disposition_first_submitted>September 21, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>September 21, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 28, 2022</disposition_first_posted>
  <last_update_submitted>September 21, 2022</last_update_submitted>
  <last_update_submitted_qc>September 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>pneumonia</keyword>
  <keyword>hyper-inflammation</keyword>
  <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>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>Yes</sharing_ipd>
    <ipd_description>The Sponsor will review IPD requests proposals from qualified researchers</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>IPD requests will be accepted after publication of the primary data manuscript</ipd_time_frame>
    <ipd_access_criteria>IPD access will be provided to qualified academic researchers pending the Sponsor's review of the proposed research, including scientific novelty, review of the analytical and publication plans, funding source of the proposed research, any potential conflicts of interest, and institutional capabilities to perform the planned research.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04447469
org study id: KPL-301-C203
nct id: NCT04447469
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development
      phases (Phase 2 and Phase 3).
The Phase 2 portion of the study will evaluate the efficacy and safety of 2 dose levels of
      mavrilimumab relative to placebo (standard of care) in participants who have tested positive
      for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with x-ray/computed
      tomography (CT) evidence of bilateral pneumonia and active or recent signs of
      hyperinflammation (fever or clinical laboratory results indicative of hyper-inflammation).
      The Phase 3 portion is intended to confirm Phase 2 efficacy and safety findings. In both
      Phase 2 and Phase 3, participants will be enrolled into 2 cohorts: Cohort 1 will include
      non-intubated, hospitalized participants who require supplemental oxygen to maintain oxygen
      saturation (SpO2) ≥ 92% (ie, "non-ventilated" participants); Cohort 2 will include
      hospitalized participants for whom mechanical ventilation was recently initiated (ie,
      "ventilated" participants). Following Screening, enrolled participants in each cohort will be
      randomized 1:1:1 to receive one of 2 mavrilimumab dose levels, or placebo as a single
      intravenous (IV) infusion (Day 1). Participants will undergo primary study assessments
      through Day 29 and will be followed for safety through Day 90.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Cohort 1: Proportion of subjects alive and free of mechanical ventilation at Day 29
time frame: Day 29
description: Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Mechanical ventilation status will be evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Subjects whose clinical outcome has met a NIAID score of 2 will be considered as using mechanical ventilation.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
measure: Cohort 2: Mortality rate at Day 29
time frame: Day 29
description: Mortality rate is defined as the proportion of subjects who have died by Day 29.
measure: Cohort 1: Mortality rate at Day 29
time frame: By Day 29
description: Mortality rate is defined as the proportion of participants who die.
measure: Cohort 1: Ventilation-free survival by Day 29
time frame: By Day 29
description: Defined as time from randomization to ventilation or death; subjects still alive will be censored at Day 29.
measure: Cohort 1: Overall survival by Day 29
time frame: Day 29
description: Defined as time from randomization to death; subjects still alive will be censored at Day 29.
measure: Cohort 2: Time to 1-point clinical improvement by Day 29
time frame: By Day 29
description: Defined as time from randomization to a 1-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever comes first. Subjects who die before Day 29 will be censored at Day 30.
arm group label: 10 mg/kg (Cohort 1)
arm group type: Active Comparator
description: Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
arm group label: 6 mg/kg (Cohort 1)
arm group type: Active Comparator
description: Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
arm group label: Placebo (Cohort 1)
arm group type: Placebo Comparator
description: Non-mechanically ventilated participants administered placebo as a single IV infusion
arm group label: 10 mg/kg (Cohort 2)
arm group type: Active Comparator
description: Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
arm group label: 6 mg/kg (Cohort 2)
arm group type: Active Comparator
description: Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
arm group label: Placebo (Cohort 2)
arm group type: Placebo Comparator
description: Mechanically ventilated participants administered placebo as a single IV infusion
intervention type: Drug
intervention name: mavrilimumab
description: anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])
arm group label: 10 mg/kg (Cohort 1)
arm group label: 10 mg/kg (Cohort 2)
arm group label: 6 mg/kg (Cohort 1)
arm group label: 6 mg/kg (Cohort 2)
other name: (KPL-301; CAM3001)
intervention type: Other
intervention name: Placebo
description: matching placebo
arm group label: Placebo (Cohort 1)
arm group label: Placebo (Cohort 2)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Brazil
country: Chile
country: Peru
country: South Africa
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Inflammation
mesh term: Mavrilimumab
sharing ipd: Yes
ipd description: The Sponsor will review IPD requests proposals from qualified researchers
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: IPD requests will be accepted after publication of the primary data manuscript
ipd access criteria: IPD access will be provided to qualified academic researchers pending the Sponsor's review of the proposed research, including scientific novelty, review of the analytical and publication plans, funding source of the proposed research, any potential conflicts of interest, and institutional capabilities to perform the planned research.