<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/NCT04492514</url>
  </required_header>
  <id_info>
    <org_study_id>IND 149353</org_study_id>
    <nct_id>NCT04492514</nct_id>
  </id_info>
  <brief_title>Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflation</brief_title>
  <official_title>Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kristin Hudock</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kiniksa Pharmaceuticals, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Cincinnati</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 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 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 COVID 19 patients to&#xD;
      evaluate for inclusion and exclusion criteria. Participants will then be approached in this&#xD;
      standard manner by study investigator and/or coordinator/research nurse.&#xD;
&#xD;
      Research interventions will take place in the hospital in accordance with privacy standards.&#xD;
&#xD;
      The study team in 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 of 4 academic centers, each participating site will have their&#xD;
      own IND for patients enrolled at their site. Data collection will occur at each of the 4&#xD;
      academic centers. Data analysis and randomization scheme will be performed by the Cleveland&#xD;
      Clinic C5 Research, data analysis, and randomization scheme will be performed by one site,&#xD;
      Cleveland Clinic C5 Research.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 20, 2020</start_date>
  <completion_date type="Anticipated">May 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <intervention_model_description>Factorial Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Quadruple (Particiapnt, Care Provider, Investigator, Outcomes Assessor)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Outcome Measure:</measure>
    <time_frame>Day 14</time_frame>
    <description>Proportion of subjects alive and off oxygen at day14</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome Measures:</measure>
    <time_frame>28 days</time_frame>
    <description>Proportion of subjects alive and without respiratory failure at 28 days</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>COVID 19</condition>
  <condition>SARS-CoV 2</condition>
  <condition>Pneumonia</condition>
  <arm_group>
    <arm_group_label>Mavrilimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mavrilimumab treatment infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</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>Mavrilimumab</arm_group_label>
    <other_name>KPL-301</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo infusion</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria (must meet all):&#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>Kristin Hudock, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kristin Hudock, MD</last_name>
    <phone>513-803-7819</phone>
    <email>hudockkn@ucmail.uc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Autumn Cresie</last_name>
    <phone>513-558-0337</phone>
    <email>studeran@ucmail.uc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristin Hudock, MD</last_name>
      <phone>513-803-7819</phone>
      <email>hudockkn@ucmail.uc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Autumn Cresie</last_name>
      <phone>513-558-0337</phone>
      <email>studeran@ucmail.uc.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>July 28, 2020</last_update_submitted>
  <last_update_submitted_qc>July 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>Kristin Hudock</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine and Pediatrics</investigator_title>
  </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>
  </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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04492514
org study id: IND 149353
nct id: NCT04492514
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: 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 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 COVID 19 patients to
      evaluate for inclusion and exclusion criteria. Participants will then be approached in this
      standard manner by study investigator and/or coordinator/research nurse.

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

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

      In this multicenter consortium of 4 academic centers, each participating site will have their
      own IND for patients enrolled at their site. Data collection will occur at each of the 4
      academic centers. Data analysis and randomization scheme will be performed by the Cleveland
      Clinic C5 Research, data analysis, and randomization scheme will be performed by one site,
      Cleveland Clinic C5 Research.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: Factorial Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Quadruple (Particiapnt, Care Provider, Investigator, Outcomes Assessor)
measure: Primary Outcome Measure:
time frame: Day 14
description: Proportion of subjects alive and off oxygen at day14
measure: Secondary Outcome Measures:
time frame: 28 days
description: Proportion of subjects alive and without respiratory failure at 28 days
arm group label: Mavrilimumab
arm group type: Experimental
description: Mavrilimumab treatment infusion
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo infusion
intervention type: Drug
intervention name: Mavrilimumab
description: treatment infusion
arm group label: Mavrilimumab
other name: KPL-301
intervention type: Drug
intervention name: Placebo
description: Placebo infusion
arm group label: Placebo
other name: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kristin Hudock, MD
role: Principal Investigator
affiliation: University of Cincinnati
last name: Kristin Hudock, MD
phone: 513-803-7819
email: hudockkn@ucmail.uc.edu
last name: Autumn Cresie
phone: 513-558-0337
email: studeran@ucmail.uc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Cincinnati
investigator full name: Kristin Hudock
investigator title: Assistant Professor of Medicine and Pediatrics
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Respiratory Insufficiency
mesh term: Mavrilimumab
sharing ipd: No