<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/NCT04429854</url>
  </required_header>
  <id_info>
    <org_study_id>S63992</org_study_id>
    <nct_id>NCT04429854</nct_id>
  </id_info>
  <brief_title>Donated Antibodies Working Against nCoV</brief_title>
  <acronym>DAWN-Plasma</acronym>
  <official_title>A Randomized, Open-label, Adaptive, Proof-of-concept Clinical Trial of Donated Antibodies Working Against With COVID-19: DAWN-PLASMA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Federal Knowledge Centre (KCE)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This a phase II, proof-of-concept study. In the present study, we investigate if the&#xD;
      administration of blood-plasma from patients recovered from COVID-19, could be effective to&#xD;
      treat patients who are severely ill because of a COVID-19 infection. The general idea behind&#xD;
      the transfusion, is that plasma of recovered patients contains antibodies that could&#xD;
      eliminate the novel coronavirus causing COVID-19, and lead to a less severe course of the&#xD;
      disease, or a faster healing. Simply put, in this study we would like to investigate whether&#xD;
      'borrowed immunity' from a person who has cured from this disease, could be applied to cure&#xD;
      other patients more rapidly.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In December 2019, a new coronavirus (the SARS-CoV-2 virus) emerged, which spread fast across&#xD;
      the world, and has led to a pandemic. The disease caused by this virus, called COVID-19, has&#xD;
      a mild course in a high number of infected people, but is known to have a more severe course&#xD;
      in some. Currently, there are no successful treatments with a known effect on the course of&#xD;
      the disease in patients suffering from COVID-19. In this study, we will examine whether&#xD;
      plasma, a treatment that has been used in human subjects for other diseases (and is known to&#xD;
      be safe), can be used to influence the course of COVID-19 towards a lower severity.&#xD;
&#xD;
      The aim of the study is to evaluate clinical efficacy and safety of convalescent plasma for&#xD;
      COVID-19.&#xD;
&#xD;
      This clinical trial is an adaptive, randomized, open-label phase II proof-of-concept study to&#xD;
      investigate the safety and effect of potentially interesting treatments, for the treatment of&#xD;
      hospitalized adult patients suffering from COVID-19.&#xD;
&#xD;
      Because an active treatment for COVID-19 is lacking, plasma donation is now being proposed.&#xD;
      To investigate this effect of plasma, we will compare two groups of patients. One group will&#xD;
      get standard treatment, plus plasma from a patient recently cured from COVID-19. A second&#xD;
      group will get standard treatment alone. In this study, 2 patients out of 3 will receive&#xD;
      plasma, and 1 patient out of 3 will receive standard treatment alone. After the study, we&#xD;
      will be able to establish whether plasma donation is useful or not.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2, 2020</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">April 30, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>483 patients with 2:1 randomization. 320 patients receiving Convalescent Plasma - 163 patients receiving Standard of Care</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Patients requiring mechanical ventilation or death</measure>
    <time_frame>No mechanical ventilation at day 15 after hospitalization.</time_frame>
    <description>Primary outcome of the study is the number of patients alive without mechanical ventilation at day 15 after hospitalization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical status of subject at day 15 and day 30 (on a 10-point &quot;WHO progression&quot; ordinal scale)</measure>
    <time_frame>day 15 and day 30</time_frame>
    <description>0. Uninfected. Non viral RNA detected&#xD;
Ambulatory, Asymptomatic, viral RNA detected&#xD;
Ambulatory, Symptomatic, Independent&#xD;
Ambulatory, Symptomatic, Assistance needed&#xD;
Hospitalized, mild disease, No oxygen therapy needed&#xD;
Hospitalized, mild disease, Oxygen by mask of nasal prongs&#xD;
Hospitalized, severe disease, Oxygen by NIV or High flow&#xD;
Hospitalized, severe disease, Intubation and mechanical ventilation (pO2/FiO2&gt;=150 OR SpO2/FIO2&gt;=200)&#xD;
Hospitalized, severe disease, Mechanical ventilation (pO2/FiO2&lt;150 OR SpO2/FIO2&lt;200) OR vasopressors (norepinephrine &gt;0.3 microg/kg/min)&#xD;
Hospitalized, severe disease, Mechanical ventilation pO2/FiO2&lt;150 AND vasopressors (norepinephrine &gt;0.3 microg/kg/min), OR Dialysis OR ECMO&#xD;
Death, Dead</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">483</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Convalescent Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 units of convalescent plasma:&#xD;
2 units of plasma are administered within 12h after randomization, but preferably as soon as practically possible&#xD;
2 units of plasma should be administered between 24h and 36h after the first infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive. Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Convalescent Plasma</intervention_name>
    <description>4 units of convalescent plasma:&#xD;
2 units of plasma are administered within 12h after randomization, but preferably as soon as practically possible&#xD;
2 units of plasma should be administered between 24h and 36h after the first infusion&#xD;
Other investigational products may be added as part of the adaptive study design.</description>
    <arm_group_label>Convalescent Plasma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of care</intervention_name>
    <description>Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive.</description>
    <arm_group_label>Convalescent Plasma</arm_group_label>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject (≥18 years old) or legally authorized representative provides informed consent&#xD;
             prior to initiation of any study procedures.&#xD;
&#xD;
          2. Subject (or legally authorized representative) understands and agrees to comply with&#xD;
             planned study procedures.&#xD;
&#xD;
          3. Male or non-pregnant female adult ≥18 years of age at time of enrolment.&#xD;
&#xD;
          4. Patient should be hospitalized&#xD;
&#xD;
          5. Has a confirmed diagnosis of SARS-CoV-2 infection, defined as either:&#xD;
&#xD;
               1. laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other&#xD;
                  commercial or public health assay in any specimen as diagnosed within 60 hours&#xD;
                  prior to randomization or&#xD;
&#xD;
               2. The combination of upper or lower respiratory infection symptoms (fever, cough,&#xD;
                  dyspnea, desaturation) and typical findings on chest CT scan and absence of other&#xD;
                  plausible diagnoses&#xD;
&#xD;
          6. Illness of any duration, and at least one of the following:&#xD;
&#xD;
               1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or&#xD;
&#xD;
               2. Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room&#xD;
                  air, or&#xD;
&#xD;
               3. Requiring supplemental oxygen.&#xD;
&#xD;
          7. ABO D typing of the patient should be done at least once and the result should be&#xD;
             known.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Receiving invasive (any mode where a patient has been intubated endotracheally, or via&#xD;
             tracheostomy) or non-invasive (for instance, but not restricted to CPAP, PSV, PCV,&#xD;
             SiMV) mechanical ventilation before or upon randomization.&#xD;
&#xD;
          2. Pregnancy or breast feeding.&#xD;
&#xD;
          3. Any medical condition which would impose an unacceptable safety hazard by&#xD;
             participation to the study.&#xD;
&#xD;
          4. Patients with a documented grade 3 allergic reaction after the administration of fresh&#xD;
             frozen plasma (i.e. systemic reaction with cardiovascular and/or respiratory&#xD;
             involvement)&#xD;
&#xD;
          5. Patients that have treatment restriction that excludes mechanical ventilation and/or&#xD;
             endotracheal intubation&#xD;
&#xD;
          6. Rituximab or another anti-CD20 monoclonal antibody (f.ex. obinutuzumab) has been&#xD;
             administered during the year prior of the date of admission.&#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>Geert Meyfroidt, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>UZ Leuven</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ZNA</name>
      <address>
        <city>Antwerpen</city>
        <zip>2050</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imelda Ziekenhuis Bonheiden</name>
      <address>
        <city>Bonheiden</city>
        <zip>2820</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bordet</name>
      <address>
        <city>Brussel</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMC Sint-Pieter</name>
      <address>
        <city>Brussel</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Brugmann</name>
      <address>
        <city>Brussel</city>
        <zip>1030</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus Ziekenhuis</name>
      <address>
        <city>Brussel</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Brussel</name>
      <address>
        <city>Brussel</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires St Luc</name>
      <address>
        <city>Brussel</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Sint-Vincentius</name>
      <address>
        <city>Deinze</city>
        <zip>9800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Maria Middelares</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Sint-Lucas</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Groeninge</name>
      <address>
        <city>Kortrijk</city>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHC Liège Mont Légia</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR Citadelle Liège</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Liège Sart-Tilman</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Ambroise Paré</name>
      <address>
        <city>Mons</city>
        <zip>7000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR Jolimont Mons-Hainaut</name>
      <address>
        <city>Mons</city>
        <zip>7100</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Delta</name>
      <address>
        <city>Roeselare</city>
        <zip>8800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sint-Trudo Ziekenhuis</name>
      <address>
        <city>Sint-Truiden</city>
        <zip>3800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Wallonie Picarde (CHwapi)</name>
      <address>
        <city>Tournai</city>
        <zip>7500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>October 18, 2021</last_update_submitted>
  <last_update_submitted_qc>October 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 27, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT04429854/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>February 12, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT04429854/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>February 7, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04429854
org study id: S63992
nct id: NCT04429854
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This a phase II, proof-of-concept study. In the present study, we investigate if the
      administration of blood-plasma from patients recovered from COVID-19, could be effective to
      treat patients who are severely ill because of a COVID-19 infection. The general idea behind
      the transfusion, is that plasma of recovered patients contains antibodies that could
      eliminate the novel coronavirus causing COVID-19, and lead to a less severe course of the
      disease, or a faster healing. Simply put, in this study we would like to investigate whether
      'borrowed immunity' from a person who has cured from this disease, could be applied to cure
      other patients more rapidly.
In December 2019, a new coronavirus (the SARS-CoV-2 virus) emerged, which spread fast across
      the world, and has led to a pandemic. The disease caused by this virus, called COVID-19, has
      a mild course in a high number of infected people, but is known to have a more severe course
      in some. Currently, there are no successful treatments with a known effect on the course of
      the disease in patients suffering from COVID-19. In this study, we will examine whether
      plasma, a treatment that has been used in human subjects for other diseases (and is known to
      be safe), can be used to influence the course of COVID-19 towards a lower severity.

      The aim of the study is to evaluate clinical efficacy and safety of convalescent plasma for
      COVID-19.

      This clinical trial is an adaptive, randomized, open-label phase II proof-of-concept study to
      investigate the safety and effect of potentially interesting treatments, for the treatment of
      hospitalized adult patients suffering from COVID-19.

      Because an active treatment for COVID-19 is lacking, plasma donation is now being proposed.
      To investigate this effect of plasma, we will compare two groups of patients. One group will
      get standard treatment, plus plasma from a patient recently cured from COVID-19. A second
      group will get standard treatment alone. In this study, 2 patients out of 3 will receive
      plasma, and 1 patient out of 3 will receive standard treatment alone. After the study, we
      will be able to establish whether plasma donation is useful or not.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 483 patients with 2:1 randomization. 320 patients receiving Convalescent Plasma - 163 patients receiving Standard of Care
primary purpose: Treatment
masking: None (Open Label)
measure: Patients requiring mechanical ventilation or death
time frame: No mechanical ventilation at day 15 after hospitalization.
description: Primary outcome of the study is the number of patients alive without mechanical ventilation at day 15 after hospitalization.
measure: Clinical status of subject at day 15 and day 30 (on a 10-point "WHO progression" ordinal scale)
time frame: day 15 and day 30
description: 0. Uninfected. Non viral RNA detected
Ambulatory, Asymptomatic, viral RNA detected
Ambulatory, Symptomatic, Independent
Ambulatory, Symptomatic, Assistance needed
Hospitalized, mild disease, No oxygen therapy needed
Hospitalized, mild disease, Oxygen by mask of nasal prongs
Hospitalized, severe disease, Oxygen by NIV or High flow
Hospitalized, severe disease, Intubation and mechanical ventilation (pO2/FiO2>=150 OR SpO2/FIO2>=200)
Hospitalized, severe disease, Mechanical ventilation (pO2/FiO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min)
Hospitalized, severe disease, Mechanical ventilation pO2/FiO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO
Death, Dead
arm group label: Convalescent Plasma
arm group type: Experimental
description: 4 units of convalescent plasma:
2 units of plasma are administered within 12h after randomization, but preferably as soon as practically possible
2 units of plasma should be administered between 24h and 36h after the first infusion
arm group label: Standard of Care
arm group type: Other
description: Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive. Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive.
intervention type: Biological
intervention name: Convalescent Plasma
description: 4 units of convalescent plasma:
2 units of plasma are administered within 12h after randomization, but preferably as soon as practically possible
2 units of plasma should be administered between 24h and 36h after the first infusion
Other investigational products may be added as part of the adaptive study design.
arm group label: Convalescent Plasma
intervention type: Drug
intervention name: Standard of care
description: Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive.
arm group label: Convalescent Plasma
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Geert Meyfroidt, MD, PhD
role: Study Director
affiliation: UZ Leuven
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No
provided document: 
provided document: 
submitted: February 7, 2023