<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/NCT04432324</url>
  </required_header>
  <id_info>
    <org_study_id>GC2004</org_study_id>
    <secondary_id>2020-001696-32</secondary_id>
    <nct_id>NCT04432324</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety and Efficacy of High Dose IVIG in Hospitalized Participants With Coronavirus Disease (COVID-19)</brief_title>
  <official_title>A Multicenter, Randomized, Open-label Parallel Group Pilot Study to Evaluate Safety and Efficacy of High Dose Intravenous Immune Globulin (IVIG) Plus Standard Medical Treatment (SMT) Versus SMT Alone in Hospitalized Subjects With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Grifols, S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grifols Therapeutics LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine if high dose Intravenous IVIG plus SMT can reduce&#xD;
      the proportion of participants dying or requiring intensive care unit (ICU) admission on or&#xD;
      before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical&#xD;
      ventilation on Day 29 versus SMT alone in hospitalized participants with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2, 2020</start_date>
  <completion_date type="Actual">March 3, 2021</completion_date>
  <primary_completion_date type="Actual">March 3, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Dying or Requiring ICU Admission</measure>
    <time_frame>Up to Day 29</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation</measure>
    <time_frame>Day 29</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in National Early Warning Score (NEWS)</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Hospital Discharge</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ICU Stay</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Any Oxygen Use</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Mechanical Ventilation</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change from Baseline in Ordinal Scale</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Value Change from Baseline in Ordinal Scale</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Time to Clinical Progression</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale</measure>
    <time_frame>Day 15 and Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Sustained Normalization of Temperature</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Normalization of Fever</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS)</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Intravenous Immune Globulin + Standard Medical Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the first intravenous (IV) infusion of IVIG on Day 1 up to a net dose of 2 gram per kilogram (g/kg), based upon participant's (body weight) administered in divided doses as infusions of 500 milligram per kilogram (mg/kg), based upon participant's body weight, over 4 days or 400 mg/kg, based upon participant's body weight, over 5 days. Participants will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Medical Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive all standard of care interventions required throughout the participant's hospitalization, from Day 1 to Day 29</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Intravenous Immune Globulin</intervention_name>
    <description>IVIG Intravenous infusion</description>
    <arm_group_label>Intravenous Immune Globulin + Standard Medical Treatment</arm_group_label>
    <other_name>Flebogamma DIF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard Medical Treatment</intervention_name>
    <description>SMT</description>
    <arm_group_label>Intravenous Immune Globulin + Standard Medical Treatment</arm_group_label>
    <arm_group_label>Standard Medical Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Hospitalized male or female subject ≥ 18 years of age at time of Screening who is&#xD;
             being treated for COVID-19.&#xD;
&#xD;
          2. Has laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by&#xD;
             qualitative Polymerase Chain Reaction (PCR) (reverse transcriptase [RT]-PCR), or other&#xD;
             commercial or public health assay (of any type) in any specimen during the current&#xD;
             hospital admission prior to randomization.&#xD;
&#xD;
          3. COVID-19 illness (symptoms) of any duration with radiographic infiltrates by imaging&#xD;
             (Chest X-Ray, Computed tomography (CT) scan, etc.).&#xD;
&#xD;
          4. PaO2/FIO2 ratio &gt; 300 to ≤ 450 mmHg (i.e., arterial oxygen in mmHg divided by fraction&#xD;
             inspired oxygen concentration [e.g., 0.21 for room air])&#xD;
&#xD;
          5. Any one of the following related to COVID-19: i. Ferritin &gt; 400 nanogram per&#xD;
             milliliter (ng/mL), ii. Lactate dehydrogenase (LDH) &gt; 300 units per liter U/L, iii.&#xD;
             D-Dimers &gt; reference range, or iv. C-reactive protein (CRP) &gt; 40 milligram per liter&#xD;
             (mg/L).&#xD;
&#xD;
          6. Subject (or a legal representative or a nearest relative or a relative by marriage, as&#xD;
             appropriate) provides oral informed consent prior to initiation of any study&#xD;
             procedures.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Subject requires invasive mechanical ventilation or ICU admission.&#xD;
&#xD;
          2. Clinical evidence of any significant acute or chronic disease that, in the opinion of&#xD;
             the investigator may place the subject at undue medical risk.&#xD;
&#xD;
          3. The subject has had a known (documented) serious anaphylactic reaction to blood, any&#xD;
             blood-derived or plasma product or commercial immunoglobulin.&#xD;
&#xD;
          4. Subject has known (documented) hereditary fructose intolerance (HFI).&#xD;
&#xD;
          5. A medical condition in which the infusion of additional fluid is contraindicated.&#xD;
&#xD;
          6. Shock that is unresponsive to fluid challenge and/or multiple vasopressors and&#xD;
             accompanied by multiorgan failure considered by the Principal Investigator not able to&#xD;
             be reversed.&#xD;
&#xD;
          7. Subject with known (documented) thrombotic complications to polyclonal IVIG therapy in&#xD;
             the past.&#xD;
&#xD;
          8. Subject with current or prior (within the past 1 month) myocardial infarction, stroke,&#xD;
             deep vein thrombosis, or thromboembolic event.&#xD;
&#xD;
          9. Subject with limitations of therapeutic effort (eg, 'do not resuscitate' status).&#xD;
&#xD;
         10. Female subject who are pregnant or of child-bearing potential with a positive test for&#xD;
             pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at&#xD;
             Screening/Baseline.&#xD;
&#xD;
         11. Subject participating in another interventional clinical trial with investigational&#xD;
             medical product or device.&#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>Hospital Universitario Infanta Sofía</name>
      <address>
        <city>San Sebastián De Los Reyes</city>
        <state>Madrid</state>
        <zip>28702</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari de Bellvitge</name>
      <address>
        <city>Barcelona</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>CP 08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Getafe</name>
      <address>
        <city>Getafe</city>
        <zip>28905</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>March 9, 2021</last_update_submitted>
  <last_update_submitted_qc>March 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Coronavirus Disease</keyword>
  <keyword>Severe acute respiratory syndrome coronavirus 2</keyword>
  <keyword>SARS-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>gamma-Globulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
    <mesh_term>Rho(D) Immune Globulin</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/NCT04432324
org study id: GC2004
secondary id: 2020-001696-32
nct id: NCT04432324
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The purpose of the study is to determine if high dose Intravenous IVIG plus SMT can reduce
      the proportion of participants dying or requiring intensive care unit (ICU) admission on or
      before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical
      ventilation on Day 29 versus SMT alone in hospitalized participants with COVID-19.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Dying or Requiring ICU Admission
time frame: Up to Day 29
measure: Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation
time frame: Day 29
measure: Change from Baseline in National Early Warning Score (NEWS)
time frame: Day 1 through Day 29
measure: Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours
time frame: Day 1 through Day 29
measure: Time to Hospital Discharge
time frame: Day 1 through Day 29
measure: Duration of ICU Stay
time frame: Up to Day 29
measure: Duration of Any Oxygen Use
time frame: Day 1 through Day 29
measure: Duration of Mechanical Ventilation
time frame: Up to Day 29
measure: Mean Change from Baseline in Ordinal Scale
time frame: Day 1 through Day 29
measure: Absolute Value Change from Baseline in Ordinal Scale
time frame: Day 1 through Day 29
measure: Length of Time to Clinical Progression
time frame: Up to Day 29
measure: Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale
time frame: Day 15 and Day 29
measure: Time to Sustained Normalization of Temperature
time frame: Day 1 through Day 29
measure: Percentage of Participants with Normalization of Fever
time frame: Day 1 through Day 29
measure: Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS)
time frame: Day 29
arm group label: Intravenous Immune Globulin + Standard Medical Treatment
arm group type: Experimental
description: Participants will receive the first intravenous (IV) infusion of IVIG on Day 1 up to a net dose of 2 gram per kilogram (g/kg), based upon participant's (body weight) administered in divided doses as infusions of 500 milligram per kilogram (mg/kg), based upon participant's body weight, over 4 days or 400 mg/kg, based upon participant's body weight, over 5 days. Participants will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29.
arm group label: Standard Medical Treatment
arm group type: Active Comparator
description: Participants will receive all standard of care interventions required throughout the participant's hospitalization, from Day 1 to Day 29
intervention type: Biological
intervention name: Intravenous Immune Globulin
description: IVIG Intravenous infusion
arm group label: Intravenous Immune Globulin + Standard Medical Treatment
other name: Flebogamma DIF
intervention type: Drug
intervention name: Standard Medical Treatment
description: SMT
arm group label: Intravenous Immune Globulin + Standard Medical Treatment
arm group label: Standard Medical Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Immunoglobulins
mesh term: Antibodies
mesh term: gamma-Globulins
mesh term: Immunoglobulins, Intravenous
mesh term: Rho(D) Immune Globulin
sharing ipd: No