<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/NCT04495101</url>
  </required_header>
  <id_info>
    <org_study_id>GC2005</org_study_id>
    <secondary_id>2020-001953-36</secondary_id>
    <nct_id>NCT04495101</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Subjects With COVID-19</brief_title>
  <official_title>A Multicenter, Randomized, Open-label, Parallel Group Pilot Study to Evaluate the Safety and Efficacy of Prolastin 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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to determine if Prolastin plus SMT can reduce the&#xD;
      proportion of subjects dying or requiring intensive care unit (ICU) admission on or before&#xD;
      Day 15 or who are dependent on invasive mechanical ventilation on Day 15 versus SMT alone in&#xD;
      hospitalized subjects with Coronavirus disease 2019 (COVID-19).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 29, 2020</start_date>
  <completion_date type="Actual">June 10, 2021</completion_date>
  <primary_completion_date type="Actual">April 26, 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 Subjects Dying or Requiring ICU Admission</measure>
    <time_frame>Up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Subjects Who are Dependent on Invasive Mechanical Ventilation</measure>
    <time_frame>Day 15</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>Percentage of Subjects in Each Severity Category of the 7-Point Ordinal Scale</measure>
    <time_frame>Day 15, 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 Subjects who Sustained Normalization of Temperature</measure>
    <time_frame>Day 1 through Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects who Develop Acute Respiratory Distress Syndrome (ARDS)</measure>
    <time_frame>Up to 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>Mortality Through Day 29</measure>
    <time_frame>Up to 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>Prolastin 120 mg/kg + Standard Medical Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive Prolastin, two intravenous infusion (IV) doses of 120 milligram per kilogram (mg/kg), based upon the subject's body weight, on Day 1 and Day 8. Subjects 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>Subjects will receive all standard of care interventions while hospitalized, from Day 1 to Day 29.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Prolastin</intervention_name>
    <description>Intravenous infusion 120 mg/kg</description>
    <arm_group_label>Prolastin 120 mg/kg + Standard Medical Treatment</arm_group_label>
    <other_name>Alpha1-proteinase inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard Medical Treatment</intervention_name>
    <description>Standard medical treatment per local policies or guidelines</description>
    <arm_group_label>Prolastin 120 mg/kg + Standard Medical Treatment</arm_group_label>
    <arm_group_label>Standard Medical Treatment</arm_group_label>
    <other_name>SMT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Hospitalized male or female subject ≥ 18 years of age at the time of Screening who is&#xD;
             being treated for COVID-19. Subjects must be screened within 48 hours (≤ 48 hours) of&#xD;
             hospital admission.&#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 in any specimen during the current hospital&#xD;
             admission prior to randomization.&#xD;
&#xD;
          3. COVID-19 illness (symptoms) of any duration, including both of the following:&#xD;
&#xD;
               1. Radiographic infiltrates by imaging (chest X-Ray, computerized tomography (CT)&#xD;
                  scan, etc.) and/or clinical assessment (evidence of rales/crackles on the exam)&#xD;
                  with peripheral oxygen saturation by pulse oximetry (SpO2) &lt;94% on room air&#xD;
&#xD;
               2. 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),&#xD;
                  iii. D-Dimers &gt; reference range, or iv. C-reactive protein (CRP) &gt; 40 milligram&#xD;
                  per liter (mg/L)&#xD;
&#xD;
          4. Subjects provides informed consent prior to the initiation of any study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects requiring invasive mechanical ventilation or ICU admission or with PaO2/FIO2&#xD;
             ≤ 150 mm Hg (ie, arterial oxygen in mm Hg divided by fraction inspired oxygen&#xD;
             concentration [eg, 0.21 for room air]).&#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 subjects have had a known serious anaphylactic reaction to blood, any&#xD;
             blood-derived or plasma product, or known selective immunoglobulin A (IgA) deficiency&#xD;
             with anti-IgA antibodies.&#xD;
&#xD;
          4. A medical condition in which the infusion of additional fluid is contraindicated.&#xD;
&#xD;
          5. Shock that is unresponsive to fluid challenge and/or multiple vasopressors and&#xD;
             accompanied by multiorgan failure considered not able to be reversed by the Principal&#xD;
             Investigator.&#xD;
&#xD;
          6. Known alpha-1 antitrypsin deficiency for which the subject is already receiving&#xD;
             alpha1-proteinase inhibitor augmentation therapy.&#xD;
&#xD;
          7. Women who are pregnant or breastfeeding. Female subjects of child-bearing potential&#xD;
             must have a negative test for pregnancy blood or urine human chorionic gonadotropin&#xD;
             (HCG)-based assay at Screening/Baseline Visit.&#xD;
&#xD;
          8. Subjects for whom there is limitation of therapeutic effort such as &quot;Do not&#xD;
             resuscitate&quot; status.&#xD;
&#xD;
          9. Currently participating in another interventional clinical trial with investigational&#xD;
             medical product or device.&#xD;
&#xD;
         10. Subjects previously requiring long-term oxygen therapy (home oxygen therapy).&#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 de Burgos</name>
      <address>
        <city>Burgos</city>
        <state>Castilla León</state>
        <zip>09006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Valle de Hebrón</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Infanta Leonor</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Príncipe de Asturias</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>July 7, 2021</last_update_submitted>
  <last_update_submitted_qc>July 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 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>Protease Inhibitors</mesh_term>
    <mesh_term>Alpha 1-Antitrypsin</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/NCT04495101
org study id: GC2005
secondary id: 2020-001953-36
nct id: NCT04495101
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The primary objective of the study is to determine if Prolastin plus SMT can reduce the
      proportion of subjects dying or requiring intensive care unit (ICU) admission on or before
      Day 15 or who are dependent on invasive mechanical ventilation on Day 15 versus SMT alone in
      hospitalized subjects with Coronavirus disease 2019 (COVID-19).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Subjects Dying or Requiring ICU Admission
time frame: Up to Day 15
measure: Percentage of Subjects Who are Dependent on Invasive Mechanical Ventilation
time frame: Day 15
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: Percentage of Subjects in Each Severity Category of the 7-Point Ordinal Scale
time frame: Day 15, Day 29
measure: Time to Sustained Normalization of Temperature
time frame: Day 1 through Day 29
measure: Percentage of Subjects who Sustained Normalization of Temperature
time frame: Day 1 through Day 29
measure: Number of Subjects who Develop Acute Respiratory Distress Syndrome (ARDS)
time frame: Up to Day 29
measure: Length of Time to Clinical Progression
time frame: Up to Day 29
measure: Mortality Through Day 29
time frame: Up to Day 29
arm group label: Prolastin 120 mg/kg + Standard Medical Treatment
arm group type: Experimental
description: Subjects will receive Prolastin, two intravenous infusion (IV) doses of 120 milligram per kilogram (mg/kg), based upon the subject's body weight, on Day 1 and Day 8. Subjects 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: Subjects will receive all standard of care interventions while hospitalized, from Day 1 to Day 29.
intervention type: Biological
intervention name: Prolastin
description: Intravenous infusion 120 mg/kg
arm group label: Prolastin 120 mg/kg + Standard Medical Treatment
other name: Alpha1-proteinase inhibitor
intervention type: Drug
intervention name: Standard Medical Treatment
description: Standard medical treatment per local policies or guidelines
arm group label: Prolastin 120 mg/kg + Standard Medical Treatment
arm group label: Standard Medical Treatment
other name: SMT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Protease Inhibitors
mesh term: Alpha 1-Antitrypsin
sharing ipd: No