<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/NCT04453384</url>
  </required_header>
  <id_info>
    <org_study_id>RC20_0230</org_study_id>
    <nct_id>NCT04453384</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia</brief_title>
  <acronym>POLYCOR</acronym>
  <official_title>A Randomized, Double-blind, Placebo-controlled Phase 2 (2a and 2b) Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>BPIfrance</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xenothera SAS</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Nantes University Hospital</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>
      Early inhibition of entry and replication of the severe acute respiratory syndrome&#xD;
      coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing&#xD;
      antibodies offers many advantages such as providing immediate immunity, consequently blunt an&#xD;
      early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug&#xD;
      interactions1-3.&#xD;
&#xD;
      Because a suboptimal endogenous early antibody response with regard to SARS-CoV-2 replication&#xD;
      in severe cases is observed, neutralising antibody treatment can be very interesting for&#xD;
      patient with COVID-19 induced moderate pneumonia4,5. Convalescent plasma to treat infected&#xD;
      patients is therefore an interesting therapeutic option currently under evaluation. However,&#xD;
      the difficulties of collecting plasma and its safety aspects are not adapted to many&#xD;
      patients.&#xD;
&#xD;
      A new polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) is being developed by&#xD;
      Xenothera, which can be administered as intravenous treatment. XAV-19 is a heterologous swine&#xD;
      glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2,&#xD;
      inhibiting infection of ACE-2 positive human cells with SARS-CoV-2. Pharmacokinetic and&#xD;
      pharmacodynamic studies have been performed in preclinical models including primates and a&#xD;
      First In Human study with another fully representative GH-pAb from Xenothera is ongoing in&#xD;
      volunteer patients recipients of a kidney graft. These studies indicated that 5 consecutive&#xD;
      administrations of GH-pAbs can be safely performed in humans.&#xD;
&#xD;
      The objective of this 2-steps phase 2 randomized double-blind, placebo-controlled study is 1)&#xD;
      to define the optimal and safety XAV-19 dose to administrate in patients with COVID-19&#xD;
      induced moderate pneumonia ; 2) to show the clinical benefit of selected dose of XAV-19 when&#xD;
      administered to patients with COVID-19 induced moderate pneumonia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For the first set of statistical analyses, to allow early reporting of primary and secondary&#xD;
      endpoints at D15, the blind will be partially broken once all patients have completed Day 29.&#xD;
      Except for statisticians, only the principal investigator and the scientific coordinator will&#xD;
      have access to the full data set for the analysis of the primary and secondary endpoints up&#xD;
      to day 29. The database will be partially locked (with all data up to day 29) as neither&#xD;
      monitors nor investigators will be informed of the unblinding until the final data for day 60&#xD;
      is completed and the final database is locked.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2020</start_date>
  <completion_date type="Actual">August 19, 2021</completion_date>
  <primary_completion_date type="Actual">May 21, 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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 2a: XAV-19 antibody titers</measure>
    <time_frame>Day 8</time_frame>
    <description>The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2a: Adverse events of XAV-19</measure>
    <time_frame>Day 29</time_frame>
    <description>Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2b: To evaluate the efficacy of XAV-19 + standard-of-care (Soc) therapy compared with placebo + Soc therapy for treatment of COVID-19 assessed by the proportion of patients who die or develop respiratory failure between baseline and Day 15.</measure>
    <time_frame>Day 15</time_frame>
    <description>Efficacy is defined by the proportion of patients who died or develop respiratory failure, as defined by the requirement of noninvasive ventilation, high-flow oxygen devices, invasive mechanical ventilation (corresponding to a score of 5 or more on the WHO 8 point ordinal scale) or by an increase of the required O2 supplement (more or equals to 10 L/minutes with a non-rebreather mask (oxygen mask with reservoir bag)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 2a: Pharmacokinetic analysis</measure>
    <time_frame>Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29</time_frame>
    <description>XAV-19 Antibody titer over the time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a: Antibody titer between the two groups</measure>
    <time_frame>day 15</time_frame>
    <description>The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a: Supplemental oxygen</measure>
    <time_frame>Day 1 to Day 29</time_frame>
    <description>Duration of supplemental oxygen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a: Evaluation of Transfer to intensive care</measure>
    <time_frame>Day 1 to Day 29</time_frame>
    <description>Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a: Normalization of Fever</measure>
    <time_frame>Day 1 to Day 29</time_frame>
    <description>Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a: Biomarkers</measure>
    <time_frame>Day 1 to Day 29</time_frame>
    <description>Biomarkers : CRP, Ferritin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a: Hospital length of stay</measure>
    <time_frame>Day 1 to Day 29</time_frame>
    <description>Evaluation of Hospital length of stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Efficacy of XAV-19</measure>
    <time_frame>Day 8 and Day 29</time_frame>
    <description>Proportion of patients who die, develop respiratory failure, as defined by the requirement of noninvasive ventilation, high-flow oxygen devices or invasive mechanical ventilation at Day 8 and D29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity</measure>
    <time_frame>Day 3, Day 5, Day 8, Day15 and Day 29</time_frame>
    <description>a) National Early Warning Score (NEWS) assessed while hospitalized and on Day 15 and Day 29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity</measure>
    <time_frame>Day 29</time_frame>
    <description>b) Clinical status using the 8-point ordinal scale assessed daily until Day 29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Improvement of clinical and biological parameters</measure>
    <time_frame>Day15, and Day 29</time_frame>
    <description>c) Temperature and blood analysis between baseline and Day 15, and Day 29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Oxygenation</measure>
    <time_frame>29 Days</time_frame>
    <description>d) Days of oxygen therapy over 29 days PaO2 / FiO2 at baseline, Day 5, Day 8, Day 15, Day 29 if available</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Non-invasive ventilation, high-flow oxygen</measure>
    <time_frame>29 Days</time_frame>
    <description>e) e) Days of non-invasive ventilation or high flow oxygen (if applicable) up to Day 29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Invasive mechanical ventilation / Extra Corporeal Membrane Oxygenation (ECMO)</measure>
    <time_frame>29 Days</time_frame>
    <description>f) Days of invasive mechanical ventilation/ECMO (if applicable) up to Day 29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Transfer in ICU by Day 29</measure>
    <time_frame>29 Days</time_frame>
    <description>g) Transfer in ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Hospitalization</measure>
    <time_frame>60 Days</time_frame>
    <description>h) Hospital length of stay (in days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Mortality</measure>
    <time_frame>60 Days</time_frame>
    <description>i) All-cause mortality evaluated between baseline and Day 15 and between baseline and at Day 29 and at Day 60</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Clinical severity : Thrombotic events</measure>
    <time_frame>60 Days</time_frame>
    <description>j) Thrombotic events (peripheral venous, pulmonary, arterial)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: mortality</measure>
    <time_frame>29 Days</time_frame>
    <description>k) All cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: safety</measure>
    <time_frame>29 days and 60 days</time_frame>
    <description>Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: safety of Study drug infusion</measure>
    <time_frame>29 days and 60 days</time_frame>
    <description>Study drug discontinuation or temporary suspension of infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: safety : study drug discontinuation</measure>
    <time_frame>29 days and 60 days</time_frame>
    <description>Proportion of participants with treatment emergent adverse events leading to study drug discontinuation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: safety : major or opportunistic bacterial or fungal infections</measure>
    <time_frame>29 days and 60 days</time_frame>
    <description>Incidence of major or opportunistic bacterial or fungal infections</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: safety : hypersensitivity reactions and infusion reactions</measure>
    <time_frame>29 days and 60 days</time_frame>
    <description>Incidence of hypersensitivity reactions and infusion reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: safety : biological parameters</measure>
    <time_frame>29 days and 60 days</time_frame>
    <description>White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D15 and D29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Exploratory analysis : qualitative and quantitative SARS-CoV-2 status</measure>
    <time_frame>Day 1, Day 8, Day 15 and Day 29</time_frame>
    <description>SARS-CoV-2 status (positive or negative and quantitatively, including variant information by sequencing) over time (D1, D8, D15, and D29)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2b: Exploratory analysis : SARS-CoV-2 status viral load</measure>
    <time_frame>Day 1, Day 8, Day 15 and Day 29</time_frame>
    <description>SARS-CoV-2 status viral load over time (D1, D8, D15, and D29)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Phase 2b : Pharmacokinetic Study</measure>
    <time_frame>Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29</time_frame>
    <description>Pharmacokinetic analysis correspond to antibody titer measurements at Day 1 (pre-dose, post-dose), Day 3, Day 5, Day 8, Day 15, and Day 29</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2b : Immunomonitoring Study</measure>
    <time_frame>Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29</time_frame>
    <description>The endpoints encompass the following analysis:&#xD;
Spike/ACE2 neutralizing antibody titers: D1 (pre-, post dose), D3, D5, D8, D15 and D29&#xD;
Lymphocytes sub-population: D1, D3, D5, D8 and D15&#xD;
Transcriptomic analyses: D1, D3, D5, D8 and D15&#xD;
Cytokines: D1, D3, D5, D8 and D15</description>
  </other_outcome>
  <other_outcome>
    <measure>Phase 2b : Terminal ancillary Study (20 additional patients receiving a fixed dose of 150mg of XAV-19 :</measure>
    <time_frame>Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29</time_frame>
    <description>to compare pharmacokinetic parameters in patients receiving a fixed dose of 150mg with patients receiving 2mg/Kg of XAV-19 (master phase 2b), in order to confirm that the exposure and variability are similar&#xD;
to compare the effects of neutralizing antibodies use on virus-induced immune response on longitudinal follow-up, and targets for &quot;immuno-monitoring&quot;&#xD;
to investigate the immunogenicity of COVID-19 during treatment with XAV19 in patients receiving a fixed dose of 150mg with patients receiving 2mg/Kg of XAV-19</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">416</enrollment>
  <condition>SARS Virus</condition>
  <arm_group>
    <arm_group_label>Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administrations of XAV-19&#xD;
Phase 2a: XAV-19 at 0.5 mg/kg at D1 and D5(Group 1) or at 2 mg/kg at D1 and D5 (Group 2), or at 2 mg/kg at D1 (groupe 3)&#xD;
Phase 2b: Selected dose from Phase 2a : one administration at 2 mg/kg on day1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>same administration as treatment arm&#xD;
Phase 2a: two administrations of placebo (day 1 and day 5) for Group 1 and 2, one administration of placebo on day 1 for Group 3&#xD;
Phase 2b: one administration of placebo on day 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>XAV-19</intervention_name>
    <description>Phase 2a: Administration on Day 1 and day 5 for Group1 and 2, Administration on Day 1 for Group 3 Phase 2b: Administration on Day 1</description>
    <arm_group_label>Treatment arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Phase 2a: Administration on Day 1 and day 5 for Group1 and 2, Administration on Day 1 for Group 3 Phase 2b: Administration on Day 1</description>
    <arm_group_label>Placebo arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Phase 2a:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent prior to performing study&#xD;
             procedures&#xD;
&#xD;
          2. Male or female ≥ 18 years and ≤ 85 years&#xD;
&#xD;
          3. Hospitalized for COVID-19&#xD;
&#xD;
          4. Positive SARS-CoV-2 RT-PCR in any body specimen (nasopharynx, saliva, sputum) ≤ 10&#xD;
             days before enrolment&#xD;
&#xD;
          5. Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or&#xD;
             chest-imaging [Chest X-ray or computed tomography])&#xD;
&#xD;
          6. Requiring O2 supplement ≤ 6L/min at screening&#xD;
&#xD;
          7. Requiring O2 supplementation with SpO2 ≥ 94% on O2 therapy at screening&#xD;
&#xD;
          8. First onset of COVID-19 symptoms ≤ 10 days, among fever and/or chills, headache,&#xD;
             myalgias, cough, shortness of breath, whichever as occurred fist&#xD;
&#xD;
          9. WOCBP must have a negative urinary pregnancy test the day of inclusion&#xD;
&#xD;
         10. All sexually active male subjects must agree to use an adequate method of&#xD;
             contraception throughout the study period and for 90 days after the last dose of study&#xD;
             drug and agree to no sperm donation until the end of the study, or for 90 days after&#xD;
             the last dose of XAV-19, whichever is longer&#xD;
&#xD;
         11. Patients with French social security&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of multiorgan failure (severe COVID-19)&#xD;
&#xD;
          2. Mechanically ventilated (including ECMO)&#xD;
&#xD;
          3. Receipt of immunoglobulins or any blood products in the past 30 days&#xD;
&#xD;
          4. Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion&#xD;
             of the investigator, would affect subject safety and/or compliance&#xD;
&#xD;
          5. End-stage renal disease (eGFR &lt; 15 ml/min/1,73 m2)&#xD;
&#xD;
          6. Child-Pugh C stage liver cirrhosis&#xD;
&#xD;
          7. Decompensated cardiac insufficiency&#xD;
&#xD;
          8. History of active drug abuse&#xD;
&#xD;
          9. Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its&#xD;
             components&#xD;
&#xD;
         10. Females of childbearing potential without contraceptive method, or with positive&#xD;
             pregnancy test, breastfeeding, or planning to become pregnant during the study period&#xD;
&#xD;
         11. Current documented and uncontrolled bacterial infection.&#xD;
&#xD;
         12. Prior severe (grade 3) allergic reactions to plasma transfusion&#xD;
&#xD;
         13. Patient participating in another interventional clinical trial&#xD;
&#xD;
         14. Life expectancy estimated to be less than 6 months&#xD;
&#xD;
         15. Patient under guardianship or trusteeship&#xD;
&#xD;
        Phase 2b:&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent prior to performing study&#xD;
             procedures&#xD;
&#xD;
          2. Male or female ≥ 18 years&#xD;
&#xD;
          3. Hospitalized for COVID-19&#xD;
&#xD;
          4. Documentation of SARS-Cov-2 infection before enrolment, by positive SARS-CoV-2 RT-PCR&#xD;
             or antigen in any body specimen (nasopharynx, oropharynx, saliva, sputum,&#xD;
             bronchoalveolar lavage …) before enrolment&#xD;
&#xD;
          5. Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or&#xD;
             chestimaging [Chest X-ray or computed tomography])&#xD;
&#xD;
          6. Requiring O2 supplement ≤ 6L/min at screening&#xD;
&#xD;
          7. Requiring O2 supplementation with SpO2 ≥ 92% on O2 therapy at screening (or ≥ 90&#xD;
&#xD;
             % if chronic obstructive pulmonary disease)&#xD;
&#xD;
          8. First onset of COVID-19 symptoms ≤ 14 days, among fever and/or chills, headache,&#xD;
             myalgias, cough, shortness of breath, whichever as occurred fist (other symptoms such&#xD;
             as asthenia not to be considered in this list)&#xD;
&#xD;
          9. WOCBP must have a negative urinary pregnancy test the day of inclusion&#xD;
&#xD;
         10. All sexually active male subjects must agree to use an adequate method of&#xD;
             contraception throughout the study period and for 90 days after the last dose of study&#xD;
             drug and agree to no sperm donation until the end of the study, or for 90 days after&#xD;
             the last dose of XAV-19, whichever is longer&#xD;
&#xD;
         11. Patients with French social security&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Evidence of multiorgan failure (severe COVID-19)&#xD;
&#xD;
          2. Mechanically ventilated (including ECMO)&#xD;
&#xD;
          3. Receipt of immunoglobulins or any blood products in the past 30 days&#xD;
&#xD;
          4. Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion&#xD;
             of the investigator, would affect subject safety and/or compliance&#xD;
&#xD;
          5. End-stage renal disease (eGFR &lt; 15 ml/min/1,73 m2)&#xD;
&#xD;
          6. Child-Pugh C stage liver cirrhosis&#xD;
&#xD;
          7. Decompensated cardiac insufficiency&#xD;
&#xD;
          8. Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its&#xD;
             components&#xD;
&#xD;
          9. Females of childbearing potential without contraceptive method, or with positive&#xD;
             pregnancy test, breastfeeding, or planning to become pregnant during the study period&#xD;
&#xD;
         10. Current documented and uncontrolled bacterial infection.&#xD;
&#xD;
         11. Prior severe (grade 3) allergic reactions to plasma transfusion&#xD;
&#xD;
         12. Patient participating in another interventional clinical trial&#xD;
&#xD;
         13. Life expectancy estimated to be less than 6 months&#xD;
&#xD;
         14. Patient under guardianship or trusteeship&#xD;
&#xD;
         15. Patient already included&#xD;
&#xD;
         16. Prior hospitalisation in intensive care unit for the current covid-19 episode&#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>Benjamin Gaborit</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Nantes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Amiens Picardie</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Privé d'Antony</name>
      <address>
        <city>Antony</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Avignon</name>
      <address>
        <city>Avignon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH de la Côte Basque</name>
      <address>
        <city>Bayonne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP - Hôpital Avicennes</name>
      <address>
        <city>Bobigny</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Caen</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Métropole Savoie</name>
      <address>
        <city>Chambéry</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Colmar</name>
      <address>
        <city>Colmar</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Sud Francilien</name>
      <address>
        <city>Corbeil-Essonnes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHD Vendée</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH de La Rochelle</name>
      <address>
        <city>La Rochelle</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Le Mans</name>
      <address>
        <city>Le Mans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Lille</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Limoges</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospices Civils Lyon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH de Mont de Marzan</name>
      <address>
        <city>Mont-de-Marsan</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GHR Mulhouse Sud-Alsace</name>
      <address>
        <city>Mulhouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nice</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nîmes</name>
      <address>
        <city>Nîmes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR Orléans La Source</name>
      <address>
        <city>Orléans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP - Hôpital Tenon</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Antoine</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH René Dubos</name>
      <address>
        <city>Pontoise</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Cornouaille</name>
      <address>
        <city>Quimper</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Reims</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Saint Etienne</name>
      <address>
        <city>Saint-Priest-en-Jarez</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital FOCH</name>
      <address>
        <city>Suresnes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Nancy</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Bretagne Atlantique</name>
      <address>
        <city>Vannes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Martinique</name>
      <address>
        <city>Fort de France</city>
        <country>Martinique</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU La Réunion</name>
      <address>
        <city>Saint-Pierre</city>
        <country>Réunion</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Martinique</country>
    <country>Réunion</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>March 24, 2022</last_update_submitted>
  <last_update_submitted_qc>March 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SARS-Cov-2</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Moderate</keyword>
  <keyword>pneumonia</keyword>
  <keyword>antibody</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>
  </condition_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/NCT04453384
org study id: RC20_0230
nct id: NCT04453384
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Early inhibition of entry and replication of the severe acute respiratory syndrome
      coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing
      antibodies offers many advantages such as providing immediate immunity, consequently blunt an
      early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug
      interactions1-3.

      Because a suboptimal endogenous early antibody response with regard to SARS-CoV-2 replication
      in severe cases is observed, neutralising antibody treatment can be very interesting for
      patient with COVID-19 induced moderate pneumonia4,5. Convalescent plasma to treat infected
      patients is therefore an interesting therapeutic option currently under evaluation. However,
      the difficulties of collecting plasma and its safety aspects are not adapted to many
      patients.

      A new polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) is being developed by
      Xenothera, which can be administered as intravenous treatment. XAV-19 is a heterologous swine
      glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2,
      inhibiting infection of ACE-2 positive human cells with SARS-CoV-2. Pharmacokinetic and
      pharmacodynamic studies have been performed in preclinical models including primates and a
      First In Human study with another fully representative GH-pAb from Xenothera is ongoing in
      volunteer patients recipients of a kidney graft. These studies indicated that 5 consecutive
      administrations of GH-pAbs can be safely performed in humans.

      The objective of this 2-steps phase 2 randomized double-blind, placebo-controlled study is 1)
      to define the optimal and safety XAV-19 dose to administrate in patients with COVID-19
      induced moderate pneumonia ; 2) to show the clinical benefit of selected dose of XAV-19 when
      administered to patients with COVID-19 induced moderate pneumonia.
For the first set of statistical analyses, to allow early reporting of primary and secondary
      endpoints at D15, the blind will be partially broken once all patients have completed Day 29.
      Except for statisticians, only the principal investigator and the scientific coordinator will
      have access to the full data set for the analysis of the primary and secondary endpoints up
      to day 29. The database will be partially locked (with all data up to day 29) as neither
      monitors nor investigators will be informed of the unblinding until the final data for day 60
      is completed and the final database is locked.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Phase 2a: XAV-19 antibody titers
time frame: Day 8
description: The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8
measure: Phase 2a: Adverse events of XAV-19
time frame: Day 29
description: Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days
measure: Phase 2b: To evaluate the efficacy of XAV-19 + standard-of-care (Soc) therapy compared with placebo + Soc therapy for treatment of COVID-19 assessed by the proportion of patients who die or develop respiratory failure between baseline and Day 15.
time frame: Day 15
description: Efficacy is defined by the proportion of patients who died or develop respiratory failure, as defined by the requirement of noninvasive ventilation, high-flow oxygen devices, invasive mechanical ventilation (corresponding to a score of 5 or more on the WHO 8 point ordinal scale) or by an increase of the required O2 supplement (more or equals to 10 L/minutes with a non-rebreather mask (oxygen mask with reservoir bag)
measure: Phase 2a: Pharmacokinetic analysis
time frame: Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29
description: XAV-19 Antibody titer over the time
measure: Phase 2a: Antibody titer between the two groups
time frame: day 15
description: The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients
measure: Phase 2a: Supplemental oxygen
time frame: Day 1 to Day 29
description: Duration of supplemental oxygen
measure: Phase 2a: Evaluation of Transfer to intensive care
time frame: Day 1 to Day 29
description: Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen
measure: Phase 2a: Normalization of Fever
time frame: Day 1 to Day 29
description: Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1
measure: Phase 2a: Biomarkers
time frame: Day 1 to Day 29
description: Biomarkers : CRP, Ferritin
measure: Phase 2a: Hospital length of stay
time frame: Day 1 to Day 29
description: Evaluation of Hospital length of stay
measure: Phase 2b: Efficacy of XAV-19
time frame: Day 8 and Day 29
description: Proportion of patients who die, develop respiratory failure, as defined by the requirement of noninvasive ventilation, high-flow oxygen devices or invasive mechanical ventilation at Day 8 and D29
measure: Phase 2b: Clinical severity
time frame: Day 3, Day 5, Day 8, Day15 and Day 29
description: a) National Early Warning Score (NEWS) assessed while hospitalized and on Day 15 and Day 29
measure: Phase 2b: Clinical severity
time frame: Day 29
description: b) Clinical status using the 8-point ordinal scale assessed daily until Day 29
measure: Phase 2b: Clinical severity : Improvement of clinical and biological parameters
time frame: Day15, and Day 29
description: c) Temperature and blood analysis between baseline and Day 15, and Day 29
measure: Phase 2b: Clinical severity : Oxygenation
time frame: 29 Days
description: d) Days of oxygen therapy over 29 days PaO2 / FiO2 at baseline, Day 5, Day 8, Day 15, Day 29 if available
measure: Phase 2b: Clinical severity : Non-invasive ventilation, high-flow oxygen
time frame: 29 Days
description: e) e) Days of non-invasive ventilation or high flow oxygen (if applicable) up to Day 29
measure: Phase 2b: Clinical severity : Invasive mechanical ventilation / Extra Corporeal Membrane Oxygenation (ECMO)
time frame: 29 Days
description: f) Days of invasive mechanical ventilation/ECMO (if applicable) up to Day 29
measure: Phase 2b: Clinical severity : Transfer in ICU by Day 29
time frame: 29 Days
description: g) Transfer in ICU
measure: Phase 2b: Clinical severity : Hospitalization
time frame: 60 Days
description: h) Hospital length of stay (in days)
measure: Phase 2b: Clinical severity : Mortality
time frame: 60 Days
description: i) All-cause mortality evaluated between baseline and Day 15 and between baseline and at Day 29 and at Day 60
measure: Phase 2b: Clinical severity : Thrombotic events
time frame: 60 Days
description: j) Thrombotic events (peripheral venous, pulmonary, arterial)
measure: Phase 2b: mortality
time frame: 29 Days
description: k) All cause mortality
measure: Phase 2b: safety
time frame: 29 days and 60 days
description: Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events
measure: Phase 2b: safety of Study drug infusion
time frame: 29 days and 60 days
description: Study drug discontinuation or temporary suspension of infusion
measure: Phase 2b: safety : study drug discontinuation
time frame: 29 days and 60 days
description: Proportion of participants with treatment emergent adverse events leading to study drug discontinuation
measure: Phase 2b: safety : major or opportunistic bacterial or fungal infections
time frame: 29 days and 60 days
description: Incidence of major or opportunistic bacterial or fungal infections
measure: Phase 2b: safety : hypersensitivity reactions and infusion reactions
time frame: 29 days and 60 days
description: Incidence of hypersensitivity reactions and infusion reactions
measure: Phase 2b: safety : biological parameters
time frame: 29 days and 60 days
description: White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D15 and D29
measure: Phase 2b: Exploratory analysis : qualitative and quantitative SARS-CoV-2 status
time frame: Day 1, Day 8, Day 15 and Day 29
description: SARS-CoV-2 status (positive or negative and quantitatively, including variant information by sequencing) over time (D1, D8, D15, and D29)
measure: Phase 2b: Exploratory analysis : SARS-CoV-2 status viral load
time frame: Day 1, Day 8, Day 15 and Day 29
description: SARS-CoV-2 status viral load over time (D1, D8, D15, and D29)
measure: Phase 2b : Pharmacokinetic Study
time frame: Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
description: Pharmacokinetic analysis correspond to antibody titer measurements at Day 1 (pre-dose, post-dose), Day 3, Day 5, Day 8, Day 15, and Day 29
measure: Phase 2b : Immunomonitoring Study
time frame: Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
description: The endpoints encompass the following analysis:
Spike/ACE2 neutralizing antibody titers: D1 (pre-, post dose), D3, D5, D8, D15 and D29
Lymphocytes sub-population: D1, D3, D5, D8 and D15
Transcriptomic analyses: D1, D3, D5, D8 and D15
Cytokines: D1, D3, D5, D8 and D15
measure: Phase 2b : Terminal ancillary Study (20 additional patients receiving a fixed dose of 150mg of XAV-19 :
time frame: Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
description: to compare pharmacokinetic parameters in patients receiving a fixed dose of 150mg with patients receiving 2mg/Kg of XAV-19 (master phase 2b), in order to confirm that the exposure and variability are similar
to compare the effects of neutralizing antibodies use on virus-induced immune response on longitudinal follow-up, and targets for "immuno-monitoring"
to investigate the immunogenicity of COVID-19 during treatment with XAV19 in patients receiving a fixed dose of 150mg with patients receiving 2mg/Kg of XAV-19
arm group label: Treatment arm
arm group type: Experimental
description: Administrations of XAV-19
Phase 2a: XAV-19 at 0.5 mg/kg at D1 and D5(Group 1) or at 2 mg/kg at D1 and D5 (Group 2), or at 2 mg/kg at D1 (groupe 3)
Phase 2b: Selected dose from Phase 2a : one administration at 2 mg/kg on day1
arm group label: Placebo arm
arm group type: Placebo Comparator
description: same administration as treatment arm
Phase 2a: two administrations of placebo (day 1 and day 5) for Group 1 and 2, one administration of placebo on day 1 for Group 3
Phase 2b: one administration of placebo on day 1
intervention type: Drug
intervention name: XAV-19
description: Phase 2a: Administration on Day 1 and day 5 for Group1 and 2, Administration on Day 1 for Group 3 Phase 2b: Administration on Day 1
arm group label: Treatment arm
intervention type: Drug
intervention name: Placebo
description: Phase 2a: Administration on Day 1 and day 5 for Group1 and 2, Administration on Day 1 for Group 3 Phase 2b: Administration on Day 1
arm group label: Placebo arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Benjamin Gaborit
role: Principal Investigator
affiliation: CHU Nantes
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country: France
country: Martinique
country: Réunion
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
sharing ipd: No