<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/NCT04413838</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL20_0478</org_study_id>
    <nct_id>NCT04413838</nct_id>
  </id_info>
  <brief_title>Efficiency and Security of NIVOLUMAB Therapy in Obese Individuals With COVID-19(COrona VIrus Disease) Infection</brief_title>
  <acronym>NIVISCO</acronym>
  <official_title>Study of the Efficiency and Security of NIVOLUMAB Therapy, Used in Immuno-stimulation, in Hospitalized Obese Individuals at Risk to Evolve Towards Severe Forms of COVID-19 Infection. Multicentric, Paralleled, Randomized, Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Although SARS-CoV-2 (Severe Acute Respiratory Syndrome-associated coronavirus) due to&#xD;
      COVID-19 evolves poorly towards ARDS (Acute Respiratory Distress Syndrome) and death, there&#xD;
      is to date no validated drug available for severe forms of COVID-19. Patients with COVID-19&#xD;
      undergo a drastic decrease of T lymphocytes (LT) count, while the remaining ones display an&#xD;
      &quot;exhausted&quot; phenotype, due to immunosuppressive pathway activation among which the Programed&#xD;
      cell Death 1 (PD1) receptor pathways. LT exhaustion is responsible for host anergy towards&#xD;
      viral infection and leads to increased risk of severe forms of COVID-19. Moreover, while the&#xD;
      number of systemic LT PD1+ correlates with poor prognosis clinical stages of COVID-19&#xD;
      infection, healing from COVID-19 associates with LT PD1 expression normalization. Chinese&#xD;
      epidemiologic data identified clinical risk factors of poor clinical evolution (i.e. ARDS or&#xD;
      death), among which is found obesity, similarly to observation previously obtained during&#xD;
      H1N1 infection (flu virus).&#xD;
&#xD;
      Obese persons display meta-inflammation and immune dysfunction, a condition similar to&#xD;
      ageing, thus termed &quot;Inflamm-aging&quot;, thus also used during obesity. Inflamm-aging,&#xD;
      characterized by cytotoxic LT exhaustion and reduced NK cell (Natural Killer cell) cytotoxic&#xD;
      function secondary to PD1 pathway activation, could contribute to the poor prognosis observed&#xD;
      during cancer and infection in obese individuals. We hypothesize that the immunocompromised&#xD;
      profile observed during obesity contribute to their vulnerability towards COVID-19.&#xD;
&#xD;
      In cancer or certain infection diseases, NIVOLUMAB, an anti-PD1 monoclonal antibody, restores&#xD;
      exhausted LT immunity. We thus hypothesize that NIVOLUMAB-induced immunity normalization&#xD;
      could (i) stimulate anti-viral response also during COVID-19 infection and (ii) prevent ARDS&#xD;
      development, which has previously been associated with low LT count concomitant with&#xD;
      increased inflammatory cytokine production.&#xD;
&#xD;
      This randomized controlled therapeutic trial, using an add-on strategy to usual standard of&#xD;
      care, aims at demonstrating the efficacy and safety of NIVOLUMAB-induced cytotoxic LT&#xD;
      normalization, to improve clinical outcomes in hospitalized COVID-19+ adult obese individuals&#xD;
      with low LT, since they are at risk of poor prognosis. We postulate that NIVOLUMAB will&#xD;
      increase the number of individuals able to stop oxygen therapy at D15&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 15, 2020</start_date>
  <completion_date type="Anticipated">September 15, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 15, 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>Patient's clinical state</measure>
    <time_frame>15 days after randomization</time_frame>
    <description>Patient's clinical state will be evaluated by the proportion of patients able to be weaned of oxygen at D15 after randomization (randomization date is the day where the experimental treatment (i.e. NIVOLUMAB) is administered).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Readmission</measure>
    <time_frame>7 days and 15 days after randomization</time_frame>
    <description>Proportion of in-coming patients in ICU at D7 and D15 post-randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>7 days and 15 days after randomization</time_frame>
    <description>Proportion of death at D7 and D15 post-randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen flow needs</measure>
    <time_frame>7 days after randomization</time_frame>
    <description>Proportion of patients weaned out of oxygen at D7 post-randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Requirement of oxygen</measure>
    <time_frame>7 days and 15 days after randomization</time_frame>
    <description>Mean oxygen flow needed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Discharge from hospital</measure>
    <time_frame>7 days and 15 days after randomization</time_frame>
    <description>Proportion of out-coming patients from hospitalization at D7 and D15 post-randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Within 15 days post-randomization and 90 days and 6 months after randomization</time_frame>
    <description>Report of all adverse events linked or not to experimental treatment during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of nasopharyngeal SARS-CoV-2</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Presence or not of nasopharyngeal SARS-CoV-2 determined by PCR response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nasopharyngeal SARS-CoV-2 viral charge</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Presence or not of nasopharyngeal SARS-CoV-2 Quantified by PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of total Lymphocytes T</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Number of total LT (using immuno-phenotyping) will explore the immune response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of CD3+ Lymphocytes T(lymphocyte subpopulation of CD3+ T cells)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Number of CD3+ LT (using immuno-phenotyping) will explore the immune response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of CD4+ Lymphocytes T(lymphocyte subpopulation of CD4+ T cells)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Number of total CD4+ LT (using immuno-phenotyping) will explore the immune response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of CD8+ Lymphocytes T(lymphocyte subpopulation of CD8+ T cells)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Evaluation of number of CD8+ LT (using immuno-phenotyping) will explore the immune response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin 6 (IL-6)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Systemic concentration measurement of IL-6 will explore the inflammatory response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin 10 (IL-10)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Systemic concentration measurement of IL-10 will explore the inflammatory response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Necrosis Factor alpha (TNFα )</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Systemic concentration measurement of TNFα will explore the inflammatory response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interferon gamma (IFNγ)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Systemic concentration measurement of IFNγ will explore the inflammatory response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type I Interferon (type I IFN)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Systemic concentration measurement of type I IFN will explore the inflammatory response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tim3 expression</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Evaluation of Tim3 expression on CD4+ and CD8+ lymphocytes will explore the fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD1 expression</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Evaluation of PD1 expression on CD4+ and CD8+ lymphocytes will explore the fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD-L1 expression</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Measurement of PD-L1 expression on monocytes will explore explore the fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Human Leukocyte Antigen - DR isotype gene expression (HLA-DR expression)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Measurement of HLA-DR expression on monocytes will explore explore the fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Production of IFNγ by lymphocytes T</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>The cytotoxic LT production of IFNγ will explore the fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Production of granzyme B by lymphocytesT</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>The cytotoxic LT production of granzyme B will explore the fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipopolysaccharides (LPS)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Measurement of LPS will explore the endotoxemia and perform fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LBP(LPS-Binding Protein)</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Measurement of LBP (endotoxin transporter) will explore the endotoxemia and perform fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>sCD14</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Measurement of sCD14 (endotoxin transporter) will explore the endotoxemia and perform fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High Density Lipoproteins</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Measurement of High Density Lipoproteins proteomic will explore the lipoprotein metabolism and perform fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apolipoprotein</measure>
    <time_frame>On day 0 before randomization and 15 days after randomization</time_frame>
    <description>Measurement of apolipoprotein proteomic will explore the lipoprotein metabolism and perform fundamental research on obesity and COVID-19</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Obesity, COVID-19 Infection</condition>
  <arm_group>
    <arm_group_label>NIVOLUMAB on top of routine standard of care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This correspond to COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2), hospitalized, obese (BMI≥30kg/m²), with low lymphocyte counts, without high biological probability of macrophage activation syndrome (hemoglobin &lt; 9.2 g/dl AND a blood platelets &lt; 110000/mm3 AND aspartate aminotransferase (AST) &gt; 30 U/l AND ferritin &gt; 600 mg/l) and upon oxygen (either using mask or nasal cannula) but without criteria for ICU admission benefiting from a NIVOLUMAB treatment and routine standard of care for COVID-19 infection at the time of study inclusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care for COVID-19 infection</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>This correspond to COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2), hospitalized, obese (BMI≥30kg/m²), with low lymphocyte counts, without high biological probability of macrophage activation syndrome (hemoglobin &lt; 9.2 g/dl AND a blood platelets &lt; 110000/mm3 AND AST &gt; 30 U/l AND ferritin &gt; 600 mg/l) and upon oxygen (either using mask or nasal cannula) but without criteria for ICU admission benefiting from a routine standard of care for COVID-19 infection at the time of study inclusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NIVOLUMAB</intervention_name>
    <description>IV injection within 30 minutes of 24ml file (=240 mg) containing NIVOLUMAB BMS(Bristol-Myers Squibb) 10mg/ml (immune check point inhibitor targeting PD-1) on top of routine standard of care for COVID-19 infection</description>
    <arm_group_label>NIVOLUMAB on top of routine standard of care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Routine standard of care</intervention_name>
    <description>No intervention is planned in this arm. Patients will follow routine standard of care for the COVID-19 treatment</description>
    <arm_group_label>Standard of care for COVID-19 infection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients between 18 and 70 years old&#xD;
&#xD;
          -  COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2)&#xD;
&#xD;
          -  Hospitalized patients&#xD;
&#xD;
          -  Obese individuals (BMI≥30kg/m²)&#xD;
&#xD;
          -  Lymphocyte counts between 500 and 1500/mm3.&#xD;
&#xD;
          -  Patients upon oxygen (either using mask or nasal cannula).&#xD;
&#xD;
          -  Patients within their first 7 days after the beginning of symptoms.&#xD;
&#xD;
          -  Women of childbearing potential: effective contraception for the duration of the study&#xD;
             and 5 months after the administration of treatment.&#xD;
&#xD;
          -  Patient who understands and accepts the need for a long term follow-up,&#xD;
&#xD;
          -  Patients who agrees to be included in the study and who signs the informed consent&#xD;
             form,&#xD;
&#xD;
          -  Patients affiliated to a healthcare insurance plan.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  CRITERIA LINKED TO THE DISEASE SEVERITY :&#xD;
&#xD;
               -  Patients hospitalized in ICU or constant care unit.&#xD;
&#xD;
               -  Patients with clinical symptoms requiring ICU admission (respiratory rate&gt;30/min,&#xD;
                  oxygen requirement&gt; 4Liters/min (using high concentration mask) to reach and&#xD;
                  maintain O2saturation&gt;90%, qSOFA≥ 2(quick score of Sepsis-related Organ Failure&#xD;
                  Assessment), or associated multi-visceral failure.&#xD;
&#xD;
               -  Patients with high biological probability of macrophage activation syndrome&#xD;
                  (hemoglobin &lt; 9.2 g/dl AND a blood platelets &lt; 110000/mm3 AND AST &gt; 30 U/l AND&#xD;
                  ferritin &gt; 600 mg/l).&#xD;
&#xD;
        CRITERIA LINKED TO THE TREATMENT TOXICITY :&#xD;
&#xD;
          -  Patients currently treated for cancer or with personal history of cancer within the&#xD;
             last 3 years.&#xD;
&#xD;
          -  Patients with Chronic Obstructive Pulmonary Disease (COPD) (GOLD 3 and 4 stages).&#xD;
&#xD;
          -  Chronic respiratory insufficiency treated with oxygen.&#xD;
&#xD;
          -  Patients aged above 70 years old.&#xD;
&#xD;
          -  Active smoking.&#xD;
&#xD;
          -  Personal history of thoracic radiotherapy.&#xD;
&#xD;
          -  Patients with known sensibility to NIVOLUMAB or one of its component.&#xD;
&#xD;
          -  Patients upon immunosuppressive dosage of corticoids.&#xD;
&#xD;
          -  Patients upon immunosuppressive therapy or immunosuppressed patients.&#xD;
&#xD;
          -  Patients already presenting severe autoimmune disease, for whom additional immunologic&#xD;
             activation response would potentially precipitate lethal prognosis&#xD;
&#xD;
        GENERAL CRITERIA:&#xD;
&#xD;
          -  Minor Patients&#xD;
&#xD;
          -  Mentally unbalanced patients, under supervision or guardianship,&#xD;
&#xD;
          -  Patient deprived of liberty,&#xD;
&#xD;
          -  Patient who does not understand French/ is unable to give consent,&#xD;
&#xD;
          -  Patient already included in a trial who may interfere with the study or in a period of&#xD;
             exclusion following participation in a previous study.&#xD;
&#xD;
          -  Pregnant (controlled by a pregnancy test) or lactating woman&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Emmanuel DISSE, Pr</last_name>
    <phone>+33 4 78 86 14 84</phone>
    <email>emmanuel.disse@chu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dominique DELAUNAY</last_name>
    <phone>+33.4.72.11.00.64</phone>
    <email>Dominique.delaunay@chu-lyon.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital Lyon Sud Service Endocrinologie, Diabète et Nutrition</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Pr</last_name>
    </contact>
    <investigator>
      <last_name>Emmanuel DISSE</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 2, 2020</last_update_submitted>
  <last_update_submitted_qc>June 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Obesity</keyword>
  <keyword>Nivolumab</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Anti-PD1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</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/NCT04413838
org study id: 69HCL20_0478
nct id: NCT04413838
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Although SARS-CoV-2 (Severe Acute Respiratory Syndrome-associated coronavirus) due to
      COVID-19 evolves poorly towards ARDS (Acute Respiratory Distress Syndrome) and death, there
      is to date no validated drug available for severe forms of COVID-19. Patients with COVID-19
      undergo a drastic decrease of T lymphocytes (LT) count, while the remaining ones display an
      "exhausted" phenotype, due to immunosuppressive pathway activation among which the Programed
      cell Death 1 (PD1) receptor pathways. LT exhaustion is responsible for host anergy towards
      viral infection and leads to increased risk of severe forms of COVID-19. Moreover, while the
      number of systemic LT PD1+ correlates with poor prognosis clinical stages of COVID-19
      infection, healing from COVID-19 associates with LT PD1 expression normalization. Chinese
      epidemiologic data identified clinical risk factors of poor clinical evolution (i.e. ARDS or
      death), among which is found obesity, similarly to observation previously obtained during
      H1N1 infection (flu virus).

      Obese persons display meta-inflammation and immune dysfunction, a condition similar to
      ageing, thus termed "Inflamm-aging", thus also used during obesity. Inflamm-aging,
      characterized by cytotoxic LT exhaustion and reduced NK cell (Natural Killer cell) cytotoxic
      function secondary to PD1 pathway activation, could contribute to the poor prognosis observed
      during cancer and infection in obese individuals. We hypothesize that the immunocompromised
      profile observed during obesity contribute to their vulnerability towards COVID-19.

      In cancer or certain infection diseases, NIVOLUMAB, an anti-PD1 monoclonal antibody, restores
      exhausted LT immunity. We thus hypothesize that NIVOLUMAB-induced immunity normalization
      could (i) stimulate anti-viral response also during COVID-19 infection and (ii) prevent ARDS
      development, which has previously been associated with low LT count concomitant with
      increased inflammatory cytokine production.

      This randomized controlled therapeutic trial, using an add-on strategy to usual standard of
      care, aims at demonstrating the efficacy and safety of NIVOLUMAB-induced cytotoxic LT
      normalization, to improve clinical outcomes in hospitalized COVID-19+ adult obese individuals
      with low LT, since they are at risk of poor prognosis. We postulate that NIVOLUMAB will
      increase the number of individuals able to stop oxygen therapy at D15
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Patient's clinical state
time frame: 15 days after randomization
description: Patient's clinical state will be evaluated by the proportion of patients able to be weaned of oxygen at D15 after randomization (randomization date is the day where the experimental treatment (i.e. NIVOLUMAB) is administered).
measure: Readmission
time frame: 7 days and 15 days after randomization
description: Proportion of in-coming patients in ICU at D7 and D15 post-randomization
measure: Mortality
time frame: 7 days and 15 days after randomization
description: Proportion of death at D7 and D15 post-randomization
measure: Oxygen flow needs
time frame: 7 days after randomization
description: Proportion of patients weaned out of oxygen at D7 post-randomization
measure: Requirement of oxygen
time frame: 7 days and 15 days after randomization
description: Mean oxygen flow needed
measure: Discharge from hospital
time frame: 7 days and 15 days after randomization
description: Proportion of out-coming patients from hospitalization at D7 and D15 post-randomization
measure: Adverse events
time frame: Within 15 days post-randomization and 90 days and 6 months after randomization
description: Report of all adverse events linked or not to experimental treatment during the study
measure: Presence of nasopharyngeal SARS-CoV-2
time frame: On day 0 before randomization and 15 days after randomization
description: Presence or not of nasopharyngeal SARS-CoV-2 determined by PCR response
measure: nasopharyngeal SARS-CoV-2 viral charge
time frame: On day 0 before randomization and 15 days after randomization
description: Presence or not of nasopharyngeal SARS-CoV-2 Quantified by PCR
measure: Number of total Lymphocytes T
time frame: On day 0 before randomization and 15 days after randomization
description: Number of total LT (using immuno-phenotyping) will explore the immune response
measure: Number of CD3+ Lymphocytes T(lymphocyte subpopulation of CD3+ T cells)
time frame: On day 0 before randomization and 15 days after randomization
description: Number of CD3+ LT (using immuno-phenotyping) will explore the immune response
measure: Number of CD4+ Lymphocytes T(lymphocyte subpopulation of CD4+ T cells)
time frame: On day 0 before randomization and 15 days after randomization
description: Number of total CD4+ LT (using immuno-phenotyping) will explore the immune response
measure: Number of CD8+ Lymphocytes T(lymphocyte subpopulation of CD8+ T cells)
time frame: On day 0 before randomization and 15 days after randomization
description: Evaluation of number of CD8+ LT (using immuno-phenotyping) will explore the immune response
measure: Interleukin 6 (IL-6)
time frame: On day 0 before randomization and 15 days after randomization
description: Systemic concentration measurement of IL-6 will explore the inflammatory response
measure: Interleukin 10 (IL-10)
time frame: On day 0 before randomization and 15 days after randomization
description: Systemic concentration measurement of IL-10 will explore the inflammatory response
measure: Tumor Necrosis Factor alpha (TNFα )
time frame: On day 0 before randomization and 15 days after randomization
description: Systemic concentration measurement of TNFα will explore the inflammatory response
measure: Interferon gamma (IFNγ)
time frame: On day 0 before randomization and 15 days after randomization
description: Systemic concentration measurement of IFNγ will explore the inflammatory response
measure: Type I Interferon (type I IFN)
time frame: On day 0 before randomization and 15 days after randomization
description: Systemic concentration measurement of type I IFN will explore the inflammatory response
measure: Tim3 expression
time frame: On day 0 before randomization and 15 days after randomization
description: Evaluation of Tim3 expression on CD4+ and CD8+ lymphocytes will explore the fundamental research on obesity and COVID-19
measure: PD1 expression
time frame: On day 0 before randomization and 15 days after randomization
description: Evaluation of PD1 expression on CD4+ and CD8+ lymphocytes will explore the fundamental research on obesity and COVID-19
measure: PD-L1 expression
time frame: On day 0 before randomization and 15 days after randomization
description: Measurement of PD-L1 expression on monocytes will explore explore the fundamental research on obesity and COVID-19
measure: Human Leukocyte Antigen - DR isotype gene expression (HLA-DR expression)
time frame: On day 0 before randomization and 15 days after randomization
description: Measurement of HLA-DR expression on monocytes will explore explore the fundamental research on obesity and COVID-19
measure: Production of IFNγ by lymphocytes T
time frame: On day 0 before randomization and 15 days after randomization
description: The cytotoxic LT production of IFNγ will explore the fundamental research on obesity and COVID-19
measure: Production of granzyme B by lymphocytesT
time frame: On day 0 before randomization and 15 days after randomization
description: The cytotoxic LT production of granzyme B will explore the fundamental research on obesity and COVID-19
measure: Lipopolysaccharides (LPS)
time frame: On day 0 before randomization and 15 days after randomization
description: Measurement of LPS will explore the endotoxemia and perform fundamental research on obesity and COVID-19
measure: LBP(LPS-Binding Protein)
time frame: On day 0 before randomization and 15 days after randomization
description: Measurement of LBP (endotoxin transporter) will explore the endotoxemia and perform fundamental research on obesity and COVID-19
measure: sCD14
time frame: On day 0 before randomization and 15 days after randomization
description: Measurement of sCD14 (endotoxin transporter) will explore the endotoxemia and perform fundamental research on obesity and COVID-19
measure: High Density Lipoproteins
time frame: On day 0 before randomization and 15 days after randomization
description: Measurement of High Density Lipoproteins proteomic will explore the lipoprotein metabolism and perform fundamental research on obesity and COVID-19
measure: Apolipoprotein
time frame: On day 0 before randomization and 15 days after randomization
description: Measurement of apolipoprotein proteomic will explore the lipoprotein metabolism and perform fundamental research on obesity and COVID-19
arm group label: NIVOLUMAB on top of routine standard of care
arm group type: Experimental
description: This correspond to COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2), hospitalized, obese (BMI≥30kg/m²), with low lymphocyte counts, without high biological probability of macrophage activation syndrome (hemoglobin < 9.2 g/dl AND a blood platelets < 110000/mm3 AND aspartate aminotransferase (AST) > 30 U/l AND ferritin > 600 mg/l) and upon oxygen (either using mask or nasal cannula) but without criteria for ICU admission benefiting from a NIVOLUMAB treatment and routine standard of care for COVID-19 infection at the time of study inclusion
arm group label: Standard of care for COVID-19 infection
arm group type: Other
description: This correspond to COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2), hospitalized, obese (BMI≥30kg/m²), with low lymphocyte counts, without high biological probability of macrophage activation syndrome (hemoglobin < 9.2 g/dl AND a blood platelets < 110000/mm3 AND AST > 30 U/l AND ferritin > 600 mg/l) and upon oxygen (either using mask or nasal cannula) but without criteria for ICU admission benefiting from a routine standard of care for COVID-19 infection at the time of study inclusion
intervention type: Drug
intervention name: NIVOLUMAB
description: IV injection within 30 minutes of 24ml file (=240 mg) containing NIVOLUMAB BMS(Bristol-Myers Squibb) 10mg/ml (immune check point inhibitor targeting PD-1) on top of routine standard of care for COVID-19 infection
arm group label: NIVOLUMAB on top of routine standard of care
intervention type: Other
intervention name: Routine standard of care
description: No intervention is planned in this arm. Patients will follow routine standard of care for the COVID-19 treatment
arm group label: Standard of care for COVID-19 infection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Emmanuel DISSE, Pr
phone: +33 4 78 86 14 84
email: emmanuel.disse@chu-lyon.fr
last name: Dominique DELAUNAY
phone: +33.4.72.11.00.64
email: Dominique.delaunay@chu-lyon.fr
facility: 
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Nivolumab
sharing ipd: No