<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/NCT04469634</url>
  </required_header>
  <id_info>
    <org_study_id>1412/20</org_study_id>
    <nct_id>NCT04469634</nct_id>
  </id_info>
  <brief_title>Are SARS-CoV-2 Specific Antibodies a Correlate for Protection?</brief_title>
  <acronym>ImmCoV</acronym>
  <official_title>Are SARS-CoV-2 Specific Antibodies a Correlate for Protection?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Tropical Medicine, Belgium</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jessa Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Antwerp</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universiteit Antwerpen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sciensano</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mensura</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Tropical Medicine, Belgium</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this study are (1) to determine the ex vivo neutralizing capacity and the&#xD;
      longevity of SARS-CoV-2-specific Ab responses and (2) to measure the memory B-cell responses&#xD;
      in a cohort of health care workers (HCW) recovering from severe, mild or asymptomatic&#xD;
      infection. By focusing on HCW, a population that is at risk for re-infection during a second&#xD;
      epidemic wave, the correlation between nAb levels and protection is investigated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      SARS-CoV-2 has spread at an unprecedented speed and scale since January 2020. Since then,&#xD;
      Belgium has been confronted with &gt;60.000 diagnosed cases and likely many more undiagnosed&#xD;
      with mild or no symptoms. The true seroprevalence of SARS-CoV-2 in the Belgian population is&#xD;
      not known, yet increasing confidence about the performance of several serological assays&#xD;
      paves the way to large-scale serosurveys. These studies will be crucial in assessing&#xD;
      population immunity and evaluating the risk of re-infection. The first, smaller-scaled,&#xD;
      antibody surveys report a range of seroprevalences, i.e. Germany (14%), The Netherlands (4%),&#xD;
      USA (2.49-4.16%) and Belgium (4.7-6.9%). These studies suffer from conceptual and technical&#xD;
      flaws yet are used for easing lockdown measures. A major limitation is that antibody (Ab)&#xD;
      capture assays measure exposure to SARS-CoV-2, rather than subsequent protection, which&#xD;
      requires assessment of the quality of the Abs including their capacity to neutralize the&#xD;
      virus. Also the Ab levels required for protection and their duration are yet unknown. The&#xD;
      proposed project aims to address these pertinent questions in a population at risk of&#xD;
      re-infection during a second epidemic wave. Sero-neutralisation assays are regarded the gold&#xD;
      standard method to measure ex vivo Ab neutralising activity against viruses, including&#xD;
      SARS-CoV-2. A recent Chinese study, using a pseudovirus neutralisation assay, found that nAbs&#xD;
      are detected from day 10-15 after onset of disease and that younger patients typically have&#xD;
      lower levels of nAbs compared to middle-aged and elderly patients. Importantly, in about 1&#xD;
      out of 3 patients the nAb titers were low and in 10 young patients nAbs were absent. A&#xD;
      pseudovirus is an imperfect model for SARS-CoV-2 because of the non-natural embedding of&#xD;
      Spike protein in the pseudovirions and differences in glycosylation. In this study, a whole&#xD;
      virus neutralisation assay will be used that was recently validated using a panel of&#xD;
      SARS-CoV-2 convalescent sera in the lab of the Principal Investigator. Preliminary results of&#xD;
      the study team show a rapid decline in nAb titer within 15-36d after diagnosis in 4/11&#xD;
      patients, while IgG and IgA remain steady and high in ELISA. Older studies with SARS-CoV-1&#xD;
      showed declining IgM and IgA antibody titers within 6 months, declining IgG titers after 1y,&#xD;
      and a complete lack of antigen-specific peripheral memory B-cell (MBC) responses after&#xD;
      recovery. Measuring only circulating Abs can be misleading as it excludes the detection of&#xD;
      the MBC pool, which can exist in the absence of detectable serum Ab levels and is a&#xD;
      pre-requisite to maintain protective immunity in the long term. Upon re-encounter with the&#xD;
      antigen, MBC can rapidly differentiate to produce Abs. So far, little is known about humoral&#xD;
      immune responses against SARS-CoV-2 and their contribution to protection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2020</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Antibody levels over time</measure>
    <time_frame>12 months</time_frame>
    <description>Antibody levels over time</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Antibody neutralizing capacity</measure>
    <time_frame>12 months</time_frame>
    <description>Antibody neutralizing capacity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Memory B-cell function</measure>
    <time_frame>12 months</time_frame>
    <description>Memory B-cell function</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Antibody-dependent enhancement</measure>
    <time_frame>12 months</time_frame>
    <description>Antibody-dependent enhancement</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Re-infection with SARS-CoV2</measure>
    <time_frame>12 months</time_frame>
    <description>Re-infection with SARS-CoV2</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>SARS-CoV2</condition>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>antibody response and memory B-cell</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Regular blood draws to measure antibody responses and memory B-cell responses Regular swab collection to test for re-infection</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Assessing antibody responses, neutralizing capacity and memory B-cell function</intervention_name>
    <description>Assessing antibody responses, neutralizing capacity and memory B-cell function and their contribution to protection against re-infection</description>
    <arm_group_label>antibody response and memory B-cell</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be diagnosed (PCR+) with COVID-19 between March-May 2020&#xD;
&#xD;
          -  Be a permanent employee (HCW: nurse, physician, paramedical) of the study hospital&#xD;
&#xD;
          -  Agree to complete a short questionnaire and be sampled 4 tubes of heparin whole blood&#xD;
             every 3 months over a one-year period&#xD;
&#xD;
          -  Have given their informed consent to participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Persons in serious clinical condition, incompatible with the informed consent&#xD;
             procedure&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Persons that have not been diagnosed with COVID-19&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin K. Ariën, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Tropical Medicine Antwerp</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Antwerp</name>
      <address>
        <city>Antwerpen</city>
        <zip>2000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jessa Hospital</name>
      <address>
        <city>Hasselt</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>March 3, 2023</last_update_submitted>
  <last_update_submitted_qc>March 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04469634
org study id: 1412/20
nct id: NCT04469634
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objectives of this study are (1) to determine the ex vivo neutralizing capacity and the
      longevity of SARS-CoV-2-specific Ab responses and (2) to measure the memory B-cell responses
      in a cohort of health care workers (HCW) recovering from severe, mild or asymptomatic
      infection. By focusing on HCW, a population that is at risk for re-infection during a second
      epidemic wave, the correlation between nAb levels and protection is investigated.
SARS-CoV-2 has spread at an unprecedented speed and scale since January 2020. Since then,
      Belgium has been confronted with >60.000 diagnosed cases and likely many more undiagnosed
      with mild or no symptoms. The true seroprevalence of SARS-CoV-2 in the Belgian population is
      not known, yet increasing confidence about the performance of several serological assays
      paves the way to large-scale serosurveys. These studies will be crucial in assessing
      population immunity and evaluating the risk of re-infection. The first, smaller-scaled,
      antibody surveys report a range of seroprevalences, i.e. Germany (14%), The Netherlands (4%),
      USA (2.49-4.16%) and Belgium (4.7-6.9%). These studies suffer from conceptual and technical
      flaws yet are used for easing lockdown measures. A major limitation is that antibody (Ab)
      capture assays measure exposure to SARS-CoV-2, rather than subsequent protection, which
      requires assessment of the quality of the Abs including their capacity to neutralize the
      virus. Also the Ab levels required for protection and their duration are yet unknown. The
      proposed project aims to address these pertinent questions in a population at risk of
      re-infection during a second epidemic wave. Sero-neutralisation assays are regarded the gold
      standard method to measure ex vivo Ab neutralising activity against viruses, including
      SARS-CoV-2. A recent Chinese study, using a pseudovirus neutralisation assay, found that nAbs
      are detected from day 10-15 after onset of disease and that younger patients typically have
      lower levels of nAbs compared to middle-aged and elderly patients. Importantly, in about 1
      out of 3 patients the nAb titers were low and in 10 young patients nAbs were absent. A
      pseudovirus is an imperfect model for SARS-CoV-2 because of the non-natural embedding of
      Spike protein in the pseudovirions and differences in glycosylation. In this study, a whole
      virus neutralisation assay will be used that was recently validated using a panel of
      SARS-CoV-2 convalescent sera in the lab of the Principal Investigator. Preliminary results of
      the study team show a rapid decline in nAb titer within 15-36d after diagnosis in 4/11
      patients, while IgG and IgA remain steady and high in ELISA. Older studies with SARS-CoV-1
      showed declining IgM and IgA antibody titers within 6 months, declining IgG titers after 1y,
      and a complete lack of antigen-specific peripheral memory B-cell (MBC) responses after
      recovery. Measuring only circulating Abs can be misleading as it excludes the detection of
      the MBC pool, which can exist in the absence of detectable serum Ab levels and is a
      pre-requisite to maintain protective immunity in the long term. Upon re-encounter with the
      antigen, MBC can rapidly differentiate to produce Abs. So far, little is known about humoral
      immune responses against SARS-CoV-2 and their contribution to protection.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Antibody levels over time
time frame: 12 months
description: Antibody levels over time
measure: Antibody neutralizing capacity
time frame: 12 months
description: Antibody neutralizing capacity
measure: Memory B-cell function
time frame: 12 months
description: Memory B-cell function
measure: Antibody-dependent enhancement
time frame: 12 months
description: Antibody-dependent enhancement
measure: Re-infection with SARS-CoV2
time frame: 12 months
description: Re-infection with SARS-CoV2
arm group label: antibody response and memory B-cell
arm group type: Experimental
description: Regular blood draws to measure antibody responses and memory B-cell responses Regular swab collection to test for re-infection
intervention type: Diagnostic Test
intervention name: Assessing antibody responses, neutralizing capacity and memory B-cell function
description: Assessing antibody responses, neutralizing capacity and memory B-cell function and their contribution to protection against re-infection
arm group label: antibody response and memory B-cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kevin K. Ariën, PhD
role: Principal Investigator
affiliation: Institute of Tropical Medicine Antwerp
facility: 
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Antibodies
sharing ipd: Undecided