<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/NCT04483908</url>
  </required_header>
  <id_info>
    <org_study_id>BASEC Project-ID 2020-00816</org_study_id>
    <nct_id>NCT04483908</nct_id>
  </id_info>
  <brief_title>COVID-19 in Baselland: Investigation and Validation of Serological Diagnostic Assays and Epidemiological Study of Sars-CoV-2 Specific Antibody Responses</brief_title>
  <acronym>SEROBL-COVID19</acronym>
  <official_title>COVID-19 in Baselland: Investigation and Validation of Serological Diagnostic Assays and Epidemiological Study of Sars-CoV-2 Specific Antibody Responses (SERO-BL-COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ETH Zurich (Switzerland)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Health Department of the Canton of Basel-Stadt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</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 study is to investigate the antibody response in the blood and saliva of people with a&#xD;
      known COVID-19 infection in the canton of Baselland.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is to analyse the antibody response in the blood and saliva of people with a known&#xD;
      COVID-19 infection in the canton of Baselland.&#xD;
&#xD;
      The study aims to validate strategies to measure antibody levels with minimal intervention&#xD;
      and to explore the antibody response and technical capacity for said measurement. The study&#xD;
      will collect the minimally necessary samples to deduce a strategy for serum or saliva&#xD;
      surveillance of the population of the canton Baselland. To achieve this, the study is&#xD;
      designed to address the following points:&#xD;
&#xD;
        -  determine specificity, sensitivity and general utility of point of care (POC) and ELISA&#xD;
           tests to deduce a strategy for serum surveillance of the population of the canton&#xD;
           Baselland&#xD;
&#xD;
        -  especially validate different POC kits in regard of their use for continuous&#xD;
           surveillance&#xD;
&#xD;
        -  gain an understanding of seroconversion and antibody levels of patients and survivors&#xD;
&#xD;
        -  gain an understanding of the individual antibody and T-cell repertoire of patients and&#xD;
           survivors&#xD;
&#xD;
        -  study whether patterns of convergent antibody evolution is generated in the surviving&#xD;
           population or whether the diseases survivors generated an antibody pool recognizing a&#xD;
           specific epitope&#xD;
&#xD;
        -  develop the technology to correlate blood antibody levels with levels detected in the&#xD;
           saliva&#xD;
&#xD;
        -  develop high throughput technologies for the precise detection of immune cell Repertoire&#xD;
           and binding epitopes&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 10, 2020</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">May 30, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Qualitative method validation (yes/ no)</measure>
    <time_frame>at baseline</time_frame>
    <description>Qualitative method validation: qualitative result of the ELISA (Patient does / does not have immunity) as the gold standard compared to the POC using univariate measures to derive sensitivity and specificity of the POC.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantitative method validation (antibody concentrations)</measure>
    <time_frame>at baseline</time_frame>
    <description>Quantitative method validation: antibody concentration from the ELISA are related to the dichotomous result from POC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune cell repertoire sequencing</measure>
    <time_frame>at baseline</time_frame>
    <description>Antibody and T cell repertoires and transcriptional profiles of cells will be used to identify potential antibody and T cell clones correlated with COVID-19 protection.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">477</enrollment>
  <condition>COVID-19 Infection</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <description>Disease survivors with a positive polymerase chain reaction (PCR) test &gt; 12days (d) ago and no symptoms (~250 participants).&#xD;
Cohort 1 &amp; 2 are supposed to have an antibody response to different levels and should provide ability to deduce the detection limit, and estimate the true positive and false negative rates of both ELISA and POC assays.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <description>Disease survivors with a positive PCR test 7 - 12d ago and no symptoms (~100 participants).&#xD;
Cohort 1 &amp; 2 are supposed to have an antibody response to different levels and should provide ability to deduce the detection limit, and estimate the true positive and false negative rates of both ELISA and POC assays.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <description>Subjects with PCR negative test &gt; 5d (~100 participants). Cohort 3 &amp; 4 are the control groups. They are supposed to not have an antibody response for COVID-19 and should therefore help estimate the true negative and false positive rates.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <description>Anonymised blood sera from the &quot;Serumbank&quot; at the Kantonsspital Basel-Land (KSBL) taken during last years influenza period (~100 participants).&#xD;
Cohort 3 &amp; 4 are the control groups. They are supposed to not have an antibody response for COVID-19 and should therefore help estimate the true negative and false positive rates.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>blood draw</intervention_name>
    <description>2x 10ml of blood, one vial to obtain the antibodies and one vial in ethylenediaminetetraacetic acid (EDTA) (or citrate-treated) to obtain peripheral blood mononuclear cells (PBMCs)</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>fingertip tests for POC assays</intervention_name>
    <description>performing POC test by taking two blood drops from the fingertip</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>saliva collection</intervention_name>
    <description>saliva collection: the patient delivers saliva into an adsorbent filter, which is placed in the Salivette tube, centrifuged at 1,600x g for 15 min at 4°C to remove cells and debris. Native supernatant is used for testing.</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>collection of swabs</intervention_name>
    <description>collection of nasopharyngeal and oropharyngeal swabs for PCR testing on the control group (eg negative subpopulation)</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Immune cells (B cells and T cells) from peripheral blood mononuclear cells (PBMC) from the&#xD;
      cohort of COVID-19 recovered patients will be subjected to bulk and single-cell RNA&#xD;
      sequencing (RNA-seq). Biological material in this project is not identified by participant&#xD;
      name but by a unique participant number. Biological material is appropriately stored in a&#xD;
      restricted area only accessible to authorized personnel. Biobank is handled by the accredited&#xD;
      diagnostic lab of the Swiss TPH according to the rules of clinical sample storage.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Study participants will be selected from the database of all positive PCR cases for&#xD;
        COVID-19 tested in the canton Basel-Land.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  tested positive for COVID-19 in Baselland&#xD;
&#xD;
          -  tested negative for COVID-19 in Baselland. Specifically, needed to show symptoms to be&#xD;
             able to deduce cross reactivities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  continuous steroid therapy / chemotherapy / immunsuppressiva&#xD;
&#xD;
          -  subject is treated for cancer&#xD;
&#xD;
          -  severe autoimmune disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Miodrag Savic, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Health, Economics and Health Directorate Canton Basel-Land</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Health, Economics and Health Directorate Canton Basel-Land</name>
      <address>
        <city>Liestal</city>
        <zip>4410</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>November 21, 2022</last_update_submitted>
  <last_update_submitted_qc>November 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sars-CoV-2 infection</keyword>
  <keyword>ELISA test</keyword>
  <keyword>lateral flow assay</keyword>
  <keyword>point of care (POC) assay</keyword>
  <keyword>saliva based serology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>The Biobank data is planned to be shared according to the Biobank regulatory approved by the EKNZ</ipd_description>
  </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/NCT04483908
org study id: BASEC Project-ID 2020-00816
nct id: NCT04483908
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is to investigate the antibody response in the blood and saliva of people with a
      known COVID-19 infection in the canton of Baselland.
This study is to analyse the antibody response in the blood and saliva of people with a known
      COVID-19 infection in the canton of Baselland.

      The study aims to validate strategies to measure antibody levels with minimal intervention
      and to explore the antibody response and technical capacity for said measurement. The study
      will collect the minimally necessary samples to deduce a strategy for serum or saliva
      surveillance of the population of the canton Baselland. To achieve this, the study is
      designed to address the following points:

        -  determine specificity, sensitivity and general utility of point of care (POC) and ELISA
           tests to deduce a strategy for serum surveillance of the population of the canton
           Baselland

        -  especially validate different POC kits in regard of their use for continuous
           surveillance

        -  gain an understanding of seroconversion and antibody levels of patients and survivors

        -  gain an understanding of the individual antibody and T-cell repertoire of patients and
           survivors

        -  study whether patterns of convergent antibody evolution is generated in the surviving
           population or whether the diseases survivors generated an antibody pool recognizing a
           specific epitope

        -  develop the technology to correlate blood antibody levels with levels detected in the
           saliva

        -  develop high throughput technologies for the precise detection of immune cell Repertoire
           and binding epitopes
observational model: Cohort
time perspective: Prospective
measure: Qualitative method validation (yes/ no)
time frame: at baseline
description: Qualitative method validation: qualitative result of the ELISA (Patient does / does not have immunity) as the gold standard compared to the POC using univariate measures to derive sensitivity and specificity of the POC.
measure: Quantitative method validation (antibody concentrations)
time frame: at baseline
description: Quantitative method validation: antibody concentration from the ELISA are related to the dichotomous result from POC.
measure: Immune cell repertoire sequencing
time frame: at baseline
description: Antibody and T cell repertoires and transcriptional profiles of cells will be used to identify potential antibody and T cell clones correlated with COVID-19 protection.
arm group label: Cohort 1
description: Disease survivors with a positive polymerase chain reaction (PCR) test > 12days (d) ago and no symptoms (~250 participants).
Cohort 1 & 2 are supposed to have an antibody response to different levels and should provide ability to deduce the detection limit, and estimate the true positive and false negative rates of both ELISA and POC assays.
arm group label: Cohort 2
description: Disease survivors with a positive PCR test 7 - 12d ago and no symptoms (~100 participants).
Cohort 1 & 2 are supposed to have an antibody response to different levels and should provide ability to deduce the detection limit, and estimate the true positive and false negative rates of both ELISA and POC assays.
arm group label: Cohort 3
description: Subjects with PCR negative test > 5d (~100 participants). Cohort 3 & 4 are the control groups. They are supposed to not have an antibody response for COVID-19 and should therefore help estimate the true negative and false positive rates.
arm group label: Cohort 4
description: Anonymised blood sera from the "Serumbank" at the Kantonsspital Basel-Land (KSBL) taken during last years influenza period (~100 participants).
Cohort 3 & 4 are the control groups. They are supposed to not have an antibody response for COVID-19 and should therefore help estimate the true negative and false positive rates.
intervention type: Diagnostic Test
intervention name: blood draw
description: 2x 10ml of blood, one vial to obtain the antibodies and one vial in ethylenediaminetetraacetic acid (EDTA) (or citrate-treated) to obtain peripheral blood mononuclear cells (PBMCs)
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
intervention type: Diagnostic Test
intervention name: fingertip tests for POC assays
description: performing POC test by taking two blood drops from the fingertip
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
intervention type: Diagnostic Test
intervention name: saliva collection
description: saliva collection: the patient delivers saliva into an adsorbent filter, which is placed in the Salivette tube, centrifuged at 1,600x g for 15 min at 4°C to remove cells and debris. Native supernatant is used for testing.
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
intervention type: Diagnostic Test
intervention name: collection of swabs
description: collection of nasopharyngeal and oropharyngeal swabs for PCR testing on the control group (eg negative subpopulation)
arm group label: Cohort 3
Immune cells (B cells and T cells) from peripheral blood mononuclear cells (PBMC) from the
      cohort of COVID-19 recovered patients will be subjected to bulk and single-cell RNA
      sequencing (RNA-seq). Biological material in this project is not identified by participant
      name but by a unique participant number. Biological material is appropriately stored in a
      restricted area only accessible to authorized personnel. Biobank is handled by the accredited
      diagnostic lab of the Swiss TPH according to the rules of clinical sample storage.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Miodrag Savic, Dr. med.
role: Principal Investigator
affiliation: Department of Health, Economics and Health Directorate Canton Basel-Land
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: Undecided
ipd description: The Biobank data is planned to be shared according to the Biobank regulatory approved by the EKNZ