<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/NCT04409405</url>
  </required_header>
  <id_info>
    <org_study_id>C19-59</org_study_id>
    <secondary_id>ESP/CE/287/2019</secondary_id>
    <nct_id>NCT04409405</nct_id>
  </id_info>
  <brief_title>Evaluation and Support to EVD Cured Patients and Their Contacts (Les Vainqueurs d'Ebola)</brief_title>
  <official_title>Evaluation and Support to Ebola Virus Disease Cured Patients and Their Contacts in the Democratic Republic of the Congo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut de Recherche pour le Developpement</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut National de la Santé Et de la Recherche Médicale, France</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>
      Ebola virus is one of the most dangerous human pathogens and is an emerging public health&#xD;
      problem in sub-Saharan Africa. Ebola virus disease (EVD) first appeared in 1976. The current&#xD;
      epidemic in the Democratic Republic of the Congo (DRC) is one of the largest and most complex&#xD;
      ever recorded, and is not yet under control: a new death has been reported on April 10th,&#xD;
      2020. The epidemic was declared a public health emergency of international scope by the World&#xD;
      Health Organization (WHO) on July 17th, 2019.&#xD;
&#xD;
      Two studies are the &quot;standard&quot; in the assessment of the consequences of infection in&#xD;
      survivors, in Liberia (PREVAIL) and Guinea (PostEbogui), especially in:&#xD;
&#xD;
        -  The observation of comparable mortality rates, even if over time there was an&#xD;
           improvement in survival, probably linked to the improvement in the quality of care and&#xD;
           symptomatic treatment;&#xD;
&#xD;
        -  And the study of the contacts of the survivors, between 4 to 10% of them had done&#xD;
           seroconversion with regard to Ebola virus (EBOV) in an asymptomatic or pauci-symptomatic&#xD;
           way and that this rate varied according to the degree of exposure to the risk.&#xD;
&#xD;
      The DRC's experience in this area and the enormous progress made in the fight against Viral&#xD;
      hemorrhagic fevers (VHFs), therapeutically and preventively (where much of which patients&#xD;
      have benefited from antiviral treatment or monoclonal antibodies), the technological&#xD;
      responses (real-time sequencing of Ebola strains in new cases, vaccination or the use of&#xD;
      individual isolation units), show the limits of their effectiveness. A large number of&#xD;
      questions therefore remain unanswered:&#xD;
&#xD;
        -  The antibody profile of the survivors, in particular the repertoire of immunoglobulin G&#xD;
           (IgG) specific to these individuals and its correlation with survival and its evolution&#xD;
           over time;&#xD;
&#xD;
        -  The impact of treatments initiated during the acute phase on these immune abnormalities;&#xD;
&#xD;
        -  Finally, genetic factors linked to the host could play an important role in the response&#xD;
           to the Ebola virus.&#xD;
&#xD;
      The aim of this study is to provide a better overall understanding of Ebola virus infection&#xD;
      and its clinical, virological, and immunological consequences, of cured people and their&#xD;
      contacts; strengthen multidisciplinary monitoring of patients after an acute phase of EVD.&#xD;
      The results will therefore have a direct impact on the clinical management of this population&#xD;
      and on the prevention of possible secondary contamination in the Democratic Republic of the&#xD;
      Congo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 16, 2020</start_date>
  <completion_date type="Actual">October 18, 2021</completion_date>
  <primary_completion_date type="Actual">October 18, 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>Cured-participant population co-infections</measure>
    <time_frame>Baseline (BL)</time_frame>
    <description>Frequencies of co-infections (human immunodeficiency virus, hepatitis B virus, hepatitis C virus)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cured-participant population co-morbidities at any time in the study</measure>
    <time_frame>Baseline (BL), month 3, month 6, month 9, month 12, month 18</time_frame>
    <description>Frequencies of co-morbidities including severity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of clinical consequences in cured participants</measure>
    <time_frame>Baseline (BL), month 3, month 6, month 9, month 12, month 18</time_frame>
    <description>Sequelae of EVD in cured participants and their evolution according to clinical characteristics and received treatment during hospitalisation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of immunological consequences in cured participants</measure>
    <time_frame>Baseline (BL), month 6, month 12</time_frame>
    <description>Proportion and evolution of IgG subclasses against nucleoprotein, VP40 and glycoprotein from isolates Mayinga1976 and Kissidougou-Makona2014.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of virological consequences in cured participants</measure>
    <time_frame>Baseline (BL), month 3, month 6, month 9, month 12, month 18</time_frame>
    <description>Evolution of EBOV virus identified by polymerase chain reaction (PCR) in biological samples (blood, urine, feces, saliva, tears, breast milk (breastfeeding women), genital secretions (women aged 15 and over) and sperm (men aged 15 and over)).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Description of contact-participants Ebola-virus-exposure risk</measure>
    <time_frame>Baseline (BL)</time_frame>
    <description>Description of exposure to the confirmed index case (duration and repetition of exposure, possible protection used, state of contagiousness of the confirmed index case including clinical condition and viremia), prevalence of EVD (living or deceased, with whom the subject was in contact), vaccination status against EVD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Asymptomatic or pauci-symptomatic Ebola infections in contact participants (clinical assessment)</measure>
    <time_frame>Baseline (BL)</time_frame>
    <description>Clinical assessment for EBOV infection since contact exposure to EVD patient.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Asymptomatic or pauci-symptomatic Ebola infections in contact participants (immunological assessment)</measure>
    <time_frame>Baseline (BL)</time_frame>
    <description>Titration of IgG subclasses against nucleoprotein, VP40 and glycoprotein.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Asymptomatic or pauci-symptomatic Ebola infections in contact participants (virological assessment)</measure>
    <time_frame>Baseline (BL)</time_frame>
    <description>Presence of Ebola virus identified by PCR in biological samples (blood, urine, feces, saliva, tears, breast milk (breastfeeding women), genital secretions and sperm (men aged 15 and over)).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of peripheral blood mononuclear cells (PBMC) in cured and contact participants (cellular immunological sub-study)</measure>
    <time_frame>Baseline (BL), month 6, month 12</time_frame>
    <description>Phenotypic characterization and activation status of the different cell populations within PBMC (T cells, B cells, natural killer cells, dendritic cells, etc.) by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of concentration of immune response analytes in cured and contact participants (cellular immunological sub-study)</measure>
    <time_frame>Baseline (BL), month 6, month 12</time_frame>
    <description>Titration of analytes involved in immune responses (using Luminex technology)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of EBOV-specific T responses in cured and contact participants (cellular immunological sub-study)</measure>
    <time_frame>Baseline (BL), month 6, month 12</time_frame>
    <description>EBOV-specific T responses after stimulation of cells by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of gene-expression profile in cured and contact participants (cellular immunological sub-study)</measure>
    <time_frame>Baseline (BL), month 6, month 12</time_frame>
    <description>Analysis of gene-expression profile in whole blood using Ilumina technology</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution over time of genetic heterogeneity in cured and contact participants (cellular immunological sub-study)</measure>
    <time_frame>Baseline (BL), month 6, month 12</time_frame>
    <description>Single-cell analysis to evaluate cellular genetic heterogeneity in cell population.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Genetic sub-study in cured and contact participants</measure>
    <time_frame>Baseline (BL)</time_frame>
    <description>Research of genetic variants implied in EBOV-infection response.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">787</enrollment>
  <condition>Ebola Virus Disease</condition>
  <arm_group>
    <arm_group_label>Cured population</arm_group_label>
    <description>• Age ≥ 5 year old</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Contact population</arm_group_label>
    <description>Age ≥ 5 year old&#xD;
Contact of a participant included in cured-population cohort&#xD;
Not diagnosed with EVD</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood sample Urine Saliva Tear drop Breast milk Stool Vaginal fluid Semen&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Cured patients: study team will approach every declared-cured EBOV-infection patients&#xD;
        discharged of a Ebola treatment center (Beni, Butembo, Mambassa or Mangina), older than 5&#xD;
        year old&#xD;
&#xD;
        Contact participants: Cured participants will identify contact with who they were in&#xD;
        contact when ill.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In cured population&#xD;
&#xD;
          -  Age ≥ 5 years&#xD;
&#xD;
          -  Adults and children after an acute episode declared cured of biologically confirmed&#xD;
             Ebola virus disease (two negative PCRs are required at least 24 hours apart so that a&#xD;
             patient without clinical symptoms can leave the Ebola treatment center),&#xD;
&#xD;
          -  Informed consent signed by at least one of the two parents or the legal guardian&#xD;
             authorizing the child's participation in the study,&#xD;
&#xD;
          -  Volunteer participant who signed the informed consent for adults.&#xD;
&#xD;
        In CONTACT population&#xD;
&#xD;
          -  Age ≥ 5 years,&#xD;
&#xD;
          -  Be a contact person of a cured patient (ie patient with a proven EVD, and with two&#xD;
             negative PCRs at least 24 hours apart) included in the cohort of Ebola Winners. Based&#xD;
             on WHO recommendations and the Centers for Disease Control and Prevention for the&#xD;
             identification and traceability of contact subjects: a contact person is defined as a&#xD;
             person who encountered the index case during his EVD in his residence, ie having the&#xD;
             same place of life as him,&#xD;
&#xD;
          -  Have not been diagnosed with EVD,&#xD;
&#xD;
          -  Participation agreement:&#xD;
&#xD;
               -  For adult participants (≥ 18 years old, emancipated or married): informed consent&#xD;
                  intended for the adult participant signed,&#xD;
&#xD;
               -  For minors ≥ 5 years old: informed consent intended for the parent(s)/legal&#xD;
                  guardian signed by at least one of the two parents or the legal guardian and&#xD;
                  assent form intended for the minor participant completed.&#xD;
&#xD;
        In cellular immunological sub-study:&#xD;
&#xD;
          -  Adult participants in the parent study ≥ 18 years old,&#xD;
&#xD;
          -  Accept to participate in this sub-study&#xD;
&#xD;
          -  Negative blood EBOV PCR&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Absence of possible follow-up over 12 months from a logistical or geographical point&#xD;
             of view (only for cured patients);&#xD;
&#xD;
          -  Non-residents in the DRC;&#xD;
&#xD;
          -  Impossibility of complying with the requirements and procedures of the study in the&#xD;
             opinion of the investigator;&#xD;
&#xD;
          -  Inability to consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Beni Hospital</name>
      <address>
        <city>Beni</city>
        <country>Congo, The Democratic Republic of the</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Butembo Hospital</name>
      <address>
        <city>Butembo</city>
        <country>Congo, The Democratic Republic of the</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mambasa Hospital</name>
      <address>
        <city>Mambasa</city>
        <country>Congo, The Democratic Republic of the</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mangina Hospital</name>
      <address>
        <city>Mangina</city>
        <country>Congo, The Democratic Republic of the</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Congo, The Democratic Republic of the</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>April 14, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>February 2, 2022</last_update_submitted>
  <last_update_submitted_qc>February 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ebola</keyword>
  <keyword>Democratic Republic of the Congo</keyword>
  <keyword>DRC</keyword>
  <keyword>Ituri</keyword>
  <keyword>North Kivu</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Hemorrhagic Fever, Ebola</mesh_term>
  </condition_browse>
  <!-- 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/NCT04409405
org study id: C19-59
secondary id: ESP/CE/287/2019
nct id: NCT04409405
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Ebola virus is one of the most dangerous human pathogens and is an emerging public health
      problem in sub-Saharan Africa. Ebola virus disease (EVD) first appeared in 1976. The current
      epidemic in the Democratic Republic of the Congo (DRC) is one of the largest and most complex
      ever recorded, and is not yet under control: a new death has been reported on April 10th,
      2020. The epidemic was declared a public health emergency of international scope by the World
      Health Organization (WHO) on July 17th, 2019.

      Two studies are the "standard" in the assessment of the consequences of infection in
      survivors, in Liberia (PREVAIL) and Guinea (PostEbogui), especially in:

        -  The observation of comparable mortality rates, even if over time there was an
           improvement in survival, probably linked to the improvement in the quality of care and
           symptomatic treatment;

        -  And the study of the contacts of the survivors, between 4 to 10% of them had done
           seroconversion with regard to Ebola virus (EBOV) in an asymptomatic or pauci-symptomatic
           way and that this rate varied according to the degree of exposure to the risk.

      The DRC's experience in this area and the enormous progress made in the fight against Viral
      hemorrhagic fevers (VHFs), therapeutically and preventively (where much of which patients
      have benefited from antiviral treatment or monoclonal antibodies), the technological
      responses (real-time sequencing of Ebola strains in new cases, vaccination or the use of
      individual isolation units), show the limits of their effectiveness. A large number of
      questions therefore remain unanswered:

        -  The antibody profile of the survivors, in particular the repertoire of immunoglobulin G
           (IgG) specific to these individuals and its correlation with survival and its evolution
           over time;

        -  The impact of treatments initiated during the acute phase on these immune abnormalities;

        -  Finally, genetic factors linked to the host could play an important role in the response
           to the Ebola virus.

      The aim of this study is to provide a better overall understanding of Ebola virus infection
      and its clinical, virological, and immunological consequences, of cured people and their
      contacts; strengthen multidisciplinary monitoring of patients after an acute phase of EVD.
      The results will therefore have a direct impact on the clinical management of this population
      and on the prevention of possible secondary contamination in the Democratic Republic of the
      Congo.
observational model: Cohort
time perspective: Prospective
measure: Cured-participant population co-infections
time frame: Baseline (BL)
description: Frequencies of co-infections (human immunodeficiency virus, hepatitis B virus, hepatitis C virus)
measure: Cured-participant population co-morbidities at any time in the study
time frame: Baseline (BL), month 3, month 6, month 9, month 12, month 18
description: Frequencies of co-morbidities including severity
measure: Evolution over time of clinical consequences in cured participants
time frame: Baseline (BL), month 3, month 6, month 9, month 12, month 18
description: Sequelae of EVD in cured participants and their evolution according to clinical characteristics and received treatment during hospitalisation.
measure: Evolution over time of immunological consequences in cured participants
time frame: Baseline (BL), month 6, month 12
description: Proportion and evolution of IgG subclasses against nucleoprotein, VP40 and glycoprotein from isolates Mayinga1976 and Kissidougou-Makona2014.
measure: Evolution over time of virological consequences in cured participants
time frame: Baseline (BL), month 3, month 6, month 9, month 12, month 18
description: Evolution of EBOV virus identified by polymerase chain reaction (PCR) in biological samples (blood, urine, feces, saliva, tears, breast milk (breastfeeding women), genital secretions (women aged 15 and over) and sperm (men aged 15 and over)).
measure: Description of contact-participants Ebola-virus-exposure risk
time frame: Baseline (BL)
description: Description of exposure to the confirmed index case (duration and repetition of exposure, possible protection used, state of contagiousness of the confirmed index case including clinical condition and viremia), prevalence of EVD (living or deceased, with whom the subject was in contact), vaccination status against EVD.
measure: Asymptomatic or pauci-symptomatic Ebola infections in contact participants (clinical assessment)
time frame: Baseline (BL)
description: Clinical assessment for EBOV infection since contact exposure to EVD patient.
measure: Asymptomatic or pauci-symptomatic Ebola infections in contact participants (immunological assessment)
time frame: Baseline (BL)
description: Titration of IgG subclasses against nucleoprotein, VP40 and glycoprotein.
measure: Asymptomatic or pauci-symptomatic Ebola infections in contact participants (virological assessment)
time frame: Baseline (BL)
description: Presence of Ebola virus identified by PCR in biological samples (blood, urine, feces, saliva, tears, breast milk (breastfeeding women), genital secretions and sperm (men aged 15 and over)).
measure: Evolution over time of peripheral blood mononuclear cells (PBMC) in cured and contact participants (cellular immunological sub-study)
time frame: Baseline (BL), month 6, month 12
description: Phenotypic characterization and activation status of the different cell populations within PBMC (T cells, B cells, natural killer cells, dendritic cells, etc.) by flow cytometry
measure: Evolution over time of concentration of immune response analytes in cured and contact participants (cellular immunological sub-study)
time frame: Baseline (BL), month 6, month 12
description: Titration of analytes involved in immune responses (using Luminex technology)
measure: Evolution over time of EBOV-specific T responses in cured and contact participants (cellular immunological sub-study)
time frame: Baseline (BL), month 6, month 12
description: EBOV-specific T responses after stimulation of cells by flow cytometry
measure: Evolution over time of gene-expression profile in cured and contact participants (cellular immunological sub-study)
time frame: Baseline (BL), month 6, month 12
description: Analysis of gene-expression profile in whole blood using Ilumina technology
measure: Evolution over time of genetic heterogeneity in cured and contact participants (cellular immunological sub-study)
time frame: Baseline (BL), month 6, month 12
description: Single-cell analysis to evaluate cellular genetic heterogeneity in cell population.
measure: Genetic sub-study in cured and contact participants
time frame: Baseline (BL)
description: Research of genetic variants implied in EBOV-infection response.
arm group label: Cured population
description: • Age ≥ 5 year old
arm group label: Contact population
description: Age ≥ 5 year old
Contact of a participant included in cured-population cohort
Not diagnosed with EVD
Blood sample Urine Saliva Tear drop Breast milk Stool Vaginal fluid Semen
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 5 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
country: Congo, The Democratic Republic of the
responsible party type: Sponsor
mesh term: Virus Diseases
mesh term: Hemorrhagic Fever, Ebola