<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/NCT04416477</url>
  </required_header>
  <id_info>
    <org_study_id>ASCLIN 001/2019</org_study_id>
    <nct_id>NCT04416477</nct_id>
  </id_info>
  <brief_title>Duration of Immunity 10 Years After a Dose-response Study With Yellow Fever Vaccine - Complementary Study</brief_title>
  <official_title>Duration of Immunity 10 Years After a Dose-response Study With Yellow Fever Vaccine - Complementary Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wellcome Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)</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>
      Yellow fever is an acute febrile infectious disease transmitted to man urban cycle by&#xD;
      mosquitoes infected by an arbovirus of the genus Flavivirus family Flaviviridae. Its&#xD;
      occurrence is recorded in South America Central America and Africa. In cities the yellow&#xD;
      fever vector is the Aedes aegypti mosquito which also transmits dengue viruses zika and&#xD;
      chikungunya. This disease is more frequent in males and the most affected age group is above&#xD;
      fifteen years due to the greater exposure related to the penetration in wild areas of the&#xD;
      endemic zone of yellow fever. Another risk group is unvaccinated people who live near wild&#xD;
      environments where the virus circulates. According to the World Health Organization a single&#xD;
      dose of the yellow fever vaccine is sufficient to maintain protective immunity against yellow&#xD;
      fever for a lifetime therefore a booster dose is not required. This question is difficult to&#xD;
      evaluate because there is no serological correlate of protection against yellow fever and&#xD;
      seropositivity is defined with several cut off points. Although studies indicate that the&#xD;
      duration of protection after vaccination is long there is considerable evidence in the&#xD;
      literature that antibody titer falls over the years reaching levels considered as&#xD;
      seronegative in at least a portion of the vaccinees. This is of more concern to people living&#xD;
      in endemic areas who are exposed to the virus throughout their lives. For this reason Brazil&#xD;
      recommended revaccinating once at least until additional studies were done. The need to&#xD;
      increase Bio Manguinhos production capacity to meet the increased demand from Brazil and&#xD;
      other countries is urgent. The occurrence of epidemics when millions of individuals need to&#xD;
      be vaccinated in a short period of time exceeds production capacity and this is a recurrent&#xD;
      problem. The current vaccine has a very high potency well above the thousand international&#xD;
      units recommended by World Health Organization. But we need to generate additional evidence&#xD;
      that very low doses of viral particles in the yellow fever vaccine are still immunogenic and&#xD;
      that their immunogenicity can be maintained for at least ten years after vaccination. This&#xD;
      evidence will support the rapid increase of their availability by the fractionation of doses&#xD;
      or other alternatives.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an observational study in young adult males who received the first dose of the yellow&#xD;
      fever vaccine when they participated in the Dose response study of the yellow fever vaccine&#xD;
      produced by Bio Manguinhos Fiocruz. The purpose of this study is to know whether reduced dose&#xD;
      immunity is maintained for at least ten years. This information is crucial to support the&#xD;
      recommendation to use fractional dose in adults a topic of great interest to World Health&#xD;
      Organization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 8, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2020</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of individuals who were protected 10 years after the first dose of the yellow fever vaccine, assessed by the neutralization test</measure>
    <time_frame>10 years after the first dose of yellow fever vaccine</time_frame>
    <description>Serological status of yellow fever in adult individuals 10 years after seroconversion in a low dose or full dose study of the 17DD yellow fever vaccine produced by Bio-Manguinhos / Fiocruz.</description>
  </primary_outcome>
  <enrollment type="Anticipated">255</enrollment>
  <condition>Yellow Fever Vaccine</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      A volume of up to 10 mL of whole blood should be collected without anticoagulant. There will&#xD;
      be at most two attempts at blood collection per participant.&#xD;
&#xD;
      The study samples will be aliquoted and after will be stored for a maximum of 10 years in the&#xD;
      biorepository of the Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fiocruz,&#xD;
      Rio de Janeiro, Brazil, and this time will begin at the end of the last participant's&#xD;
      collection.&#xD;
&#xD;
      An additional written Informed Consent Form will assess whether the participant wishes to&#xD;
      donate part of the samples to Bio-Manguinhos BioBank. In this case, the biological sample&#xD;
      shall be stored for an indeterminate period.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will be healthy male adults who received the first dose of the yellow fever&#xD;
        vaccine in 2009 when they participated in the &quot;Dose-response study of the yellow fever&#xD;
        vaccine 17DD produced by Bio-Manguinhos / Fiocruz&quot;.&#xD;
&#xD;
        Participation in the study will be documented at the time of signing the Informed Consent&#xD;
        Form.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have participated as a volunteer of the study carried out in 2009.&#xD;
&#xD;
          -  Seronegative volunteers before vaccination in the study &quot;Dose-response study of yellow&#xD;
             fever vaccine 17DD produced by Bio-Manguinhos / Fiocruz&quot; carried out in 2009.&#xD;
             Non-revaccinated volunteers, seropositive in the study &quot;Duration of immunity to yellow&#xD;
             fever in volunteers eight years after a dose-response study&quot;, conducted in 2017.&#xD;
&#xD;
          -  Not having received another yellow fever vaccine after participating in the study&#xD;
             &quot;Dose-response study of the yellow fever vaccine produced by Bio-Manguinhos / Fiocruz&quot;&#xD;
             carried out in 2009 and the study &quot;Duration of immunity to yellow fever in volunteers&#xD;
             eight years after a dose-response study&quot;, conducted in 2017.&#xD;
&#xD;
          -  Available to follow up during the field study period.&#xD;
&#xD;
          -  Agree to give name, address, phone, and other contact information, if necessary.&#xD;
&#xD;
          -  Agree to strictly follow the study protocol.&#xD;
&#xD;
          -  Able to understand and sign the Informed Consent Form (ICF).&#xD;
&#xD;
          -  Understand the impossibility of participating in another clinical trial during the&#xD;
             time of participation in this study.&#xD;
&#xD;
        Note: Individuals with a history of travel to areas endemic for yellow fever may be&#xD;
        included but will be analyzed separately.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to collect biological material (blood).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Akira Homma</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos / FIOCRUZ</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Akira Homma</last_name>
    <phone>+55 (21) 3882-9479</phone>
    <email>Akira@bio.fiocruz.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maria de Lourdes de Sousa Maia</last_name>
    <phone>+55 (21) 3882-9474</phone>
    <email>lourdes.maia@bio.fiocruz.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Unidade de Ensaios Clínicos em Imunobiológicos / Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos / Fiocruz</name>
      <address>
        <city>Rio De Janeiro</city>
        <state>RJ</state>
        <zip>21040-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Akira Homma</last_name>
      <phone>+55 (21) 3882-9479</phone>
      <email>Akira@bio.fiocruz.br</email>
    </contact>
    <contact_backup>
      <last_name>Maria de Lourdes de Sousa Maia</last_name>
      <phone>+55 (21) 3882-9474</phone>
      <email>lourdes.maia@bio.fiocruz.br</email>
    </contact_backup>
    <investigator>
      <last_name>Akira Homma</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria de Lourdes de Sousa Maia</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 1, 2020</last_update_submitted>
  <last_update_submitted_qc>June 1, 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>Immunity duration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Yellow Fever</mesh_term>
    <mesh_term>Fever</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>December 29, 2022</submitted>
  </pending_results>
  <!-- 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/NCT04416477
org study id: ASCLIN 001/2019
nct id: NCT04416477
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Yellow fever is an acute febrile infectious disease transmitted to man urban cycle by
      mosquitoes infected by an arbovirus of the genus Flavivirus family Flaviviridae. Its
      occurrence is recorded in South America Central America and Africa. In cities the yellow
      fever vector is the Aedes aegypti mosquito which also transmits dengue viruses zika and
      chikungunya. This disease is more frequent in males and the most affected age group is above
      fifteen years due to the greater exposure related to the penetration in wild areas of the
      endemic zone of yellow fever. Another risk group is unvaccinated people who live near wild
      environments where the virus circulates. According to the World Health Organization a single
      dose of the yellow fever vaccine is sufficient to maintain protective immunity against yellow
      fever for a lifetime therefore a booster dose is not required. This question is difficult to
      evaluate because there is no serological correlate of protection against yellow fever and
      seropositivity is defined with several cut off points. Although studies indicate that the
      duration of protection after vaccination is long there is considerable evidence in the
      literature that antibody titer falls over the years reaching levels considered as
      seronegative in at least a portion of the vaccinees. This is of more concern to people living
      in endemic areas who are exposed to the virus throughout their lives. For this reason Brazil
      recommended revaccinating once at least until additional studies were done. The need to
      increase Bio Manguinhos production capacity to meet the increased demand from Brazil and
      other countries is urgent. The occurrence of epidemics when millions of individuals need to
      be vaccinated in a short period of time exceeds production capacity and this is a recurrent
      problem. The current vaccine has a very high potency well above the thousand international
      units recommended by World Health Organization. But we need to generate additional evidence
      that very low doses of viral particles in the yellow fever vaccine are still immunogenic and
      that their immunogenicity can be maintained for at least ten years after vaccination. This
      evidence will support the rapid increase of their availability by the fractionation of doses
      or other alternatives.
This is an observational study in young adult males who received the first dose of the yellow
      fever vaccine when they participated in the Dose response study of the yellow fever vaccine
      produced by Bio Manguinhos Fiocruz. The purpose of this study is to know whether reduced dose
      immunity is maintained for at least ten years. This information is crucial to support the
      recommendation to use fractional dose in adults a topic of great interest to World Health
      Organization.
observational model: Cohort
time perspective: Other
measure: Number of individuals who were protected 10 years after the first dose of the yellow fever vaccine, assessed by the neutralization test
time frame: 10 years after the first dose of yellow fever vaccine
description: Serological status of yellow fever in adult individuals 10 years after seroconversion in a low dose or full dose study of the 17DD yellow fever vaccine produced by Bio-Manguinhos / Fiocruz.
A volume of up to 10 mL of whole blood should be collected without anticoagulant. There will
      be at most two attempts at blood collection per participant.

      The study samples will be aliquoted and after will be stored for a maximum of 10 years in the
      biorepository of the Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fiocruz,
      Rio de Janeiro, Brazil, and this time will begin at the end of the last participant's
      collection.

      An additional written Informed Consent Form will assess whether the participant wishes to
      donate part of the samples to Bio-Manguinhos BioBank. In this case, the biological sample
      shall be stored for an indeterminate period.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
last name: Akira Homma
role: Principal Investigator
affiliation: Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos / FIOCRUZ
last name: Akira Homma
phone: +55 (21) 3882-9479
email: Akira@bio.fiocruz.br
last name: Maria de Lourdes de Sousa Maia
phone: +55 (21) 3882-9474
email: lourdes.maia@bio.fiocruz.br
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Brazil
responsible party type: Sponsor
mesh term: Yellow Fever
mesh term: Fever
sharing ipd: No
submitted: December 29, 2022