<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/NCT03820739</url>
  </required_header>
  <id_info>
    <org_study_id>VAC52150EBL3005</org_study_id>
    <nct_id>NCT03820739</nct_id>
  </id_info>
  <brief_title>EBOVAC-Salone Extension</brief_title>
  <official_title>A Cohort Study to Evaluate the Long-term Safety and Immunogenicity of the Candidate Ebola Vaccines Ad26.ZEBOV and MVA-BN®-Filo in Adults and Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>London School of Hygiene and Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Sierra Leone</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Janssen Vaccines &amp; Prevention B.V.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universiteit Antwerpen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>London School of Hygiene and Tropical Medicine</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 VAC52150EBL3005 (EBOVAC-Salone Extension) is a cohort study evaluating the long-term&#xD;
      safety and immunogenicity of the candidate Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in&#xD;
      participants who were exposed to these vaccines in the VAC52150EBL3001 trial (EBOVAC-Salone,&#xD;
      ClinicalTrials.gov Identifier: NCT02509494). No investigational vaccine will be administered&#xD;
      during this study. The study will consist of an enrolment visit, a number of study visits and&#xD;
      an end-of-study visit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The VAC52150EBL3005 (EBOVAC-Salone Extension) is a cohort study to evaluate the long-term&#xD;
      safety and immunogenicity of the candidate Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in&#xD;
      adults and children.&#xD;
&#xD;
      Ad26.ZEBOV consists of the Janssen Vaccines &amp; Prevention B.V. adenovirus serotype 26 (Ad26)&#xD;
      vector expressing the glycoprotein (GP) of the Ebola virus (EBOV) Mayinga variant.&#xD;
&#xD;
      MVA-BN®-Filo consists of the Modified Vaccinia Ankara (MVA) - Bavarian Nordic (BN) vector&#xD;
      expressing the GPs of EBOV, Sudan virus and Marburg virus and the nucleoprotein of Tai Forest&#xD;
      virus.&#xD;
&#xD;
      These candidate Ebola vaccines are being evaluated in phase 1, 2 and 3 clinical studies, in&#xD;
      different heterologous prime-boost regimens, in which one study vaccine is used to prime a&#xD;
      filovirus-specific immune response and the other study vaccine is used to boost the humoral&#xD;
      immune responses. The VAC52150EBL3001 study (EBOVAC-Salone, ClinicalTrials.gov Identifier:&#xD;
      NCT02509494) taking place in Kambia District, Northern Sierra Leone, is a phase 3 trial with&#xD;
      an open-label Stage 1 followed by a randomised double-blind controlled Stage 2. In Stage 1,&#xD;
      43 adults (aged 18 years or older) received Ad26.ZEBOV as prime followed by MVA-BN®-Filo&#xD;
      boost vaccination at day 57. In Stage 2, approximately 400 adults and 576 children (aged 1 to&#xD;
      17 years - divided into three age groups; 12 to 17 years, 4 to 11 years, and 1 to 3 years),&#xD;
      have been randomised to receive a vaccine regimen of Ad26.ZEBOV as prime and MVA-BN®-Filo as&#xD;
      boost at day 57, or control vaccination for both prime and boost vaccination. The control&#xD;
      used is a World Health Organisation (WHO)-prequalified Meningococcal Group A, C, W135 and Y&#xD;
      conjugate vaccine. EBOVAC-Salone Extension has been designed to extend the total follow-up&#xD;
      period of participants exposed to the candidate Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in&#xD;
      the EBOVAC-Salone study, and to follow-up infants conceived by a female participant during&#xD;
      the 3-month period following vaccination with Ad26.ZEBOV or during the 28 day period&#xD;
      following vaccination with MVA-BN®-Filo in EBOVAC-Salone.&#xD;
&#xD;
      STUDY OBJECTIVES&#xD;
&#xD;
      This study aims to evaluate the long-term safety and immunogenicity of the candidate Ebola&#xD;
      vaccines Ad26.ZEBOV and MVA-BN®-Filo administered to adults and children in EBOVAC-Salone and&#xD;
      the long-term safety of infants conceived by a female participant during the 3-month period&#xD;
      following vaccination with Ad26.ZEBOV and the 28 day period following vaccination with&#xD;
      MVA-BN®-Filo in EBOVAC-Salone.&#xD;
&#xD;
      Primary Objectives&#xD;
&#xD;
        -  To assess the long-term safety of Ad26.ZEBOV at a dose of 5x1010 viral particles and&#xD;
           MVA-BN®-Filo at a dose of 1x108 TCID50 (50% Tissue Culture Infective Dose) in African&#xD;
           adults (for 5 years) and children (for 4 years).&#xD;
&#xD;
        -  To assess binding antibody responses against EBOV GP, up to 5 years post-prime in adults&#xD;
           and 4 years post-prime in children using Filovirus Animal Non-Clinical Group (FANG)&#xD;
           enzyme-linked immunosorbent assay (ELISA).&#xD;
&#xD;
        -  To assess safety, up to their fifth birthday, in infants conceived by a female&#xD;
           participant during the 3-month period following vaccination with Ad26.ZEBOV or during&#xD;
           the 28 day period following vaccination with MVA-BN®-Filo.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        -  To assess neutralising antibody responses directed against EBOV GP as measured by a&#xD;
           pseudovirion neutralisation assay (psVNA) at years 2, 3 and 4 post-prime in children and&#xD;
           years 3, 4 and 5 post-prime in adults, depending on sample and assay availability.&#xD;
&#xD;
        -  To evaluate the effect of previous infection with malaria, determined using validated&#xD;
           ELISA and bead based assays, on the persistence of the humoral immune response to&#xD;
           vaccination up to 5 years post-prime in adults and 4 years post-prime in children. The&#xD;
           bead based assays will allow the inclusion of antigens associated with short term&#xD;
           humoral immune responses and thus assessment of intra study exposure to malaria.&#xD;
&#xD;
      OVERVIEW OF STUDY DESIGN&#xD;
&#xD;
      This is a cohort study evaluating the long-term safety and immunogenicity of the candidate&#xD;
      Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in participants who were exposed to these vaccines&#xD;
      in the EBOVAC-Salone trial. Cohort 1 will consist of participants who received an Ebola&#xD;
      vaccine during the EBOVAC-Salone study. Adults (defined as participants 18 years of age or&#xD;
      older at the time of the EBOVAC-Salone prime vaccination) will be followed up annually for 5&#xD;
      years from receipt of prime vaccination and children (defined as participants aged 1 to 17&#xD;
      years at the time of the EBOVAC-Salone prime vaccination) will be followed up annually for 4&#xD;
      years from the receipt of prime vaccination. Cohort 2 (offspring) will consist of infants&#xD;
      conceived by a female participant in EBOVAC-Salone during the 3 months following vaccination&#xD;
      with Ad26.ZEBOV or during the 28 days following vaccination with MVA-BN®-Filo. Offspring will&#xD;
      be followed annually for occurrence of serious adverse events (SAEs) until their fifth&#xD;
      birthday.&#xD;
&#xD;
      No investigational vaccine will be administered during EBOVAC-Salone Extension. The study&#xD;
      will consist of an enrolment visit, a number of study visits and an end-of-study visit.&#xD;
&#xD;
      No study-related activities will be performed until a subject, or parent/guardian has given&#xD;
      informed consent for their, or their child's, participation in the study. For cohort 1,&#xD;
      enrolment into EBOVAC-Salone Extension will occur at the subject's final study visit in&#xD;
      EBOVAC-Salone once the informed consent form (ICF) has been signed. If a subject has already&#xD;
      completed their final study visit in EBOVAC-Salone, enrolment and baseline information will&#xD;
      be collected at the time the participant signs the EBOVAC-Salone Extension ICF. Information&#xD;
      from the participant's final EBOVAC-Salone study visit up to the moment of enrolment into&#xD;
      this study will be captured retrospectively. For cohort 2, enrolment will occur once the&#xD;
      subject's parent/guardian has signed the EBOVAC-Salone Extension ICF. Baseline information&#xD;
      and information from birth up to the moment of enrolment into this study will be collected at&#xD;
      the time the ICF is signed.&#xD;
&#xD;
      Study visits will take place as follows:&#xD;
&#xD;
      Cohort 1: Once yearly, on the anniversary of their prime vaccination (± 1 month), cohort 1&#xD;
      participants will attend the study clinic for collection of information on any SAEs since&#xD;
      their previous visit. In a subsample of participants, blood sampling for serology assays will&#xD;
      also be collected at each study visit.&#xD;
&#xD;
      Cohort 2: Once yearly, on their birthday (± 1 month), cohort 2 participants (offspring) will&#xD;
      be seen at the study clinic) for collection of information on any SAEs they experienced since&#xD;
      their previous study visit.&#xD;
&#xD;
      Between clinic visits, reminder phone calls and/or home visits will be used for retention&#xD;
      purposes, if needed.&#xD;
&#xD;
      SUBJECT POPULATION&#xD;
&#xD;
      Cohort 1: subjects who received Ebola vaccine prime vaccination in EBOVAC-Salone are eligible&#xD;
      for enrolment in this study.&#xD;
&#xD;
      Cohort 2: any infant conceived by a female EBOVAC-Salone participant during the 3-month&#xD;
      period following vaccination with Ad26.ZEBOV or during the 28 day period following&#xD;
      vaccination with MVA-BN®-Filo in EBOVAC- Salone are also eligible for this study.&#xD;
&#xD;
      DOSAGE AND ADMINISTRATION&#xD;
&#xD;
      No investigational vaccine will be administered during this study.&#xD;
&#xD;
      SAFETY EVALUATIONS&#xD;
&#xD;
      All SAEs occurring from the final EBOVAC-Salone study visit (or from birth for eligible&#xD;
      offspring) will be collected annually as indicated in the Time and Events Schedules.&#xD;
&#xD;
      IMMUNOGENICITY EVALUATIONS&#xD;
&#xD;
      Blood sampling to assess vaccine-induced immune responses will be conducted only in cohort 1&#xD;
      in a subsample consisting of approximately 102 adults and 165 children (55 from each of the&#xD;
      three paediatric age groups that were enrolled in EBOVAC-Salone: 12-17 year olds, 4-11 year&#xD;
      olds, and 1-3 year olds). Some of the blood collected will also be used to determine previous&#xD;
      exposure to malaria using validated ELISA and bead based assay. The immune response to&#xD;
      malaria will be considered when evaluating the persistence of antibody response induced by&#xD;
      the Ebola vaccines.&#xD;
&#xD;
      OTHER CLINICAL ASSESSMENTS&#xD;
&#xD;
      In both cohort 1 and cohort 2, a physical examination including vital signs will be conducted&#xD;
      at the first study visit and at yearly visits. In cohort 2, growth measurements will also be&#xD;
      collected. In cohort 1, a haematology assessment will be conducted in the subsample providing&#xD;
      immunogenicity blood samples.&#xD;
&#xD;
      STATISTICAL METHODS&#xD;
&#xD;
      The primary analysis will be done when all participants have completed their final study&#xD;
      visit or discontinued. This analysis will include all available data up to this point. No&#xD;
      interim analyses are planned. There are no formal hypotheses tests planned for the safety&#xD;
      data. The primary endpoint for long term safety of Ad26.ZEBOV and MVA-BN®-Filo is the&#xD;
      occurrence of SAEs in the total vaccine cohort during the follow up period of up to 5 years&#xD;
      (in adults) or 4 years (in children), and separately in infants in cohort 2. The primary&#xD;
      analysis for immunogenicity will involve assessing humoral immune responses to Ad26.ZEBOV or&#xD;
      MVA-BN®-Filo using a longitudinal design in children and adults vaccinated with Ad26.ZEBOV or&#xD;
      MVA-BN®-Filo (cohort 1).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 22, 2019</start_date>
  <completion_date type="Actual">July 14, 2022</completion_date>
  <primary_completion_date type="Actual">June 28, 2022</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>Number of Serious Adverse Events in subjects who received an Ebola vaccine prime vaccination in the EBOVAC-Salone trial.</measure>
    <time_frame>Up to approximately 5 years in adults and 4 years in children from prime vaccination</time_frame>
    <description>An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Binding antibody responses against EBOV GP using Filovirus Animal Non-Clinical Group (FANG) enzyme-linked immunosorbent assay (ELISA).</measure>
    <time_frame>Up to approximately 5 years in adults and 4 years in children from prime vaccination</time_frame>
    <description>Serum Concentration of Antibodies Binding to EBOV GP measured by Filovirus Animal Non-Clinical Group (FANG) enzyme-linked immunosorbent assay (ELISA).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Serious Adverse Events, in infants conceived by an EBOVAC-Salone trial female participant during the 3-month period following vaccination with Ad26.ZEBOV or during the 28 day period following vaccination with MVA-BN®-Filo.</measure>
    <time_frame>From birth to their fifth birthday</time_frame>
    <description>An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neutralising antibody responses directed against EBOV GP as measured by a pseudovirion neutralisation assay (psVNA)</measure>
    <time_frame>At years 2, 3 and 4 post-prime in children and years 3, 4 and 5 post-prime in adults</time_frame>
    <description>psVNA: pseudovirion neutralising antibody reactivity against the EBOV GP defined as the serum titre that is able to inhibit viral infection by 50% (IC50 titer).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of previous infection with malaria, determined using validated ELISA and bead based assays, on the persistence of the humoral immune response to vaccination.</measure>
    <time_frame>Up to approximately 5 years in adults and 4 years in children from prime vaccination</time_frame>
    <description>Serum concentration of malaria specific antibodies, determined using validated ELISA and bead based assays. The bead based assays will allow the inclusion of antigens associated with short term humoral immune responses and thus assessment of intra study exposure to malaria.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">653</enrollment>
  <condition>Ebola Virus Disease</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <description>Subjects who received an Ebola vaccine prime vaccination in EBOVAC-Salone are eligible for enrolment in this study. Adults are defined as participants 18 years of age or older at the time of prime vaccination, and children are defined as participants aged 1 to 17 years at the time of prime vaccination in EBOVAC-Salone.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 (offspring)</arm_group_label>
    <description>Infants conceived by a female participant in EBOVAC-Salone during the 3 months following vaccination with Ad26.ZEBOV or during the 28 days following vaccination with MVA-BN®-Filo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Follow-up</intervention_name>
    <description>No investigational vaccine will be administered during this study</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2 (offspring)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood sample collection</intervention_name>
    <description>Blood sampling to assess vaccine-induced immune responses will be conducted only in cohort 1 in a subsample consisting of approximately 102 adults and 165 children (55 from each of the three paediatric age groups that were enrolled in EBOVAC-Salone: 12-17 year olds, 4-11 year olds, and 1-3 year olds).</description>
    <arm_group_label>Cohort 1</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study will be open to subjects who were exposed to Ad26.ZEBOV and/or MVA-BN®-Filo in&#xD;
        the EBOVAC-Salone study.&#xD;
&#xD;
        The study population will consist of two cohorts:&#xD;
&#xD;
          -  Cohort 1: subjects who received an Ebola vaccine prime vaccination in EBOVAC-Salone&#xD;
             are eligible for enrolment in this study. Adults are defined as participants 18 years&#xD;
             of age or older at the time of prime vaccination, and children are defined as&#xD;
             participants aged 1 to 17 years at the time of prime vaccination.&#xD;
&#xD;
          -  Cohort 2 (offspring) will consist of infants conceived by a female participant in&#xD;
             EBOVAC-Salone during the 3 months following vaccination with Ad26.ZEBOV or during the&#xD;
             28 days following vaccination with MVA-BN®-Filo.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must be a participant, or former participant, of the EBOVAC-Salone study, and received&#xD;
             Ebola vaccine prime vaccination.&#xD;
&#xD;
             or Must be an infant conceived by a female participant of EBOVAC-Salone during the&#xD;
             3-month period following vaccination with Ad26.ZEBOV or the 28 day period following&#xD;
             vaccination with MVA-BN®-Filo.&#xD;
&#xD;
          2. Must consent to participate in the EBOVAC-Salone Extension study by signing (or&#xD;
             thumbprinting, if illiterate) an ICF, indicating that he or she understands the&#xD;
             purpose of, and procedures required for, the study and is willing to participate in&#xD;
             the study. If a potential participant cannot read or write, the procedures must be&#xD;
             explained and informed consent must be witnessed by a literate third party not&#xD;
             involved in the conduct of the study. If the potential participant is under 18 years&#xD;
             of age, they and their parent/guardian will be informed about the study and the&#xD;
             parent/guardian will be asked to give consent. Children aged 7 years and older will be&#xD;
             asked to give positive assent for their participation in the study and the assent&#xD;
             procedure must be witnessed by an adult, literate parent/guardian/third party not&#xD;
             involved in the conduct of the study, and documented.&#xD;
&#xD;
          3. Must confirm that he/she will return to the study site for each yearly visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants in the EBOVAC-Salone study who were allocated to the control arm&#xD;
             receiving the WHO-prequalified Meningococcal Group A, C, W135 and Y conjugate vaccine&#xD;
&#xD;
          2. Subjects who, in the opinion of the investigator, are unlikely to adhere to the&#xD;
             requirements of the study, or unlikely to complete follow up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Deborah Watson-Jones, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>London School of Hygiene and Tropical Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bailah Leigh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sierra Leone</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>EBOVAC Rokupr clinic</name>
      <address>
        <city>Rokupr</city>
        <state>Kambia</state>
        <country>Sierra Leone</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EBOVAC Kambia 1 clinic</name>
      <address>
        <city>Kambia</city>
        <country>Sierra Leone</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sierra Leone</country>
  </location_countries>
  <link>
    <url>http://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease</url>
    <description>WHO. Ebola virus disease - key facts.</description>
  </link>
  <results_reference>
    <citation>Portugal S, Tipton CM, Sohn H, Kone Y, Wang J, Li S, Skinner J, Virtaneva K, Sturdevant DE, Porcella SF, Doumbo OK, Doumbo S, Kayentao K, Ongoiba A, Traore B, Sanz I, Pierce SK, Crompton PD. Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. Elife. 2015 May 8;4:e07218. doi: 10.7554/eLife.07218.</citation>
    <PMID>25955968</PMID>
  </results_reference>
  <results_reference>
    <citation>Ryg-Cornejo V, Ioannidis LJ, Ly A, Chiu CY, Tellier J, Hill DL, Preston SP, Pellegrini M, Yu D, Nutt SL, Kallies A, Hansen DS. Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation. Cell Rep. 2016 Jan 5;14(1):68-81. doi: 10.1016/j.celrep.2015.12.006. Epub 2015 Dec 24.</citation>
    <PMID>26725120</PMID>
  </results_reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  <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/NCT03820739
org study id: VAC52150EBL3005
nct id: NCT03820739
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The VAC52150EBL3005 (EBOVAC-Salone Extension) is a cohort study evaluating the long-term
      safety and immunogenicity of the candidate Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in
      participants who were exposed to these vaccines in the VAC52150EBL3001 trial (EBOVAC-Salone,
      ClinicalTrials.gov Identifier: NCT02509494). No investigational vaccine will be administered
      during this study. The study will consist of an enrolment visit, a number of study visits and
      an end-of-study visit.
The VAC52150EBL3005 (EBOVAC-Salone Extension) is a cohort study to evaluate the long-term
      safety and immunogenicity of the candidate Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in
      adults and children.

      Ad26.ZEBOV consists of the Janssen Vaccines & Prevention B.V. adenovirus serotype 26 (Ad26)
      vector expressing the glycoprotein (GP) of the Ebola virus (EBOV) Mayinga variant.

      MVA-BN®-Filo consists of the Modified Vaccinia Ankara (MVA) - Bavarian Nordic (BN) vector
      expressing the GPs of EBOV, Sudan virus and Marburg virus and the nucleoprotein of Tai Forest
      virus.

      These candidate Ebola vaccines are being evaluated in phase 1, 2 and 3 clinical studies, in
      different heterologous prime-boost regimens, in which one study vaccine is used to prime a
      filovirus-specific immune response and the other study vaccine is used to boost the humoral
      immune responses. The VAC52150EBL3001 study (EBOVAC-Salone, ClinicalTrials.gov Identifier:
      NCT02509494) taking place in Kambia District, Northern Sierra Leone, is a phase 3 trial with
      an open-label Stage 1 followed by a randomised double-blind controlled Stage 2. In Stage 1,
      43 adults (aged 18 years or older) received Ad26.ZEBOV as prime followed by MVA-BN®-Filo
      boost vaccination at day 57. In Stage 2, approximately 400 adults and 576 children (aged 1 to
      17 years - divided into three age groups; 12 to 17 years, 4 to 11 years, and 1 to 3 years),
      have been randomised to receive a vaccine regimen of Ad26.ZEBOV as prime and MVA-BN®-Filo as
      boost at day 57, or control vaccination for both prime and boost vaccination. The control
      used is a World Health Organisation (WHO)-prequalified Meningococcal Group A, C, W135 and Y
      conjugate vaccine. EBOVAC-Salone Extension has been designed to extend the total follow-up
      period of participants exposed to the candidate Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in
      the EBOVAC-Salone study, and to follow-up infants conceived by a female participant during
      the 3-month period following vaccination with Ad26.ZEBOV or during the 28 day period
      following vaccination with MVA-BN®-Filo in EBOVAC-Salone.

      STUDY OBJECTIVES

      This study aims to evaluate the long-term safety and immunogenicity of the candidate Ebola
      vaccines Ad26.ZEBOV and MVA-BN®-Filo administered to adults and children in EBOVAC-Salone and
      the long-term safety of infants conceived by a female participant during the 3-month period
      following vaccination with Ad26.ZEBOV and the 28 day period following vaccination with
      MVA-BN®-Filo in EBOVAC-Salone.

      Primary Objectives

        -  To assess the long-term safety of Ad26.ZEBOV at a dose of 5x1010 viral particles and
           MVA-BN®-Filo at a dose of 1x108 TCID50 (50% Tissue Culture Infective Dose) in African
           adults (for 5 years) and children (for 4 years).

        -  To assess binding antibody responses against EBOV GP, up to 5 years post-prime in adults
           and 4 years post-prime in children using Filovirus Animal Non-Clinical Group (FANG)
           enzyme-linked immunosorbent assay (ELISA).

        -  To assess safety, up to their fifth birthday, in infants conceived by a female
           participant during the 3-month period following vaccination with Ad26.ZEBOV or during
           the 28 day period following vaccination with MVA-BN®-Filo.

      Secondary Objectives

        -  To assess neutralising antibody responses directed against EBOV GP as measured by a
           pseudovirion neutralisation assay (psVNA) at years 2, 3 and 4 post-prime in children and
           years 3, 4 and 5 post-prime in adults, depending on sample and assay availability.

        -  To evaluate the effect of previous infection with malaria, determined using validated
           ELISA and bead based assays, on the persistence of the humoral immune response to
           vaccination up to 5 years post-prime in adults and 4 years post-prime in children. The
           bead based assays will allow the inclusion of antigens associated with short term
           humoral immune responses and thus assessment of intra study exposure to malaria.

      OVERVIEW OF STUDY DESIGN

      This is a cohort study evaluating the long-term safety and immunogenicity of the candidate
      Ebola vaccines Ad26.ZEBOV and MVA-BN®-Filo in participants who were exposed to these vaccines
      in the EBOVAC-Salone trial. Cohort 1 will consist of participants who received an Ebola
      vaccine during the EBOVAC-Salone study. Adults (defined as participants 18 years of age or
      older at the time of the EBOVAC-Salone prime vaccination) will be followed up annually for 5
      years from receipt of prime vaccination and children (defined as participants aged 1 to 17
      years at the time of the EBOVAC-Salone prime vaccination) will be followed up annually for 4
      years from the receipt of prime vaccination. Cohort 2 (offspring) will consist of infants
      conceived by a female participant in EBOVAC-Salone during the 3 months following vaccination
      with Ad26.ZEBOV or during the 28 days following vaccination with MVA-BN®-Filo. Offspring will
      be followed annually for occurrence of serious adverse events (SAEs) until their fifth
      birthday.

      No investigational vaccine will be administered during EBOVAC-Salone Extension. The study
      will consist of an enrolment visit, a number of study visits and an end-of-study visit.

      No study-related activities will be performed until a subject, or parent/guardian has given
      informed consent for their, or their child's, participation in the study. For cohort 1,
      enrolment into EBOVAC-Salone Extension will occur at the subject's final study visit in
      EBOVAC-Salone once the informed consent form (ICF) has been signed. If a subject has already
      completed their final study visit in EBOVAC-Salone, enrolment and baseline information will
      be collected at the time the participant signs the EBOVAC-Salone Extension ICF. Information
      from the participant's final EBOVAC-Salone study visit up to the moment of enrolment into
      this study will be captured retrospectively. For cohort 2, enrolment will occur once the
      subject's parent/guardian has signed the EBOVAC-Salone Extension ICF. Baseline information
      and information from birth up to the moment of enrolment into this study will be collected at
      the time the ICF is signed.

      Study visits will take place as follows:

      Cohort 1: Once yearly, on the anniversary of their prime vaccination (± 1 month), cohort 1
      participants will attend the study clinic for collection of information on any SAEs since
      their previous visit. In a subsample of participants, blood sampling for serology assays will
      also be collected at each study visit.

      Cohort 2: Once yearly, on their birthday (± 1 month), cohort 2 participants (offspring) will
      be seen at the study clinic) for collection of information on any SAEs they experienced since
      their previous study visit.

      Between clinic visits, reminder phone calls and/or home visits will be used for retention
      purposes, if needed.

      SUBJECT POPULATION

      Cohort 1: subjects who received Ebola vaccine prime vaccination in EBOVAC-Salone are eligible
      for enrolment in this study.

      Cohort 2: any infant conceived by a female EBOVAC-Salone participant during the 3-month
      period following vaccination with Ad26.ZEBOV or during the 28 day period following
      vaccination with MVA-BN®-Filo in EBOVAC- Salone are also eligible for this study.

      DOSAGE AND ADMINISTRATION

      No investigational vaccine will be administered during this study.

      SAFETY EVALUATIONS

      All SAEs occurring from the final EBOVAC-Salone study visit (or from birth for eligible
      offspring) will be collected annually as indicated in the Time and Events Schedules.

      IMMUNOGENICITY EVALUATIONS

      Blood sampling to assess vaccine-induced immune responses will be conducted only in cohort 1
      in a subsample consisting of approximately 102 adults and 165 children (55 from each of the
      three paediatric age groups that were enrolled in EBOVAC-Salone: 12-17 year olds, 4-11 year
      olds, and 1-3 year olds). Some of the blood collected will also be used to determine previous
      exposure to malaria using validated ELISA and bead based assay. The immune response to
      malaria will be considered when evaluating the persistence of antibody response induced by
      the Ebola vaccines.

      OTHER CLINICAL ASSESSMENTS

      In both cohort 1 and cohort 2, a physical examination including vital signs will be conducted
      at the first study visit and at yearly visits. In cohort 2, growth measurements will also be
      collected. In cohort 1, a haematology assessment will be conducted in the subsample providing
      immunogenicity blood samples.

      STATISTICAL METHODS

      The primary analysis will be done when all participants have completed their final study
      visit or discontinued. This analysis will include all available data up to this point. No
      interim analyses are planned. There are no formal hypotheses tests planned for the safety
      data. The primary endpoint for long term safety of Ad26.ZEBOV and MVA-BN®-Filo is the
      occurrence of SAEs in the total vaccine cohort during the follow up period of up to 5 years
      (in adults) or 4 years (in children), and separately in infants in cohort 2. The primary
      analysis for immunogenicity will involve assessing humoral immune responses to Ad26.ZEBOV or
      MVA-BN®-Filo using a longitudinal design in children and adults vaccinated with Ad26.ZEBOV or
      MVA-BN®-Filo (cohort 1).
observational model: Cohort
time perspective: Prospective
measure: Number of Serious Adverse Events in subjects who received an Ebola vaccine prime vaccination in the EBOVAC-Salone trial.
time frame: Up to approximately 5 years in adults and 4 years in children from prime vaccination
description: An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
measure: Binding antibody responses against EBOV GP using Filovirus Animal Non-Clinical Group (FANG) enzyme-linked immunosorbent assay (ELISA).
time frame: Up to approximately 5 years in adults and 4 years in children from prime vaccination
description: Serum Concentration of Antibodies Binding to EBOV GP measured by Filovirus Animal Non-Clinical Group (FANG) enzyme-linked immunosorbent assay (ELISA).
measure: Number of Serious Adverse Events, in infants conceived by an EBOVAC-Salone trial female participant during the 3-month period following vaccination with Ad26.ZEBOV or during the 28 day period following vaccination with MVA-BN®-Filo.
time frame: From birth to their fifth birthday
description: An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
measure: Neutralising antibody responses directed against EBOV GP as measured by a pseudovirion neutralisation assay (psVNA)
time frame: At years 2, 3 and 4 post-prime in children and years 3, 4 and 5 post-prime in adults
description: psVNA: pseudovirion neutralising antibody reactivity against the EBOV GP defined as the serum titre that is able to inhibit viral infection by 50% (IC50 titer).
measure: Effect of previous infection with malaria, determined using validated ELISA and bead based assays, on the persistence of the humoral immune response to vaccination.
time frame: Up to approximately 5 years in adults and 4 years in children from prime vaccination
description: Serum concentration of malaria specific antibodies, determined using validated ELISA and bead based assays. The bead based assays will allow the inclusion of antigens associated with short term humoral immune responses and thus assessment of intra study exposure to malaria.
arm group label: Cohort 1
description: Subjects who received an Ebola vaccine prime vaccination in EBOVAC-Salone are eligible for enrolment in this study. Adults are defined as participants 18 years of age or older at the time of prime vaccination, and children are defined as participants aged 1 to 17 years at the time of prime vaccination in EBOVAC-Salone.
arm group label: Cohort 2 (offspring)
description: Infants conceived by a female participant in EBOVAC-Salone during the 3 months following vaccination with Ad26.ZEBOV or during the 28 days following vaccination with MVA-BN®-Filo.
intervention type: Other
intervention name: Follow-up
description: No investigational vaccine will be administered during this study
arm group label: Cohort 1
arm group label: Cohort 2 (offspring)
intervention type: Other
intervention name: Blood sample collection
description: Blood sampling to assess vaccine-induced immune responses will be conducted only in cohort 1 in a subsample consisting of approximately 102 adults and 165 children (55 from each of the three paediatric age groups that were enrolled in EBOVAC-Salone: 12-17 year olds, 4-11 year olds, and 1-3 year olds).
arm group label: Cohort 1
Blood serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Year
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Deborah Watson-Jones, PhD
role: Principal Investigator
affiliation: London School of Hygiene and Tropical Medicine
last name: Bailah Leigh, MD
role: Principal Investigator
affiliation: University of Sierra Leone
facility: 
facility: 
country: Sierra Leone
url: http://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease
description: WHO. Ebola virus disease - key facts.
citation: Portugal S, Tipton CM, Sohn H, Kone Y, Wang J, Li S, Skinner J, Virtaneva K, Sturdevant DE, Porcella SF, Doumbo OK, Doumbo S, Kayentao K, Ongoiba A, Traore B, Sanz I, Pierce SK, Crompton PD. Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. Elife. 2015 May 8;4:e07218. doi: 10.7554/eLife.07218.
PMID: 25955968
citation: Ryg-Cornejo V, Ioannidis LJ, Ly A, Chiu CY, Tellier J, Hill DL, Preston SP, Pellegrini M, Yu D, Nutt SL, Kallies A, Hansen DS. Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation. Cell Rep. 2016 Jan 5;14(1):68-81. doi: 10.1016/j.celrep.2015.12.006. Epub 2015 Dec 24.
PMID: 26725120
responsible party type: Sponsor
mesh term: Virus Diseases
mesh term: Hemorrhagic Fever, Ebola
sharing ipd: Undecided