<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/NCT02240875</url>
  </required_header>
  <id_info>
    <org_study_id>EBL01</org_study_id>
    <secondary_id>2014-003518-10</secondary_id>
    <nct_id>NCT02240875</nct_id>
  </id_info>
  <brief_title>A Study to Assess New Ebola Vaccines, cAd3-EBO Z and MVA-BN® Filo</brief_title>
  <official_title>A Phase Ia, Dose-Escalating, Safety and Immunogenicity Trial of the Monovalent Zaire Ebola Viral Vector Candidate Vaccine cAd3-EBO Z and the Heterologous Prime-boost Candidate Vaccine Regimen cAd3-EBO Z and MVA-BN® Filo in Healthy UK Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wellcome Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess two new Ebola vaccines: cAd3-EBO Z at 3 different&#xD;
      doses, and a second vaccine, MVA-BN® Filo, at 3 different doses. The study will enable us to&#xD;
      assess the safety of the vaccines and the extent of the immune response in healthy&#xD;
      volunteers. The investigators will do this by giving volunteers a either one or two&#xD;
      vaccinations, doing blood and saliva tests and collecting information about any symptoms that&#xD;
      occur after vaccination. This is the first trial to use either of these vaccines in humans.&#xD;
      We plan to recruit a total of 92 volunteers to be vaccinated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Long- term immunology follow-up: In order to assess the durability of vaccine induced&#xD;
      immunogenicity, all vaccinated subjects will be invited back to attend a maximum of 3 further&#xD;
      optional follow up visits at least 12 months after their final vaccination. The 3 visits will&#xD;
      have a minimum interval of 3 months between them, and the final visit must take place no&#xD;
      longer than 12 months after the first optional visit.&#xD;
&#xD;
      Volunteers who attend these visits will be asked about occurrence of any SAEs during the&#xD;
      intervening period. SAE data for this period will not be collected in those volunteers who&#xD;
      decline to attend these additional visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 17, 2014</start_date>
  <completion_date type="Actual">August 22, 2017</completion_date>
  <primary_completion_date type="Actual">August 22, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of the Ebola Zaire vaccine cAd3-EBO Z when administered to healthy volunteers at 3 doses</measure>
    <time_frame>6 months</time_frame>
    <description>The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cellular and humoral immunogenicity of the Ebola Zaire vaccine cAd3-EBO Z when administered to healthy volunteers at 3 doses</measure>
    <time_frame>6 months</time_frame>
    <description>The primary immunogenicity outcome measures are ELISA and neutralization antigen-specific assays for antibody responses and intracellular cytokine staining (ICS) assay for T cell responses.</description>
  </secondary_outcome>
  <number_of_arms>13</number_of_arms>
  <enrollment type="Actual">91</enrollment>
  <condition>Ebola</condition>
  <condition>Ebola Zaire</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1c</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2c</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3c</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 2.2 x 10^8 TCID50s MVA-BN® Filo at day 7</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 2.2 x 10^8 TCID50s MVA-BN® Filo at day 14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 4.4 x 10^7 TCID50s MVA-BN® Filo at day 7</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 4.4 x 10^7 TCID50s MVA-BN® Filo at day 14</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>cAd3-EBO Z at 1 x 10^10 vp</intervention_name>
    <description>Low dose cAd3-EBO Z</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 1b</arm_group_label>
    <arm_group_label>Group 1c</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>cAd3-EBO Z at 2.5 x 10^10 vp</intervention_name>
    <description>Medium dose cAd3-EBO Z</description>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 2b</arm_group_label>
    <arm_group_label>Group 2c</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_label>Group 6</arm_group_label>
    <arm_group_label>Group 7</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>cAd3-EBO Z at 5 x 10^10 vp</intervention_name>
    <description>High dose cAd3-EBO Z</description>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 3b</arm_group_label>
    <arm_group_label>Group 3c</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4.4x10^8 TCID50s MVA-BN® Filo</intervention_name>
    <description>High dose MVA-BN® Filo</description>
    <arm_group_label>Group 1b</arm_group_label>
    <arm_group_label>Group 2b</arm_group_label>
    <arm_group_label>Group 3b</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>2.2x10^8 TCID50s MVA-BN® Filo</intervention_name>
    <description>Low dose MVA-BN® Filo</description>
    <arm_group_label>Group 1c</arm_group_label>
    <arm_group_label>Group 2c</arm_group_label>
    <arm_group_label>Group 3c</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4.4 x 10^7 TCID50s MVA-BN® Filo</intervention_name>
    <description>Very low dose MVA-BN® Filo</description>
    <arm_group_label>Group 6</arm_group_label>
    <arm_group_label>Group 7</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adults aged 18 to 50 years&#xD;
&#xD;
          -  Able and willing (in the Investigator's opinion) to comply with all study requirements&#xD;
&#xD;
          -  Willing to allow the investigators to discuss the volunteer's medical history with&#xD;
             their general practitioner (GP)&#xD;
&#xD;
          -  For females only, willingness to practice continuous effective contraception during&#xD;
             the study and a negative pregnancy test on the day(s) of screening and vaccination&#xD;
&#xD;
          -  Agreement to refrain from blood donation during the course of the study&#xD;
&#xD;
          -  Provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in another research study involving receipt of an investigational&#xD;
             product in the 30 days preceding enrolment, or planned use during the study period&#xD;
&#xD;
          -  Prior receipt of an investigational Ebola or Marburg vaccine, a chimpanzee adenovirus&#xD;
             vectored vaccine or any other investigational vaccine likely to impact on&#xD;
             interpretation of the trial data&#xD;
&#xD;
          -  Receipt of any live, attenuated vaccine within 28 days prior to enrolment&#xD;
&#xD;
          -  Receipt of any subunit or killed vaccine within 14 days prior to enrolment&#xD;
&#xD;
          -  Administration of immunoglobulins and/or any blood products within the three months&#xD;
             preceding the planned administration of the vaccine candidate&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV&#xD;
             infection; asplenia; recurrent, severe infections and chronic (more than 14 days)&#xD;
             immunosuppressant medication within the past 6 months (inhaled and topical steroids&#xD;
             are allowed)&#xD;
&#xD;
          -  History of allergic disease or reactions likely to be exacerbated by any component of&#xD;
             the vaccine, (e.g. egg products) including urticaria, respiratory difficulty or&#xD;
             abdominal pain&#xD;
&#xD;
          -  Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.&#xD;
&#xD;
          -  Any history of anaphylaxis in reaction to vaccination&#xD;
&#xD;
          -  Pregnancy, lactation or willingness/intention to become pregnant during the study&#xD;
&#xD;
          -  History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in&#xD;
             situ)&#xD;
&#xD;
          -  History of serious psychiatric condition&#xD;
&#xD;
          -  Poorly controlled asthma or thyroid disease&#xD;
&#xD;
          -  Seizure in the past 3 years or treatment for seizure disorder in the past 3 years&#xD;
&#xD;
          -  Bleeding disorder (eg. Factor deficiency, coagulopathy or platelet disorder), or prior&#xD;
             history of significant bleeding or bruising following intramuscular injections or&#xD;
             venepuncture&#xD;
&#xD;
          -  Any other serious chronic illness requiring hospital specialist supervision&#xD;
&#xD;
          -  Current anti-tuberculosis prophylaxis or therapy&#xD;
&#xD;
          -  Suspected or known current alcohol abuse as defined by an alcohol intake of greater&#xD;
             than 42 units every week&#xD;
&#xD;
          -  Suspected or known injecting drug abuse in the 5 years preceding enrolment&#xD;
&#xD;
          -  Seropositive for hepatitis B surface antigen (HBsAg)&#xD;
&#xD;
          -  Seropositive for hepatitis C virus (antibodies to HCV)&#xD;
&#xD;
          -  Travel to a Ebola or Marburg endemic region during the study period or within the&#xD;
             previous six months&#xD;
&#xD;
          -  Any clinically significant abnormal finding on screening biochemistry or haematology&#xD;
             blood tests or urinalysis (see Appendix A and Appendix B)&#xD;
&#xD;
          -  Any other significant disease, disorder or finding which may significantly increase&#xD;
             the risk to the volunteer because of participation in the study, affect the ability of&#xD;
             the volunteer to participate in the study or impair interpretation of the study data&#xD;
&#xD;
          -  Inability of the study team to contact the volunteer's GP to confirm medical history&#xD;
             and safety to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adrian V Hill</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>July 4, 2018</last_update_submitted>
  <last_update_submitted_qc>July 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ebola</keyword>
  <keyword>Zaire</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemorrhagic Fever, Ebola</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic</mesh_term>
  </intervention_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/NCT02240875
org study id: EBL01
secondary id: 2014-003518-10
nct id: NCT02240875
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to assess two new Ebola vaccines: cAd3-EBO Z at 3 different
      doses, and a second vaccine, MVA-BN® Filo, at 3 different doses. The study will enable us to
      assess the safety of the vaccines and the extent of the immune response in healthy
      volunteers. The investigators will do this by giving volunteers a either one or two
      vaccinations, doing blood and saliva tests and collecting information about any symptoms that
      occur after vaccination. This is the first trial to use either of these vaccines in humans.
      We plan to recruit a total of 92 volunteers to be vaccinated.
Long- term immunology follow-up: In order to assess the durability of vaccine induced
      immunogenicity, all vaccinated subjects will be invited back to attend a maximum of 3 further
      optional follow up visits at least 12 months after their final vaccination. The 3 visits will
      have a minimum interval of 3 months between them, and the final visit must take place no
      longer than 12 months after the first optional visit.

      Volunteers who attend these visits will be asked about occurrence of any SAEs during the
      intervening period. SAE data for this period will not be collected in those volunteers who
      decline to attend these additional visits.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Safety and tolerability of the Ebola Zaire vaccine cAd3-EBO Z when administered to healthy volunteers at 3 doses
time frame: 6 months
description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events.
measure: Cellular and humoral immunogenicity of the Ebola Zaire vaccine cAd3-EBO Z when administered to healthy volunteers at 3 doses
time frame: 6 months
description: The primary immunogenicity outcome measures are ELISA and neutralization antigen-specific assays for antibody responses and intracellular cytokine staining (ICS) assay for T cell responses.
arm group label: Group 1
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly
arm group label: Group 1b
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo
arm group label: Group 1c
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo
arm group label: Group 2
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly
arm group label: Group 2b
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo
arm group label: Group 2c
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo
arm group label: Group 3
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly
arm group label: Group 3b
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo
arm group label: Group 3c
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo
arm group label: Group 4
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 2.2 x 10^8 TCID50s MVA-BN® Filo at day 7
arm group label: Group 5
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 2.2 x 10^8 TCID50s MVA-BN® Filo at day 14
arm group label: Group 6
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 4.4 x 10^7 TCID50s MVA-BN® Filo at day 7
arm group label: Group 7
arm group type: Experimental
description: Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly at day 0, followed by 4.4 x 10^7 TCID50s MVA-BN® Filo at day 14
intervention type: Biological
intervention name: cAd3-EBO Z at 1 x 10^10 vp
description: Low dose cAd3-EBO Z
arm group label: Group 1
arm group label: Group 1b
arm group label: Group 1c
intervention type: Biological
intervention name: cAd3-EBO Z at 2.5 x 10^10 vp
description: Medium dose cAd3-EBO Z
arm group label: Group 2
arm group label: Group 2b
arm group label: Group 2c
arm group label: Group 4
arm group label: Group 5
arm group label: Group 6
arm group label: Group 7
intervention type: Biological
intervention name: cAd3-EBO Z at 5 x 10^10 vp
description: High dose cAd3-EBO Z
arm group label: Group 3
arm group label: Group 3b
arm group label: Group 3c
intervention type: Biological
intervention name: 4.4x10^8 TCID50s MVA-BN® Filo
description: High dose MVA-BN® Filo
arm group label: Group 1b
arm group label: Group 2b
arm group label: Group 3b
intervention type: Biological
intervention name: 2.2x10^8 TCID50s MVA-BN® Filo
description: Low dose MVA-BN® Filo
arm group label: Group 1c
arm group label: Group 2c
arm group label: Group 3c
arm group label: Group 4
arm group label: Group 5
intervention type: Biological
intervention name: 4.4 x 10^7 TCID50s MVA-BN® Filo
description: Very low dose MVA-BN® Filo
arm group label: Group 6
arm group label: Group 7
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Adrian V Hill
role: Principal Investigator
affiliation: University of Oxford
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Hemorrhagic Fever, Ebola
mesh term: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic