<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/NCT03027193</url>
  </required_header>
  <id_info>
    <org_study_id>HAV001</org_study_id>
    <nct_id>NCT03027193</nct_id>
  </id_info>
  <brief_title>A Study to Determine the Safety and Immunogenicity of a Candidate MAP Vaccines ChAdOx2 HAV and MVA in Healthy Adult Volunteers</brief_title>
  <official_title>A Phase I Clinical Trial to Determine the Safety and Immunogenicity of the Candidate Mycobacterium Avium Subspecies Paratuberculosis (MAP) Vaccines ChAdOx2 HAV and MVA HAV in Healthy Adult Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Oxford</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase I dose escalation study to assess the safety and immunogenicity of the candidate&#xD;
      vaccines ChAdOx2 HAV and MVA HAV in healthy volunteers.&#xD;
&#xD;
      Volunteers will be recruited and vaccinated in Oxford, England.&#xD;
&#xD;
      All vaccinations will be administered intramuscularly. Three different doses of the ChAdOx2&#xD;
      HAV will be tested (5x10^9 vp, 2.5x10^10 vp and 5x10^10vp). MVA HAV will be assessed at 2&#xD;
      different doses (5x10^7 and 2x10^8 pfu)&#xD;
&#xD;
      The total duration of the study will be 52 weeks from the day of enrolment for volunteers&#xD;
      receiving ChAdOx2 HAV only, 12 weeks for volunteers receiving MVA HAV only and 20 weeks for&#xD;
      volunteers receiving ChAdOx2 HAV and MVA HAV.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I, open label, dose escalation trial to assess the safety and immunogenicity&#xD;
      of the ChAdOx2 and MVA HAV vaccines against Mycobacterium avium subspecies paratuberculosis&#xD;
      (MAP) in healthy volunteers&#xD;
&#xD;
      There will be 5 study groups with a total of 28 volunteers. ChAdOx2 HAV will be administered&#xD;
      intramuscularly as a single vaccination at 3 different doses: 5x10^9 vp (group 1), 2.5x10^10&#xD;
      (group 2) and 5x10^10 vp (group 3) and as a prime vaccine in group 6 (prime/boost group). MVA&#xD;
      HAV will be administered intramuscularly as a single vaccination at 2 different doses: 5x10^7&#xD;
      pfu (group 4), 2x10^8 pfu (group 5) and as a boost vaccine in group 6 (prime/boost group)&#xD;
&#xD;
      Vaccination of groups will be sequential from Group 1 to Group 6 with interim safety reviews&#xD;
      prior to dose escalation&#xD;
&#xD;
      Volunteers will be recruited and undergo screening visits, vaccination and clinic visits&#xD;
      post-vaccination at the trial site. Blood samples for safety and immunology purposes will be&#xD;
      performed on the visit time points indicated in the schedule of attendances.&#xD;
&#xD;
      Safety will be assessed by the frequency, incidence and nature of adverse events and serious&#xD;
      adverse events arising during the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 15, 2017</start_date>
  <completion_date type="Actual">January 16, 2020</completion_date>
  <primary_completion_date type="Actual">January 16, 2020</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of solicited and unsolicited local and systemic adverse events</measure>
    <time_frame>up to 28 days following vaccination</time_frame>
    <description>The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measures of Immunogenicity of ChAdOx2 HAV and MVA HAV</measure>
    <time_frame>Approximately 2 months post each vaccination</time_frame>
    <description>To assess the immunogenicity of ChAdOx2 HAV and MVA HAV in healthy adult volunteers when administered alone and in a prime-boost regimen</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Crohn Disease</condition>
  <condition>Mycobacterium Avium Subspecies Paratuberculosis</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1 volunteers (n= 3 to 6) will be administered ChAdOx2 HAV, 5 x 10^9 vp through intramuscular route.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 2 volunteers (n= 3 to 6) will be administered ChAdOx2 HAV, 2.5 x 10^10 vp through intramuscular route.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 3 volunteers (n= 3 to 6) will be administered ChAdOx2 HAV, 5 x 10^10 vp through intramuscular route.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 4 volunteers (n= 3) will be administered MVA HAV, 5 x 10^7 pfu through intramuscular route.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 5 volunteers (n= 3) will be administered MVA HAV, 2 x 10^8 pfu through intramuscular route.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 6 volunteers (n= 10) will be administered ChAdOx2 HAV, 5 x 10^10 vp followed by MVA HAV, 2 x 10^8 pfu (8 weeks apart) through intramuscular route.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAdOx2 HAV</intervention_name>
    <description>The ChAdOx2 HAV vaccine consists of the replication-deficient simian adenovirus vector ChAdOx2, containing the Mycobacterium avium subspecies paratuberculosis (MAP) antigens</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 6</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MVA HAV</intervention_name>
    <description>The MVA HAV vaccine consists of the replication deficient modified vaccinia virus Ankara (MVA) containing the Mycobacterium avium subspecies paratuberculosis (MAP) antigens.</description>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_label>Group 6</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy adults aged 18 to 50 years&#xD;
&#xD;
          2. Able and willing (in the Investigator's opinion) to comply with all study requirements&#xD;
&#xD;
          3. Willing to allow the investigators to discuss the volunteer's medical history with&#xD;
             their General Practitioner&#xD;
&#xD;
          4. For females only, willingness to practice continuous effective contraception (see&#xD;
             below) during the study and a negative pregnancy test on the day(s) of screening and&#xD;
             vaccination&#xD;
&#xD;
          5. Agreement to refrain from blood donation during the course of the study&#xD;
&#xD;
          6. Provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. 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;
          2. Prior receipt of an investigational vaccine likely to impact on interpretation of the&#xD;
             trial data.&#xD;
&#xD;
          3. Prior receipt of an adenoviral vectored vaccine in the last 12 months&#xD;
&#xD;
          4. Administration of immunoglobulins and/or any blood products within the three months&#xD;
             preceding the planned administration of the vaccine candidate&#xD;
&#xD;
          5. 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;
          6. History of allergic disease or reactions likely to be exacerbated by any component of&#xD;
             the vaccine&#xD;
&#xD;
          7. Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.&#xD;
&#xD;
          8. Any history of anaphylaxis in relation to vaccination&#xD;
&#xD;
          9. Pregnancy, lactation or willingness/intention to become pregnant during the study&#xD;
&#xD;
         10. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in&#xD;
             situ)&#xD;
&#xD;
         11. History of serious psychiatric condition likely to affect participation in the study&#xD;
&#xD;
         12. Bleeding disorder (eg. Factor deficiency, coagulopathy or platelet disorder), or prior&#xD;
             history of significant bleeding or bruising following IM injections or venepuncture&#xD;
&#xD;
         13. Any other serious chronic illness requiring hospital specialist supervision&#xD;
&#xD;
         14. Suspected or known current alcohol abuse as defined by an alcohol intake of greater&#xD;
             than 42 units every week&#xD;
&#xD;
         15. Suspected or known injecting drug abuse in the 5 years preceding enrolment&#xD;
&#xD;
         16. Seropositive for hepatitis C (antibodies to HCV)&#xD;
&#xD;
         17. Seropositive for hepatitis B surface antigen(HBsAg)&#xD;
&#xD;
         18. Any clinically significant abnormal finding on screening biochemistry or haematology&#xD;
             blood tests or urinalysis&#xD;
&#xD;
         19. 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;
         20. 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, DPhill FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hosptal, Oxford, United Kingdom</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>February 24, 2020</last_update_submitted>
  <last_update_submitted_qc>February 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vaccine</keyword>
  <keyword>MAP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycobacterium Infections</mesh_term>
    <mesh_term>Mycobacterium avium-intracellulare Infection</mesh_term>
    <mesh_term>Paratuberculosis</mesh_term>
    <mesh_term>Crohn Disease</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/NCT03027193
org study id: HAV001
nct id: NCT03027193
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
A phase I dose escalation study to assess the safety and immunogenicity of the candidate
      vaccines ChAdOx2 HAV and MVA HAV in healthy volunteers.

      Volunteers will be recruited and vaccinated in Oxford, England.

      All vaccinations will be administered intramuscularly. Three different doses of the ChAdOx2
      HAV will be tested (5x10^9 vp, 2.5x10^10 vp and 5x10^10vp). MVA HAV will be assessed at 2
      different doses (5x10^7 and 2x10^8 pfu)

      The total duration of the study will be 52 weeks from the day of enrolment for volunteers
      receiving ChAdOx2 HAV only, 12 weeks for volunteers receiving MVA HAV only and 20 weeks for
      volunteers receiving ChAdOx2 HAV and MVA HAV.
This is a phase I, open label, dose escalation trial to assess the safety and immunogenicity
      of the ChAdOx2 and MVA HAV vaccines against Mycobacterium avium subspecies paratuberculosis
      (MAP) in healthy volunteers

      There will be 5 study groups with a total of 28 volunteers. ChAdOx2 HAV will be administered
      intramuscularly as a single vaccination at 3 different doses: 5x10^9 vp (group 1), 2.5x10^10
      (group 2) and 5x10^10 vp (group 3) and as a prime vaccine in group 6 (prime/boost group). MVA
      HAV will be administered intramuscularly as a single vaccination at 2 different doses: 5x10^7
      pfu (group 4), 2x10^8 pfu (group 5) and as a boost vaccine in group 6 (prime/boost group)

      Vaccination of groups will be sequential from Group 1 to Group 6 with interim safety reviews
      prior to dose escalation

      Volunteers will be recruited and undergo screening visits, vaccination and clinic visits
      post-vaccination at the trial site. Blood samples for safety and immunology purposes will be
      performed on the visit time points indicated in the schedule of attendances.

      Safety will be assessed by the frequency, incidence and nature of adverse events and serious
      adverse events arising during the study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of solicited and unsolicited local and systemic adverse events
time frame: up to 28 days following vaccination
description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration
measure: Measures of Immunogenicity of ChAdOx2 HAV and MVA HAV
time frame: Approximately 2 months post each vaccination
description: To assess the immunogenicity of ChAdOx2 HAV and MVA HAV in healthy adult volunteers when administered alone and in a prime-boost regimen
arm group label: Group 1
arm group type: Experimental
description: Group 1 volunteers (n= 3 to 6) will be administered ChAdOx2 HAV, 5 x 10^9 vp through intramuscular route.
arm group label: Group 2
arm group type: Experimental
description: Group 2 volunteers (n= 3 to 6) will be administered ChAdOx2 HAV, 2.5 x 10^10 vp through intramuscular route.
arm group label: Group 3
arm group type: Experimental
description: Group 3 volunteers (n= 3 to 6) will be administered ChAdOx2 HAV, 5 x 10^10 vp through intramuscular route.
arm group label: Group 4
arm group type: Experimental
description: Group 4 volunteers (n= 3) will be administered MVA HAV, 5 x 10^7 pfu through intramuscular route.
arm group label: Group 5
arm group type: Experimental
description: Group 5 volunteers (n= 3) will be administered MVA HAV, 2 x 10^8 pfu through intramuscular route.
arm group label: Group 6
arm group type: Experimental
description: Group 6 volunteers (n= 10) will be administered ChAdOx2 HAV, 5 x 10^10 vp followed by MVA HAV, 2 x 10^8 pfu (8 weeks apart) through intramuscular route.
intervention type: Biological
intervention name: ChAdOx2 HAV
description: The ChAdOx2 HAV vaccine consists of the replication-deficient simian adenovirus vector ChAdOx2, containing the Mycobacterium avium subspecies paratuberculosis (MAP) antigens
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 6
intervention type: Biological
intervention name: MVA HAV
description: The MVA HAV vaccine consists of the replication deficient modified vaccinia virus Ankara (MVA) containing the Mycobacterium avium subspecies paratuberculosis (MAP) antigens.
arm group label: Group 4
arm group label: Group 5
arm group label: Group 6
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Adrian V Hill, DPhill FRCP
role: Principal Investigator
affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hosptal, Oxford, United Kingdom
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Mycobacterium Infections
mesh term: Mycobacterium avium-intracellulare Infection
mesh term: Paratuberculosis
mesh term: Crohn Disease