<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/NCT03300362</url>
  </required_header>
  <id_info>
    <org_study_id>FLU007 INVICTUS</org_study_id>
    <nct_id>NCT03300362</nct_id>
  </id_info>
  <brief_title>Improved Novel VaccIne CombinaTion InflUenza Study</brief_title>
  <acronym>INVICTUS</acronym>
  <official_title>A Phase IIb Study to Determine the Safety and Efficacy of Candidate INfluenza Vaccine MVA-NP+M1 in Combination With Licensed InaCTivated inflUenza Vaccine in adultS Aged 65 Years and Above</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vaccitech (UK) Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vaccitech (UK) Limited</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>
      A Phase IIb randomised, participant-blinded, placebo-controlled, multi-centre phase IIb&#xD;
      efficacy study in 2030 volunteers aged 65 and over. The study will assess the safety and&#xD;
      efficacy of the co-administration of a viral vectored vaccine, MVA- NP+M1, and the annual&#xD;
      recommended licensed inactivated influenza vaccine (IIV). Within the main cohort 100&#xD;
      participants will be recruited to an immunology sub-cohort.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The efficacy of current seasonal influenza vaccines is limited in the face of antigenic&#xD;
      mismatch between circulating viral strains and those in the given vaccine. Additionally&#xD;
      vaccination in older adults, a major target group for vaccination, prevents&#xD;
      laboratory-confirmed influenza in only 30-40% compared to 70-90% in young adults. The&#xD;
      hypothesis in this Phase IIb efficacy study is that a new vaccine MVA-NP+M1 with licensed&#xD;
      inactivated influenza vaccine (IIV) in the older age group will be able to induce immune&#xD;
      responses that protect individuals against influenza illness, severity of symptoms and reduce&#xD;
      viral shedding, thereby increasing the protection conferred by seasonal influenza vaccine&#xD;
      alone. A total of 2030 participants who are 65 years of age or over and eligible for annual&#xD;
      seasonal influenza vaccination and provide informed consent will be recruited to the study.&#xD;
      Potential volunteers will be mailed an invitation to take part by their GPs or recruited by&#xD;
      local advertisements. Participants will be randomised to receive either MVA- NP+M1 with&#xD;
      licensed IIV or saline placebo with licensed IIV. In the first 28 days after vaccination,&#xD;
      participants will record adverse events using an electronic or paper diary. The participants&#xD;
      will be contacted by telephone 1 day and 7 days post-vaccination to enquire about any serious&#xD;
      adverse events and support follow up. During influenza season participants will record weekly&#xD;
      whether or not they have had an influenza like illness (ILI). For every ILI episode&#xD;
      experienced, the participants will record the severity of their symptoms daily. Among the&#xD;
      participants, a total of 100 volunteers (50 in each group) will be recruited into an&#xD;
      immunology sub-cohort. They will have blood samples collected on the day of vaccination, 1&#xD;
      week, 3 weeks and 26 weeks post-vaccination for monitoring of laboratory adverse events and&#xD;
      immunogenicity purposes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Change to recommended season flu vaccine in UK&#xD;
  </why_stopped>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Actual">October 31, 2018</completion_date>
  <primary_completion_date type="Actual">October 31, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Investigators recording clinical outcomes will also be blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of days with moderate or severe influenza-like symptoms</measure>
    <time_frame>6-7 months</time_frame>
    <description>Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of influenza-like-illness</measure>
    <time_frame>6-7 months</time_frame>
    <description>Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of influenza-like symptoms</measure>
    <time_frame>6-7 months</time_frame>
    <description>Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of influenza-like-illnes</measure>
    <time_frame>6-7 months</time_frame>
    <description>Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of GP consultations from respiratory illness</measure>
    <time_frame>6-7 months</time_frame>
    <description>Throughout the influenza season - self-reported and Medical Records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of hospitalisations and deaths due to respiratory illness</measure>
    <time_frame>6-7 months</time_frame>
    <description>Throughout the influenza season - self-reported and Medical Records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination</measure>
    <time_frame>Day 0-7</time_frame>
    <description>Self-reported symptoms recorded using electronic or paper diaries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of serious adverse events during the whole study duration</measure>
    <time_frame>6-7 months</time_frame>
    <description>Telephone calls on Day 1-3, day 7-9 and every 3-4 weeks throughout volunteers' participation in the trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of unsolicited adverse events for 28 days following vaccination</measure>
    <time_frame>Day 0-28</time_frame>
    <description>Self-reported symptoms recorded using electronic or paper diaries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of influenza-specific T-cells measured by IFNg ELISpot</measure>
    <time_frame>6-7 months</time_frame>
    <description>To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre of influenza-specific neutralising antibodies</measure>
    <time_frame>6-7 months</time_frame>
    <description>To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breadth of influenza-specific T-cells and antibodies</measure>
    <time_frame>6-7 months</time_frame>
    <description>To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Estimated frequency of influenza infection using historical data on the proportion of ILIs that is caused by influenza virus infection.</measure>
    <time_frame>6-7 months</time_frame>
    <description>To explore novel clinical endpoints for future Phase III efficacy trials of influenza vaccines</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">862</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Seasonal influenza &amp; MVA-NP+M1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two vaccinations will be administered: Seasonal influenza vaccine &amp; MVA-NP+M1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Seasonal influenza &amp; saline placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Two vaccinations will be administered: Seasonal influenza vaccine &amp; sodium chloride</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Seasonal influenza vaccine</intervention_name>
    <description>Seasonal influenza vaccine</description>
    <arm_group_label>Seasonal influenza &amp; MVA-NP+M1</arm_group_label>
    <arm_group_label>Seasonal influenza &amp; saline placebo</arm_group_label>
    <other_name>Quadrivalent Influenza Vaccine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MVA-NP+M1</intervention_name>
    <description>Trial vaccine</description>
    <arm_group_label>Seasonal influenza &amp; MVA-NP+M1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium chloride</intervention_name>
    <description>Saline placebo</description>
    <arm_group_label>Seasonal influenza &amp; saline placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Volunteer is willing and has capacity to provide written informed consent for&#xD;
             participation in the trial (in the Investigator's opinion).&#xD;
&#xD;
          -  Male or female adults, aged 65 years and above&#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&#xD;
&#xD;
          -  Eligible to receive seasonal influenza vaccine&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any history of anaphylaxis in reaction to vaccination or history of allergic reactions&#xD;
             likely to be exacerbated by any component of the vaccine (e.g. egg allergy)&#xD;
&#xD;
          -  Ongoing terminal illness with a life expectancy estimated to be approximately &lt;6&#xD;
             months.&#xD;
&#xD;
          -  Continuous use of oral anticoagulants, such as coumarins and related anticoagulants&#xD;
             (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran&#xD;
             and edoxaban)&#xD;
&#xD;
          -  Any other significant disease, disorder or finding (including blood test results),&#xD;
             which, in the opinion of the Investigators, would either put the volunteer at risk&#xD;
             because of participation in the study, or may influence the result of the study&#xD;
&#xD;
          -  Participation in another clinical trial of an investigational medicinal product in the&#xD;
             30 days preceding enrolment, or planned use during the study period&#xD;
&#xD;
          -  Prior receipt of an investigational vaccine likely to impact on interpretation of the&#xD;
             trial data&#xD;
&#xD;
          -  Receipt of annual seasonal influenza vaccine prior to enrolment (for the same&#xD;
             influenza season volunteers are recruited in)&#xD;
&#xD;
          -  Not willing to comply with study procedures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Butler</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sussex</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Boathouse Surgery</name>
      <address>
        <city>Pangbourne</city>
        <state>Berkshire</state>
        <zip>RG8 7DF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wokingham Medical Centre</name>
      <address>
        <city>Wokingham</city>
        <state>Berkshire</state>
        <zip>RG40 1XS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bicester Health Centre</name>
      <address>
        <city>Bicester</city>
        <state>Oxfordshire</state>
        <zip>OX26 6AT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre for Clinical Vaccinology and Tropical Medicine (CCVTM</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 7LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Windrush Health Centre</name>
      <address>
        <city>Witney</city>
        <state>Oxfordshire</state>
        <zip>OX28 6JS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>November 20, 2018</last_update_submitted>
  <last_update_submitted_qc>November 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2018</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>Influenza, Human</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03300362
org study id: FLU007 INVICTUS
nct id: NCT03300362
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A Phase IIb randomised, participant-blinded, placebo-controlled, multi-centre phase IIb
      efficacy study in 2030 volunteers aged 65 and over. The study will assess the safety and
      efficacy of the co-administration of a viral vectored vaccine, MVA- NP+M1, and the annual
      recommended licensed inactivated influenza vaccine (IIV). Within the main cohort 100
      participants will be recruited to an immunology sub-cohort.
The efficacy of current seasonal influenza vaccines is limited in the face of antigenic
      mismatch between circulating viral strains and those in the given vaccine. Additionally
      vaccination in older adults, a major target group for vaccination, prevents
      laboratory-confirmed influenza in only 30-40% compared to 70-90% in young adults. The
      hypothesis in this Phase IIb efficacy study is that a new vaccine MVA-NP+M1 with licensed
      inactivated influenza vaccine (IIV) in the older age group will be able to induce immune
      responses that protect individuals against influenza illness, severity of symptoms and reduce
      viral shedding, thereby increasing the protection conferred by seasonal influenza vaccine
      alone. A total of 2030 participants who are 65 years of age or over and eligible for annual
      seasonal influenza vaccination and provide informed consent will be recruited to the study.
      Potential volunteers will be mailed an invitation to take part by their GPs or recruited by
      local advertisements. Participants will be randomised to receive either MVA- NP+M1 with
      licensed IIV or saline placebo with licensed IIV. In the first 28 days after vaccination,
      participants will record adverse events using an electronic or paper diary. The participants
      will be contacted by telephone 1 day and 7 days post-vaccination to enquire about any serious
      adverse events and support follow up. During influenza season participants will record weekly
      whether or not they have had an influenza like illness (ILI). For every ILI episode
      experienced, the participants will record the severity of their symptoms daily. Among the
      participants, a total of 100 volunteers (50 in each group) will be recruited into an
      immunology sub-cohort. They will have blood samples collected on the day of vaccination, 1
      week, 3 weeks and 26 weeks post-vaccination for monitoring of laboratory adverse events and
      immunogenicity purposes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
masking description: Investigators recording clinical outcomes will also be blinded
measure: Number of days with moderate or severe influenza-like symptoms
time frame: 6-7 months
description: Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries
measure: Incidence of influenza-like-illness
time frame: 6-7 months
description: Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries
measure: Severity of influenza-like symptoms
time frame: 6-7 months
description: Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries
measure: Duration of influenza-like-illnes
time frame: 6-7 months
description: Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries
measure: Occurrence of GP consultations from respiratory illness
time frame: 6-7 months
description: Throughout the influenza season - self-reported and Medical Records
measure: Occurrence of hospitalisations and deaths due to respiratory illness
time frame: 6-7 months
description: Throughout the influenza season - self-reported and Medical Records
measure: Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination
time frame: Day 0-7
description: Self-reported symptoms recorded using electronic or paper diaries
measure: Occurrence of serious adverse events during the whole study duration
time frame: 6-7 months
description: Telephone calls on Day 1-3, day 7-9 and every 3-4 weeks throughout volunteers' participation in the trial
measure: Occurrence of unsolicited adverse events for 28 days following vaccination
time frame: Day 0-28
description: Self-reported symptoms recorded using electronic or paper diaries
measure: Frequency of influenza-specific T-cells measured by IFNg ELISpot
time frame: 6-7 months
description: To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above
measure: Geometric mean titre of influenza-specific neutralising antibodies
time frame: 6-7 months
description: To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above
measure: Breadth of influenza-specific T-cells and antibodies
time frame: 6-7 months
description: To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above
measure: Estimated frequency of influenza infection using historical data on the proportion of ILIs that is caused by influenza virus infection.
time frame: 6-7 months
description: To explore novel clinical endpoints for future Phase III efficacy trials of influenza vaccines
arm group label: Seasonal influenza & MVA-NP+M1
arm group type: Experimental
description: Two vaccinations will be administered: Seasonal influenza vaccine & MVA-NP+M1
arm group label: Seasonal influenza & saline placebo
arm group type: Placebo Comparator
description: Two vaccinations will be administered: Seasonal influenza vaccine & sodium chloride
intervention type: Drug
intervention name: Seasonal influenza vaccine
description: Seasonal influenza vaccine
arm group label: Seasonal influenza & MVA-NP+M1
arm group label: Seasonal influenza & saline placebo
other name: Quadrivalent Influenza Vaccine
intervention type: Drug
intervention name: MVA-NP+M1
description: Trial vaccine
arm group label: Seasonal influenza & MVA-NP+M1
intervention type: Drug
intervention name: Sodium chloride
description: Saline placebo
arm group label: Seasonal influenza & saline placebo
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Christopher Butler
role: Principal Investigator
affiliation: University of Sussex
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Vaccines
sharing ipd: No