<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/NCT01682369</url>
  </required_header>
  <id_info>
    <org_study_id>OVG 2012/04</org_study_id>
    <secondary_id>2012-002443-26</secondary_id>
    <nct_id>NCT01682369</nct_id>
  </id_info>
  <brief_title>ADITEC FLU STUDY: Understanding the Genetic Basis for Immune Responses</brief_title>
  <official_title>A Multi-centre, Phase II, Open Labelled Randomised Control Trial to Describe Immune &amp; Transcriptomic Responses to Trivalent Inactivated Vaccine (TIV) &amp; MF59 Adjuvanted Influenza Vaccine (ATIV) in 14 -26 Month Healthy Children</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>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Infants and young children do not respond as well as adults to the flu vaccines currently&#xD;
      available in the UK. Fluad, is a different type of influenza vaccine that has been available&#xD;
      in the European continent for the last decade, and contains an adjuvant known as MF59.&#xD;
&#xD;
      This vaccine has been used extensively in adults over 65 years of age. It has been&#xD;
      administered to over 4000 children in previous studies, which have shown that it produces an&#xD;
      enhanced immune response in children compared with traditional vaccines, and that it is safe&#xD;
      in this age group. It is, however, not yet licensed for use in children. The reason for this&#xD;
      new study is to gain a better understanding of the how this vaccine is stimulating the immune&#xD;
      system, by looking to see which parts of the genetic code are 'switched on' in response to&#xD;
      immunisation, and to see how this differs from the response to currently used flu vaccines.&#xD;
&#xD;
      To do this the Oxford Vaccine Group will enrol children aged 14 to 26 months to receive&#xD;
      either the influenza vaccine with the MF59 adjuvant (ATIV) or one of the influenza vaccines&#xD;
      currently available in the UK (Agrippal/ Begripal or TIV). The study will also help to find&#xD;
      out whether it is possible to identify patterns of genetic response which can predict&#xD;
      responses to immunisation. Being able to do so could potentially enable more rapid&#xD;
      development of vaccines against influenza and other diseases in the future. We will also&#xD;
      measure how well the immune system responds to the two vaccines and look at any side effects.&#xD;
&#xD;
      The study is funded by Aditec is a collaborative research programme that aims to accelerate&#xD;
      the development of novel and powerful immunisation technologies for the next generation of&#xD;
      human vaccines.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">February 2013</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Descriptive analyses of gene expression profiles of participants following immunisation with TIV or ATIV in relation to baseline profiles.</measure>
    <time_frame>56 days</time_frame>
    <description>To describe gene expression profiles of participants following immunisation with TIV or ATIV in relation to baseline profiles.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To describe the immunogenicity of TIV &amp; ATIV in terms of haemagglutination-Inhibition test (HAI) against each of the three vaccine strains (A/H1N1, A/H3N2, B), four weeks after completion of vaccination.</measure>
    <time_frame>56 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the reactogenicity &amp; safety of ATIV in terms of local &amp; systemic reactions following vaccination.</measure>
    <time_frame>56 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study T&amp;B cell responses following immunisation with each vaccine.</measure>
    <time_frame>56 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To explore the relationship between gene expression and the T cell, B cell and HIA response to immunisation with TIV and ATIV.</measure>
    <time_frame>56 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To explore the relationship between gene expression and the reactogenicity of TIV and ATIV.</measure>
    <time_frame>56 days</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Group 1 a - TIV</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>V1- Day 0- Administer a dose of 0.25ml of vaccine TIV (Agrippal) + Collect blood sample (up to 6.0 ml)&#xD;
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine TIV (Agrippal)&#xD;
V3-(Day V2+1)- Collect blood sample (up to 6.0 ml)&#xD;
V4- Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1 b - TIV</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>V1- Day 0- Administer a dose of 0.25ml of vaccine TIV (Agrippal) + Collect blood sample (up to 6.0 ml)&#xD;
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine TIV (Agrippal)&#xD;
V3-(Day V2+3)- Collect blood sample (up to 6.0 ml)&#xD;
V4- Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1 c - TIV</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>V1- Day 0- Administer a dose of 0.25ml of vaccine TIV (Aggripal) + Collect blood sample (up to 6.0 ml)&#xD;
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine TIV (Aggripal)&#xD;
V3-(Day V2+7)- Collect blood sample (up to 6.0 ml)&#xD;
V4- Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 a - ATIV</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>V1- Day 0- Administer a dose of 0.25ml of vaccine ATIV (Fluad) + Collect blood sample (up to 6.0 ml)&#xD;
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine ATIV (Fluad)&#xD;
V3- V3(Day V2+1)- Collect blood sample (up to 6.0 ml)&#xD;
V4- V4 Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 b - ATIV</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>V1- Day 0- Administer a dose of 0.25ml of vaccine ATIV (Fluad) + Collect blood sample (up to 6.0 ml)&#xD;
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine ATIV (Fluad)&#xD;
V3- V3(Day V2+3)- Collect blood sample (up to 6.0 ml)&#xD;
V4- V4 Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 c - ATIV</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>V1- Day 0- Administer a dose of 0.25ml of vaccine ATIV (Fluad) + Collect blood sample (up to 6.0 ml)&#xD;
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine ATIV (Fluad)&#xD;
V3- V3(Day V2+7)- Collect blood sample (up to 6.0 ml)&#xD;
V4- V4 Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TIV (Aggripal)</intervention_name>
    <arm_group_label>Group 1 a - TIV</arm_group_label>
    <arm_group_label>Group 1 b - TIV</arm_group_label>
    <arm_group_label>Group 1 c - TIV</arm_group_label>
    <other_name>Begripal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ATIV (Fluad)</intervention_name>
    <arm_group_label>Group 2 a - ATIV</arm_group_label>
    <arm_group_label>Group 2 b - ATIV</arm_group_label>
    <arm_group_label>Group 2 c - ATIV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The investigator believes that the parents / LAR (s) of the child can and will comply&#xD;
             with requirements of the protocol (e.g. completion of diary cards, understanding of&#xD;
             study procedure, consent process, availability at visits)&#xD;
&#xD;
          -  Written informed consent obtained from parent / LAR (s) of the subject&#xD;
&#xD;
          -  Age from 14 months to 26 months (from start of 14 months up to &amp; excluding 27 months&#xD;
             of age)&#xD;
&#xD;
          -  Subject is healthy as determined by medical history and clinical examination&#xD;
&#xD;
          -  Have received the standard UK immunisation schedule&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Child in care&#xD;
&#xD;
          -  Use or planned use of any non-registered or investigational product in last 30 days&#xD;
&#xD;
          -  Previous influenza vaccination&#xD;
&#xD;
          -  Microbiologically proven influenza illness or treatment with antiviral medications&#xD;
&#xD;
          -  Confirmed or suspected egg allergy.&#xD;
&#xD;
          -  Chronic serious medical conditions which may, in the opinion of the investigator,&#xD;
             interfere with evaluation of study objectives e.g. Chronic lung disease, chronic&#xD;
             liver/renal disease, chronic renal failure chronic heart disease, congenital genetic&#xD;
             syndromes (e.g. Trisomy 21).&#xD;
&#xD;
          -  Suspected or confirmed immunosuppressive or immunodeficiency conditions (including&#xD;
             splenic dysfunction &amp; HIV)&#xD;
&#xD;
          -  Autoimmune conditions e.g. Type 1/2 diabetes mellitus, thyroid disease, juvenile&#xD;
             idiopathic arthritis etc.&#xD;
&#xD;
          -  Bleeding disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Months</minimum_age>
    <maximum_age>26 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew J Pollard, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oxford Vaccine Group</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Matthew Snape, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oxford Vaccine Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Clinical Vaccinology &amp; Tropical Medicine (CCVTM)</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>
  <link>
    <url>http://www.ovg.ox.ac.uk</url>
    <description>OVG website</description>
  </link>
  <reference>
    <citation>Nakaya HI, Clutterbuck E, Kazmin D, Wang L, Cortese M, Bosinger SE, Patel NB, Zak DE, Aderem A, Dong T, Del Giudice G, Rappuoli R, Cerundolo V, Pollard AJ, Pulendran B, Siegrist CA. Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1853-8. doi: 10.1073/pnas.1519690113. Epub 2016 Jan 11.</citation>
    <PMID>26755593</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>September 29, 2017</last_update_submitted>
  <last_update_submitted_qc>September 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 2, 2017</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>
  <!-- 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/NCT01682369
org study id: OVG 2012/04
secondary id: 2012-002443-26
nct id: NCT01682369
lead sponsor: 
has dmc: Yes
Infants and young children do not respond as well as adults to the flu vaccines currently
      available in the UK. Fluad, is a different type of influenza vaccine that has been available
      in the European continent for the last decade, and contains an adjuvant known as MF59.

      This vaccine has been used extensively in adults over 65 years of age. It has been
      administered to over 4000 children in previous studies, which have shown that it produces an
      enhanced immune response in children compared with traditional vaccines, and that it is safe
      in this age group. It is, however, not yet licensed for use in children. The reason for this
      new study is to gain a better understanding of the how this vaccine is stimulating the immune
      system, by looking to see which parts of the genetic code are 'switched on' in response to
      immunisation, and to see how this differs from the response to currently used flu vaccines.

      To do this the Oxford Vaccine Group will enrol children aged 14 to 26 months to receive
      either the influenza vaccine with the MF59 adjuvant (ATIV) or one of the influenza vaccines
      currently available in the UK (Agrippal/ Begripal or TIV). The study will also help to find
      out whether it is possible to identify patterns of genetic response which can predict
      responses to immunisation. Being able to do so could potentially enable more rapid
      development of vaccines against influenza and other diseases in the future. We will also
      measure how well the immune system responds to the two vaccines and look at any side effects.

      The study is funded by Aditec is a collaborative research programme that aims to accelerate
      the development of novel and powerful immunisation technologies for the next generation of
      human vaccines.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Descriptive analyses of gene expression profiles of participants following immunisation with TIV or ATIV in relation to baseline profiles.
time frame: 56 days
description: To describe gene expression profiles of participants following immunisation with TIV or ATIV in relation to baseline profiles.
measure: To describe the immunogenicity of TIV & ATIV in terms of haemagglutination-Inhibition test (HAI) against each of the three vaccine strains (A/H1N1, A/H3N2, B), four weeks after completion of vaccination.
time frame: 56 days
measure: To evaluate the reactogenicity & safety of ATIV in terms of local & systemic reactions following vaccination.
time frame: 56 days
measure: To study T&B cell responses following immunisation with each vaccine.
time frame: 56 days
measure: To explore the relationship between gene expression and the T cell, B cell and HIA response to immunisation with TIV and ATIV.
time frame: 56 days
measure: To explore the relationship between gene expression and the reactogenicity of TIV and ATIV.
time frame: 56 days
arm group label: Group 1 a - TIV
arm group type: Other
description: V1- Day 0- Administer a dose of 0.25ml of vaccine TIV (Agrippal) + Collect blood sample (up to 6.0 ml)
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine TIV (Agrippal)
V3-(Day V2+1)- Collect blood sample (up to 6.0 ml)
V4- Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)
arm group label: Group 1 b - TIV
arm group type: Other
description: V1- Day 0- Administer a dose of 0.25ml of vaccine TIV (Agrippal) + Collect blood sample (up to 6.0 ml)
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine TIV (Agrippal)
V3-(Day V2+3)- Collect blood sample (up to 6.0 ml)
V4- Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)
arm group label: Group 1 c - TIV
arm group type: Other
description: V1- Day 0- Administer a dose of 0.25ml of vaccine TIV (Aggripal) + Collect blood sample (up to 6.0 ml)
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine TIV (Aggripal)
V3-(Day V2+7)- Collect blood sample (up to 6.0 ml)
V4- Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)
arm group label: Group 2 a - ATIV
arm group type: Other
description: V1- Day 0- Administer a dose of 0.25ml of vaccine ATIV (Fluad) + Collect blood sample (up to 6.0 ml)
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine ATIV (Fluad)
V3- V3(Day V2+1)- Collect blood sample (up to 6.0 ml)
V4- V4 Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)
arm group label: Group 2 b - ATIV
arm group type: Other
description: V1- Day 0- Administer a dose of 0.25ml of vaccine ATIV (Fluad) + Collect blood sample (up to 6.0 ml)
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine ATIV (Fluad)
V3- V3(Day V2+3)- Collect blood sample (up to 6.0 ml)
V4- V4 Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)
arm group label: Group 2 c - ATIV
arm group type: Other
description: V1- Day 0- Administer a dose of 0.25ml of vaccine ATIV (Fluad) + Collect blood sample (up to 6.0 ml)
V2- Day 28 (26-35)- Vaccination 2nd dose, Administer a dose of 0.25ml of vaccine ATIV (Fluad)
V3- V3(Day V2+7)- Collect blood sample (up to 6.0 ml)
V4- V4 Day V2+28 (26-35)- Collect blood sample (up to 6.0 ml)
intervention type: Biological
intervention name: TIV (Aggripal)
arm group label: Group 1 a - TIV
arm group label: Group 1 b - TIV
arm group label: Group 1 c - TIV
other name: Begripal
intervention type: Biological
intervention name: ATIV (Fluad)
arm group label: Group 2 a - ATIV
arm group label: Group 2 b - ATIV
arm group label: Group 2 c - ATIV
criteria: 
gender: All
minimum age: 14 Months
maximum age: 26 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Andrew J Pollard, PhD
role: Principal Investigator
affiliation: Oxford Vaccine Group
last name: Matthew Snape, PhD
role: Principal Investigator
affiliation: Oxford Vaccine Group
facility: 
country: United Kingdom
url: http://www.ovg.ox.ac.uk
description: OVG website
citation: Nakaya HI, Clutterbuck E, Kazmin D, Wang L, Cortese M, Bosinger SE, Patel NB, Zak DE, Aderem A, Dong T, Del Giudice G, Rappuoli R, Cerundolo V, Pollard AJ, Pulendran B, Siegrist CA. Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1853-8. doi: 10.1073/pnas.1519690113. Epub 2016 Jan 11.
PMID: 26755593
responsible party type: Sponsor
mesh term: Influenza, Human