<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/NCT01666925</url>
  </required_header>
  <id_info>
    <org_study_id>VAC046</org_study_id>
    <nct_id>NCT01666925</nct_id>
  </id_info>
  <brief_title>Efficacy of Malaria Vaccines in Kenyan Adults</brief_title>
  <official_title>Efficacy Study of ChAd63MVA ME-TRAP Prime-boost Vaccination Against Plasmodium Falciparum Infection.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European and Developing Countries Clinical Trials Partnership (EDCTP)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Malaria transmission is falling in some parts of Africa as bed nets and anti-malarials become&#xD;
      more widely available. However, transmission still persists and it appears that additional&#xD;
      control measures are required. The leading malaria vaccine candidate in development is RTS,S&#xD;
      which has efficacy against clinical malaria measured at 30-50% in the field. This partial&#xD;
      protection might be enhanced by combination with other components. The other vaccination&#xD;
      approach that has produced repeatable efficacy in humans is the use of viral vectors to&#xD;
      induce T cell responses. Previous attempts with this vaccine approach have been effective in&#xD;
      challenge studies in Oxford, but ineffective in the field, probably because of reduced&#xD;
      immunogenicity.&#xD;
&#xD;
      Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity&#xD;
      by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified&#xD;
      vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with&#xD;
      thrombospondin- related adhesion protein (ME-TRAP).&#xD;
&#xD;
      The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and&#xD;
      partial protection in 5 out of 14 volunteers in challenge studies.&#xD;
&#xD;
      The investigators propose a Phase 2b study of 120 healthy adult men in Kenya. The&#xD;
      investigators will assess the efficacy and further evaluate the immunogenicity and safety&#xD;
      profile of the vaccine regimen. The investigators also intend to assess the correlates of&#xD;
      efficacy and natural immunity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2012</start_date>
  <completion_date type="Actual">August 2012</completion_date>
  <primary_completion_date type="Actual">August 2012</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>
  </study_design_info>
  <primary_outcome>
    <measure>Vaccine Efficacy</measure>
    <time_frame>18 weeks</time_frame>
    <description>The first episode of P.falciparum infection positive by PCR, for P.falciparum.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vaccine immunogenicity</measure>
    <time_frame>24 weeks</time_frame>
    <description>Measures of immunogenicity will include:&#xD;
Ex vivo ELISPOT responses to overlapping pools of ME - TRAP peptides. Cultured ELISPOT responses to overlapping pools of ME - TRAP peptides. ICS by flow cytometry for cell mediated immune responses ELISA for antibodies to malaria antigens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reactogenicity</measure>
    <time_frame>24 weeks</time_frame>
    <description>All solicited and unsolicited local and systemic vaccine- linked adverse events (AEs) including clinically significant laboratory abnormalities.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>ChAd63 ME-TRAP and MVA ME-TRAP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ChAd63 ME-TRAP / MVA ME-TRAP heterologous prime-boost immunisation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rabies vaccine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 x 2.5IU Verorab</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation</intervention_name>
    <description>ChAd63 ME-TRAP: 5 x 10^10vp MVA ME-TRAP: 2 x 10^8 pfu</description>
    <arm_group_label>ChAd63 ME-TRAP and MVA ME-TRAP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rabies vaccine</intervention_name>
    <description>2 x 2.5IU Verorab</description>
    <arm_group_label>Rabies vaccine</arm_group_label>
    <other_name>Verorab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Consenting adult males aged 18 - 50 years in good health.&#xD;
&#xD;
          -  Will remain resident in the study area for the study duration.&#xD;
&#xD;
          -  Able and willing (in the Investigator's opinion) to comply with all study requirements&#xD;
&#xD;
          -  Informed Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any significant medical 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;
          -  Hypersensitivity to Verorab, the trial vaccines or the antimalarial used.&#xD;
&#xD;
          -  History of allergic disease or reactions likely to be exacerbated by any component of&#xD;
             the vaccines, e.g. egg products, kathon, neomycin&#xD;
&#xD;
          -  History of splenectomy.&#xD;
&#xD;
          -  Haemoglobin less than 10.0 g/dl&#xD;
&#xD;
          -  Clinically significant abnormalities of laboratory screening tests (full blood count,&#xD;
             ALT, creatinine levels).&#xD;
&#xD;
          -  Blood transfusion within the month preceding enrolment.&#xD;
&#xD;
          -  History of vaccination with previous experimental malaria vaccines or other vaccines&#xD;
             likely to impact on findings of study (e.g. other MVA or adenovirus vectored vaccines)&#xD;
&#xD;
          -  Administration of any other vaccine or immunoglobulin within 2 weeks before&#xD;
             vaccination.&#xD;
&#xD;
          -  HIV or Hepatitis B surface antigen seropositivity.&#xD;
&#xD;
          -  Current participation in another clinical trial or recent participation within 12&#xD;
             weeks of this study.&#xD;
&#xD;
          -  Any other finding which in the opinion of the investigators would increase the risk of&#xD;
             an adverse outcome from participation in the trial.&#xD;
&#xD;
          -  Likelihood of travel away from the study area&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast</name>
      <address>
        <city>Kilifi</city>
        <zip>PO Box 230, 80108</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Kenya</country>
  </location_countries>
  <verification_date>December 2013</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>December 11, 2013</last_update_submitted>
  <last_update_submitted_qc>December 11, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 12, 2013</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>Malaria</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/NCT01666925
org study id: VAC046
nct id: NCT01666925
lead sponsor: 
collaborator: 
has dmc: Yes
Malaria transmission is falling in some parts of Africa as bed nets and anti-malarials become
      more widely available. However, transmission still persists and it appears that additional
      control measures are required. The leading malaria vaccine candidate in development is RTS,S
      which has efficacy against clinical malaria measured at 30-50% in the field. This partial
      protection might be enhanced by combination with other components. The other vaccination
      approach that has produced repeatable efficacy in humans is the use of viral vectors to
      induce T cell responses. Previous attempts with this vaccine approach have been effective in
      challenge studies in Oxford, but ineffective in the field, probably because of reduced
      immunogenicity.

      Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity
      by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified
      vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with
      thrombospondin- related adhesion protein (ME-TRAP).

      The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and
      partial protection in 5 out of 14 volunteers in challenge studies.

      The investigators propose a Phase 2b study of 120 healthy adult men in Kenya. The
      investigators will assess the efficacy and further evaluate the immunogenicity and safety
      profile of the vaccine regimen. The investigators also intend to assess the correlates of
      efficacy and natural immunity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Vaccine Efficacy
time frame: 18 weeks
description: The first episode of P.falciparum infection positive by PCR, for P.falciparum.
measure: Vaccine immunogenicity
time frame: 24 weeks
description: Measures of immunogenicity will include:
Ex vivo ELISPOT responses to overlapping pools of ME - TRAP peptides. Cultured ELISPOT responses to overlapping pools of ME - TRAP peptides. ICS by flow cytometry for cell mediated immune responses ELISA for antibodies to malaria antigens
measure: Reactogenicity
time frame: 24 weeks
description: All solicited and unsolicited local and systemic vaccine- linked adverse events (AEs) including clinically significant laboratory abnormalities.
arm group label: ChAd63 ME-TRAP and MVA ME-TRAP
arm group type: Experimental
description: ChAd63 ME-TRAP / MVA ME-TRAP heterologous prime-boost immunisation
arm group label: Rabies vaccine
arm group type: Active Comparator
description: 2 x 2.5IU Verorab
intervention type: Biological
intervention name: ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation
description: ChAd63 ME-TRAP: 5 x 10^10vp MVA ME-TRAP: 2 x 10^8 pfu
arm group label: ChAd63 ME-TRAP and MVA ME-TRAP
intervention type: Biological
intervention name: Rabies vaccine
description: 2 x 2.5IU Verorab
arm group label: Rabies vaccine
other name: Verorab
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Kenya
responsible party type: Sponsor
mesh term: Malaria