<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/NCT02992119</url>
  </required_header>
  <id_info>
    <org_study_id>BAKMAL1605</org_study_id>
    <nct_id>NCT02992119</nct_id>
  </id_info>
  <brief_title>Malaria Vaccine Safety and Immunogenicity Study in Healthy Adults</brief_title>
  <acronym>RTSS</acronym>
  <official_title>Safety and Immunogenicity Evaluation of the Malaria Vaccine, RTS,S/AS01, in Healthy Thai Adults</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Targeted malaria elimination (TME), which comprises appropriate case management by village&#xD;
      health workers, vector control and mass drug administration, is currently being implemented&#xD;
      through pilot projects in selected villages in the Greater Mekong Subregion (GMS) and the&#xD;
      scale-up of the intervention to the regional level are underway. Based on mathematical&#xD;
      modelling, extending the post-TME parasitaemia-free period in the majority of villagers for&#xD;
      as short as 200 days will substantially increase the chances of achieving the interruption of&#xD;
      malaria transmission. Immunogenicity of RTS,S is greater in older children, and the short&#xD;
      term malaria protective effect is stronger than the overall effect assessed over 1-2 years.&#xD;
      Addition of mass RTS,S/AS01E vaccination to the TME arsenal could provide this much needed&#xD;
      additional protection.&#xD;
&#xD;
      Currently there are no safety and immunogenicity data for the use of RTS,S/AS01 in Asian&#xD;
      populations. This trial will generate the required data for the use of this vaccine in Asian&#xD;
      populations. For integration with the current TME activities, which provide mass drug&#xD;
      administrations at months M0, M1, and M2, it would be most efficient and practical to provide&#xD;
      the vaccine at the same intervals. To address a two round intervention (M0, M2) where a three&#xD;
      round intervention is not feasible, one study arm will look at the immune response generated&#xD;
      by only two doses of vaccine and antimalarial medications. Recent evidence suggests that a&#xD;
      vaccination schedule which includes a fractional dose of RTS,S/AS01 (1/5th of the standard&#xD;
      dose) could be similarly or more protective than a schedule with three standard full doses,&#xD;
      while requiring less vaccine and resources. The trial therefore includes study arms which&#xD;
      will assess the safety and immunogenicity of fractional dose schedules.&#xD;
&#xD;
      Each participant will be randomized into one of the following study arms in a ratio of&#xD;
      20:20:30:30:30:30:30, as follows:&#xD;
&#xD;
        -  RTS,S/AS01B Fractional dose group (Group 1)&#xD;
&#xD;
        -  Double RTS,S /AS01E Fractional dose group (Group 2)&#xD;
&#xD;
        -  RTS,S/AS01E Standard dose group (Group 3)&#xD;
&#xD;
        -  RTS,S/AS01E + DHA-PIP+PQ Standard dose group (Group 4)&#xD;
&#xD;
        -  RTS,S/AS01E Fractional dose group (Group 5)&#xD;
&#xD;
        -  RTS,S/AS01E + DHA-PIP+PQ Fractional dose group (Group 6)&#xD;
&#xD;
        -  RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group (Group 7)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label, single centre, Phase 2 trial of RTS,S/AS01 in healthy Thai&#xD;
      adults.&#xD;
&#xD;
      Screening and eligibility assessment (Screening visit)&#xD;
&#xD;
      All potential volunteers will have a screening visit, which may take place up to 30 days&#xD;
      prior to enrolment. Once informed consent is given, a screening number will be assigned in&#xD;
      sequential order. Screening numbers will be issued consecutively (e.g. A-01, A-02, A-03…).&#xD;
&#xD;
      Enrolment, baseline assessment, regimen allocation, and first vaccination (Month 0 / Day 0&#xD;
      visit; Baseline visit) All inclusion and exclusion criteria will be checked before enrolment&#xD;
      in the study. Physical examination will be performed. Any new medical issues or symptoms that&#xD;
      have arisen will be assessed. Blood will be collected for baseline parasite microscopy,&#xD;
      haemoglobin and biochemistry. Participants with parasitaemia or anaemia will be treated&#xD;
      according to national guidelines. Blood will be collected and stored for measurement of&#xD;
      antibodies against P. falciparum circumsporozoite (anti-CS antibody) until shipment to the&#xD;
      reference laboratory. Urine will be collected from women of child-bearing age for immediate&#xD;
      pregnancy test.&#xD;
&#xD;
      If all inclusion criteria are fulfilled and none of the exclusion criteria apply, the patient&#xD;
      will be enrolled into the study and a CRF specific to each participant completed. Regimen&#xD;
      allocation and administration of the vaccine(s) will be on Day 0. The randomization lists&#xD;
      will be prepared by MORU.&#xD;
&#xD;
      Randomization numbers will be generated in blocks, for the 7 intervention arms in a ratio of&#xD;
      20:20:30:30:30:30:30, as follows:&#xD;
&#xD;
      Each participant will be randomized into one of the following study arms Group 1: RTS,S/AS01B&#xD;
      Fractional dose group Month 0 and Month 1 will receive RTS,S/AS01B full dose Month 2 will&#xD;
      receive RTS,S/AS01B fractional dose (1/5th dose)&#xD;
&#xD;
      Group 2: RTS,S/AS01E Fractional dose group Month 0 and Month 1will receive a double dose of&#xD;
      RTS,S/AS01E full dose Month 2 will receive a double dose of RTS,S/AS01E fractional dose&#xD;
      (1/5th dose)&#xD;
&#xD;
      Group 3: RTS,S/AS01E Full dose group Month 0, Month 1 and Month 2 will receive RTS,S/AS01E&#xD;
      full dose&#xD;
&#xD;
      Group 4: RTS,S/AS01E + DHA-PIP+PQ Full dose group Month 0, Month 1 and Month 2 will receive&#xD;
      RTS,S/AS01E full dose + DHA-PIP+PQ&#xD;
&#xD;
      Group 5: RTS,S/AS01E Fractional dose group Month 0 and Month 1 will receive RTS,S/AS01E full&#xD;
      dose Month 2 will receive RTS,S/AS01E fractional dose (1/5th dose)&#xD;
&#xD;
      Group 6: RTS,S/AS01E + DHA-PIP+PQ Fractional dose group Month 0 and Month 1 will receive&#xD;
      RTS,S/AS01E full dose + DHA-PIP+PQ Month 2 will receive RTS,S/AS01E fractional dose (1/5th&#xD;
      dose) + DHA-PIP+PQ&#xD;
&#xD;
      Group 7: RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group Month 0 will receive RTS,S/AS01E&#xD;
      full dose + DHA-PIP+PQ Month 2 will receive RTS,S/AS01E fractional dose (1/5th dose) +&#xD;
      DHA-PIP+PQ&#xD;
&#xD;
      RTS,S/AS01B = Standard dose RTS,S/AS01B: 50µg RTS,S + standard dose AS01B RTS,S/AS01E =&#xD;
      Standard dose RTS,S/AS01E: 25µg RTS,S + standard dose AS01E DHA-PIP =&#xD;
      Dihydroartemisinin/piperaquine PQ = Primaquine&#xD;
&#xD;
      Study participants will be assigned the next available randomization number on the list, and&#xD;
      thus will be randomly allocated to Group 1, 2, 3, 4, 5, 6 or 7.&#xD;
&#xD;
      Subsequent vaccination visits (Month 1 / Day 0 and Month 2 / Day 0 visits) Subsequent&#xD;
      vaccination visits will be done according to the schedule of procedures. Physical examination&#xD;
      will be performed. Any new medical issues or symptoms that have arisen will be assessed.&#xD;
      Blood will be collected for parasite microscopy, haemoglobin and biochemistry. Participants&#xD;
      with parasitaemia or anaemia will be treated according to national guidelines. Blood will be&#xD;
      collected and stored for measurement of antibodies against P. falciparum circumsporozoite&#xD;
      (anti-CS antibody) until shipment to the reference laboratory. Urine will be collected from&#xD;
      women of child-bearing age for immediate pregnancy test.&#xD;
&#xD;
      Before vaccination, the on-going eligibility of the volunteer will be reviewed. All&#xD;
      participants will attend the clinic for vaccination visits, will be observed closely for at&#xD;
      least 30 minutes following the administration of each study vaccine, and will receive a paper&#xD;
      diary card for recording solicited AEs, as described above. Information will be recorded in&#xD;
      the CRF for subsequent vaccination visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 4, 2017</start_date>
  <completion_date type="Actual">February 20, 2018</completion_date>
  <primary_completion_date type="Actual">February 20, 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>
    <intervention_model_description>Randomized 7 groups</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination</measure>
    <time_frame>29 days after last vaccination</time_frame>
    <description>Occurrence of serious adverse events (SAEs) from the date of the first vaccination to 29 days after the last vaccination, according to the MedRA classification.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Experience a Serious Adverse Events (SAEs) During a 6 Month Follow up Period From the Receipt of First Vaccination</measure>
    <time_frame>6 months</time_frame>
    <description>Occurrence of SAEs during the whole study period, i.e. during a 6 month follow up period from the receipt of first vaccination, according to the MedRA classification.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Seroconverted One Month After First Dose.</measure>
    <time_frame>1 months</time_frame>
    <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Seroconverted One Month After the Second Dose.</measure>
    <time_frame>2 months</time_frame>
    <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Seroconverted One Month After the Third Dose.</measure>
    <time_frame>3 months</time_frame>
    <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Seroconverted at Month Six After First Dose.</measure>
    <time_frame>6 months</time_frame>
    <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Received RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose (Group 7) That Seroconverted at Month Two After First Dose.</measure>
    <time_frame>2 months</time_frame>
    <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).(For group 7)</description>
  </primary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">193</enrollment>
  <condition>Malaria Vaccine</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RTS,S/AS01B Fractional dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Double RTS,S/AS01E Fractional dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RTS,S/AS01E Standard dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RTS,S/AS01E Fractional dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01B Fractional dose</intervention_name>
    <description>RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Double RTS,S/AS01E Fractional dose</intervention_name>
    <description>A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01E Standard dose</intervention_name>
    <description>RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01E + DHA-PIP+PQ Standard dose</intervention_name>
    <description>RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01E Fractional dose</intervention_name>
    <description>RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
    <arm_group_label>Group 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01E + DHA-PIP+PQ Fractional dose</intervention_name>
    <description>RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
    <arm_group_label>Group 6</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose</intervention_name>
    <description>RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
    <arm_group_label>Group 7</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is a healthy male or non-pregnant female, aged 18 to 55 years (inclusive),&#xD;
             of Thai origin.&#xD;
&#xD;
          -  Participant is willing and able to give informed consent to participate in the trial&#xD;
&#xD;
          -  Able, in the investigators opinion, and willing to comply with the study requirements&#xD;
             and follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female participant who is pregnant, lactating or planning pregnancy during the course&#xD;
             of the study.&#xD;
&#xD;
          -  Presence of any condition which in the judgment of the investigator would place the&#xD;
             participant at undue risk or interfere with the results of the study (e.g. serious&#xD;
             underlying cardiac, renal, hepatic or neurological disease; severe malnutrition;&#xD;
             congenital defects or febrile condition).&#xD;
&#xD;
          -  Hepatitis B surface antigen (HBsAg) detected in serum.&#xD;
&#xD;
          -  Screening ECG demonstrates a QTc interval ≥ 450 ms&#xD;
&#xD;
          -  Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless has taken&#xD;
             part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior&#xD;
             to participation in that study, and negative HCV RNA PCR at screening for this study).&#xD;
&#xD;
          -  Anaemia (Hb &lt; 10 g/dL)&#xD;
&#xD;
          -  Positive malaria parasitaemia at screening or baseline (Month 0, Day 0).&#xD;
&#xD;
          -  Use of any investigational or non-registered product or investigational use of a&#xD;
             registered product (drug or vaccine), other than the study vaccines, during the period&#xD;
             from the date of screening to the first vaccination, or planned use during the study&#xD;
             period.&#xD;
&#xD;
          -  Any medical condition that in the judgment of the investigator would make&#xD;
             intramuscular (IM) injection unsafe.&#xD;
&#xD;
          -  Any medical condition that in the judgment of the investigator would make the&#xD;
             administration of the antimalarial treatment unsafe, such as prior allergic reactions&#xD;
             to one or more component of the drug regimen: artemisinins, piperaquine or primaquine.&#xD;
&#xD;
          -  Contraindications to the use of artemisinins, piperaquine or primaquine or use of&#xD;
             medications known to have a potentially clinically significant interaction with these&#xD;
             medications.&#xD;
&#xD;
          -  Chronic administration (defined as more than 14 days in total) of immunosuppressants&#xD;
             or other immune-modifying drugs during the period starting six months prior to the&#xD;
             first vaccine dose. For corticosteroids, this will mean prednisone &gt; 20 mg/day (for&#xD;
             adult subjects), or equivalent. Inhaled and topical steroids are allowed.&#xD;
&#xD;
          -  Planned administration/administration of a vaccine not foreseen by the study protocol&#xD;
             in the period starting seven days before the first dose.&#xD;
&#xD;
          -  Concurrently participating in another clinical study, at any time during the study&#xD;
             period, in which the subject has been or will be exposed to an investigational or a&#xD;
             non-investigational vaccine/product.&#xD;
&#xD;
          -  History of splenectomy.&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, including&#xD;
             HIV infection or based on medical history and physical examination.&#xD;
&#xD;
          -  History of anaphylaxis post-vaccination.&#xD;
&#xD;
          -  Serious chronic illness.&#xD;
&#xD;
          -  Any abnormal baseline laboratory screening tests: ALT, AST, creatinine, haemoglobin,&#xD;
             platelet count, total WBC, out of normal range as defined in the protocol.&#xD;
&#xD;
          -  Hepatomegaly, right upper quadrant abdominal pain or tenderness.&#xD;
&#xD;
          -  Personal history of autoimmune disease.&#xD;
&#xD;
          -  Administration of immunoglobulins and/or any blood products during the period starting&#xD;
             three months before the first dose of study vaccine or planned administration during&#xD;
             the study period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lorenz von Seidlein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mahidol Oxford Tropical Medicine Research Unit</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital of Tropical Diseases, Faculty of Tropical Medicine, Mahidol University</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <results_first_submitted>January 14, 2019</results_first_submitted>
  <results_first_submitted_qc>July 26, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 29, 2019</results_first_posted>
  <last_update_submitted>March 29, 2022</last_update_submitted>
  <last_update_submitted_qc>March 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>safety</keyword>
  <keyword>immunogenicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 2, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT02992119/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT02992119/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Group 1 RTS,S/AS01B Fractional Dose</title>
          <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="P2">
          <title>Group 2 Double RTS,S/AS01E Fractional Dose</title>
          <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="P3">
          <title>Group 3 RTS,S/AS01E Standard Dose</title>
          <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
        </group>
        <group group_id="P4">
          <title>Group 4 RTS,S/AS01E + DHA-PIP+PQ Standard Dose</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
        </group>
        <group group_id="P5">
          <title>Group 5 RTS,S/AS01E Fractional Dose</title>
          <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="P6">
          <title>Group 6 RTS,S/AS01E + DHA-PIP+PQ Fractional Dose</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
        </group>
        <group group_id="P7">
          <title>Group 7 RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="30"/>
                <participants group_id="P4" count="30"/>
                <participants group_id="P5" count="30"/>
                <participants group_id="P6" count="30"/>
                <participants group_id="P7" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="29"/>
                <participants group_id="P4" count="30"/>
                <participants group_id="P5" count="30"/>
                <participants group_id="P6" count="30"/>
                <participants group_id="P7" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group 1</title>
          <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="B2">
          <title>Group 2</title>
          <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="B3">
          <title>Group 3</title>
          <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
        </group>
        <group group_id="B4">
          <title>Group 4</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
        </group>
        <group group_id="B5">
          <title>Group 5</title>
          <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="B6">
          <title>Group 6</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
        </group>
        <group group_id="B7">
          <title>Group 7</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
        </group>
        <group group_id="B8">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="21"/>
            <count group_id="B2" value="21"/>
            <count group_id="B3" value="30"/>
            <count group_id="B4" value="30"/>
            <count group_id="B5" value="30"/>
            <count group_id="B6" value="30"/>
            <count group_id="B7" value="31"/>
            <count group_id="B8" value="193"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="21"/>
                    <count group_id="B2" value="21"/>
                    <count group_id="B3" value="30"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="30"/>
                    <count group_id="B6" value="30"/>
                    <count group_id="B7" value="31"/>
                    <count group_id="B8" value="193"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="30"/>
                    <measurement group_id="B5" value="30"/>
                    <measurement group_id="B6" value="30"/>
                    <measurement group_id="B7" value="31"/>
                    <measurement group_id="B8" value="193"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="21"/>
                    <count group_id="B2" value="21"/>
                    <count group_id="B3" value="30"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="30"/>
                    <count group_id="B6" value="30"/>
                    <count group_id="B7" value="31"/>
                    <count group_id="B8" value="193"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="17"/>
                    <measurement group_id="B6" value="16"/>
                    <measurement group_id="B7" value="17"/>
                    <measurement group_id="B8" value="106"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="13"/>
                    <measurement group_id="B6" value="14"/>
                    <measurement group_id="B7" value="14"/>
                    <measurement group_id="B8" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="0"/>
                    <count group_id="B6" value="0"/>
                    <count group_id="B7" value="0"/>
                    <count group_id="B8" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>fever</title>
          <description>Fever is defined as temperature &gt;= 37.5°C / 99.5°F for oral, axillary or tympanic route, or &gt;= 38.0°C / 100.4°F for rectal route. The preferred route for recording temperature in this study will be oral.&#xD;
For subjects self temperature recording at home, they were instructed to record temperature in the evening time.</description>
          <population>Analysed all participants at the baseline visit</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="21"/>
                    <count group_id="B2" value="21"/>
                    <count group_id="B3" value="30"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="30"/>
                    <count group_id="B6" value="30"/>
                    <count group_id="B7" value="31"/>
                    <count group_id="B8" value="193"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination</title>
        <description>Occurrence of serious adverse events (SAEs) from the date of the first vaccination to 29 days after the last vaccination, according to the MedRA classification.</description>
        <time_frame>29 days after last vaccination</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 4</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
          </group>
          <group group_id="O5">
            <title>Group 5</title>
            <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O6">
            <title>Group 6</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
          </group>
          <group group_id="O7">
            <title>Group 7</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination</title>
          <description>Occurrence of serious adverse events (SAEs) from the date of the first vaccination to 29 days after the last vaccination, according to the MedRA classification.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="30"/>
                <count group_id="O7" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Experience a Serious Adverse Events (SAEs) During a 6 Month Follow up Period From the Receipt of First Vaccination</title>
        <description>Occurrence of SAEs during the whole study period, i.e. during a 6 month follow up period from the receipt of first vaccination, according to the MedRA classification.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 4</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
          </group>
          <group group_id="O5">
            <title>Group 5</title>
            <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O6">
            <title>Group 6</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
          </group>
          <group group_id="O7">
            <title>Group 7</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experience a Serious Adverse Events (SAEs) During a 6 Month Follow up Period From the Receipt of First Vaccination</title>
          <description>Occurrence of SAEs during the whole study period, i.e. during a 6 month follow up period from the receipt of first vaccination, according to the MedRA classification.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="30"/>
                <count group_id="O7" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Seroconverted One Month After First Dose.</title>
        <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
        <time_frame>1 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 4</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
          </group>
          <group group_id="O5">
            <title>Group 5</title>
            <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O6">
            <title>Group 6</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
          </group>
          <group group_id="O7">
            <title>Group 7</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Seroconverted One Month After First Dose.</title>
          <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="30"/>
                <count group_id="O7" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="29"/>
                    <measurement group_id="O4" value="30"/>
                    <measurement group_id="O5" value="28"/>
                    <measurement group_id="O6" value="29"/>
                    <measurement group_id="O7" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Seroconverted One Month After the Second Dose.</title>
        <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
        <time_frame>2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 4</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
          </group>
          <group group_id="O5">
            <title>Group 5</title>
            <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O6">
            <title>Group 6</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Seroconverted One Month After the Second Dose.</title>
          <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="30"/>
                    <measurement group_id="O4" value="30"/>
                    <measurement group_id="O5" value="30"/>
                    <measurement group_id="O6" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Seroconverted One Month After the Third Dose.</title>
        <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
        <time_frame>3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 4</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
          </group>
          <group group_id="O5">
            <title>Group 5</title>
            <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O6">
            <title>Group 6</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
          </group>
          <group group_id="O7">
            <title>Group 7</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Seroconverted One Month After the Third Dose.</title>
          <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="30"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="30"/>
                <count group_id="O7" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="30"/>
                    <measurement group_id="O4" value="30"/>
                    <measurement group_id="O5" value="30"/>
                    <measurement group_id="O6" value="30"/>
                    <measurement group_id="O7" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Seroconverted at Month Six After First Dose.</title>
        <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
        <time_frame>6 months</time_frame>
        <population>Analysed subjects who returned for the month 6 follow-up.&#xD;
There are 4 subjects lost follow-up as follows:&#xD;
1 subject from group 1&#xD;
subject from group 3&#xD;
subjects from group 7</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 4</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
          </group>
          <group group_id="O5">
            <title>Group 5</title>
            <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
          </group>
          <group group_id="O6">
            <title>Group 6</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
          </group>
          <group group_id="O7">
            <title>Group 7</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Seroconverted at Month Six After First Dose.</title>
          <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).</description>
          <population>Analysed subjects who returned for the month 6 follow-up.&#xD;
There are 4 subjects lost follow-up as follows:&#xD;
1 subject from group 1&#xD;
subject from group 3&#xD;
subjects from group 7</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="30"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="30"/>
                <count group_id="O7" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="29"/>
                    <measurement group_id="O4" value="30"/>
                    <measurement group_id="O5" value="30"/>
                    <measurement group_id="O6" value="30"/>
                    <measurement group_id="O7" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Received RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose (Group 7) That Seroconverted at Month Two After First Dose.</title>
        <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).(For group 7)</description>
        <time_frame>2 months</time_frame>
        <population>There were 30 subjects at group 7 received 1st vaccination and came back for follow-up at month 2 visit</population>
        <group_list>
          <group group_id="O1">
            <title>Group 7</title>
            <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Received RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose (Group 7) That Seroconverted at Month Two After First Dose.</title>
          <description>The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).(For group 7)</description>
          <population>There were 30 subjects at group 7 received 1st vaccination and came back for follow-up at month 2 visit</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <desc>clinicaltrials.gov definitions</desc>
      <group_list>
        <group group_id="E1">
          <title>Group 1</title>
          <description>RTS,S/AS01B Fractional dose&#xD;
RTS,S/AS01B Fractional dose: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="E2">
          <title>Group 2</title>
          <description>Double RTS,S/AS01E Fractional dose&#xD;
Double RTS,S/AS01E Fractional dose: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="E3">
          <title>Group 3</title>
          <description>RTS,S/AS01E Standard dose&#xD;
RTS,S/AS01E Standard dose: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.</description>
        </group>
        <group group_id="E4">
          <title>Group 4</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Standard dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Standard dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2</description>
        </group>
        <group group_id="E5">
          <title>Group 5</title>
          <description>RTS,S/AS01E Fractional dose&#xD;
RTS,S/AS01E Fractional dose: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.</description>
        </group>
        <group group_id="E6">
          <title>Group 6</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Fractional dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.</description>
        </group>
        <group group_id="E7">
          <title>Group 7</title>
          <description>RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose&#xD;
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>acute pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="30"/>
                <counts group_id="E4" subjects_affected="29" subjects_at_risk="30"/>
                <counts group_id="E5" subjects_affected="30" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="29" subjects_at_risk="30"/>
                <counts group_id="E7" subjects_affected="30" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E3" events="6" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E4" events="22" subjects_affected="12" subjects_at_risk="30"/>
                <counts group_id="E5" events="5" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="8" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E7" events="7" subjects_affected="4" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="41" subjects_affected="18" subjects_at_risk="21"/>
                <counts group_id="E2" events="23" subjects_affected="16" subjects_at_risk="21"/>
                <counts group_id="E3" events="53" subjects_affected="24" subjects_at_risk="30"/>
                <counts group_id="E4" events="44" subjects_affected="21" subjects_at_risk="30"/>
                <counts group_id="E5" events="34" subjects_affected="19" subjects_at_risk="30"/>
                <counts group_id="E6" events="56" subjects_affected="25" subjects_at_risk="30"/>
                <counts group_id="E7" events="31" subjects_affected="19" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="13" subjects_at_risk="21"/>
                <counts group_id="E2" events="19" subjects_affected="13" subjects_at_risk="21"/>
                <counts group_id="E3" events="22" subjects_affected="16" subjects_at_risk="30"/>
                <counts group_id="E4" events="21" subjects_affected="14" subjects_at_risk="30"/>
                <counts group_id="E5" events="18" subjects_affected="12" subjects_at_risk="30"/>
                <counts group_id="E6" events="22" subjects_affected="16" subjects_at_risk="30"/>
                <counts group_id="E7" events="9" subjects_affected="8" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="15" subjects_affected="9" subjects_at_risk="21"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E3" events="12" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E4" events="15" subjects_affected="11" subjects_at_risk="30"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E6" events="15" subjects_affected="14" subjects_at_risk="30"/>
                <counts group_id="E7" events="9" subjects_affected="8" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Haemoglobin low</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="30"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E7" events="6" subjects_affected="6" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="46" subjects_affected="20" subjects_at_risk="21"/>
                <counts group_id="E2" events="42" subjects_affected="20" subjects_at_risk="21"/>
                <counts group_id="E3" events="79" subjects_affected="30" subjects_at_risk="30"/>
                <counts group_id="E4" events="60" subjects_affected="25" subjects_at_risk="30"/>
                <counts group_id="E5" events="65" subjects_affected="29" subjects_at_risk="30"/>
                <counts group_id="E6" events="57" subjects_affected="27" subjects_at_risk="30"/>
                <counts group_id="E7" events="48" subjects_affected="28" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Injection site reaction (pain)</sub_title>
                <counts group_id="E1" events="14" subjects_affected="8" subjects_at_risk="21"/>
                <counts group_id="E2" events="10" subjects_affected="6" subjects_at_risk="21"/>
                <counts group_id="E3" events="18" subjects_affected="9" subjects_at_risk="30"/>
                <counts group_id="E4" events="10" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E5" events="16" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Injection site reaction (redness)</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="14" subjects_affected="10" subjects_at_risk="21"/>
                <counts group_id="E3" events="14" subjects_affected="7" subjects_at_risk="30"/>
                <counts group_id="E4" events="7" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E5" events="10" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="7" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E4" events="8" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E7" events="4" subjects_affected="3" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Loose stools</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E7" events="7" subjects_affected="7" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>chills</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="27" subjects_affected="14" subjects_at_risk="21"/>
                <counts group_id="E2" events="17" subjects_affected="13" subjects_at_risk="21"/>
                <counts group_id="E3" events="42" subjects_affected="19" subjects_at_risk="30"/>
                <counts group_id="E4" events="23" subjects_affected="14" subjects_at_risk="30"/>
                <counts group_id="E5" events="20" subjects_affected="14" subjects_at_risk="30"/>
                <counts group_id="E6" events="29" subjects_affected="17" subjects_at_risk="30"/>
                <counts group_id="E7" events="17" subjects_affected="11" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E6" events="15" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E7" events="4" subjects_affected="3" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Lorenz von Seidlein</name_or_title>
      <organization>MORU</organization>
      <phone>662036663</phone>
      <email>Lorenz@tropmedres.ac</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02992119
org study id: BAKMAL1605
nct id: NCT02992119
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Targeted malaria elimination (TME), which comprises appropriate case management by village
      health workers, vector control and mass drug administration, is currently being implemented
      through pilot projects in selected villages in the Greater Mekong Subregion (GMS) and the
      scale-up of the intervention to the regional level are underway. Based on mathematical
      modelling, extending the post-TME parasitaemia-free period in the majority of villagers for
      as short as 200 days will substantially increase the chances of achieving the interruption of
      malaria transmission. Immunogenicity of RTS,S is greater in older children, and the short
      term malaria protective effect is stronger than the overall effect assessed over 1-2 years.
      Addition of mass RTS,S/AS01E vaccination to the TME arsenal could provide this much needed
      additional protection.

      Currently there are no safety and immunogenicity data for the use of RTS,S/AS01 in Asian
      populations. This trial will generate the required data for the use of this vaccine in Asian
      populations. For integration with the current TME activities, which provide mass drug
      administrations at months M0, M1, and M2, it would be most efficient and practical to provide
      the vaccine at the same intervals. To address a two round intervention (M0, M2) where a three
      round intervention is not feasible, one study arm will look at the immune response generated
      by only two doses of vaccine and antimalarial medications. Recent evidence suggests that a
      vaccination schedule which includes a fractional dose of RTS,S/AS01 (1/5th of the standard
      dose) could be similarly or more protective than a schedule with three standard full doses,
      while requiring less vaccine and resources. The trial therefore includes study arms which
      will assess the safety and immunogenicity of fractional dose schedules.

      Each participant will be randomized into one of the following study arms in a ratio of
      20:20:30:30:30:30:30, as follows:

        -  RTS,S/AS01B Fractional dose group (Group 1)

        -  Double RTS,S /AS01E Fractional dose group (Group 2)

        -  RTS,S/AS01E Standard dose group (Group 3)

        -  RTS,S/AS01E + DHA-PIP+PQ Standard dose group (Group 4)

        -  RTS,S/AS01E Fractional dose group (Group 5)

        -  RTS,S/AS01E + DHA-PIP+PQ Fractional dose group (Group 6)

        -  RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group (Group 7)
This is a randomized, open-label, single centre, Phase 2 trial of RTS,S/AS01 in healthy Thai
      adults.

      Screening and eligibility assessment (Screening visit)

      All potential volunteers will have a screening visit, which may take place up to 30 days
      prior to enrolment. Once informed consent is given, a screening number will be assigned in
      sequential order. Screening numbers will be issued consecutively (e.g. A-01, A-02, A-03…).

      Enrolment, baseline assessment, regimen allocation, and first vaccination (Month 0 / Day 0
      visit; Baseline visit) All inclusion and exclusion criteria will be checked before enrolment
      in the study. Physical examination will be performed. Any new medical issues or symptoms that
      have arisen will be assessed. Blood will be collected for baseline parasite microscopy,
      haemoglobin and biochemistry. Participants with parasitaemia or anaemia will be treated
      according to national guidelines. Blood will be collected and stored for measurement of
      antibodies against P. falciparum circumsporozoite (anti-CS antibody) until shipment to the
      reference laboratory. Urine will be collected from women of child-bearing age for immediate
      pregnancy test.

      If all inclusion criteria are fulfilled and none of the exclusion criteria apply, the patient
      will be enrolled into the study and a CRF specific to each participant completed. Regimen
      allocation and administration of the vaccine(s) will be on Day 0. The randomization lists
      will be prepared by MORU.

      Randomization numbers will be generated in blocks, for the 7 intervention arms in a ratio of
      20:20:30:30:30:30:30, as follows:

      Each participant will be randomized into one of the following study arms Group 1: RTS,S/AS01B
      Fractional dose group Month 0 and Month 1 will receive RTS,S/AS01B full dose Month 2 will
      receive RTS,S/AS01B fractional dose (1/5th dose)

      Group 2: RTS,S/AS01E Fractional dose group Month 0 and Month 1will receive a double dose of
      RTS,S/AS01E full dose Month 2 will receive a double dose of RTS,S/AS01E fractional dose
      (1/5th dose)

      Group 3: RTS,S/AS01E Full dose group Month 0, Month 1 and Month 2 will receive RTS,S/AS01E
      full dose

      Group 4: RTS,S/AS01E + DHA-PIP+PQ Full dose group Month 0, Month 1 and Month 2 will receive
      RTS,S/AS01E full dose + DHA-PIP+PQ

      Group 5: RTS,S/AS01E Fractional dose group Month 0 and Month 1 will receive RTS,S/AS01E full
      dose Month 2 will receive RTS,S/AS01E fractional dose (1/5th dose)

      Group 6: RTS,S/AS01E + DHA-PIP+PQ Fractional dose group Month 0 and Month 1 will receive
      RTS,S/AS01E full dose + DHA-PIP+PQ Month 2 will receive RTS,S/AS01E fractional dose (1/5th
      dose) + DHA-PIP+PQ

      Group 7: RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group Month 0 will receive RTS,S/AS01E
      full dose + DHA-PIP+PQ Month 2 will receive RTS,S/AS01E fractional dose (1/5th dose) +
      DHA-PIP+PQ

      RTS,S/AS01B = Standard dose RTS,S/AS01B: 50µg RTS,S + standard dose AS01B RTS,S/AS01E =
      Standard dose RTS,S/AS01E: 25µg RTS,S + standard dose AS01E DHA-PIP =
      Dihydroartemisinin/piperaquine PQ = Primaquine

      Study participants will be assigned the next available randomization number on the list, and
      thus will be randomly allocated to Group 1, 2, 3, 4, 5, 6 or 7.

      Subsequent vaccination visits (Month 1 / Day 0 and Month 2 / Day 0 visits) Subsequent
      vaccination visits will be done according to the schedule of procedures. Physical examination
      will be performed. Any new medical issues or symptoms that have arisen will be assessed.
      Blood will be collected for parasite microscopy, haemoglobin and biochemistry. Participants
      with parasitaemia or anaemia will be treated according to national guidelines. Blood will be
      collected and stored for measurement of antibodies against P. falciparum circumsporozoite
      (anti-CS antibody) until shipment to the reference laboratory. Urine will be collected from
      women of child-bearing age for immediate pregnancy test.

      Before vaccination, the on-going eligibility of the volunteer will be reviewed. All
      participants will attend the clinic for vaccination visits, will be observed closely for at
      least 30 minutes following the administration of each study vaccine, and will receive a paper
      diary card for recording solicited AEs, as described above. Information will be recorded in
      the CRF for subsequent vaccination visits.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized 7 groups
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination
time frame: 29 days after last vaccination
description: Occurrence of serious adverse events (SAEs) from the date of the first vaccination to 29 days after the last vaccination, according to the MedRA classification.
measure: Number of Participants Who Experience a Serious Adverse Events (SAEs) During a 6 Month Follow up Period From the Receipt of First Vaccination
time frame: 6 months
description: Occurrence of SAEs during the whole study period, i.e. during a 6 month follow up period from the receipt of first vaccination, according to the MedRA classification.
measure: Number of Participants Who Seroconverted One Month After First Dose.
time frame: 1 months
description: The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).
measure: Number of Participants Who Seroconverted One Month After the Second Dose.
time frame: 2 months
description: The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).
measure: Number of Participants Who Seroconverted One Month After the Third Dose.
time frame: 3 months
description: The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).
measure: Number of Participants Who Seroconverted at Month Six After First Dose.
time frame: 6 months
description: The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).
measure: Number of Participants Who Received RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose (Group 7) That Seroconverted at Month Two After First Dose.
time frame: 2 months
description: The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).(For group 7)
arm group label: Group 1
arm group type: Experimental
description: RTS,S/AS01B Fractional dose
arm group label: Group 2
arm group type: Experimental
description: Double RTS,S/AS01E Fractional dose
arm group label: Group 3
arm group type: Experimental
description: RTS,S/AS01E Standard dose
arm group label: Group 4
arm group type: Experimental
description: RTS,S/AS01E + DHA-PIP+PQ Standard dose
arm group label: Group 5
arm group type: Experimental
description: RTS,S/AS01E Fractional dose
arm group label: Group 6
arm group type: Experimental
description: RTS,S/AS01E + DHA-PIP+PQ Fractional dose
arm group label: Group 7
arm group type: Experimental
description: RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose
intervention type: Biological
intervention name: RTS,S/AS01B Fractional dose
description: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.
arm group label: Group 1
intervention type: Biological
intervention name: Double RTS,S/AS01E Fractional dose
description: A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.
arm group label: Group 2
intervention type: Biological
intervention name: RTS,S/AS01E Standard dose
description: RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.
arm group label: Group 3
intervention type: Biological
intervention name: RTS,S/AS01E + DHA-PIP+PQ Standard dose
description: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2
arm group label: Group 4
intervention type: Biological
intervention name: RTS,S/AS01E Fractional dose
description: RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.
arm group label: Group 5
intervention type: Biological
intervention name: RTS,S/AS01E + DHA-PIP+PQ Fractional dose
description: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.
arm group label: Group 6
intervention type: Biological
intervention name: RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose
description: RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2
arm group label: Group 7
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lorenz von Seidlein, MD
role: Principal Investigator
affiliation: Mahidol Oxford Tropical Medicine Research Unit
facility: 
country: Thailand
responsible party type: Sponsor
mesh term: Malaria
sharing ipd: Yes
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 