<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/NCT03276962</url>
  </required_header>
  <id_info>
    <org_study_id>204889</org_study_id>
    <secondary_id>2016-000290-20</secondary_id>
    <nct_id>NCT03276962</nct_id>
  </id_info>
  <brief_title>Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or Without Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age</brief_title>
  <official_title>Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or With-out Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study intends to establish proof of concept for a fractional dose schedule under&#xD;
      conditions of natural exposure in children 5-17 months old at first vaccination. The study&#xD;
      also aims to establish the role of third dose spacing in a fractional dose schedule, describe&#xD;
      the effect of an earlier full fourth dose at Month 14 and describe the effect of multiple&#xD;
      fractional or full yearly doses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current study intends to establish proof of concept (POC) for a fractional dose schedule&#xD;
      under conditions of natural exposure. The study will be conducted in children 5-17 months old&#xD;
      at first vaccination living in areas of mid to high malaria transmission, in line with the&#xD;
      age group recommended by the World Health Organization (WHO) for the implementation of the&#xD;
      RTS,S/AS01E vaccine. Results from this study will be critical in informing future&#xD;
      possibilities for the development of vaccine-based strategies which, in combination with&#xD;
      other interventions, may contribute to the malaria elimination agenda.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 28, 2017</start_date>
  <completion_date type="Actual">November 11, 2022</completion_date>
  <primary_completion_date type="Actual">November 4, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The occurrence of clinical malaria meeting the primary case definition</measure>
    <time_frame>From Month 2.5 up to Month 14</time_frame>
    <description>The primary case definition will be P. falciparum asexual parasitemia greater than (&gt;) 5000 parasites/microliters (μl) and presence of fever (axillary temperature greater than or equal to [≥] 37.5 degrees Celsius [°C]) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The occurrence of clinical malaria meeting the primary and secondary case definitions</measure>
    <time_frame>From Day 0 up to Month 50</time_frame>
    <description>The primary case definition will be P. falciparum asexual parasitemia &gt; 5000 parasites/μl and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.&#xD;
The secondary case definition will be P. falciparum asexual parasitemia &gt; 0 and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation or history of fever within 24 hours of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The occurrence of incident P. falciparum infections</measure>
    <time_frame>From Day 0 to Month 50</time_frame>
    <description>Vaccine efficacy against incident P. falciparum infections defined by positive blood slide.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The prevalence of P. falciparum infections defined by positive blood slide at each cross-sectional survey</measure>
    <time_frame>Monthly from Month 0-20 and every three months thereafter till study end (Month 50)</time_frame>
    <description>Prevalence of P. falciparum infections of each RTS,S/AS01E schedule at cross-sectional visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of seropositive subjects for anti-circumsporozoite (anti-CS) antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site)</measure>
    <time_frame>Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50)</time_frame>
    <description>A seropositive subject is defined as a subject with antibody concentrations ≥ 0.5 ELISA units per milliliter (EU/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of seropositive subjects for anti-hepatitis B (anti-HB) antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site)</measure>
    <time_frame>Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50)</time_frame>
    <description>A seropositive subject is defined as a subject with antibody concentrations ≥ 10 milli-international units per milliliter (mIU/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody concentrations for anti-CS (in a sub-cohort of first 25 subjects enrolled in each group per site)</measure>
    <time_frame>Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50)</time_frame>
    <description>Concentrations are expressed as geometric mean concentrations (GMC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody concentrations for anti-HB (in a sub-cohort of first 25 subjects enrolled in each group per site)</measure>
    <time_frame>Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50).</time_frame>
    <description>Concentrations are expressed as geometric mean concentrations (GMC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with any, fatal and related serious adverse events (SAEs)</measure>
    <time_frame>From Day 0 to Month 50</time_frame>
    <description>SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with any adverse events (AEs) and serious adverse events (SAEs) leading to withdrawal from further vaccination</measure>
    <time_frame>From Day 0 to Month 50</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.&#xD;
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with severe malaria and cerebral malaria</measure>
    <time_frame>From Day 0 to Month 50</time_frame>
    <description>Cerebral malaria is defined as Severe P. falciparum malaria with coma (Blantyre coma score score less than [&lt;] 3); and if malaria with seizure: coma persisting for &gt; 30 min after the seizure. Other treatable causes of coma should be excluded before diagnosing cerebral malaria (e.g. hypoglycaemia, bacterial meningitis).&#xD;
Severe malaria is defined as P. falciparum parasitemia &gt; 0 detected by microscopy and/or rapid diagnostic test (RDT) and one or more of the following, occurring in the absence of an identified alternative cause: Impaired consciousness, Prostration, Multiple convulsions, Acidosis, Hypoglycemia, Severe malarial anemia, Renal impairment, Jaundice, Pulmonary edema, Significant bleeding: including recurrent or prolonged bleeding from the nose, gums or venipuncture sites, hematemesis or melaena, Shock, Hyperparasitemia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with potential Immune mediated diseases (pIMDs)</measure>
    <time_frame>From Day 0 to Month 50</time_frame>
    <description>Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with meningitis</measure>
    <time_frame>From Day 0 to Month 50</time_frame>
    <description>The number of subjects with meningitis per study group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with seizures</measure>
    <time_frame>During the 30-day (Days 0-29) follow-up period after each dose of study vaccine</time_frame>
    <description>The number of subjects with seizures per study group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with generalized convulsive seizures</measure>
    <time_frame>During the 7-day (Days 0-6) follow-up period after each dose of study vaccine</time_frame>
    <description>The number of subjects with generalized convulsive seizures per study group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with any unsolicited adverse events (AEs)</measure>
    <time_frame>During the 30-day (Days 0-29) follow-up period after each dose of study vaccine</time_frame>
    <description>An unsolicited AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal laboratory values (in a sub-cohort of first 25 subjects enrolled in each group per site)</measure>
    <time_frame>Before Dose 3, seven days post-Dose 3 and 30 days post-Dose 3</time_frame>
    <description>The assessed parameters (alanine aminotransferase [ALT], creatinine, haemoglobin, white blood cells [WBC], platelets) will be summarised by toxicity grading scales and by group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with any solicited local symptoms (in the reactogenicity sub-cohort of first 25 subjects enrolled per site)</measure>
    <time_frame>During the 4-day (Days 0-3) follow-up period after each vaccination</time_frame>
    <description>Solicited local symptoms assessed will be pain, redness and swelling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with any solicited general symptoms (in the reactogenicity sub-cohort of first 25 subjects enrolled per site)</measure>
    <time_frame>During the 4-day (Days 0-3) follow-up period after each vaccina-tion</time_frame>
    <description>Solicited general symptoms assessed will be drowsiness, fever, irritability/fussiness and loss of appetite.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">1498</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>R012-20 Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive full doses of RTS,S/AS01E at Month 0, Month 1, Month 2 and a full dose at Month 20.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>R012-14-mD Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and yearly full doses at Month 14, Month 26, Month 38.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fx012-14-mFxD Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26, Month 38.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fx017-mFxD Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 7, Month 20, Month 32.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive rabies vaccine at Month 0, Month 1, Month 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01E (Full dose)</intervention_name>
    <description>Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).</description>
    <arm_group_label>Fx012-14-mFxD Group</arm_group_label>
    <arm_group_label>Fx017-mFxD Group</arm_group_label>
    <arm_group_label>R012-14-mD Group</arm_group_label>
    <arm_group_label>R012-20 Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RTS,S/AS01E (1/5th dose)</intervention_name>
    <description>Subjects will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).</description>
    <arm_group_label>Fx012-14-mFxD Group</arm_group_label>
    <arm_group_label>Fx017-mFxD Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rabies vaccine</intervention_name>
    <description>Subjects will receive intramuscular injection of rabies vaccine (0.1 ml).</description>
    <arm_group_label>Control Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects' parent(s)/LAR(s) who, in the opinion of the investigator, can and will&#xD;
             comply with the requirements of the protocol (e.g. return for follow-up visits).&#xD;
&#xD;
          -  Signed or thumb-printed and witnessed informed consent obtained from the&#xD;
             parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.&#xD;
             Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by an&#xD;
             independent witness.&#xD;
&#xD;
          -  A male or female between, and including, five and 17 months of age at the time of the&#xD;
             first vaccination.&#xD;
&#xD;
          -  Healthy subjects as established by medical history and clinical examination before&#xD;
             entering into the study.&#xD;
&#xD;
          -  Previously received three documented doses of diphtheria, tetanus, pertussis,&#xD;
             hepatitis B vaccine (DTPHepB), and at least three doses of oral polio vaccine.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Child in care.&#xD;
&#xD;
          -  Use of a drug or vaccine that is not approved for that indication (by one of the&#xD;
             following regulatory authorities: Food and Drug Administration [FDA; USA] or European&#xD;
             Union member state or WHO [with respect to prequalification]) other than the study&#xD;
             vaccines during the period starting 30 days before the first dose of study vaccines&#xD;
             (Day -29 to Day 0), or planned use during the study period.&#xD;
&#xD;
          -  Any medical condition that in the judgment of the investigator would make&#xD;
             intramuscular injection unsafe.&#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 (0.5 mg/kg/day (for&#xD;
             pediatric 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 each dose and ending seven days after each&#xD;
             dose of vaccine administration.&#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 (pharmaceutical product or device).&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on&#xD;
             medical history and physical examination (no laboratory testing required).&#xD;
&#xD;
          -  Family history of congenital or hereditary immunodeficiency.&#xD;
&#xD;
          -  History of any reaction or hypersensitivity likely to be exacerbated by any component&#xD;
             of the vaccines.&#xD;
&#xD;
          -  History of anaphylaxis post-vaccination.&#xD;
&#xD;
          -  History of any, or documented, serious adverse reaction to rabies vaccination.&#xD;
&#xD;
          -  Contraindication to rabies vaccination (Rabipur is contraindicated in subjects with an&#xD;
             history of a severe hypersensitivity to any of the ingredients in the vaccine. Note&#xD;
             that the vaccine contains polygeline and residues of chicken proteins, and may contain&#xD;
             traces of neomycin, chlortetracycline and amphotericin B).&#xD;
&#xD;
          -  Major congenital defects.&#xD;
&#xD;
          -  Serious chronic illness.&#xD;
&#xD;
          -  Children with a past history of a neurological disorder or atypical febrile seizure (a&#xD;
             febrile seizure is atypical if it meets one of the following criteria: not associated&#xD;
             with fever; lasts &gt; 5 minutes; focal (not generalized); followed by transient or&#xD;
             persistent neurological abnormality; occurs in a child &lt; 6 months of age).&#xD;
&#xD;
          -  Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥&#xD;
             37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal&#xD;
             route.&#xD;
&#xD;
        Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection)&#xD;
        without fever may, be enrolled at the discretion of the investigator.&#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;
&#xD;
          -  Moderate or severe malnutrition at screening defined as weight for age or weight for&#xD;
             height Z-score &lt; -2.&#xD;
&#xD;
          -  Hemoglobin concentration &lt; 8 g/dl at screening.&#xD;
&#xD;
          -  Same sex twins (to avoid misidentification).&#xD;
&#xD;
          -  Maternal death.&#xD;
&#xD;
          -  Prior receipt of an investigational malaria vaccine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Months</minimum_age>
    <maximum_age>17 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kumasi</city>
        <country>Ghana</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kisumu</city>
        <zip>40100</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ghana</country>
    <country>Kenya</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>January 24, 2023</last_update_submitted>
  <last_update_submitted_qc>January 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>falciparum, efficacy</keyword>
  <keyword>RTS,S/AS01</keyword>
  <keyword>malaria vaccine</keyword>
  <keyword>safety</keyword>
  <keyword>Malaria</keyword>
  <keyword>immunogenicity</keyword>
  <keyword>infants</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>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>https://clinicalstudydatarequest.com</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03276962
org study id: 204889
secondary id: 2016-000290-20
nct id: NCT03276962
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The study intends to establish proof of concept for a fractional dose schedule under
      conditions of natural exposure in children 5-17 months old at first vaccination. The study
      also aims to establish the role of third dose spacing in a fractional dose schedule, describe
      the effect of an earlier full fourth dose at Month 14 and describe the effect of multiple
      fractional or full yearly doses.
The current study intends to establish proof of concept (POC) for a fractional dose schedule
      under conditions of natural exposure. The study will be conducted in children 5-17 months old
      at first vaccination living in areas of mid to high malaria transmission, in line with the
      age group recommended by the World Health Organization (WHO) for the implementation of the
      RTS,S/AS01E vaccine. Results from this study will be critical in informing future
      possibilities for the development of vaccine-based strategies which, in combination with
      other interventions, may contribute to the malaria elimination agenda.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The occurrence of clinical malaria meeting the primary case definition
time frame: From Month 2.5 up to Month 14
description: The primary case definition will be P. falciparum asexual parasitemia greater than (>) 5000 parasites/microliters (μl) and presence of fever (axillary temperature greater than or equal to [≥] 37.5 degrees Celsius [°C]) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.
measure: The occurrence of clinical malaria meeting the primary and secondary case definitions
time frame: From Day 0 up to Month 50
description: The primary case definition will be P. falciparum asexual parasitemia > 5000 parasites/μl and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.
The secondary case definition will be P. falciparum asexual parasitemia > 0 and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation or history of fever within 24 hours of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.
measure: The occurrence of incident P. falciparum infections
time frame: From Day 0 to Month 50
description: Vaccine efficacy against incident P. falciparum infections defined by positive blood slide.
measure: The prevalence of P. falciparum infections defined by positive blood slide at each cross-sectional survey
time frame: Monthly from Month 0-20 and every three months thereafter till study end (Month 50)
description: Prevalence of P. falciparum infections of each RTS,S/AS01E schedule at cross-sectional visits.
measure: Number of seropositive subjects for anti-circumsporozoite (anti-CS) antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site)
time frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50)
description: A seropositive subject is defined as a subject with antibody concentrations ≥ 0.5 ELISA units per milliliter (EU/mL).
measure: Number of seropositive subjects for anti-hepatitis B (anti-HB) antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site)
time frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50)
description: A seropositive subject is defined as a subject with antibody concentrations ≥ 10 milli-international units per milliliter (mIU/mL).
measure: Antibody concentrations for anti-CS (in a sub-cohort of first 25 subjects enrolled in each group per site)
time frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50)
description: Concentrations are expressed as geometric mean concentrations (GMC).
measure: Antibody concentrations for anti-HB (in a sub-cohort of first 25 subjects enrolled in each group per site)
time frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50).
description: Concentrations are expressed as geometric mean concentrations (GMC).
measure: Number of subjects with any, fatal and related serious adverse events (SAEs)
time frame: From Day 0 to Month 50
description: SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
measure: Number of subjects with any adverse events (AEs) and serious adverse events (SAEs) leading to withdrawal from further vaccination
time frame: From Day 0 to Month 50
description: An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
measure: Number of subjects with severe malaria and cerebral malaria
time frame: From Day 0 to Month 50
description: Cerebral malaria is defined as Severe P. falciparum malaria with coma (Blantyre coma score score less than [<] 3); and if malaria with seizure: coma persisting for > 30 min after the seizure. Other treatable causes of coma should be excluded before diagnosing cerebral malaria (e.g. hypoglycaemia, bacterial meningitis).
Severe malaria is defined as P. falciparum parasitemia > 0 detected by microscopy and/or rapid diagnostic test (RDT) and one or more of the following, occurring in the absence of an identified alternative cause: Impaired consciousness, Prostration, Multiple convulsions, Acidosis, Hypoglycemia, Severe malarial anemia, Renal impairment, Jaundice, Pulmonary edema, Significant bleeding: including recurrent or prolonged bleeding from the nose, gums or venipuncture sites, hematemesis or melaena, Shock, Hyperparasitemia.
measure: Number of subjects with potential Immune mediated diseases (pIMDs)
time frame: From Day 0 to Month 50
description: Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
measure: Number of subjects with meningitis
time frame: From Day 0 to Month 50
description: The number of subjects with meningitis per study group.
measure: Number of subjects with seizures
time frame: During the 30-day (Days 0-29) follow-up period after each dose of study vaccine
description: The number of subjects with seizures per study group.
measure: Number of subjects with generalized convulsive seizures
time frame: During the 7-day (Days 0-6) follow-up period after each dose of study vaccine
description: The number of subjects with generalized convulsive seizures per study group.
measure: Number of subjects with any unsolicited adverse events (AEs)
time frame: During the 30-day (Days 0-29) follow-up period after each dose of study vaccine
description: An unsolicited AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
measure: Number of subjects with abnormal laboratory values (in a sub-cohort of first 25 subjects enrolled in each group per site)
time frame: Before Dose 3, seven days post-Dose 3 and 30 days post-Dose 3
description: The assessed parameters (alanine aminotransferase [ALT], creatinine, haemoglobin, white blood cells [WBC], platelets) will be summarised by toxicity grading scales and by group.
measure: Number of subjects with any solicited local symptoms (in the reactogenicity sub-cohort of first 25 subjects enrolled per site)
time frame: During the 4-day (Days 0-3) follow-up period after each vaccination
description: Solicited local symptoms assessed will be pain, redness and swelling.
measure: Number of subjects with any solicited general symptoms (in the reactogenicity sub-cohort of first 25 subjects enrolled per site)
time frame: During the 4-day (Days 0-3) follow-up period after each vaccina-tion
description: Solicited general symptoms assessed will be drowsiness, fever, irritability/fussiness and loss of appetite.
arm group label: R012-20 Group
arm group type: Experimental
description: Subjects will receive full doses of RTS,S/AS01E at Month 0, Month 1, Month 2 and a full dose at Month 20.
arm group label: R012-14-mD Group
arm group type: Experimental
description: Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and yearly full doses at Month 14, Month 26, Month 38.
arm group label: Fx012-14-mFxD Group
arm group type: Experimental
description: Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26, Month 38.
arm group label: Fx017-mFxD Group
arm group type: Experimental
description: Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 7, Month 20, Month 32.
arm group label: Control Group
arm group type: Experimental
description: Subjects will receive rabies vaccine at Month 0, Month 1, Month 2.
intervention type: Biological
intervention name: RTS,S/AS01E (Full dose)
description: Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).
arm group label: Fx012-14-mFxD Group
arm group label: Fx017-mFxD Group
arm group label: R012-14-mD Group
arm group label: R012-20 Group
intervention type: Biological
intervention name: RTS,S/AS01E (1/5th dose)
description: Subjects will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).
arm group label: Fx012-14-mFxD Group
arm group label: Fx017-mFxD Group
intervention type: Biological
intervention name: Rabies vaccine
description: Subjects will receive intramuscular injection of rabies vaccine (0.1 ml).
arm group label: Control Group
criteria: 
gender: All
minimum age: 5 Months
maximum age: 17 Months
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
facility: 
country: Ghana
country: Kenya
responsible party type: Sponsor
mesh term: Malaria
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: https://clinicalstudydatarequest.com