<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/NCT03281291</url>
  </required_header>
  <id_info>
    <org_study_id>206213</org_study_id>
    <nct_id>NCT03281291</nct_id>
  </id_info>
  <brief_title>An Ancillary Study Protocol to GSK's Phase IIb Malaria Vaccine Trial Entitled &quot;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&quot;</brief_title>
  <official_title>An Ancillary Study Protocol to GlaxoSmithKline Phase IIb RTS,S/AS01E Malaria Vaccine Trial (Study Number 204889 [MALARIA-094]) Entitled, &quot;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&quot;</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 goal of the proposed amplicon sequencing and genotyping study is to assess vaccine&#xD;
      efficacy against clinical and asymptomatic malaria infection using ultra-sensitive molecular&#xD;
      amplification and sequencing methodology to detect Plasmodium falciparum (P. falciparum)&#xD;
      parasites from serial blood samples to be collected from children immunized with the primary&#xD;
      and yearly booster immunizations of the RTS,S/AS01E vaccine as part of their participation in&#xD;
      Protocol MALARIA-094 (parent clinical study protocol). Genomic analysis will be performed on&#xD;
      parasites from blood spot samples collected from children aged 5 17 months immunized with&#xD;
      RTS,S/AS01E on different dosage and schedule regimens under the parent clinical study&#xD;
      protocol.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This genotyping study of malaria parasites collected from serial blood samples following&#xD;
      RTS,S/AS01E immunization will assess vaccine efficacy using molecular genetic data to&#xD;
      identify first infections following vaccination, and to distinguish new from existing&#xD;
      infections, using an amplicon sequencing-based strategy: deep sequencing of small, highly&#xD;
      variable regions of the parasite genome to allow for both:&#xD;
&#xD;
        1. Highly sensitive detection of parasitemia (analogous to conventional polymerase chain&#xD;
           reaction [PCR]-based detection), and&#xD;
&#xD;
        2. Identification of genetically distinct parasite populations within or between affected&#xD;
           individuals.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 11, 2022</start_date>
  <completion_date type="Anticipated">June 29, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 29, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Time to the first new malaria infection.</measure>
    <time_frame>Up to 20 months post Dose 1</time_frame>
    <description>New malaria infection from genomic analysis of blood spots detected from active screening of infection or passive detection of clinical malaria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of new malaria infections during a specified follow-up period.</measure>
    <time_frame>Up to 20 months post Dose 1</time_frame>
    <description>New malaria infection from genomic analysis of blood spots detected from active screening of infection or passive detection of clinical malaria.</description>
  </primary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Anticipated">1</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>R012-20 Group</arm_group_label>
    <description>Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>R012-14-mD Group</arm_group_label>
    <description>Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 Month 14, Month 26, Month 38 of study NCT03276962.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fx012-14-mFxD Group</arm_group_label>
    <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 of study NCT03276962.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fx017-mFxD Group</arm_group_label>
    <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 of study NCT03276962.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <description>Subjects will receive rabies vaccine at Month 0, Month 1, Month 2 of study NCT03276962.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Community sample&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <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.&#xD;
&#xD;
               -  Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic&#xD;
                  route, or ≥ 38.0°C/100.4°F for rectal route.&#xD;
&#xD;
               -  Subjects with a minor illness (such as mild diarrhea, mild upper respiratory&#xD;
                  infection) 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>June 2022</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>June 23, 2022</last_update_submitted>
  <last_update_submitted_qc>June 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>malaria vaccine</keyword>
  <keyword>infants</keyword>
  <keyword>Malaria</keyword>
  <keyword>RTS,S/AS01</keyword>
  <keyword>falciparum</keyword>
  <keyword>genomics</keyword>
  <keyword>efficacy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03281291
org study id: 206213
nct id: NCT03281291
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The goal of the proposed amplicon sequencing and genotyping study is to assess vaccine
      efficacy against clinical and asymptomatic malaria infection using ultra-sensitive molecular
      amplification and sequencing methodology to detect Plasmodium falciparum (P. falciparum)
      parasites from serial blood samples to be collected from children immunized with the primary
      and yearly booster immunizations of the RTS,S/AS01E vaccine as part of their participation in
      Protocol MALARIA-094 (parent clinical study protocol). Genomic analysis will be performed on
      parasites from blood spot samples collected from children aged 5 17 months immunized with
      RTS,S/AS01E on different dosage and schedule regimens under the parent clinical study
      protocol.
This genotyping study of malaria parasites collected from serial blood samples following
      RTS,S/AS01E immunization will assess vaccine efficacy using molecular genetic data to
      identify first infections following vaccination, and to distinguish new from existing
      infections, using an amplicon sequencing-based strategy: deep sequencing of small, highly
      variable regions of the parasite genome to allow for both:

        1. Highly sensitive detection of parasitemia (analogous to conventional polymerase chain
           reaction [PCR]-based detection), and

        2. Identification of genetically distinct parasite populations within or between affected
           individuals.
observational model: Cohort
time perspective: Prospective
measure: Time to the first new malaria infection.
time frame: Up to 20 months post Dose 1
description: New malaria infection from genomic analysis of blood spots detected from active screening of infection or passive detection of clinical malaria.
measure: Number of new malaria infections during a specified follow-up period.
time frame: Up to 20 months post Dose 1
description: New malaria infection from genomic analysis of blood spots detected from active screening of infection or passive detection of clinical malaria.
arm group label: R012-20 Group
description: Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.
arm group label: R012-14-mD Group
description: Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 Month 14, Month 26, Month 38 of study NCT03276962.
arm group label: Fx012-14-mFxD Group
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 of study NCT03276962.
arm group label: Fx017-mFxD Group
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 of study NCT03276962.
arm group label: Control Group
description: Subjects will receive rabies vaccine at Month 0, Month 1, Month 2 of study NCT03276962.
study pop: 
sampling method: Probability Sample
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