<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/NCT03799510</url>
  </required_header>
  <id_info>
    <org_study_id>Sm14 Phase 2b - Sn</org_study_id>
    <nct_id>NCT03799510</nct_id>
  </id_info>
  <brief_title>Anti-Schistosomiasis Vaccine: Sm14 Phase 2b-Sn in School Children</brief_title>
  <official_title>Safety and Immunogenicity Evaluation of the Vaccine Candidate Sm14 Against Schistosomiasis in Senegalese School Children Healthy or Infected With S. Mansoni and/or S. Haematobium. A Comparative, Randomized, Controlled, Open-label Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oswaldo Cruz Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orygen Biotecnologia SA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Biomedical Research Center EPLS</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Access to Advanced Health Institute (AAHI)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oswaldo Cruz Foundation</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>
      The clinical trial phase 2b is designed to assess the safety and the specific immune response&#xD;
      of the active ingredient (protein + adjuvant) in healthy and then in infected school children&#xD;
      from 8 to 11 years of age with intestinal and/or urinary schistosomiasis, living in the&#xD;
      Valley of the Senegal River, a highly endemic area for schistosomiasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A phase 2b trial, self-contained, open-label, controlled, randomized study in three parallel&#xD;
      arms, two of them formed by groups of healthy or infected school children, both receiving&#xD;
      three (3) injections at D0, W4 (Week 4), W8; both groups receiving 50 μg Sm14 vaccine&#xD;
      candidate solution, combined with 2.5μg GLA-SE. The third group is composed by non-vaccinated&#xD;
      infected school children.&#xD;
&#xD;
      Sm14: recombinant protein produced in yeast following Good Manufacturing Practices (GMP)&#xD;
      conditions, presented in vials containing 0.55 ml solution Sm14, 0.4 ml solution is diluted&#xD;
      with 0.4 ml of GLA (Synthetic Glucopyranosyl lipid A) for intramuscular administration.&#xD;
&#xD;
      Medical examinations are performed at D0 (before injection, 1 hr and 4 hr after), and a&#xD;
      safety evaluation at 24 hrs and 48 hrs, after each injection.&#xD;
&#xD;
      Blood analysis: Liver function tests - renal function tests - blood counts, at W-1 before&#xD;
      inclusion, and at W9 and W21 during the follow-up.&#xD;
&#xD;
      Blood samples for immune response analysis at D0, W12 and W21.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 13, 2018</start_date>
  <completion_date type="Actual">August 7, 2019</completion_date>
  <primary_completion_date type="Actual">July 1, 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>
    <masking_description>No masking</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>within 2 days of the administration of the first dose (Day 0)</time_frame>
    <description>Local signs and symptoms included Pain, Swelling and Inflammation at the injection site, heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates.&#xD;
General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Day 30-Day 32: within 2 days of the administration of the second dose (Week 4)</time_frame>
    <description>Local signs and symptoms included Pain, Swelling and Inflammation at the injection site, Heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates.&#xD;
General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Days 60-67 : within 7 days of the administration of the third dose (Week 8)</time_frame>
    <description>Local signs and symptoms included Pain, Swelling and Inflammation at the injection site. Heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates.&#xD;
General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances. Laboratory tests (blood count, liver and kidney biological functions).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Day 90: three months after the first injection (Week 12)</time_frame>
    <description>Injection local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Day 120: four months after the first injection (Week 16)</time_frame>
    <description>Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection.&#xD;
Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Day 150: five months after the first injection (Week 21)</time_frame>
    <description>Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection.&#xD;
Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Qualitative and quantitative assessment of the Immunogenicity</measure>
    <time_frame>The Day of first Sm14 vaccine administration (Day 0)</time_frame>
    <description>Immunogenicity was evaluated by Isotype analysis of the antibodies produced specifically against the rSm14 and vaccine-induced (ELISA) and Specific rSm14 cellular response (on PBMC), production of intracellular cytokines (PBMCs stimulation and cytokine dosing). Cellular immune responses measured by PBMC luminex assay for T-cell cytokines (Milliplex ® MAP kit).&#xD;
Correlation between the development and magnitude of humoral responses measured by antibody IgG production to the Sm14 Schisto protein using enzyme-linked immunosorbent assay (ELISA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualitative and quantitative assessment of the Immunogenicity</measure>
    <time_frame>At the 30th day after the third Sm14 vaccine administration (Week 12)</time_frame>
    <description>Immunogenicity was evaluated by Isotype analysis of the antibodies produced specifically against the rSm14 and vaccine-induced (ELISA) and Specific rSm14 cellular response (on PBMC), production of intracellular cytokines (PBMCs stimulation and cytokine dosing). Cellular immune responses measured by PBMC luminex assay for T-cell cytokines (Milliplex ® MAP kit).&#xD;
Correlation between the development and magnitude of humoral responses measured by antibody IgG production to the Sm14 Schisto protein using enzyme-linked immunosorbent assay (ELISA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualitative and quantitative assessment of the Immunogenicity</measure>
    <time_frame>At the 90th day after the third Sm14 vaccine administration (Week 21)</time_frame>
    <description>Immunogenicity was evaluated by Isotype analysis of the antibodies produced specifically against the rSm14 andvaccine-induced (ELISA) and Specific rSm14 cellular response (on PBMC), production of intracellular cytokines (PBMCs stimulation and cytokine dosing). Cellular immune responses measured by PBMC luminex assay for T-cell cytokines (Milliplex ® MAP kit).&#xD;
Correlation between the development and magnitude of humoral responses measured by antibody IgG production to the Sm14 Schisto protein using enzyme-linked immunosorbent assay (ELISA).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">95</enrollment>
  <condition>Schistosomiasis</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy school children with no infectious history of Schistosomiasis receiving three (3) intramuscular injections of 50 μg Sm14 with 2.5 μg GLA-SE solution at D0, W4, W8 (D=day; W=week). Three-month follow-up (W12, W20).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>School children with an infectious history of S. haematobium and-or S. mansoni and pretreated with 1 dose of Praziquantel (2-4 weeks prior to the first vaccine injection) receiving three (3) intramuscular injections of 50 μg Sm14 with 2.5 μg GLA-SE solution at D0, W4, W8 (D=day; W=week). Three-month follow-up (W12, W20).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>School children with an infectious history of S. haematobium and S. mansoni and pretreated with 1 dose of Praziquantel (2-4 weeks prior to the first vaccine injection) not receiving vaccine. Control group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Sm14</intervention_name>
    <description>Three 0.5 mL intra-muscular injections of the vaccine solution (50μg Sm14) will be administered on D0, W4, W8 (D = day, W = week).</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>rSm14</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GLA-SE solution</intervention_name>
    <description>The lot concentration 10μg/mL for injection of 2.5μg GLA-SE/injection.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>• Glucopyranosyl Lipid A in Stable Emulsion</other_name>
    <other_name>• Glucopyranosyl Lipid Adjuvant-Stable Emulsion</other_name>
    <other_name>• Toll-like Receptor 4 Agonist GLA-SE</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  School children, of public schools in villages of Saint Louis region (Senegal), female&#xD;
             or male, 8 to 11 years old (inclusive) at the time of inclusion.&#xD;
&#xD;
          -  Residence in the area during the period of the study.&#xD;
&#xD;
          -  Free of obvious/severe health problems except schistosomiasis, as established by&#xD;
             clinical examination.&#xD;
&#xD;
          -  Written informed consent to participate obtained from subject's parents or legal&#xD;
             guardian.&#xD;
&#xD;
          -  Free of obvious/severe health problems except schistosomiasis, established by blood&#xD;
             analysis, i.e. hematological exams, liver and renal function tests.&#xD;
&#xD;
          -  Treated with 40mg/kg Praziquantel (PZQ) before inclusion (W-2 to W-4 before the first&#xD;
             injection) in case of infection with S. mansoni and S. haematobium&#xD;
&#xD;
          -  Children of Group 1: not infected, no schistosomiasis history and living in&#xD;
             area/village free of Sm and Sh transmission.&#xD;
&#xD;
          -  Children Groups 2 &amp; 3: infected with mansoni or/and haematobium schistosomiasis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  School child who does not respond to one of the inclusion criteria&#xD;
&#xD;
          -  Child under 20kg of body weight&#xD;
&#xD;
          -  Vaccination within 90 days preceding the first dose of Sm14 vaccine candidate, or&#xD;
             planned use during the study period.&#xD;
&#xD;
          -  Current or previous chronic administration (defined as more than 14 days) of&#xD;
             immunosuppressive drugs or other immuno-modifying drugs.&#xD;
&#xD;
          -  Known hypersensitivity to any component in the Sm14 vaccine or history of allergic&#xD;
             disease.&#xD;
&#xD;
          -  Knowledge of non-infectious chronic disease&#xD;
&#xD;
          -  Known acute disease.&#xD;
&#xD;
          -  Other conditions which in opinion of the PI may potentially represent a danger for the&#xD;
             patient to be enrolled.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>11 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Miriam Tendler, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Oswaldo Cruz Foundation</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Modou DIOP, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gilles RIVEAU, PharmD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anne-Marie SCHACHT, CRA</last_name>
    <role>Study Director</role>
    <affiliation>Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Biomedical Research Center EPLS</name>
      <address>
        <city>Saint Louis</city>
        <zip>BP226</zip>
        <country>Senegal</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Senegal</country>
  </location_countries>
  <results_reference>
    <citation>Moser D, Tendler M, Griffiths G, Klinkert MQ. A 14-kDa Schistosoma mansoni polypeptide is homologous to a gene family of fatty acid binding proteins. J Biol Chem. 1991 May 5;266(13):8447-54.</citation>
    <PMID>2022660</PMID>
  </results_reference>
  <results_reference>
    <citation>Ramos CR, Spisni A, Oyama S Jr, Sforca ML, Ramos HR, Vilar MM, Alves AC, Figueredo RC, Tendler M, Zanchin NI, Pertinhez TA, Ho PL. Stability improvement of the fatty acid binding protein Sm14 from S. mansoni by Cys replacement: structural and functional characterization of a vaccine candidate. Biochim Biophys Acta. 2009 Apr;1794(4):655-62. doi: 10.1016/j.bbapap.2008.12.010. Epub 2008 Dec 25.</citation>
    <PMID>19150418</PMID>
  </results_reference>
  <results_reference>
    <citation>Coler RN, Bertholet S, Moutaftsi M, Guderian JA, Windish HP, Baldwin SL, Laughlin EM, Duthie MS, Fox CB, Carter D, Friede M, Vedvick TS, Reed SG. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One. 2011 Jan 26;6(1):e16333. doi: 10.1371/journal.pone.0016333.</citation>
    <PMID>21298114</PMID>
  </results_reference>
  <results_reference>
    <citation>Santini-Oliveira M, Coler RN, Parra J, Veloso V, Jayashankar L, Pinto PM, Ciol MA, Bergquist R, Reed SG, Tendler M. Schistosomiasis vaccine candidate Sm14/GLA-SE: Phase 1 safety and immunogenicity clinical trial in healthy, male adults. Vaccine. 2016 Jan 20;34(4):586-594. doi: 10.1016/j.vaccine.2015.10.027. Epub 2015 Nov 10.</citation>
    <PMID>26571311</PMID>
  </results_reference>
  <results_reference>
    <citation>Lambert SL, Yang CF, Liu Z, Sweetwood R, Zhao J, Cheng L, Jin H, Woo J. Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A. PLoS One. 2012;7(12):e51618. doi: 10.1371/journal.pone.0051618. Epub 2012 Dec 28.</citation>
    <PMID>23284726</PMID>
  </results_reference>
  <results_reference>
    <citation>Tendler M, Almeida MS, Vilar MM, Pinto PM, Limaverde-Sousa G. Current Status of the Sm14/GLA-SE Schistosomiasis Vaccine: Overcoming Barriers and Paradigms towards the First Anti-Parasitic Human(itarian) Vaccine. Trop Med Infect Dis. 2018 Nov 21;3(4):121. doi: 10.3390/tropicalmed3040121. Erratum In: Trop Med Infect Dis. 2019 Jan 19;4(1):</citation>
    <PMID>30469320</PMID>
  </results_reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>December 5, 2019</last_update_submitted>
  <last_update_submitted_qc>December 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Schistosomiasis</keyword>
  <keyword>Recombinant vaccine</keyword>
  <keyword>rSm14</keyword>
  <keyword>GLA-SE</keyword>
  <keyword>Fatty acid-binding protein (FABP)</keyword>
  <keyword>Phase II Clinical Trial</keyword>
  <keyword>Senegal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schistosomiasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03799510
org study id: Sm14 Phase 2b - Sn
nct id: NCT03799510
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The clinical trial phase 2b is designed to assess the safety and the specific immune response
      of the active ingredient (protein + adjuvant) in healthy and then in infected school children
      from 8 to 11 years of age with intestinal and/or urinary schistosomiasis, living in the
      Valley of the Senegal River, a highly endemic area for schistosomiasis.
A phase 2b trial, self-contained, open-label, controlled, randomized study in three parallel
      arms, two of them formed by groups of healthy or infected school children, both receiving
      three (3) injections at D0, W4 (Week 4), W8; both groups receiving 50 μg Sm14 vaccine
      candidate solution, combined with 2.5μg GLA-SE. The third group is composed by non-vaccinated
      infected school children.

      Sm14: recombinant protein produced in yeast following Good Manufacturing Practices (GMP)
      conditions, presented in vials containing 0.55 ml solution Sm14, 0.4 ml solution is diluted
      with 0.4 ml of GLA (Synthetic Glucopyranosyl lipid A) for intramuscular administration.

      Medical examinations are performed at D0 (before injection, 1 hr and 4 hr after), and a
      safety evaluation at 24 hrs and 48 hrs, after each injection.

      Blood analysis: Liver function tests - renal function tests - blood counts, at W-1 before
      inclusion, and at W9 and W21 during the follow-up.

      Blood samples for immune response analysis at D0, W12 and W21.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
masking description: No masking
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: within 2 days of the administration of the first dose (Day 0)
description: Local signs and symptoms included Pain, Swelling and Inflammation at the injection site, heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates.
General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Day 30-Day 32: within 2 days of the administration of the second dose (Week 4)
description: Local signs and symptoms included Pain, Swelling and Inflammation at the injection site, Heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates.
General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Days 60-67 : within 7 days of the administration of the third dose (Week 8)
description: Local signs and symptoms included Pain, Swelling and Inflammation at the injection site. Heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates.
General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances. Laboratory tests (blood count, liver and kidney biological functions).
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Day 90: three months after the first injection (Week 12)
description: Injection local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Day 120: four months after the first injection (Week 16)
description: Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection.
Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Day 150: five months after the first injection (Week 21)
description: Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection.
Complete physical examination including an examination of general appearance, body weight and forehead temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances.
measure: Qualitative and quantitative assessment of the Immunogenicity
time frame: The Day of first Sm14 vaccine administration (Day 0)
description: Immunogenicity was evaluated by Isotype analysis of the antibodies produced specifically against the rSm14 and vaccine-induced (ELISA) and Specific rSm14 cellular response (on PBMC), production of intracellular cytokines (PBMCs stimulation and cytokine dosing). Cellular immune responses measured by PBMC luminex assay for T-cell cytokines (Milliplex ® MAP kit).
Correlation between the development and magnitude of humoral responses measured by antibody IgG production to the Sm14 Schisto protein using enzyme-linked immunosorbent assay (ELISA).
measure: Qualitative and quantitative assessment of the Immunogenicity
time frame: At the 30th day after the third Sm14 vaccine administration (Week 12)
description: Immunogenicity was evaluated by Isotype analysis of the antibodies produced specifically against the rSm14 and vaccine-induced (ELISA) and Specific rSm14 cellular response (on PBMC), production of intracellular cytokines (PBMCs stimulation and cytokine dosing). Cellular immune responses measured by PBMC luminex assay for T-cell cytokines (Milliplex ® MAP kit).
Correlation between the development and magnitude of humoral responses measured by antibody IgG production to the Sm14 Schisto protein using enzyme-linked immunosorbent assay (ELISA).
measure: Qualitative and quantitative assessment of the Immunogenicity
time frame: At the 90th day after the third Sm14 vaccine administration (Week 21)
description: Immunogenicity was evaluated by Isotype analysis of the antibodies produced specifically against the rSm14 andvaccine-induced (ELISA) and Specific rSm14 cellular response (on PBMC), production of intracellular cytokines (PBMCs stimulation and cytokine dosing). Cellular immune responses measured by PBMC luminex assay for T-cell cytokines (Milliplex ® MAP kit).
Correlation between the development and magnitude of humoral responses measured by antibody IgG production to the Sm14 Schisto protein using enzyme-linked immunosorbent assay (ELISA).
arm group label: Group 1
arm group type: Experimental
description: Healthy school children with no infectious history of Schistosomiasis receiving three (3) intramuscular injections of 50 μg Sm14 with 2.5 μg GLA-SE solution at D0, W4, W8 (D=day; W=week). Three-month follow-up (W12, W20).
arm group label: Group 2
arm group type: Experimental
description: School children with an infectious history of S. haematobium and-or S. mansoni and pretreated with 1 dose of Praziquantel (2-4 weeks prior to the first vaccine injection) receiving three (3) intramuscular injections of 50 μg Sm14 with 2.5 μg GLA-SE solution at D0, W4, W8 (D=day; W=week). Three-month follow-up (W12, W20).
arm group label: Group 3
arm group type: No Intervention
description: School children with an infectious history of S. haematobium and S. mansoni and pretreated with 1 dose of Praziquantel (2-4 weeks prior to the first vaccine injection) not receiving vaccine. Control group.
intervention type: Biological
intervention name: Sm14
description: Three 0.5 mL intra-muscular injections of the vaccine solution (50μg Sm14) will be administered on D0, W4, W8 (D = day, W = week).
arm group label: Group 1
arm group label: Group 2
other name: rSm14
intervention type: Drug
intervention name: GLA-SE solution
description: The lot concentration 10μg/mL for injection of 2.5μg GLA-SE/injection.
arm group label: Group 1
arm group label: Group 2
other name: • Glucopyranosyl Lipid A in Stable Emulsion
other name: • Glucopyranosyl Lipid Adjuvant-Stable Emulsion
other name: • Toll-like Receptor 4 Agonist GLA-SE
criteria: 
gender: All
minimum age: 8 Years
maximum age: 11 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Miriam Tendler, MD, PhD
role: Study Chair
affiliation: Oswaldo Cruz Foundation
last name: Modou DIOP, MD
role: Principal Investigator
affiliation: Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS)
last name: Gilles RIVEAU, PharmD, PhD
role: Study Director
affiliation: Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).
last name: Anne-Marie SCHACHT, CRA
role: Study Director
affiliation: Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).
facility: 
country: Senegal
citation: Moser D, Tendler M, Griffiths G, Klinkert MQ. A 14-kDa Schistosoma mansoni polypeptide is homologous to a gene family of fatty acid binding proteins. J Biol Chem. 1991 May 5;266(13):8447-54.
PMID: 2022660
citation: Ramos CR, Spisni A, Oyama S Jr, Sforca ML, Ramos HR, Vilar MM, Alves AC, Figueredo RC, Tendler M, Zanchin NI, Pertinhez TA, Ho PL. Stability improvement of the fatty acid binding protein Sm14 from S. mansoni by Cys replacement: structural and functional characterization of a vaccine candidate. Biochim Biophys Acta. 2009 Apr;1794(4):655-62. doi: 10.1016/j.bbapap.2008.12.010. Epub 2008 Dec 25.
PMID: 19150418
citation: Coler RN, Bertholet S, Moutaftsi M, Guderian JA, Windish HP, Baldwin SL, Laughlin EM, Duthie MS, Fox CB, Carter D, Friede M, Vedvick TS, Reed SG. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One. 2011 Jan 26;6(1):e16333. doi: 10.1371/journal.pone.0016333.
PMID: 21298114
citation: Santini-Oliveira M, Coler RN, Parra J, Veloso V, Jayashankar L, Pinto PM, Ciol MA, Bergquist R, Reed SG, Tendler M. Schistosomiasis vaccine candidate Sm14/GLA-SE: Phase 1 safety and immunogenicity clinical trial in healthy, male adults. Vaccine. 2016 Jan 20;34(4):586-594. doi: 10.1016/j.vaccine.2015.10.027. Epub 2015 Nov 10.
PMID: 26571311
citation: Lambert SL, Yang CF, Liu Z, Sweetwood R, Zhao J, Cheng L, Jin H, Woo J. Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A. PLoS One. 2012;7(12):e51618. doi: 10.1371/journal.pone.0051618. Epub 2012 Dec 28.
PMID: 23284726
citation: Tendler M, Almeida MS, Vilar MM, Pinto PM, Limaverde-Sousa G. Current Status of the Sm14/GLA-SE Schistosomiasis Vaccine: Overcoming Barriers and Paradigms towards the First Anti-Parasitic Human(itarian) Vaccine. Trop Med Infect Dis. 2018 Nov 21;3(4):121. doi: 10.3390/tropicalmed3040121. Erratum In: Trop Med Infect Dis. 2019 Jan 19;4(1):
PMID: 30469320
responsible party type: Sponsor
mesh term: Schistosomiasis
sharing ipd: No