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Anti-Schistosomiasis Vaccine: Sm14 Phase 2b-Sn in School Children

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ClinicalTrials.gov Identifier: NCT03799510
Recruitment Status : Completed
First Posted : January 10, 2019
Last Update Posted : December 9, 2019
Sponsor:
Collaborators:
Orygen Biotecnologia SA
Biomedical Research Center EPLS
IDRI
Information provided by (Responsible Party):
Oswaldo Cruz Foundation

Tracking Information
First Submitted Date  ICMJE January 8, 2019
First Posted Date  ICMJE January 10, 2019
Last Update Posted Date December 9, 2019
Actual Study Start Date  ICMJE December 13, 2018
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2019)
  • 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) ]
    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.
  • 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) ]
    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.
  • 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) ]
    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).
  • 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) ]
    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.
  • 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) ]
    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.
  • 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) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2019)
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: within 7 days of the administration of the first dose ]
    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).
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Day 30-Day 37: within 7 days of the administration of the second dose ]
    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).
  • 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 ]
    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).
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Day 90: three months after the first injection ]
    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. Laboratory tests (blood count, liver and kidney biological functions).
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Day 120: four months after the first inject ]
    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. Laboratory tests (blood count, liver and kidney biological functions).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2019)
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: The Day of first Sm14 vaccine administration (Day 0) ]
    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).
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: At the 30th day after the third Sm14 vaccine administration (Week 12) ]
    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).
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: At the 90th day after the third Sm14 vaccine administration (Week 21) ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2019)
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: 1 Day of first administration ]
    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).
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: 30 days after the first administration ]
    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).
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: 60 days after the first administration ]
    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).
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: 90 days after the first administration ]
    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).
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: 120 days after the first administration ]
    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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-Schistosomiasis Vaccine: Sm14 Phase 2b-Sn in School Children
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
No masking
Primary Purpose: Prevention
Condition  ICMJE Schistosomiasis
Intervention  ICMJE
  • Biological: Sm14
    Three 0.5 mL intra-muscular injections of the vaccine solution (50μg Sm14) will be administered on D0, W4, W8 (D = day, W = week).
    Other Name: rSm14
  • Drug: GLA-SE solution
    The lot concentration 10μg/mL for injection of 2.5μg GLA-SE/injection.
    Other Names:
    • • Glucopyranosyl Lipid A in Stable Emulsion
    • • Glucopyranosyl Lipid Adjuvant-Stable Emulsion
    • • Toll-like Receptor 4 Agonist GLA-SE
Study Arms  ICMJE
  • Experimental: Group 1
    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).
    Interventions:
    • Biological: Sm14
    • Drug: GLA-SE solution
  • Experimental: Group 2
    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).
    Interventions:
    • Biological: Sm14
    • Drug: GLA-SE solution
  • No Intervention: Group 3
    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.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 9, 2019)
95
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 7, 2019
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • School children, of public schools in villages of Saint Louis region (Senegal), female or male, 8 to 11 years old (inclusive) at the time of inclusion.
  • Residence in the area during the period of the study.
  • Free of obvious/severe health problems except schistosomiasis, as established by clinical examination.
  • Written informed consent to participate obtained from subject's parents or legal guardian.
  • Free of obvious/severe health problems except schistosomiasis, established by blood analysis, i.e. hematological exams, liver and renal function tests.
  • Treated with 40mg/kg Praziquantel (PZQ) before inclusion (W-2 to W-4 before the first injection) in case of infection with S. mansoni and S. haematobium
  • Children of Group 1: not infected, no schistosomiasis history and living in area/village free of Sm and Sh transmission.
  • Children Groups 2 & 3: infected with mansoni or/and haematobium schistosomiasis.

Exclusion Criteria:

  • School child who does not respond to one of the inclusion criteria
  • Child under 20kg of body weight
  • Vaccination within 90 days preceding the first dose of Sm14 vaccine candidate, or planned use during the study period.
  • Current or previous chronic administration (defined as more than 14 days) of immunosuppressive drugs or other immuno-modifying drugs.
  • Known hypersensitivity to any component in the Sm14 vaccine or history of allergic disease.
  • Knowledge of non-infectious chronic disease
  • Known acute disease.
  • Other conditions which in opinion of the PI may potentially represent a danger for the patient to be enrolled.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 11 Years   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Senegal
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03799510
Other Study ID Numbers  ICMJE Sm14 Phase 2b - Sn
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Oswaldo Cruz Foundation
Study Sponsor  ICMJE Oswaldo Cruz Foundation
Collaborators  ICMJE
  • Orygen Biotecnologia SA
  • Biomedical Research Center EPLS
  • IDRI
Investigators  ICMJE
Study Chair: Miriam Tendler, MD, PhD Oswaldo Cruz Foundation
Principal Investigator: Modou DIOP, MD Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS)
Study Director: Gilles RIVEAU, PharmD, PhD Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).
Study Director: Anne-Marie SCHACHT, CRA Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).
PRS Account Oswaldo Cruz Foundation
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP