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Study of Safety and Immune Response of the Sm14 Vaccine in Adults of Endemic Regions

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ClinicalTrials.gov Identifier: NCT03041766
Recruitment Status : Completed
First Posted : February 3, 2017
Last Update Posted : December 14, 2017
Sponsor:
Collaborators:
Orygen Biotecnologia SA
Biomedical Research Center EPLS
IDRI
Information provided by (Responsible Party):
MIRIAM TENDLER, Oswaldo Cruz Foundation

Tracking Information
First Submitted Date  ICMJE November 16, 2016
First Posted Date  ICMJE February 3, 2017
Last Update Posted Date December 14, 2017
Actual Study Start Date  ICMJE December 6, 2016
Actual Primary Completion Date April 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
  • 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: D30-D37: 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: D60-67 : 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: D90 : 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: D120 : four months after the first 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
  • Qualitative and quantitative assessment of the Immunogenicity [ Time Frame: 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 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: 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Safety and Immune Response of the Sm14 Vaccine in Adults of Endemic Regions
Official Title  ICMJE Safety and Immunogenicity Evaluation of the Vaccine Candidate Sm14 in Combination With the Adjuvant Glucopyranosyl Lipid A (GLA-SE) in Adults Living in Endemic Regions for S. Mansoni and S. Haematobium in Senegal. A Comparative, Randomized, Open-label Trial
Brief Summary The clinical trial phase 2a is designed to assess the safety of the active ingredient (protein + adjuvant) and secondarily its immunogenicity in healthy male adults from 18 to 49 years of age with a history of infection with intestinal and urinary schistosomiasis, living in the Valley of the Senegal River, a highly endemic area for schistosomiasis. Two arms in the study will test different doses of GLA-SE adjuvant (2.5 and 5 μg). This phase IIA in adults is considered to be a preliminary step in safety before starting trials in children in endemic areas to S. mansoni or S. haematobium, target population of the vaccine.
Detailed Description

A phase 2a trial, self-contained, open-label, randomized, dose-escalation study in two parallel arms receiving three (3) injections at D0, D28, D56; both groups receiving 50 μg Sm14 vaccine candidate solution, either combined with 2.5µg GLA-SE for the first group and 5µg for the second one in adults living in a S. mansoni and S. haematobium endemic area.

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 then 7 days after each injections and at W13 and W21 during the follow-up.

Blood samples for immune response analysis at time of each injection, and then W12 and W20.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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
    Two (2) adjuvant concentrations will be made and packaged at 0.4 mL/vial, per GMP standards. One lot at the concentration of 10µg/mL for injection in the first cohort at 2.5µg GLA-SE/injection and one lot at the concentration of 20µg/mL for the second cohort intended to receive 5.0µg of 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
    Adults with an infectious history of S. haematobium and S. mansoni and pretreated with 1 dose of Praziquantel (3 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
  • Experimental: Group 2
    Adults with an infectious history of S. haematobium and S. mansoni and pretreated with 1 dose of Praziquantel (3 weeks prior to the first vaccine injection) receiving three (3) intramuscular injections of 50 μg Sm14 with 5.0 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
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 31, 2017)
30
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2, 2017
Actual Primary Completion Date April 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults, male, 18 to 49 years old (inclusive) at the time of inclusion.
  • Living in one of selected villages in Saint-Louis Region (Senegal).
  • Free of obvious/severe health problems except schistosomiasis, as established by clinical examination and blood analysis, i.e. hematological exams, liver and renal function tests.
  • Written informed consent to participate obtained
  • Treated with 40mg/kg Praziquantel (PZQ) before inclusion (W-5 to W-4 before the first injection) in case of infection with S. mansoni and S. haematobium
  • Residence in the area during the period of the study.

Exclusion Criteria:

  • Adult who does not respond to one of the inclusion criteria
  • 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
  • Acute disease at time of enrollment.
  • Other conditions which in opinion of the PI may potentially represent a danger for the patient to be enrolled.
  • Non residence in the study area or intent to move during the study period
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 49 Years   (Adult)
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 NCT03041766
Other Study ID Numbers  ICMJE Sm14-2a-Sn
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party MIRIAM TENDLER, 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: Doudou 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)
PRS Account Oswaldo Cruz Foundation
Verification Date January 2017

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