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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Schistosomiasis

Intervention / Treatment
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* Biological: Sm14
* Drug: GLA-SE solution


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>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). | Biological: Sm14<br>* Three 0.5 mL intra-muscular injections of the vaccine solution (50μg Sm14) will be administered on D0, W4, W8 (D = day, W = week).<br>* Other names: rSm14;Drug: GLA-SE solution<br>* The lot concentration 10μg/mL for injection of 2.5μg GLA-SE/injection.<br>* Other names: • Toll-like Receptor 4 Agonist GLA-SE;|
| Experimental: Group 2<br>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). | Biological: Sm14<br>* Three 0.5 mL intra-muscular injections of the vaccine solution (50μg Sm14) will be administered on D0, W4, W8 (D = day, W = week).<br>* Other names: rSm14;Drug: GLA-SE solution<br>* The lot concentration 10μg/mL for injection of 2.5μg GLA-SE/injection.<br>* Other names: • Toll-like Receptor 4 Agonist GLA-SE;|
| No Intervention: Group 3<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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. | within 2 days of the administration of the first dose (Day 0) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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. | Day 30-Day 32: within 2 days of the administration of the second dose (Week 4) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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). | Days 60-67 : within 7 days of the administration of the third dose (Week 8) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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. | Day 90: three months after the first injection (Week 12) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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. | Day 120: four months after the first injection (Week 16) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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. | Day 150: five months after the first injection (Week 21) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative and quantitative assessment of the Immunogenicity | 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). | The Day of first Sm14 vaccine administration (Day 0) | 
| Qualitative and quantitative assessment of the Immunogenicity | 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). | At the 30th day after the third Sm14 vaccine administration (Week 12) | 
| Qualitative and quantitative assessment of the Immunogenicity | 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). | At the 90th day after the third Sm14 vaccine administration (Week 21) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schistosomiasis, Recombinant vaccine, rSm14, GLA-SE, Fatty acid-binding protein (FABP), Phase II Clinical Trial, Senegal