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| Name | Class |
|---|---|
| Orygen Biotecnologia SA | UNKNOWN |
| Biomedical Research Center EPLS | OTHER |
| Access to Advanced Health Institute (AAHI) | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | 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). |
|
| Group 2 | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sm14 | Biological | Three 0.5 mL intra-muscular injections of the vaccine solution (50µg Sm14) will be administered on D0, W4, W8 (D = day, W = week). |
|
| 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. Laboratory tests (blood count, liver and kidney biological functions). | within 7 days of the administration of the first dose |
| 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). | D30-D37: within 7 days of the administration of the second dose |
| 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). |
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Miriam Tendler, MD, PhD | Oswaldo Cruz Foundation | Study Chair |
| Doudou DIOP, MD | Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS) | Principal Investigator |
| Gilles RIVEAU, PharmD, PhD | Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biomedical Research Center EPLS | Saint-Louis | BP226 | Senegal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2022660 | Result | 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. | |
| 19150418 | Result | 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. |
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| ID | Term |
|---|---|
| D012552 | Schistosomiasis |
| ID | Term |
|---|---|
| D014201 | Trematode Infections |
| D006373 | Helminthiasis |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C068709 | SM14 protein, Schistosoma mansoni |
| C000608161 | glucopyranosyl lipid-A |
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| GLA-SE solution | Drug | 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 |
|
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| D60-67 : within 7 days of the administration of the third dose |
| 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. Laboratory tests (blood count, liver and kidney biological functions). | D90 : three months after the first injection |
| 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. Laboratory tests (blood count, liver and kidney biological functions). | D120 : four months after the first injection |
| Day of first administration |
| 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). | 30 days after the first administration |
| 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). | 60 days after the first administration |
| 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). | 90 days after the first administration |
| 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). | 120 days after the first administration |
| 21298114 | Result | 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. |
| 26571311 | Result | 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. |
| 23284726 | Result | 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. |
| D000079426 |
| Vector Borne Diseases |