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

Schistosomiasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03799510
• Other study ID #: Sm14 Phase 2b - Sn
• Status: Completed
• Phase: Phase 2
• Start date: December 13, 2018
• Est. completion date: August 7, 2019

Study information

• Verified date: December 2019
• Source: Oswaldo Cruz Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: August 7, 2019
• Est. primary completion date: July 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schistosomiasis

Intervention

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).

Drug:
• GLA-SE solution
The lot concentration 10µg/mL for injection of 2.5µg GLA-SE/injection.

Locations

Country	Name	City	State
Senegal	Biomedical Research Center EPLS	Saint Louis

Sponsors (4)

Lead Sponsor	Collaborator
Oswaldo Cruz Foundation	Biomedical Research Center EPLS, IDRI, Orygen Biotecnologia SA

Country where clinical trial is conducted

Senegal, 

References & Publications (6)

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. PLo — View 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 D — View 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. — View Citation

Ramos CR, Spisni A, Oyama S Jr, Sforça 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 c — View 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 — View 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). pii: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)