Back to results

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

Primary Purpose

Schistosomiasis

Status

Completed

Phase

Phase 2

Locations

Senegal

Study Type

Interventional

Intervention

Sm14

GLA-SE solution

About this trial

This is an interventional prevention trial for Schistosomiasis focused on measuring Schistosomiasis, Recombinant vaccine, rSm14, GLA-SE, Fatty acid-binding protein (FABP), Phase II Clinical Trial, Senegal

Eligibility Criteria

8 Years - 11 Years (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Biomedical Research Center EPLS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Arm Label

Group 1

Group 2

Group 3

Arm Description

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).

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).

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.

Outcomes

Primary Outcome Measures

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.

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.

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).

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.

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.

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Secondary Outcome Measures

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).

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).

Full Information

NCT ID

NCT03799510

First Posted

January 8, 2019

Last Updated

December 5, 2019

Sponsor

Oswaldo Cruz Foundation

Collaborators

Orygen Biotecnologia SA, Biomedical Research Center EPLS, Access to Advanced Health Institute (AAHI)

1. Study Identification

Unique Protocol Identification Number

NCT03799510

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

December 13, 2018 (Actual)

Primary Completion Date

July 1, 2019 (Actual)

Study Completion Date

August 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Oswaldo Cruz Foundation

Collaborators

Orygen Biotecnologia SA, Biomedical Research Center EPLS, Access to Advanced Health Institute (AAHI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schistosomiasis

Keywords

Schistosomiasis, Recombinant vaccine, rSm14, GLA-SE, Fatty acid-binding protein (FABP), Phase II Clinical Trial, Senegal

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Masking Description

No masking

Allocation

Randomized

Enrollment

95 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

Arm Title

Group 2

Arm Type

Experimental

Arm Description

Arm Title

Group 3

Arm Type

No Intervention

Arm Description

Intervention Type

Biological

Intervention Name(s)

Sm14

Other Intervention Name(s)

rSm14

Intervention Description

Three 0.5 mL intra-muscular injections of the vaccine solution (50μg Sm14) will be administered on D0, W4, W8 (D = day, W = week).

Intervention Type

Drug

Intervention Name(s)

GLA-SE solution

Other Intervention Name(s)

• Glucopyranosyl Lipid A in Stable Emulsion, • Glucopyranosyl Lipid Adjuvant-Stable Emulsion, • Toll-like Receptor 4 Agonist GLA-SE

Intervention Description

The lot concentration 10μg/mL for injection of 2.5μg GLA-SE/injection.

Primary Outcome Measure Information:

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

within 2 days of the administration of the first dose (Day 0)

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

Day 30-Day 32: within 2 days of the administration of the second dose (Week 4)

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

Days 60-67 : within 7 days of the administration of the third dose (Week 8)

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

Day 90: three months after the first injection (Week 12)

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

Day 120: four months after the first injection (Week 16)

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

Day 150: five months after the first injection (Week 21)

Secondary Outcome Measure Information:

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

Time Frame

The Day of first Sm14 vaccine administration (Day 0)

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

Time Frame

At the 30th day after the third Sm14 vaccine administration (Week 12)

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

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).

Time Frame

At the 90th day after the third Sm14 vaccine administration (Week 21)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Maximum Age & Unit of Time

11 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Miriam Tendler, MD, PhD

Organizational Affiliation

Oswaldo Cruz Foundation

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Modou DIOP, MD

Organizational Affiliation

Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS)

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gilles RIVEAU, PharmD, PhD

Organizational Affiliation

Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Anne-Marie SCHACHT, CRA

Organizational Affiliation

Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).

Official's Role

Study Director

Facility Information:

Facility Name

Biomedical Research Center EPLS

City

Saint Louis

ZIP/Postal Code

BP226

Country

Senegal

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

2022660

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.

Results Reference

result

PubMed Identifier

19150418

Citation

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.

Results Reference

result

PubMed Identifier

21298114

Citation

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.

Results Reference

result

PubMed Identifier

26571311

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 20;34(4):586-594. doi: 10.1016/j.vaccine.2015.10.027. Epub 2015 Nov 10.

Results Reference

result

PubMed Identifier

23284726

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 Dec 28.

Results Reference

result

PubMed Identifier

30469320

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):121. doi: 10.3390/tropicalmed3040121. Erratum In: Trop Med Infect Dis. 2019 Jan 19;4(1):

Results Reference

result

Learn more about this trial

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

We'll reach out to this number within 24 hrs