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

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

18 Years - 49 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

Biomedical Research Center EPLS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group 1

Group 2

Arm Description

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).

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).

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. Laboratory tests (blood count, liver and kidney biological functions).

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. Laboratory tests (blood count, liver and kidney biological functions).

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).

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

Full Information

NCT ID

NCT03041766

First Posted

November 16, 2016

Last Updated

December 12, 2017

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

NCT03041766

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

December 6, 2016 (Actual)

Primary Completion Date

April 6, 2017 (Actual)

Study Completion Date

June 2, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oswaldo Cruz Foundation

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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)

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

Arm Title

Group 2

Arm Type

Experimental

Arm Description

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).

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

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

within 7 days of the administration of the first dose

Title

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

Description

Time Frame

D30-D37: within 7 days of the administration of the second dose

Title

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

Description

Time Frame

D60-67 : within 7 days of the administration of the third dose

Title

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

Description

Time Frame

D90 : three months after the first injection

Title

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

Description

Time Frame

D120 : four months after the first injection

Secondary Outcome Measure Information:

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

Time Frame

Day of first administration

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

Time Frame

30 days after the first administration

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

Time Frame

60 days after the first administration

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

Time Frame

90 days after the first administration

Title

Qualitative and quantitative assessment of the Immunogenicity

Description

Time Frame

120 days after the first administration

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

49 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

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

Doudou 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

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

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

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