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

NCT ID: NCT03041766

Last Updated: 2017-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-06

Study Completion Date

2017-06-02

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Schistosomiasis

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group 1

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 Type EXPERIMENTAL

Sm14

Intervention Type 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).

GLA-SE solution

Intervention Type 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

Group 2

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).

Group Type EXPERIMENTAL

Sm14

Intervention Type 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).

GLA-SE solution

Intervention Type 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

Interventions

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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).

Intervention Type BIOLOGICAL

GLA-SE solution

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

Intervention Type DRUG

Other Intervention Names

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rSm14 Glucopyranosyl Lipid A in Stable Emulsion Glucopyranosyl Lipid Adjuvant-Stable Emulsion Toll-like Receptor 4 Agonist GLA-SE

Eligibility Criteria

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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.

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Orygen Biotecnologia SA

UNKNOWN

Sponsor Role collaborator

Biomedical Research Center EPLS

OTHER

Sponsor Role collaborator

Access to Advanced Health Institute (AAHI)

OTHER

Sponsor Role collaborator

Oswaldo Cruz Foundation

OTHER

Sponsor Role lead

Responsible Party

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MIRIAM TENDLER

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Miriam Tendler, MD, PhD

Role: STUDY_CHAIR

Oswaldo Cruz Foundation

Doudou DIOP, MD

Role: PRINCIPAL_INVESTIGATOR

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

Gilles RIVEAU, PharmD, PhD

Role: STUDY_DIRECTOR

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

Locations

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Biomedical Research Center EPLS

Saint-Louis, , Senegal

Site Status

Countries

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Senegal

References

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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.

Reference Type RESULT
PMID: 2022660 (View on PubMed)

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.

Reference Type RESULT
PMID: 19150418 (View on PubMed)

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.

Reference Type RESULT
PMID: 21298114 (View on PubMed)

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.

Reference Type RESULT
PMID: 26571311 (View on PubMed)

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.

Reference Type RESULT
PMID: 23284726 (View on PubMed)

Other Identifiers

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Sm14-2a-Sn

Identifier Type: -

Identifier Source: org_study_id