Clinical trial NCT03799510: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schistosomiasis
Keywords: Schistosomiasis
Recombinant vaccine
rSm14
GLA-SE
Fatty acid-binding protein (FABP)
Phase II Clinical Trial
Senegal
Lead sponsor: Oswaldo Cruz Foundation
Sponsor class: OTHER
Collaborators: name: Orygen Biotecnologia SA
name: Biomedical Research Center EPLS
name: Access to Advanced Health Institute (AAHI)
First posted: 2019-01-10
Enrollment: 95
Sex: ALL
Minimum age (years): 8
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: within 2 days of the administration of the first dose (Day 0)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Day 30-Day 32: within 2 days of the administration of the second dose (Week 4)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Days 60-67 : within 7 days of the administration of the third dose (Week 8)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Day 90: three months after the first injection (Week 12)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Day 120: four months after the first injection (Week 16)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Day 150: five months after the first injection (Week 21)
Secondary outcomes:
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: The Day of first Sm14 vaccine administration (Day 0)
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: At the 30th day after the third Sm14 vaccine administration (Week 12)
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: At the 90th day after the third Sm14 vaccine administration (Week 21)
Other outcomes:
Locations:
city: Saint Louis
country: Senegal
facility: Biomedical Research Center EPLS
Study officials:
affiliation: Oswaldo Cruz Foundation
name: Miriam Tendler, MD, PhD
role: STUDY_CHAIR
affiliation: Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS)
name: Modou DIOP, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).
name: Gilles RIVEAU, PharmD, PhD
role: STUDY_DIRECTOR
affiliation: Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).
name: Anne-Marie SCHACHT, CRA
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.