Clinical trial NCT03041766: 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
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: 2017-02-03
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
timeFrame: within 7 days of the administration of the first dose
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D30-D37: within 7 days of the administration of the second dose
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D60-67 : within 7 days of the administration of the third dose
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D90 : three months after the first injection
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D120 : four months after the first injection
Secondary outcomes:
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: Day of first administration
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: 30 days after the first administration
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: 60 days after the first administration
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: 90 days after the first administration
measure: Qualitative and quantitative assessment of the Immunogenicity
timeFrame: 120 days after the first administration
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: Doudou DIOP, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS)
name: Gilles RIVEAU, PharmD, PhD
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.