This is a prospective, randomized, double-blinded, multicenter, pivotal study evaluating the final dose of VLA1553 (1 x10E4 TCID50 per dose) in comparison to a placebo control. The final dose of VLA1553 or control will be administered as single immunization on Day 1. Overall, approximately 750 male and female subjects aged 12 years to \<18 years will be enrolled into the study.
This is a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study comprising approximately 750 subjects aged 12 years to \<18 years randomized in a 2:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The final dose of lyophilized VLA1553 or placebo will be administered as a single intramuscular immunization. Subjects in this study will be stratified by baseline serostatus. The primary objective of the study is to evaluate the immunogenicity and safety of the adult dose of VLA1553 28 days following the single immunization. Immunogenicity evaluations in the immunogenicity subset will include the proportion of subjects with seroprotective neutralizing CHIKV antibody titers above a surrogate threshold indicative of protection. The surrogate of protection reasonably likely to predict clinical benefit has been established in non-human primate passive transfer studies using human sera from the Phase 1 study. Safety data collection and immunogenicity will continue to be assessed until Month 12.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
750
CECOR - Centro Oncológico de Roraima
Boa Vista, Acre, Brazil
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Manaus, Amazonas, Brazil
Núcleo de Medicina Tropical - Universidade Federal do Ceará
Fortaleza, Ceará, Brazil
Seroprotection
Proportion of subjects with a seroprotective CHIKV antibody level determined by µPRNT (Micro Plaque Reduction Neutralization Test) for baseline negative subjects 28 days post-vaccination.
Time frame: up to Day 29 after single vaccination
Immunogenicity
Immune response as measured by CHIKV-specific neutralizing antibody titers determined by μPRNT assay
Time frame: until Day 8, Day 85, Day 180, and Month 12 after vaccination
Seroprotection up to 1 year
Proportion of subjects with seroprotective CHIKV antibody levels as determined by µPRNT Month 12.
Time frame: until Day 8, Day 29, Day 85, Day 180, and Month 12 after vaccination
Seroconversion up to 1 year
Proportion of subjects with seroconversion as compared to baseline at Day 29, Month 6 and Month 12 as determined by μPRNT assay
Time frame: 12 months after vaccination
Fold Increase in neutralizing antibodies
Fold increase of CHIKV-specific neutralizing antibody titers determined by μPRNT assay at Days 8, 29, 85, 180 and at Month 12 post-vaccination as compared to baseline
Time frame: 12 months after vaccination
Proportion of increase of neutralizing antibodies
Proportion of subjects reaching an at least 4-fold, 8-fold, 16-fold or 64-fold increase in CHIKV-specific neutralizing antibody titer compared to baseline as measured by μPRNT assay
Time frame: 12 months after vaccination
Immunogenicity per baseline serostatus
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Associação Obras Sociais Irmã Dulce / Centro de Pesquisa Clínica - CPEC
Salvador, Estado de Bahia, Brazil
Centro de Pesquisa e Desenvolvimento de Fármacos (CPDF) - Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas
Belo Horizonte, Minas Gerais, Brazil
Real Hospital Português de Beneficência em Pernambuco
Recife, Pernambuco, Brazil
Centro de Pesquisas Clínicas Universidade Federal Sergipe
Aracaju, Sergipe, Brazil
Faculdade de Medicina de São José do Rio Preto - FAMERP
São José do Rio Preto, São Paulo, Brazil
Centro de Pesquisa Clínica da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul - UFMS
Campo Grande, Brazil
Centro de Estudos do Instituto de Infectologia Emílio Ribas
São Paulo, Brazil
Antibody titers, seroprotection and fold increases for CHIKV-specific neutralizing antibodies, determined by μPRNT assay at Days 1, 8, 29, 85, 180, and Month 12 post-vaccination stratified by baseline serostatus
Time frame: 12 months after vaccination
Unsolicited adverse events
Frequency and severity of unsolicited AEs until Day 29 and Month 6 post-vaccination
Time frame: 6 months after vaccination
Solicited adverse reactions
Frequency and severity of solicited injection site and systemic reactions within ten days post-vaccination
Time frame: 10 days after vaccination
Frequency of adverse event of special interest
Frequency and severity of any Adverse Event of Special Interest
Time frame: until 12 month after vaccination
Viremia of vaccine strain
Frequency of viremia of vaccine strain detected on Days 1 and 8 (and Day 29, if applicable) after vaccination
Time frame: 29 days after vaccination
Frequency of Serious Adverse Event
Frequency and relatedness of any Serious Adverse Event (SAE) during the entire study period
Time frame: until 12 month after vaccination