Phase 3b Trial To Evaluate Safety And Immune Response (Superiority) of a Two-Dose Butantan-DV Regimen And The Standard Single Dose In Dengue-Naive Children/Adolescents and Immune Response (Non-inferiority) in a Manufacturing Facility Change (DEN-06-IB) (DEN-06-IB)
A Multicenter, Randomized, Controlled, Parallel-Group, Phase 3b Clinical Trial To Evaluate The Immunological Superiority Of The Two-Dose Butantan-Dv Regimen-Administered With A 9-Month Interval-Compared To The Single-Dose Regimen, And The Immunological Non-Inferiority Following A Change In Manufacturing Facility, In Children And Adolescents With No Prior Dengue Exposure.
Visão geral do estudo
Status
Status
Condições
Condições
Intervenção / Tratamento
Intervenção / Tratamento
Descrição detalhada
Tipo de estudo
Tipo de estudo
Inscrição (Estimado)
Inscrição
Estágio
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
Contato de estudo
- Nome: Fernanda C Boulos, MD, PhD
- Número de telefone: +551137237054
- E-mail: fernanda.boulos@fundacaobutantan.org.br
Estude backup de contato
- Nome: Érique JF Peixoto de Miranda, MD, PhD
- Número de telefone: +551137237054
- E-mail: erique.miranda@fundacaobutantan.org.br
Critérios de participação
Critérios de elegibilidade
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Participants aged 2 to 17 years at the time of study enrollment with no prior dengue exposure (as determined by IgG ELISA), at research centers located in cities within areas of low to medium endemicity for dengue virus infection.
- Agreement to periodic contact via telephone, electronic means, and home or research center visits.
- Participants of reproductive potential must be using an effective contraceptive method for at least 30 days at screening and continue doing so until Day 363 post-first vaccination; exceptions apply if the participant (or their legal representative) declares the participant to be at no risk of pregnancy-whether due to sexual abstinence or engaging in non-reproductive sexual practices-through Day 363 post-first vaccination.
- Demonstrated intention to participate in the study, documented by the signature of the informed consent form by the participant's parents and the informed assent form by the participant (where applicable), as well as agreement to study procedures, including completing participant diaries, undergoing blood sampling, and being available for scheduled study visits and contacts.
Exclusion Criteria:
- Reactive or unavailable dengue IgG ELISA test result.
- For female participants of reproductive potential: pregnancy (confirmed by a positive β-hCG test), breastfeeding, or expressed intention to engage in sexual practices with reproductive potential without using a contraceptive method up to Day 363 after the first vaccination;
- Planned donation of blood, semen, or ova up to Day 363 after the first vaccination;
- Evidence of active, uncontrolled neurological, cardiac, pulmonary, hepatic, or renal disease-defined as disease requiring a change in treatment or hospitalization due to worsening of the condition within the 90 days prior to study screening, based on medical history or physical examination, at the investigator's judgement;
- Diseases compromising the immune system, including: decompensated diabetes mellitus; active neoplasms or a history of neoplasms within the last five years (except basal cell carcinoma); congenital or acquired immunodeficiencies (except HIV infection with undetectable viral load and CD4+ T-lymphocyte count > 500 cells/mm³); solid organ transplantation (heart, liver, pancreas, lung, kidney); or uncontrolled autoimmune diseases (based on medical history or physical examination); as well as a history of hepatic insufficiency, heart failure, or end-stage or dialysis-dependent chronic kidney disease;
- Behavioral, cognitive, or psychiatric condition that, in the opinion of the principal investigator or their medical representative, affects the potential participant's ability to understand and comply with the study protocol requirements;
- Any use of alcohol or drugs considered abusive within the 12 months prior to study enrollment that has caused medical, occupational, or family problems, as indicated by clinical history;
- History of severe allergic reaction or anaphylaxis to the study vaccine or its components;
- History of asplenia;
- Participation in another clinical trial involving the administration of an investigational product during the six months prior to study enrollment, or participation in another clinical trial during the 12 months following enrollment;
- Prior participation in a clinical study of (or exposure to) any dengue vaccine;
- Use of potent immunosuppressive therapies (excluding corticosteroids) in the six months prior to study enrollment. Potent immunosuppressive therapies are considered to include: antineoplastic chemotherapy, radiotherapy, immunosuppressants used to induce transplant tolerance, and potent monoclonal antibody therapy for the treatment of rheumatological diseases, among others;
- Receipt of an immunosuppressive dose of corticosteroids within the three months prior to study enrollment. An immunosuppressive corticosteroid dose is defined as equivalent to a prednisone dose of 2 mg/kg/day for children and 20 mg/day for adolescents for 14 days (a cumulative equivalent dose of at least 280 mg of prednisone). Continuous use of topical or nasal corticosteroids is not considered immunosuppressive;
- Receipt of blood components (transfusions) or blood derivatives (immunoglobulins) within the six months prior to study enrollment;
- Any other condition that, in the opinion of the principal investigator or their medical representative, could jeopardize the safety or rights of a potential participant or prevent them from complying with this protocol.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Número de braços
Armas e Intervenções
Grupo de Participantes / BraçoGrupo de Participantes / Braço |
Intervenção / TratamentoIntervenção / Tratamento |
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Experimental: Butantan-DV (IB) - Intervention 1
Butantan-DV manufactured at the Butantan Institute
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Butantan-DV manufactured at the Instituto Butantan - Butantan-DV (IB), mean 10³ PFU (per dose), subcutaneously, in the deltoid region.
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Experimental: Butantan-DV (WuXi) - Intervention 2
Butantan-DV manufactured at the WuXi Biologics CRDMO
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Butantan-DV manufactured at the WuXi Biologics CRDMO - Butantan-DV (WuXi),mean 10³ PFU (per dose), subcutaneously, in the deltoid region.
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Comparador de Placebo: Placebo (IB)
Placebo (0 PFU), solution of the simplified lyophilized formulation, manufactured at the Butantan Institute
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Placebo manufactured at the Instituto Butantan - Placebo (IB), mean 0 PFU (per dose), subcutaneously, in the deltoid region.
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O que o estudo está medindo?
Medidas de resultados primários
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Immunogenicity - 1
Prazo: Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
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Geometric Mean Fold-Rise ratio of neutralizing antibodies measured by PRNT50 against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) in participants in the Butantan-DV (IB) + Butantan-DV (IB) group, compared to participants in the Butantan-DV (IB) + Placebo (IB) group, in children aged 2 to 11 years.
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Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
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Immunogenicity - 2
Prazo: Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
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Geometric Mean Fold-Rise ratio of neutralizing antibodies measured by PRNT50 against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) in participants of the Butantan-DV (IB) + Butantan-DV (IB) group at Day 302, compared to participants of the Butantan-DV (IB) + Placebo (IB) group at Day 29, in adolescents aged 12 to 17 years.
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Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
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Immunogenicity - 3
Prazo: Day 29 post vaccination.
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Geometric Mean Fold-Rise ratio of neutralizing antibodies measured by PRNT50 against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) in participants of the Butantan-DV (WuXi) Group compared to participants of the other two Butantan-DV (IB) groups, in adolescents aged 12 to 17 years.
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Day 29 post vaccination.
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Safety - 1
Prazo: First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
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Frequency of solicited and unsolicited adverse reactions in participants in the Butantan-DV + Butantan-DV group and in participants in the Butantan-DV (IB) + Placebo (IB) group, among children aged 2 to 11 years.
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First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
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Safety - 2
Prazo: First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
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Frequency of solicited and unsolicited adverse reactions after each vaccine dose in participants in the Butantan-DV (IB) + Butantan-DV (IB) group and in participants in the Butantan-DV (IB) + Placebo (IB) group, among adolescents aged 12 to 17 years.
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First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
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Safety - 3
Prazo: First 21 days after each vaccine dose (up to Day 22).
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Frequency of solicited and unsolicited adverse reactions in participants in the Butantan-DV (WuXi) Group and in participants in the other two Butantan-DV (IB) groups who received the first dose of the primary immunization series, among adolescents aged 12 to 17 years.
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First 21 days after each vaccine dose (up to Day 22).
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Medidas de resultados secundários
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Immunogenicity - 4
Prazo: Day 29 postvaccination.
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Geometric Mean Fold-Rise ratio (rGMFR) in neutralizing antibody titers measured by PRNT50, for each dengue virus serotype (DENV-1, DENV-2, DENV-3, and DENV-4), postvaccination, for participants in the Butantan-DV (IB) + Butantan-DV (IB) group compared to participants in the Butantan-DV (IB) + Placebo (IB) group, among children aged 2 to 11 years and adolescents aged 12 to 17 years.
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Day 29 postvaccination.
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Immunogenicity - 5
Prazo: Day 182 postvaccination.
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Geometric Mean Fold-Rise ratio (rGMFR) of neutralizing antibody titers measured by PRNT50-for each dengue virus serotype (DENV-1, DENV-2, DENV-3, and DENV-4)-comparing the Butantan-DV (WuXi) Group to the other Butantan-DV (IB) groups that received only the first vaccination.
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Day 182 postvaccination.
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Immunogenicity - 6
Prazo: Day 302 in the Butantan-DV (IB) + Butantan-DV (IB) Group and Day 29 in the Butantan-DV (IB) + Placebo (IB) Group.
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Difference between proportions of seroconversion (95% CI) in the Butantan-DV (IB) + Butantan-DV (IB) group and seroconversion in the Butantan-DV (IB) + Placebo (IB) group, for the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4).
Seroconversion defined as ≥1:10 from a baseline titer <1:10 post-vaccination or a fourfold increase relative to baseline for a baseline titer ≥1:10.
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Day 302 in the Butantan-DV (IB) + Butantan-DV (IB) Group and Day 29 in the Butantan-DV (IB) + Placebo (IB) Group.
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Immunogenicity - 7
Prazo: Days 1, 29, 182, 302, and 456 post vaccination.
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Cellular immune response in a cohort of 50 consecutive participants from the Butantan-DV (IB) + Butantan-DV (IB) group and the Butantan-DV (IB) + Placebo (IB) group, against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4).
The immune response will consist of the proportion (%) of DENV-1- through DENV-4-specific CD4+ and CD8+ T cells (producing IFN-γ) following vaccine stimulation.
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Days 1, 29, 182, 302, and 456 post vaccination.
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Safety - 4
Prazo: Period between the second dose and Day 294.
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Frequency (95% CI and p-value) for the difference in proportions of participants with solicited (local and systemic) and unsolicited adverse reactions comparing the Butantan-DV (IB) + Butantan-DV (IB) group with the Butantan-DV (IB) + Placebo (IB) group, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
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Period between the second dose and Day 294.
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Safety - 5
Prazo: Period between the first dose and Day 22.
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Frequency (95% CI and p-value) for the difference in proportions of participants with solicited (local and systemic) and unsolicited adverse reactions, among participants in the Butantan-DV (WuXi) Group and participants in the other Butantan-DV (IB) groups who received the first dose of the primary immunization series, in adolescents aged 12 to 17 years.
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Period between the first dose and Day 22.
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Safety - 6
Prazo: Day 1 to Day 43 and Day 273 to Day 315
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Frequency (95% CI) of the difference in proportions of participants with adverse events requiring medical attention (AERMA) post-vaccination across the three groups, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
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Day 1 to Day 43 and Day 273 to Day 315
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Safety - 7
Prazo: Throughout the entire study period, an average of 1 year.
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Frequency (95% CI and p-value) of the difference between proportions, of participants with serious adverse events (SAEs) post-vaccination across the three groups, among children aged 2 to 11 and adolescents aged 12 to 17 years.
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Throughout the entire study period, an average of 1 year.
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Safety - 8
Prazo: Throughout the entire study period, an average of 1 year.
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Frequency (95% CI and p-value) of the difference in proportions of participants with adverse events of special interest (AESI) post-vaccination, across the three groups, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
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Throughout the entire study period, an average of 1 year.
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Safety - 9
Prazo: Throughout the entire study period, an average of 1 year.
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Frequency (95% CI and p-value) of the difference in proportions of participants with adverse events of special interest (AESI) post-vaccination, across the three groups, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
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Throughout the entire study period, an average of 1 year.
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Safety - 10
Prazo: Days 1, 6, 9, 12, 22, 273, 279, 282, 285, and 294.
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Frequency of viremia after each dose of the primary immunization and laboratory changes at visits on in a cohort of 50 adolescent participants aged 12 to 17 years from the Butantan-DV (IB) + Butantan-DV (IB) group and the Butantan-DV (IB) + Placebo (IB) group, for all dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) and by valence.
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Days 1, 6, 9, 12, 22, 273, 279, 282, 285, and 294.
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Colaboradores
Colaboradores
Investigadores
Investigadores
- Diretor de estudo: Fernanda C Boulos, MD, PhD, Instituto Butantan
Publicações e links úteis
Publicações Gerais
- Nogueira ML, Cintra MAT, Moreira JA, Patino EG, Braga PE, Tenorio JCV, de Oliveira Alves LB, Infante V, Silveira DHR, de Lacerda MVG, Pereira DB, da Fonseca AJ, Gurgel RQ, Coelho IC, Fontes CJF, Marques ETA, Romero GAS, Teixeira MM, Siqueira AM, Boaventura VS, Ramos F, Junior EE, de Moraes JC, Whitehead SS, Esteves-Jaramillo A, Shekar T, Lee JJ, Macey J, Kelner SG, Coller BG, Boulos FC, Kallas EG; Phase 3 Butantan-DV Working Group. Efficacy and safety of Butantan-DV in participants aged 2-59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil. Lancet Infect Dis. 2024 Nov;24(11):1234-1244. doi: 10.1016/S1473-3099(24)00376-1. Epub 2024 Aug 5.
- Kallas EG, Cintra MAT, Moreira JA, Patino EG, Braga PE, Tenorio JCV, Infante V, Palacios R, de Lacerda MVG, Batista Pereira D, da Fonseca AJ, Gurgel RQ, Coelho IC, Fontes CJF, Marques ETA, Romero GAS, Teixeira MM, Siqueira AM, Barral AMP, Boaventura VS, Ramos F, Elias Junior E, Cassio de Moraes J, Covas DT, Kalil J, Precioso AR, Whitehead SS, Esteves-Jaramillo A, Shekar T, Lee JJ, Macey J, Kelner SG, Coller BG, Boulos FC, Nogueira ML. Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults. N Engl J Med. 2024 Feb 1;390(5):397-408. doi: 10.1056/NEJMoa2301790.
- Kallas EG, Precioso AR, Palacios R, Thome B, Braga PE, Vanni T, Campos LMA, Ferrari L, Mondini G, da Graca Salomao M, da Silva A, Espinola HM, do Prado Santos J, Santos CLS, Timenetsky MDCST, Miraglia JL, Gallina NMF, Weiskopf D, Sette A, Goulart R, Salles RT, Maestri A, Sallum AME, Farhat SCL, Sakita NK, Ferreira JCOA, Silveira CGT, Costa PR, Raw I, Whitehead SS, Durbin AP, Kalil J. Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial. Lancet Infect Dis. 2020 Jul;20(7):839-850. doi: 10.1016/S1473-3099(20)30023-2. Epub 2020 Mar 24.
- Peixoto de Miranda EJF, de Sousa Moreira JA, da Silva Braga R, Silveira DHR, Infante V, de Oliveira Alves LB, de Camargo Vieira Tenorio J, Dos Santos Silva GF, Patino EG, de Mesquita Pacheco PHT, Ramos F, Oliveira DS, Kallas EG, Boulos FC. Randomized, double-blind, placebo-controlled, phase 3 trial to demonstrate lot-to-lot consistency of 3 lots of the simplified formulation of Butantan-dengue vaccine. Vaccine. 2025 Nov 14;66:127836. doi: 10.1016/j.vaccine.2025.127836. Epub 2025 Oct 14.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Início do estudo
Conclusão Primária (Estimado)
Conclusão Primária
Conclusão do estudo (Estimado)
Conclusão do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Primeira postagem
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última Atualização Postada
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Última verificação
Mais Informações
Termos relacionados a este estudo
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Outros números de identificação do estudo
- DEN-06-IB
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