| Author | Nogueira, Mauricio L. | |
| Author | Cintra, Monica A. T. | |
| Author | Moreira, José A. | |
| Author | Patiño, Elizabeth G. | |
| Author | Braga, Patrícia Emília | |
| Author | Tenório, Juliana C. V. | |
| Author | Alves, Lucas Bassolli de Oliveira | |
| Author | Infante, Vanessa | |
| Author | Silveira, Daniela Haydee Ramos | |
| Author | Lacerda, Marcus Vinícius Guimarães de | |
| Author | Pereira, Dhelio Batista | |
| Author | Fonseca, Allex Jardim da | |
| Author | Gurgel, Ricardo Queiroz | |
| Author | Coelho, Ivo Castelo-Branco | |
| Author | Fontes, Cor Jesus Fernandes | |
| Author | Marques, Ernesto T. A. | |
| Author | Romero, Gustavo Adolfo Sierra | |
| Author | Teixeira, Mauro Martins | |
| Author | Siqueira, André M. | |
| Author | Boaventura, Viviane Sampaio | |
| Author | Ramos, Fabiano | |
| Author | Elias Júnior, Erivaldo | |
| Author | Moraes, José Cassio de | |
| Author | Whitehead, Stephen S. | |
| Author | Esteves-Jaramillo, Alejandra | |
| Author | Shekar, Tulin | |
| Author | Lee, ,Jung-Jin | |
| Author | Macey, Julieta | |
| Author | Kelner, Sabrina Gozlan | |
| Author | Coller, Beth-Ann G. | |
| Author | Boulos, Fernanda Castro | |
| Author | Kallás, Esper G. | |
| Access date | 2024-12-10T17:09:35Z | |
| Available date | 2024-12-10T17:09:35Z | |
| Document date | 2024 | |
| Citation | NOGUEIRA, Mauricio L. et al. 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. The Lancet Infectious Diseases, v. 24, 1-11, 2024. | en_US |
| ISSN | 1474-4457 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/67520 | |
| Sponsorship | Instituto Butantan.
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. | en_US |
| Language | eng | en_US |
| Publisher | Elsevier | en_US |
| Rights | restricted access | |
| Title | 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 | en_US |
| Type | Article | |
| DOI | 10.1016/S1473-3099(24)00376-1 | |
| Abstract | Background: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. Methods: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. Findings: Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. Interpretation: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. | en_US |
| Affilliation | Faculdade de Medicina de São José do Rio Preto. São José do Rio Preto, SP, Brasil / Department of Pathology. University of Texas Medical Branch. Galveston, TX, USA. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil. | en_US |
| Affilliation | Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brasil. | en_US |
| Affilliation | Universidade Federal de Roraima. Boa Vista, RO, Brasil. | en_US |
| Affilliation | Universidade Federal de Sergipe. Programa de Pós-Graduação em Ciências da Saúde. Aracaju, SE, Brasil. | en_US |
| Affilliation | Universidade Federal do Ceará. Faculdade de Medicina. Fortaleza, CE, Brasil. | en_US |
| Affilliation | Hospital Universitário Júlio Müller. Cuiabá, MT, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Institute Aggeu Magalhães, Recife, PB, Brasil / School of Public Ealth. University of Pittsburgh. Pittsburgh, PA, USA. | en_US |
| Affilliation | Universidade de Brasília. Faculdade de Medicina. Núcleo de Medicina Tropical. Brasília, DF, Brasil. | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Centre for Advanced and Innovative Therapies. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Dengue. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Medicina e Saúde pública de Precisão. Salvador, BA, Brasil. | en_US |
| Affilliation | Hospital São Lucas da PUC do Rio Grande do Sul. Porto Alegre, RS, Brasil. | en_US |
| Affilliation | Universidade Federal de Mato Grosso do Sul. Faculdade de Medicina. Campo Grande, MS, Brasil. | en_US |
| Affilliation | Faculdade de Ciências Médicas Santa Casa de São Paulo. Departamento de Saúde Coletiva. São Paulo, SP, Brasil. | en_US |
| Affilliation | National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD, USA. | en_US |
| Affilliation | Merck & Co. Rahway, NJ, USA. | en_US |
| Affilliation | Merck & Co. Rahway, NJ, USA. | en_US |
| Affilliation | Merck & Co. Rahway, NJ, USA. | en_US |
| Affilliation | MSD. Munro, Argentina. | en_US |
| Affilliation | Merck & Co. Rahway, NJ, USA. | en_US |
| Affilliation | Merck & Co. Rahway, NJ, USA. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil. | en_US |
| Affilliation | Instituto Butantan. São Paulo, SP, Brasil / Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas. São Paulo, SP, Brasil. | en_US |
| Subject | Dengue vaccines | en_US |
| Subject | Antibodies | en_US |
| Subject | Viral | en_US |
| Subject | Vaccines | en_US |
| Subject | Attenuated | en_US |
| DeCS | Vacinas contra dengue | en_US |
| DeCS | Anticorpos | en_US |
| DeCS | Vacinas | en_US |
| Embargo date | 2027 | |
