Dados do Trabalho

Título

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Demonstrate Lot-to-Lot Consistency of 3 Lots of the Butantan-Dengue Vaccine in Healthy Adults in Non-Endemic Regions for Dengue in Brazil

Introdução

Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease. A randomized, double-blind, placebo-controlled trial was conducted to demonstrate immunogenic equivalence of three consecutive manufacturing lots of Butantan-DV, and further assessed safety and reactogenicity.

Objetivo (s)

The aim was to evaluate the consistency of the immune response at day-28 post-vaccination with three consecutive lots of Butantan-DV and to describe the frequency of adverse reactions from vaccination through day-28.

Material e Métodos

Healthy Brazilian adults aged 18-59 years dengue-naive from two non-endemic regions in Rio Grande do Sul state (Porto Alegre and Pelotas) were recruited. Subjects were alocated in a 2:2:2:1 ratio to four parallel arms and received single dose of one of three Butantan-DV lots or placebo on Day-0, with follow-up to Day-28. The consistency of the immune response to the three lots of the Butantan-DV was evaluated by analyzing the serum neutralizing antibody titers against  each of the 4 dengue serotypes using the virus reduction neutralization test 60% performed at baseline and Day-28. The criterion for lot-to-lot equivalence was a 95% confidence interval (95% CI) of the geometric mean titer ratio within the margins of equivalence of greater than 0.5 and lower than 2.0 for the 12 possible pairwise comparisions of the three vaccine lots and 4 dengue serotypes in the Per-Protocol Set (PPS). Solicited local and systemic, and unsolicted adverse events (AE) were assessed for 28 days post-vaccination. Serious AEs were also monitored for 28 Days. 

Resultados e Conclusão

Between November 4th, 2022, and January 16th, 2023, 700 participants were randomized, and 616 were inclued in the PPS. Females predominated (68.1%), mean age was 36.5 years, and white ethnicity was self-declared in 80.4%. Ten out of 12 prespecified comparisions were met, while 2 failed marginally. All Butantan-DV lots elicited high GMT for the 4 dengue serotypes and had similar reatogenicity profiles. Most of the adverse reactions were solicited, with incidence of 90% and 74% in the vaccine and placebo arm, respectively. The most common adverse reactions were headache (66.5%) and rash (65.5%). The frequency of unsolicited adverse reactions was 27% and 19% in the vaccine and placebo, respectively. Three serious AEs occured but none related to the vaccination.  Conclusion: Three lots of Butantan-DV were immunogenic for all four dengue serotypes and well tolerated in healthy Brazilian adults.

Palavras Chave

dengue; Dengue Vaccine; Butantan-DV; Immunogenicity; Safety; Brazil