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

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-10-14 DOI:10.1016/j.vaccine.2025.127836

Érique José Farias Peixoto de Miranda , José Alfredo de Sousa Moreira , Regiane da Silva Braga , Daniela Haydee Ramos Silveira , Vanessa Infante , Lucas Bassolli de Oliveira Alves , Juliana de Camargo Vieira Tenorio , Gabriel Ferreira dos Santos Silva , Elizabeth Gonzalez Patiño , Pedro Henrique Theotonio de Mesquita Pacheco , Fabiano Ramos , Danise Senna Oliveira , Esper Georges Kallás , Fernanda Castro Boulos

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引用次数: 0

Abstract

Summary

Background

We aimed to evaluate the consistency of the immune response on Day 28 postvaccination with three consecutive lots of simplified formulation of Butantan-Dengue Vaccine (Butantan-DV) and to describe the frequency of vaccine-related adverse events from vaccination through Day 21 postvaccination in comparison to placebo.

Methods

We included 700 participants allocated in a ratio 2:2:2:1 in parallel arms to receive any of three lots of simplified Butantan-DV or placebo, aged 18 to 59 years, without previous exposure to dengue in two study sites from a non-endemic area in Southern of Brazil. The consistency of three lots of the Butantan-DV were evaluated by analyzing the serum neutralizing antibody titers against four dengue virus serotypes by virus reduction neutralization test (VRNT₆₀), on the Day 28 post-vaccination. Criterion for lot-to-lot consistency was two-sided 95 % confidence interval (95 % CI) of geometric mean titers (GMT) ratio within the margins of equivalence of >1/2 and < 2.0 for 12 possible pairwise comparison for the three lots and four serotypes in the Per-Protocol Set. Adverse events were analysed according to the frequency and Miettinen & Nurminen method to build 95 % CI for the difference in the binomial proportions of each lot with the placebo group. This trial is registered with ClinicalTrials.gov, NCT02406729.

Findings

Between November 4th, 2022 and January 16th, 2023, 700 participants were randomized and vaccinated, while 607 (86.7 %) were included in the Per-Protocol Set. From the 12 possible pairwise comparison between three lots and four serotypes of DENV, 10 met the endpoint of equivalence of lots and 2 failed marginally. The overall frequency of vaccine-related adverse events was 90.8 % (544/599) in Butantan-DV group and 76 % (76/100) in placebo group.

Interpretation

Three lots of simplified formulation were safe and achieved the endpoint of equivalence of lots.

Funding

Intramural Research Program US NIH National Institute of Allergy and Infectious Diseases, Brazilian National Bank for Economic and Social Development, and Fundação Butantan.

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随机、双盲、安慰剂对照、3期试验，以证明三批布丹坦-登革热疫苗简化配方的批次对批次一致性。

研究背景：我们旨在评估连续三批简化配方的butantan -登革热疫苗（buantan - dv）接种后第28天免疫反应的一致性，并与安慰剂相比，描述从接种疫苗到接种后第21天疫苗相关不良事件的频率。方法：我们纳入了700名参与者，以2:2:2:1的比例在平行组中分配，接受3批简化Butantan-DV或安慰剂中的任何一组，年龄在18至59岁之间，来自巴西南部非流行地区的两个研究地点，以前没有接触过登革热。接种后第28天，采用病毒还原中和试验（VRNT60）分析3批布丹坦- dv对4种登革热病毒血清型的血清中和抗体滴度，评价其一致性。批对批一致性的标准是几何平均滴度（GMT）比在等值范围内的双侧95%置信区间（95% CI）。研究结果：在2022年11月4日至2023年1月16日期间，700名参与者随机接种疫苗，其中607名（86.7%）被纳入Per-Protocol Set。在3个批次和4个血清型之间的12个可能的两两比较中，10个达到了等效的终点，2个失败。布丹坦- dv组疫苗相关不良事件的总发生率为90.8%(544/599)，安慰剂组为76%（76/100）。解释：3批简化制剂是安全的，达到了批次等效的终点。资助：校内研究计划，美国国立卫生研究院国家过敏和传染病研究所，巴西国家经济和社会发展银行，以及帕拉奥布坦基金会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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