Non-inferiority comparisons (YF PPS and PPS).

BackgroundYellow fever (YF) vaccination is often mandatory for travelers to YF-endemic areas. The areas with risk of YF partially overlap with those of dengue, for which there is currently no recommended vaccine available for dengue-naïve individuals. This phase 3 study assessed the immunogenicity and safety of concomitant and sequential administration of YF (YF-17D) and tetravalent dengue (TAK-003) vaccines in healthy adults aged 18–60 years living in areas of the US non-endemic for either virus.MethodsParticipants were randomized 1:1:1 to receive the following vaccinations at Months 0, 3, and 6, respectively: YF-17D+placebo, TAK-003, and TAK-003 (Group 1); TAK-003+placebo, TAK-003, and YF-17D (Group 2); or YF-17D+TAK-003, TAK-003, and placebo (Group 3). The primary objective was to demonstrate non-inferiority (upper bound of 95% confidence interval [UB95%CI] of difference Results900 adults were randomized. YF seroprotection rates one month post-YF-17D (Month 1) were 99.5% and 99.1% in Group 1 and 3, respectively, and non-inferiority was demonstrated (UB95%CI = 2.69% i.e. ConclusionsIn this study, YF-17D vaccine and TAK-003 were immunogenic and well tolerated when sequentially or concomitantly administered. The non-inferiority of immune responses to YF-17D and TAK-003 was demonstrated for concomitant administration of the 2 vaccines compared to separate vaccination, except against DENV-1 but with GMTs similar to those observed in other TAK-003 trials.Trial registrationClinicalTrials.gov identified: NCT03342898.【背景】黄热病（Yellow Fever, YF）疫苗接种通常是前往黄热病流行区旅行者的强制要求。黄热病高风险区域与登革热（dengue）流行区域存在部分重叠，而目前尚无针对未感染过登革热个体的推荐登革热疫苗。本项III期临床试验旨在评估居住于美国境内两种病毒均非流行区域的18~60岁健康成人，联合接种（concomitant administration）与序贯接种（sequential administration）黄热病疫苗（YF-17D）与四价登革疫苗（TAK-003）的免疫原性（immunogenicity）与安全性（safety）。 【方法】受试者以1:1:1的比例随机分组，分别在第0、3、6个月接受如下疫苗接种方案：第1组：YF-17D+安慰剂（placebo）、TAK-003、TAK-003；第2组：TAK-003+安慰剂、TAK-003、YF-17D；第3组：YF-17D+TAK-003、TAK-003、安慰剂。本研究的主要终点为证明两种疫苗联合接种时的免疫应答非劣效性（差异的95%置信区间上限[UB95%CI]） 【结果】共计900名成人完成随机分组。在接种YF-17D后1个月（第1个月），第1组与第3组的黄热病血清保护率分别为99.5%与99.1%，且证实了非劣效性（95%置信区间上限=2.69%）。 【结论】本研究显示，黄热病疫苗YF-17D与TAK-003在序贯或联合接种时均具有良好的免疫原性与耐受性。相较于单独接种方案，两种疫苗联合接种时，除登革病毒1型（DENV-1）外，其余各型的免疫应答均达到非劣效标准，且几何平均滴度（GMT, geometric mean titer）与其他TAK-003临床试验中的观测值相当。 【试验注册】ClinicalTrials.gov 注册号：NCT03342898。