一种新型单剂量减毒活基孔肯雅热疫苗的汇总安全性评估†

Pooled safety evaluation for a new single-shot live-attenuated chikungunya vaccine†.

作者信息

Maurer Gabriele, Buerger Vera, Larcher-Senn Julian, Erlsbacher Florian, Dubischar Katrin, Eder-Lingelbach Susanne, Jaramillo Juan Carlos

机构信息

Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.

Assign Data Management and Biostatistics GmbH, Stadlweg 23, 6020 Innsbruck, Austria.

出版信息

J Travel Med. 2024 Dec 10;31(8). doi: 10.1093/jtm/taae133.

DOI:10.1093/jtm/taae133

PMID:39400050

Abstract

BACKGROUND

Chikungunya disease, caused by chikungunya virus (CHIKV), is associated with substantial morbidity, including debilitating CHIKV-related arthralgia.

METHODS

Three clinical trials of a CHIKV vaccine (VLA1553, IXCHIQ®) were conducted in the USA: a Phase 1 dose-finding trial, a pivotal Phase 3 trial and a Phase 3 lot-to-lot consistency trial. Participants were healthy adults (≥18 years) and received a single intramuscular dose of VLA1553 (3520 participants) or placebo (1033 participants). Solicited injection site and systemic adverse events (AEs) (10-14 days post-vaccination), unsolicited AEs (28 and 180 days post-vaccination), AEs of special interest (AESIs) (28 days post-vaccination), medically attended AEs (MAAEs), serious AEs (SAEs) (180 days post-vaccination) and pregnancies were evaluated. Safety data were pooled, and analyses were descriptive.

RESULTS

Overall, 63.7% of participants receiving VLA1553 experienced AEs (44.7% for placebo) that were generally mild. Solicited injection-site AEs, solicited systemic AEs and unsolicited (Day 29) AEs were reported by 15.5, 50.9 and 22.7% of participants who received VLA1553 and 11.1, 26.9 and 13.4% who received placebo. Arthralgia was reported by 16.7% of participants who received VLA1553 and 4.8% of participants who received placebo; none required medical attention. MAAEs, AESIs and SAEs were reported by 12.4, 0.3 and 1.5% of participants who received VLA1553 and 11.3, 0.1 and 0.8% of participants who received placebo. Protocol-defined AESIs were mild and short-lived, and two VLA1553-related SAEs resolved without sequelae. There were no clinically important differences in AE incidence based on age or medical history and no VLA1553-related adverse pregnancy outcomes. There were three deaths (two in the VLA1553 group and one in the placebo group); none was vaccine-related.

CONCLUSIONS

A single dose of VLA1553 presented with an excellent local tolerability profile and overall safety in line with that expected for a live-attenuated vaccine. The safety profile was comparable in participants aged 18-64 years and ≥65 years.

摘要

背景

基孔肯雅病由基孔肯雅病毒（CHIKV）引起，与严重发病相关，包括使人衰弱的CHIKV相关关节痛。

方法

在美国进行了三项CHIKV疫苗（VLA1553，IXCHIQ®）临床试验：1期剂量探索试验、关键3期试验和3期批次间一致性试验。参与者为健康成年人（≥18岁），接受一剂VLA1553肌肉注射（3520名参与者）或安慰剂（1033名参与者）。评估了主动报告的注射部位和全身不良事件（AEs）（接种疫苗后10 - 14天）、非主动报告的AEs（接种疫苗后28天和180天）、特殊关注的AEs（AESIs）（接种疫苗后28天）、需就医的AEs（MAAEs）、严重AEs（SAEs）（接种疫苗后180天）以及妊娠情况。汇总安全数据并进行描述性分析。

结果

总体而言，接受VLA1553的参与者中有63.7%出现了AEs（安慰剂组为44.7%），一般为轻度。接受VLA1553的参与者中，有15.5%、50.9%和22.7%报告了主动报告的注射部位AEs、主动报告的全身AEs和非主动报告的（第29天）AEs，接受安慰剂的参与者中这一比例分别为11.1%、26.9%和13.4%。接受VLA1553的参与者中有16.7%报告了关节痛，接受安慰剂的参与者中有4.8%报告了关节痛；均无需就医。接受VLA1553的参与者中，有12.4%、0.3%和1.5%报告了MAAEs、AESIs和SAEs，接受安慰剂的参与者中这一比例分别为11.3%、0.1%和0.8%。方案定义的AESIs为轻度且持续时间短，两例与VLA1553相关的SAEs均无后遗症地得到解决。基于年龄或病史的AE发生率无临床重要差异，也没有与VLA1553相关的不良妊娠结局。有三例死亡（VLA1553组两例，安慰剂组一例）；均与疫苗无关。