Phase 3 study of an Ad26.RSV.preF/RSV preF protein vaccine to evaluate the prevention efficacy of RSV-mediated lower tract disease, immunogenicity and safety in Japanese adults

IF 2.4 Q2 RESPIRATORY SYSTEM

Respiratory investigation Pub Date : 2025-05-03 DOI:10.1016/j.resinv.2025.04.016

Hiroshi Tamura , Atsushi Momose , Yumi Takato , Zheng Richuan , Arangassery Rosemary Bastian , Benoit Callendret , Esther Heijnen

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Abstract

Background

Safety and efficacy of Ad26.RSV.preF/RSV preF-based vaccine in preventing lower respiratory tract disease (LRTD) was assessed in controlled clinical trials globally. This phase 3 study evaluated efficacy, immunogenicity, and safety of Ad26.RSV.preF/RSV preF-based vaccine for respiratory syncytial virus (RSV)-mediated LRTD prevention in Japanese older adults (Cohort 1: ≥60 years), and immunogenicity and safety in Japanese younger adults (Cohort 2: 20–59 years).

Methods

The primary objective in Cohort 1 (≥60 years) was to assess the efficacy of vaccine against reverse transcriptase polymerase chain reaction (RT-PCR)-confirmed RSV-mediated LRTD over one RSV season versus placebo; in Cohort 2 the primary objective was to demonstrate non-inferiority of humoral response to RSV vaccine in younger adults versus older adults (20–59 years).

Results

In Cohort 1, 2003 participants were randomized (1:1) to vaccine (n = 996) or placebo (n = 1007). None had RSV-mediated LRTD during the first RSV season in vaccine group (study terminated prematurely). In Cohort 2, 180 participants were randomized (3:1) to vaccine (n = 135) or placebo (n = 45). Post-vaccination humoral response in younger adults was found non-inferior to that of older adults. Substantial rise in RSV binding and neutralizing antibody titers from baseline to Day 15 was observed in both Cohorts. Solicited and unsolicited adverse events were more frequent in vaccine group versus placebo group (Cohort 1: 119/149 [79.9 %] and 18/149 [12.1 %] versus 39/150 [26.0 %] and 10/150 [6.7 %]; Cohort 2: 134/138 [97.1 %] and 12/138 [8.7 %] versus 15/46 [32.6 %] and 0/46 [0 %]).

Conclusions

Although vaccine efficacy could not be concluded, it was immunogenic with acceptable safety profile in both Japanese younger and older adult population.

Clinical trial registration number

NCT05242432

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Ad26.RSV的3期研究。preF/RSV preF蛋白疫苗在日本成人中预防RSV介导下呼吸道疾病的有效性、免疫原性和安全性

背景：Ad26.RSV的安全性和有效性。preF/RSV基于preF的疫苗预防下呼吸道疾病（LRTD）在全球对照临床试验中进行了评估。这项3期研究评估了Ad26.RSV的有效性、免疫原性和安全性。preF/RSV基于preF的疫苗在日本老年人（队列1:≥60岁）中预防呼吸道合胞病毒（RSV）介导的LRTD，以及在日本年轻人（队列2:20-59岁）中的免疫原性和安全性。队列1（≥60岁）的主要目的是评估在一个RSV季节内，与安慰剂相比，疫苗对逆转录酶聚合酶链反应（RT-PCR）证实的RSV介导的LRTD的疗效；在队列2中，主要目的是证明年轻人与老年人（20-59岁）对RSV疫苗的体液反应的非劣效性。结果在队列1中，2003名参与者按1:1的比例随机分为疫苗组（n = 996）和安慰剂组（n = 1007）。在疫苗组的第一个RSV季节（研究过早终止）中，没有人发生RSV介导的LRTD。在队列2中，180名参与者（3:1）随机分为疫苗组（n = 135）和安慰剂组（n = 45）。接种疫苗后，年轻人的体液反应不逊于老年人。从基线到第15天，在两个队列中观察到RSV结合和中和抗体滴度的显著上升。与安慰剂组相比，疫苗组主动和非主动的不良事件发生率更高(队列1:119/149[79.9%]和18/149 [12.1%]vs 39/150[26.0%]和10/150 [6.7%]；组2:134/138(97.1%)和12/138(8.7%)和15/46(32.6%)和0/46[0%])。结论该疫苗的有效性尚不能确定，但在日本青年和老年人群中均具有免疫原性，安全性可接受。临床试验注册号：bernct05242432

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