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

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.

Keywords: Immunogenicity; Japan; Non-inferiority; RSVpreF protein vaccine; Respiratory syncytial virus.