A randomised, double-blind, multicentre, placebo-controlled phase 3 efficacy, safety, and immunogenicity study of an Ad26.RSV.preF/RSV prefusion F-protein vaccine for the prevention of respiratory syncytial virus-mediated lower respiratory tract disease in adults aged 60 years and older

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Abstract

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease (LRTD) in older adults. This study evaluated efficacy, immunogenicity, and safety of the investigational recombinant, replication-incompetent, adenovirus type 26 vector RSV preF protein (Ad26.RSV.preF/RSV preF vaccine). METHODS: EVERGREEN was a randomised, double-blind, placebo-controlled phase 3 trial conducted in 14 countries. Adults aged 60 years or older (stratified by age and risk of severe RSV disease) were randomly assigned 2:1 using an interactive web response system to receive one dose of vaccine or placebo. Participants, study site personnel, investigators, and sponsor were blinded to vaccine allocation. The primary endpoint was the first occurrence of RSV-mediated LRTD, defined as new onset/worsening of at least three symptoms occurring 14 or more days postvaccination. The study had at least 90% power to demonstrate statistically significant vaccine efficacy greater than 20% against the primary endpoint and to achieve a point estimate for vaccine efficacy of more than 50%. The trial is registered at ClinicalTrials.gov, NCT04908683. The study is completed. FINDINGS: The study was conducted between 21 July 2021 and 20 July 2023. At the time of the primary analysis, 26,299 individuals were screened, 23,707 were enrolled and 23,555 were vaccinated, 15,698 (67%) in the active vaccine group and 7857 (33%) in the placebo group. In all 23,555 vaccinated participants, 13,515 (54%) were female, 11,558 (46%) were male and the mean age was 70.2 years (SD 5.24). In the per protocol efficacy set, 17 of 15,337 participants (0.1%) in the vaccine group and 31 of 7683 participants (0.4%) in the placebo group had an RSV-mediated LRTD event. Vaccine efficacy was 72.7% (96.326% confidence interval, 47.2-86.4) for prevention of RSV-mediated LRTD over a mean follow-up time of 233.9 days (database cutoff: 15 September 2022). Solicited local and systemic adverse events were more frequent with vaccine versus placebo; none were grade four. The frequency of serious adverse events was similar in the vaccine (n = 842, 5.0%) and placebo (n = 457, 5.5%) groups, of which 15 (0.1%) and two (<0.1%), respectively, were considered vaccine related. There were 105 (0.63%) deaths in the vaccine group and 61 (0.73%) in the placebo group. None were considered related to study vaccine by the investigator. The study and vaccine development were discontinued in March 2023 due to a strategic decision by the study sponsor. INTERPRETATION: In adults aged 60 years and older, the Ad26.RSV.preF/RSV preF protein vaccine was efficacious in preventing RSV-mediated LRTD and had an acceptable safety profile. FUNDING: Johnson & Johnson.

Abstract as published, via PubMed.