RESUMO
BACKGROUND: The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions. METHODS: This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. RESULTS: The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. CONCLUSIONS: RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05590403.
RESUMO
BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-µg peanut protein (Viaskin Peanut 250 µg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use. METHODS: REAL LIfe Use and Safety of EPIT (REALISE) is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n = 294) or placebo (n = 99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued because of adverse events (AEs). Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall, AE rates were similar among participants with and without a history of peanut anaphylaxis. CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.