Prevention of COPD exacerbations with a mucosal trained immunity–based vaccine (MV130): a randomised phase 3 trial

Background Respiratory infections are the primary trigger of acute exacerbations in COPD, yet preventive strategies remain limited. This study aims to evaluate the efficacy and safety of MV130, a sublingual mucosal vaccine, in preventing COPD exacerbations alongside maintenance therapy. Methods A phase 3, multicentre, double-blind, placebo-controlled, randomised clinical trial included 198 subjects across seven hospitals in Spain, with 1:1 allocation to MV130 or placebo. Eligible patients had ≥3 moderate COPD exacerbations or≥2 with at least one requiring hospitalisation in the previous year. Patients received MV130 (300 FTU) or placebo daily for 12 months. The primary outcome, assessed in both intention-to-treat (ITT) and per-protocol (PP) populations, was the number of exacerbations over 18 months (12 months of treatment +6 months follow-up). Secondary exploratory endpoints related to healthcare resource utilisation and medication use were also evaluated in the ITT population. Safety was also assessed in the ITT population. (ClinicalTrials.gov: NCT01842360 ; EudraCT: 2012-003253-28). Results Between May 2013 and January 2018, 198 eligible participants (154 men, 44 women; 97 MV130, 101 placebo) were enrolled. Baseline COPD medication use was well balanced between the treatment groups. Median number of acute exacerbations in the ITT set was 3.0 [interquartile range, IQR, 1.0–5.0] for placebo versus 2.0 [IQR, 1.0–3.0] for MV130 (p = 0.001). MV130 reduced exacerbation rate from 2.68 to 1.87 events per patient-year (95% CI 0.44–1.18; p <0.001). There were 229 adverse events (AEs) reported in 103 participants (52%), 113 (48.5%) in the placebo group and 116 (55.7%) in the MV130 group. Two AEs, urticaria (placebo) and pruritus (MV130), were non-serious and assessed as possibly related to the study medication. Conclusion MV130 reduces moderate and severe COPD exacerbations, suggesting its potential role as an adjunct preventive therapy.