Bacterial Mucosal Immunotherapy with MV130 Prevents Recurrent Wheezing in Children: A Randomized, Double-Blind, Placebo-controlled Clinical Trial

Abstract

Rationale: Recurrent wheezing in children represents a severe public health concern. Wheezing attacks (WA), mainly associated with viral infections, lack effective preventive therapies. Objectives: To evaluate the efficacy and safety of mucosal sublingual immunotherapy based on whole inactivated bacteria (MV130) in preventing WA in children. Methods: A Phase 3 randomized, double-blind, placebo-controlled, parallel-group trial including a cohort of 120 children <3 years old with ⩾3 WA during the previous year was conducted. Children with a positive skin test to common aeroallergens in the area where the clinical trial was performed were excluded from the trial. Subjects received MV130 or placebo daily for 6 months. The primary endpoint was the number of WA within 1 year after the first dose comparing MV130 and placebo. Measurements and Main Results: There was a significant lower number of WA in MV130 versus the placebo group, 3.0 (interquartile range [IQR], 2.0-4.0) versus 5.0 (IQR, 3.0-7.0) (P < 0.001). As secondary outcomes, a decrease in the duration of WA and a reduction in symptoms and medication scores in the MV130 versus placebo group were found. No adverse events were reported related to the active treatment. Conclusions: Mucosal bacterial immunotherapy with MV130 shows safety and clinical efficacy against recurrent WA in children.Clinical trial registered with www.clinicaltrials.gov (NCT01734811).

Keywords: MV130; clinical trial; mucosal vaccination; wheezing attacks.

Figure 1.

Trial profile.

Figure 2.

MV130 reduces the number and duration of wheezing attacks (WA). (A–C) WA episodes during the whole study: (A) number of WA, (B) days with WA, and (C) duration of WA. The results in the scatter plots represent values from single patients; the horizontal lines indicate medians, and error bars show the interquartile range. The P values were calculated using a Mann-Whitney U test. (D and E) A survival analysis (Kaplan-Meier estimator) representing the number of days until the appearance of the first WA (D) during the whole study period (1 yr) and (E) during the posttreatment period of the study (6 mo). The P values were calculated using log-rank (Mantel-Cox) test. CI = confidence interval.

Figure 3.

MV130 decreases symptom and medication scores (SMS). (A–C) The combination of SMS (A), overall symptom scores (B), and medication scores (C) during wheezing attacks. (D–F) The combination of SMS (D), overall symptom scores (E), and medication scores (F) throughout the study. Data are displayed in scatter dot plots in which values from single patients are represented. The line indicates the median, and error bars show the interquartile range. The P values were calculated using Mann-Whitney U test.