Efficacy Of Bacterial Lysate In Asthmatic Children (EOLIA)

Influence of Polyvalent Mechanical Bacterial Lysate ISMIGEN® on Clinical Course of Asthma and Related Immunological Parameters in Asthmatic Children (EOLIA Study): Randomised Double-blind Placebo-controlled Multicentre Parallel-group Study

This study evaluate the efficacy of Mechanical Bacterial Lysate (PMBL - Ismigen®) to improve the asthma control level (ACT score) as add-on treatment to routine asthma treatment in children aged 6 to 16 with uncontrolled or partly controlled asthma. Half of the 150 participants will receive Ismigen® and their current asthma therapy while the other half will receive Placebo and their current asthma treatment.

Acute and recurrent respiratory infections of the upper and middle respiratory tracts in the paediatric population of asthmatic patients represent a leading clinical burden, particularly during the winter. Respiratory tract infections, mainly viral infection are important factors that exacerbate asthma course in children. Currently no clinical data demonstrated the benefit of oral or sublingual bacterial lysates on asthma clinical course in children apart from one trial with OM-85 BV (Bronchovaxom®) suggesting reduced number and duration of infection-related wheezing attacks in children with asthma wheezing. Therefore it was hypothesized that PMBL (Ismigen®) used in asthmatic children should significantly improve asthma course and control. A seasonal approach of active prevention, based on full-fledged antibacterial oral vaccination would be useful to show the potential benefit of this type of products. The Primary objective was to assess the benefit of Ismigen® versus Placebo on the mean ACT score after administration of a Polyvalent Mechanical Bacterial Lysate (PMBL - Ismigen®) as add-on to routine asthma treatment. Secondary objectives investigated: the potential reduction (vs Placebo) of number of asthma exacerbations, time to first event with Ismigen®; the potential decrease in number of respiratory tract infections during the observation period (3-month treatment and 6-month follow-up) after treatment; the specific changes occurring in a panel of immunological markers as the result of Ismigen® effect (subset of 48 patients).

Tablets of 30 billion organisms/mg - Sublingual use 1 tablet per day over 10 days for 3 successive months.

The main criterion is the improvement in mean ACT/P-ACT score versus baseline (between-groups comparison)

Number of respiratory infections occurring during the 3-mo treatment and the 6-mo follow-up after treatment

To assess the amount of current asthma treatment (ICS) required to maintain a stable asthma control level (between-groups comparison)

To assess the necessary amount of rescue medication to cure exacerbations (between-groups comparison)

Levels of total IgE, IgA, IgM, IgG (including IgG1, IgG2, IgG3, IgG4) (between-groups comparison, biology subset)

Specific immunological response to Ismigen vaccination: IgG levels of Streptococcus pneumonia, Haemophilus Influenzae, Staphylococcus aureus, Klebsiella pneumonia, Streptococcus pyogenes, Klebsiella Ozenae, Streptococcus group A-G (between-groups comparison, biology subset)

Levels of CD23 (B cells), CD25 (T cells) and CD69 (T, B and NK cells) (between-groups comparison, biology subset)

Flow cytometric analyses of Foxp3 and CD25 expression as markers of conversion of T cells into nTreg and iTreg (between-groups comparison, biology subset)

Number of vaccine specific T cells positive to IFN-gamma, IL-4, IL-13 assessed as spot-forming units by ELISPOT assay (between-groups comparison, biology subset)

PAQLQ (Paediatric Asthma Quality of Life Questionnaire) and PACQLQ (Paediatric Asthma Caregivers Quality of Life Questionnaire)

Patient and caregiver auto-questionnaires to assess the change in quality of life relative to asthma (between-groups comparison)

Inclusion Criteria: Children of both genders aged 6 to 16 years. Allergic asthma diagnosis with at least one perennial allergen according to the Global Strategy for Asthma Management and Prevention (GINA 2012 guidelines) prior to screening visit. Patient shows clinical characteristics of partly controlled or uncontrolled asthma according to GINA 2012. Already treated with SABA prn and ICS or ICS + LABA during the previous 3 months. Patient shows antigen-specific IgE against HDM ≥ class 2 or positive skin prick test or RAST for at least one perennial allergen. Patient who had at least 2 exacerbations of asthma within the 12-mo period before V1. Patient not treated with Polyvalent Mechanical Bacterial Lysate (Ismigen®) within the previous 6 months prior to Visit 1. Exclusion Criteria: Patient received mechanical or any other bacterial lysate immunostimulation within the previous 6 months before Visit 1. Patient received oral/subcutaneous allergen-immunotherapy within the previous 6 months before Visit 1. History of near fatal asthma (e.g. brittle asthma, hospitalization for asthma exacerbation in Intensive Care Unit). Pregnant or breastfeeding woman.

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