Allergic Asthma
Conditions
Keywords
IgE-dependent asthma
Brief summary
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.
Detailed description
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).
Interventions
BIOLOGICALISMIGEN
Tablets of 30 billion organisms/mg - Sublingual use 1 tablet per day over 10 days for 3 successive months.
BIOLOGICALPLACEBO
Matched tablets without any active substance.
Sponsors
Lallemand Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. Children of both genders aged 6 to 16 years. 2. 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. 3. Patient shows clinical characteristics of partly controlled or uncontrolled asthma according to GINA 2012. 4. Already treated with SABA prn and ICS or ICS + LABA during the previous 3 months. 5. Patient shows antigen-specific IgE against HDM ≥ class 2 or positive skin prick test or RAST for at least one perennial allergen. 6. Patient who had at least 2 exacerbations of asthma within the 12-mo period before V1. 7. Patient not treated with Polyvalent Mechanical Bacterial Lysate (Ismigen®) within the previous 6 months prior to Visit 1.
Exclusion criteria
1. Patient received mechanical or any other bacterial lysate immunostimulation within the previous 6 months before Visit 1. 2. Patient received oral/subcutaneous allergen-immunotherapy within the previous 6 months before Visit 1. 3. History of near fatal asthma (e.g. brittle asthma, hospitalization for asthma exacerbation in Intensive Care Unit). 4. Pregnant or breastfeeding woman.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in asthma control level (mean ACT or P-ACT) score | at 3-months | The main criterion is the improvement in mean ACT/P-ACT score versus baseline (between-groups comparison) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of respiratory infections occurring during the 3-mo treatment and the 6-mo follow-up after treatment | at 3-months, at 6-months and at 9-months | Comparison of frequency of events between groups during the observation period. |
| Time to first mild or severe asthma exacerbation | From baseline | To assess the exacerbation-free time after baseline (between-groups comparison) |
| Standardized mean daily dose of Inhaled Corticosteroids (ICS) used | From baseline, up to the 9-month time point | To assess the amount of current asthma treatment (ICS) required to maintain a stable asthma control level (between-groups comparison) |
| Frequency of short acting beta-2 agonists use as rescue medication | From baseline, up to the 9-month time point | To assess the necessary amount of rescue medication to cure exacerbations (between-groups comparison) |
| Serum Immunoglobulins | At baseline and at 3-months | Levels of total IgE, IgA, IgM, IgG (including IgG1, IgG2, IgG3, IgG4) (between-groups comparison, biology subset) |
| Serum antibacterial antibodies concentration | At baseline, at 3-weeks and at 3-months | 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) |
| Time-dependent change in asthma control level (mean ACT or P-ACT) score | at 6-months and at 9-months | Improvement in ACT/P-ACT score versus baseline (between-groups comparison) |
| Activation of CD4 T cells in peripheral blood | At baseline and at 3-months | Flow cytometric analyses of Foxp3 and CD25 expression as markers of conversion of T cells into nTreg and iTreg (between-groups comparison, biology subset) |
| Specific T cells responses in peripheral blood mononuclear cells (PBMC) | At baseline, at 3-weeks and at 3-months | 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) | At baseline and at 9-months | Patient and caregiver auto-questionnaires to assess the change in quality of life relative to asthma (between-groups comparison) |
| Cumulative number of days with respiratory tract infections | From baseline, up to the 9-month time point | Cumulative number of days with an event (Between-groups comparison) |
| Number of lost school days due to respiratory infections and to asthma exacerbations | From baseline, up to the 9-month time point | Cumulative number of days of absences (Between-groups comparison) |
| Blood Specific markers of Lymphocyte activation | At baseline and at 3-months | Levels of CD23 (B cells), CD25 (T cells) and CD69 (T, B and NK cells) (between-groups comparison, biology subset) |
Countries
Poland
Outcome results
None listed