Efficacy Of Bacterial Lysate In Asthmatic Children
- Conditions
- Allergic Asthma
- Interventions
- Biological: PLACEBOBiological: ISMIGEN
- Registration Number
- NCT02541331
- Lead Sponsor
- Lallemand Pharma AG
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 150
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PLACEBO PLACEBO Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest ISMIGEN ISMIGEN Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
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)
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)
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)
Trial Locations
- Locations (4)
LASERMED Diagnosis and Treatment Centre
🇵🇱Chelm, Poland
Children University Hospital - Pneumology and Rheumatology Dept
🇵🇱Lublin, Poland
Medical Centre Lucyna and Andrzej Dymek
🇵🇱Zawadzkie, Poland
ALERGOTEST s.c. Medical Centre
🇵🇱Lublin, Poland