Clinical trial NCT02541331: Efficacy Of Bacterial Lysate In Asthmatic Children
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Allergic Asthma
Keywords: IgE-dependent asthma
Lead sponsor: Lallemand Pharma AG
Sponsor class: INDUSTRY
First posted: 2015-09-04
Enrollment: 150
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in asthma control level (mean ACT or P-ACT) score
timeFrame: at 3-months
Secondary outcomes:
measure: Time-dependent change in asthma control level (mean ACT or P-ACT) score
timeFrame: at 6-months and at 9-months
measure: Number of respiratory infections occurring during the 3-mo treatment and the 6-mo follow-up after treatment
timeFrame: at 3-months, at 6-months and at 9-months
measure: Time to first mild or severe asthma exacerbation
timeFrame: From baseline
measure: Standardized mean daily dose of Inhaled Corticosteroids (ICS) used
timeFrame: From baseline, up to the 9-month time point
measure: Frequency of short acting beta-2 agonists use as rescue medication
timeFrame: From baseline, up to the 9-month time point
measure: Serum Immunoglobulins
timeFrame: At baseline and at 3-months
measure: Serum antibacterial antibodies concentration
timeFrame: At baseline, at 3-weeks and at 3-months
measure: Blood Specific markers of Lymphocyte activation
timeFrame: At baseline and at 3-months
measure: Activation of CD4 T cells in peripheral blood
timeFrame: At baseline and at 3-months
measure: Specific T cells responses in peripheral blood mononuclear cells (PBMC)
timeFrame: At baseline, at 3-weeks and at 3-months
measure: PAQLQ (Paediatric Asthma Quality of Life Questionnaire) and PACQLQ (Paediatric Asthma Caregivers Quality of Life Questionnaire)
timeFrame: At baseline and at 9-months
measure: Cumulative number of days with respiratory tract infections
timeFrame: From baseline, up to the 9-month time point
measure: Number of lost school days due to respiratory infections and to asthma exacerbations
timeFrame: From baseline, up to the 9-month time point
Other outcomes:
Locations:
city: Chelm
country: Poland
facility: LASERMED Diagnosis and Treatment Centre
city: Lublin
country: Poland
facility: Children University Hospital - Pneumology and Rheumatology Dept
city: Lublin
country: Poland
facility: ALERGOTEST s.c. Medical Centre
city: Zawadzkie
country: Poland
facility: Medical Centre Lucyna and Andrzej Dymek
Study officials:
affiliation: Lallemand Pharma International AG
name: Frederic Durmont, MD
role: STUDY_DIRECTOR
References:
citation: Razi CH, Harmanci K, Abaci A, Ozdemir O, Hizli S, Renda R, Keskin F. The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol. 2010 Oct;126(4):763-9. doi: 10.1016/j.jaci.2010.07.038.
citation: Sly PD, Boner AL, Bjorksten B, Bush A, Custovic A, Eigenmann PA, Gern JE, Gerritsen J, Hamelmann E, Helms PJ, Lemanske RF, Martinez F, Pedersen S, Renz H, Sampson H, von Mutius E, Wahn U, Holt PG. Early identification of atopy in the prediction of persistent asthma in children. Lancet. 2008 Sep 20;372(9643):1100-6. doi: 10.1016/S0140-6736(08)61451-8.
citation: Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, Printz MC, Lee WM, Shult PA, Reisdorf E, Carlson-Dakes KT, Salazar LP, DaSilva DF, Tisler CJ, Gern JE, Lemanske RF Jr. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008 Oct 1;178(7):667-72. doi: 10.1164/rccm.200802-309OC. Epub 2008 Jun 19.
citation: Bartkowiak-Emeryk M, Emeryk A, Rolinski J, Wawryk-Gawda E, Markut-Miotla E. Impact of Polyvalent Mechanical Bacterial Lysate on lymphocyte number and activity in asthmatic children: a randomized controlled trial. Allergy Asthma Clin Immunol. 2021 Jan 20;17(1):10. doi: 10.1186/s13223-020-00503-4.
citation: Emeryk A, Bartkowiak-Emeryk M, Raus Z, Braido F, Ferlazzo G, Melioli G. Mechanical bacterial lysate administration prevents exacerbation in allergic asthmatic children-The EOLIA study. Pediatr Allergy Immunol. 2018 Jun;29(4):394-401. doi: 10.1111/pai.12894.