Efficacy Of Bacterial Lysate In Asthmatic Children

Allergic Asthma Clinical Trial

— EOLIA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02541331
• Other study ID #: LPI-1201
• Status: Completed
• Phase: Phase 3
• First received: August 31, 2015
• Last updated: September 3, 2015
• Start date: July 2014
• Est. completion date: June 2015

Study information

• Verified date: September 2015
• Source: Lallemand Pharma International
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 16 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Allergic Asthma

Intervention

Biological:
• ISMIGEN
Tablets of 30 billion organisms/mg - Sublingual use 1 tablet per day over 10 days for 3 successive months.
• PLACEBO
Matched tablets without any active substance.

Locations

Country	Name	City	State
Poland	LASERMED Diagnosis and Treatment Centre	Chelm
Poland	ALERGOTEST s.c. Medical Centre	Lublin
Poland	Children University Hospital - Pneumology and Rheumatology Dept	Lublin
Poland	Medical Centre Lucyna and Andrzej Dymek	Zawadzkie

Sponsors (1)

Lead Sponsor	Collaborator
Lallemand Pharma International

Country where clinical trial is conducted

Poland, 

References & Publications (3)

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. — View Citation

Razi CH, Harmanci K, Abaci A, Özdemir 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. — View Citation

Sly PD, Boner AL, Björksten 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in asthma control level (mean ACT or P-ACT) score	The main criterion is the improvement in mean ACT/P-ACT score versus baseline (between-groups comparison)	at 3-months	No
Secondary	Time-dependent change in asthma control level (mean ACT or P-ACT) score	Improvement in ACT/P-ACT score versus baseline (between-groups comparison)	at 6-months and at 9-months	No
Secondary	Number of respiratory infections occurring during the 3-mo treatment and the 6-mo follow-up after treatment	Comparison of frequency of events between groups during the observation period.	at 3-months, at 6-months and at 9-months	No
Secondary	Time to first mild or severe asthma exacerbation	To assess the exacerbation-free time after baseline (between-groups comparison)	From baseline	No
Secondary	Standardized mean daily dose of Inhaled Corticosteroids (ICS) used	To assess the amount of current asthma treatment (ICS) required to maintain a stable asthma control level (between-groups comparison)	From baseline, up to the 9-month time point	No
Secondary	Frequency of short acting beta-2 agonists use as rescue medication	To assess the necessary amount of rescue medication to cure exacerbations (between-groups comparison)	From baseline, up to the 9-month time point	No
Secondary	Serum Immunoglobulins	Levels of total IgE, IgA, IgM, IgG (including IgG1, IgG2, IgG3, IgG4) (between-groups comparison, biology subset)	At baseline and at 3-months	No
Secondary	Serum antibacterial antibodies concentration	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)	At baseline, at 3-weeks and at 3-months	No
Secondary	Blood Specific markers of Lymphocyte activation	Levels of CD23 (B cells), CD25 (T cells) and CD69 (T, B and NK cells) (between-groups comparison, biology subset)	At baseline and at 3-months	No
Secondary	Activation of CD4 T cells in peripheral blood	Flow cytometric analyses of Foxp3 and CD25 expression as markers of conversion of T cells into nTreg and iTreg (between-groups comparison, biology subset)	At baseline and at 3-months	No
Secondary	Specific T cells responses in peripheral blood mononuclear cells (PBMC)	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)	At baseline, at 3-weeks and at 3-months	No
Secondary	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)	At baseline and at 9-months	No
Secondary	Cumulative number of days with respiratory tract infections	Cumulative number of days with an event (Between-groups comparison)	From baseline, up to the 9-month time point	No
Secondary	Number of lost school days due to respiratory infections and to asthma exacerbations	Cumulative number of days of absences (Between-groups comparison)	From baseline, up to the 9-month time point	No