Efficacy Of Bacterial Lysate In Children With Allergic Rhinitis

Study Overview
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Brief Summary
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This study evaluate the efficacy of Polyvalent Mechanical Bacterial Lysate (PMBL - Ismigen) to improve the clinical course of grass pollen-induced allergic rhinitis (using: TNSS, TOSS, VAS, PNIF) in children aged 5 to 17. Half of the 70 participants will receive PMBL while the other half will receive placebo.

Detailed Description
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Seasonal allergic rhinitis (SAR) is caused by the allergens of wind-pollinated plants, and in Poland mainly by grass pollen allergens. During the grass pollen season, patients may suffer from fatigue, weakness, lack of fitness, difficulty in sleeping and reduced performance at school. In people allergic to the above-mentioned pollen, the disease significantly reduces the quality of life and requires intensive treatment in the pollen period. Due to the high incidence of allergic rhinitis, the negative impact of the disease on the quality of life, and incomplete effectiveness of previously available therapeutic methods, new methods of treatment are being developed. Recent research highlights the immunoregulatory potential of bacterial lysates, indicating the possibility of their future use in the prevention and treatment of allergic diseases, including atopic dermatitis, allergic rhinitis, and asthma. However, so far no randomized, double-blind, placebo-controlled, study with bacterial lysate in children's SAR therapy has been conducted. The main aim of this study was to evaluate the clinical course of the pollen allergic rhinitis, caused by grass pollen allergens in children during the grass pollen season, treated with polyvalent mechanical bacterial lysate (PMBL). The approval of the Bioethics Committee at the Medical University in Lublin was obtained for the study. Seventy children with SAR were enrolled to this study and were randomly assigned to the PMBL group (n=35) and placebo group (n=35). Three visits took place as part of the study: at the beginning of the grass pollen season, at the peak, and at the end of the season. The time frame of the grass pollen season for south-eastern Poland was determined using the 95% method on the basis of measurements of grass pollen concentration in the atmospheric air, which were obtained from the Environmental Allergy Research Centre in Warsaw. Nasal and ocular SAR symptoms were recorded by parents of children in the daily patient diary according to the standard scoring systems (TNSS, total nasal symptom score and TOSS, total ocular symptom score), and their intensity was also evaluated during three visits using VAS (visual analogue scale). At each visit, peak nasal inspiratory flow (PNIF) was also measured. In order to determine the mechanism responsible for the possible effects of PMBL, samples were taken from patients for additional testing: nasal smears for the presence of eosinophils and nasal lavage fluids for the presence of allergen-specific IgE (asIgE) against timothy grass pollen allergens.

Official Title
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The Effect Of Polivalent Mechanical Bacterial Lysate On The Clinical Course Of Grass Pollen-Induced Allergic Rhinitis In Children

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Drug: Ismigen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children of both genders aged 5 to 17 years. Children with grass pollen-induced allergic rhinitis recognized and treated according to current ARIA (Allergic Rhinitis and its Impact on Asthma) recommendations. Positive skin prick test to grass pollen allergens or positive specific IgE (defined as ≥ class 2, ≥ 0,70 kU/l) against timothy grass pollen allergens. Presentation of clinical symptoms of the allergic rhinitis (rhinorrhea, nasal congestion, nasal itching, sneezing) in at least two recent grass pollen seasons in Poland before inclusion in the study. Proper use of PMBL sublingual tablets. Written informed consent obtained from parents/guardians before any study related procedures are performed. Exclusion Criteria: Patient received mechanical or any other polyvalent bacterial lysate immunostimulation within the previous 12 months before visit 1. Patient received oral/subcutaneous allergen-immunotherapy within the previous 3 years before the start of the study. Vaccination performed within 3 months before the beginning of the study. Deficiencies in cellular and humoral immunity. Treatment with systemic corticosteroids within the last 6 months before the start of the study. Pregnant or breastfeeding woman. Other chronic conditions of the nose or nasal sinuses.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ismigen<br>Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest. | Drug: Ismigen<br>* Sublingual tablets containing 7 mg of bacterial lysate from the following bacteria: Staphylococcus aureus, Haemophilus influenzae serotype B, Klebsiella pneumoniae, Klebsiella ozaenae, Neiserria catarrhalis, Streptococcus viridans, Streptococcus pyogenes, Streptococcus pneumoniae (6 strains: TY1/EQ11, TY2/EQ22, TY3/EQ14, TY5/EQ15, TY8/EQ23, TY47/EQ24) - sublingual use 1 tablet per day over 10 days for 3 successive months.<br>* Other names: Polyvalent Mechanical Bacterial Lysate (PMBL);|
| Placebo Comparator: Placebo<br>Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest. | Drug: Placebo<br>* Matched tablets without any active substance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the severity of nasal SAR symptoms as assessed by Total Nasal Symptom Score (TNSS) | The severity of nasal SAR symptoms (sneezing, runny nose, itchy nose and nasal congestion) were recorded by parents of children in the daily patient diary using the following scale: 0 = absent (no symptom); 1 = mild (symptom present, easily tolerated); 2 = moderate (awareness of symptom, bothersome but tolerable); 3 = severe (symptoms hard to tolerate, interfere with daily activities and/or sleeping). The Total Nasal Symptom Score (sum of the 4 symptom scores) ranges from 0 (no symptoms) to 12 (worst symptoms). Weekly average TNSS values from the baseline period (beginning of the grass pollen season) and obtained 1 month (grass pollen season - significant intensification of SAR symptoms), 2 months (peak grass pollen season) and 3 months (3 weeks before the end of the grass pollen season) after initiating therapy were used for statistical analysis. | at baseline, at 1-month, at 2-months and at 3-months | 
| Change in the severity of ocular SAR symptoms as assessed by Total Ocular Symptom Score (TOSS) | The severity of ocular SAR symptoms (redness of the eyes, watery eyes, itching of the eyes) were recorded by parents of children in the daily patient diary using the following scale: 0 = absent (no symptom); 1 = mild (symptom present, easily tolerated); 2 = moderate (awareness of symptom, bothersome but tolerable); 3 = severe (symptoms hard to tolerate, interfere with daily activities and/or sleeping). The Total Ocular Symptom Score (sum of the 3 symptom scores) ranges from 0 (no symptoms) to 9 (worst symptoms). Weekly average TOSS values from the baseline period (beginning of the grass pollen season) and obtained 1 month (grass pollen season - significant intensification of SAR symptoms), 2 months (peak grass pollen season) and 3 months (3 weeks before the end of the grass pollen season) after initiating therapy were used for statistical analysis. | at baseline, at 1-month, at 2-months and at 3-months | 
| Change in the nasal obstruction using Peak Nasal Inspiratory Flow (PNIF) | Assessment of the nasal obstruction before (visit 1) and 2 months (visit 2) and 3 months (visit 3) after initiating therapy based on measurement of Peak Nasal Inspiratory Flow by Youlten Peak Flow Meter (Clement Clarke International, UK). The higher PNIF value, the smaller nasal obstruction. | at baseline, at 2-months and at 3-months | 
| Change in the severity of nasal SAR symptoms as assessed by Visual Analogue Scale (VAS) | Assessment of the severity of nasal SAR symptoms before (visit 1) and 2 months (visit 2) and 3 months (visit 3) after initiating therapy with the use of Visual Analogue Scale.The patient was asked to indicate the severity of nasal SAR symptoms on a 100 mm Visual Analogue Scale, were 0 is no symptoms and 100 the worst possible symptoms. | at baseline, at 2-months and at 3-months | 
| Change in the severity of ocular SAR symptoms as assessed by Visual Analogue Scale (VAS) | Assessment of the severity of ocular SAR symptoms before (visit 1) and 2 months (visit 2) and 3 months (visit 3) after initiating therapy with the use of Visual Analogue Scale. The patient was asked to indicate the severity of ocular SAR symptoms on a 100 mm Visual Analogue Scale, were 0 is no symptoms and 100 the worst possible symptoms. | at baseline, at 2-months and at 3-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal eosinophil count | To assess the change in the number of eosinophils in nasal smears. | at baseline, at 2-months and at 3-months | 
| Specific immunoglobulin E concentration | To assess the change in the level of allergen-specific immunoglobulin E (asIgE) against timothy grass pollen allergens in nasal lavage fluid and blood serum. | at baseline, at 2-months and at 3-months | 
| Frequency of oral H1-antihistamines use | To assess the mean number of days of oral H1-antihistamines use for the relief of SAR symptoms. | from baseline, up to the 3-month time point | 
| Frequency of intranasal corticosteroids use | To assess the mean number of days of intranasal corticosteroids use for the relief of SAR symptoms. | from baseline, up to the 3-month time point | 
| Incidence of treatment emergent adverse events [safety and tolerability] | Incidence, frequency and severity of treatment emergent adverse events. | from baseline, up to the 3-month time point | 
| Incidence of treatment emergent adverse events leading to discontinuation [safety and tolerability] | The number of participants with adverse events leading to discontinuation. | from baseline, up to the 3-month time point | 
| Time to discontinuation due to treatment emergent adverse events [safety and tolerability] | To assess the time that has elapsed since treatment initiation to the occurrence of an adverse event leading to discontinuation. | From date of randomization until the date of occurrence of an adverse event leading to discontinuation, assessed up to 3 months | 
| Incidence of treatment emergent clinical laboratory test abnormalities [safety and tolerability] | Complete blood count assessment at baseline and at 3-months. | at baseline and at 3-months | 
| Incidence of treatment emergent abnormalities in physical examination findings [safety and tolerability] | Observe skin, lymph nodes, ears, eyes, nose, throat, cardiac and pulmonary status, abdomen and extremities for any abnormalities. | at baseline, at 2-months and at 3-months | 
| Incidence of treatment emergent abnormalities in pulse rate [safety and tolerability] | Measure resting pulse rate as beats per minute. | at baseline, at 2-months and at 3-months | 
| Incidence of treatment emergent abnormalities in blood pressure [safety and tolerability] | Measure systolic and diastolic blood pressure (in mmHg). | at baseline, at 2-months and at 3-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allergic rhinitis, seasonal allergic rhinitis, children, grass pollen season, bacterial lysate, Th2 inflammation, eosinophils, specific immunoglobulin E