Efficacy Of Bacterial Lysate In Children With Allergic Rhinitis

NCT04270552 | Completed Phase 3

• 1 other identifier: KE-0254/41/2018
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Allergic Rhinitis

Keywords

allergic rhinitis; seasonal allergic rhinitis; children; grass pollen season; bacterial lysate; Th2 inflammation; eosinophils; specific immunoglobulin E

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (11)

• Nasal eosinophil count

  at baseline, at 2-months and at 3-months

• Specific immunoglobulin E concentration

  at baseline, at 2-months and at 3-months

• Frequency of oral H1-antihistamines use

  from baseline, up to the 3-month time point

• Frequency of intranasal corticosteroids use

  from baseline, up to the 3-month time point

• Incidence of treatment emergent adverse events [safety and tolerability]

  from baseline, up to the 3-month time point

Study Arms (2)

Ismigen

EXPERIMENTAL

Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest.

Drug: Ismigen

Placebo

PLACEBO COMPARATOR

Treatment over 3 successive months with one daily tablet over 10 days followed by 20 days of rest.

Drug: Placebo

Interventions

Ismigen DRUG

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.

Also known as: Polyvalent Mechanical Bacterial Lysate (PMBL)

Ismigen

Placebo DRUG

Matched tablets without any active substance.

Placebo

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Proper use of PMBL sublingual tablets.
• Written informed consent obtained from parents/guardians before any study related procedures are performed.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of Lublin: lead

Study Sites (1)

Department of Pulmonary Diseases and Children Rheumatology, Medical University of Lublin

Lublin, 20-093, Poland

Location

Related Publications (8)

• Janeczek KP, Emeryk A, Rapiejko P. Effect of polyvalent bacterial lysate on the clinical course of pollen allergic rhinitis in children. Postepy Dermatol Alergol. 2019 Aug;36(4):504-505. doi: 10.5114/ada.2019.87457. Epub 2019 Aug 30. No abstract available.

  PMID: 31616231 BACKGROUND

• Banche G, Allizond V, Mandras N, Garzaro M, Cavallo GP, Baldi C, Scutera S, Musso T, Roana J, Tullio V, Carlone NA, Cuffini AM. Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects. Int J Immunopathol Pharmacol. 2007 Jan-Mar;20(1):129-38. doi: 10.1177/039463200702000115.

  PMID: 17346436 BACKGROUND

• Meng Q, Li P, Li Y, Chen J, Wang L, He L, Xie J, Gao X. Broncho-vaxom alleviates persistent allergic rhinitis in patients by improving Th1/Th2 cytokine balance of nasal mucosa. Rhinology. 2019 Dec 1;57(6):451-459. doi: 10.4193/Rhin19.161.

  PMID: 31403136 BACKGROUND

• Han L, Zheng CP, Sun YQ, Xu G, Wen W, Fu QL. A bacterial extract of OM-85 Broncho-Vaxom prevents allergic rhinitis in mice. Am J Rhinol Allergy. 2014 Mar-Apr;28(2):110-6. doi: 10.2500/ajra.2013.27.4021.

  PMID: 24717947 BACKGROUND

• Liu C, Huang R, Yao R, Yang A. The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma. Lung. 2017 Oct;195(5):563-569. doi: 10.1007/s00408-017-0003-8. Epub 2017 May 4.

  PMID: 28474108 BACKGROUND

• Esposito S, Soto-Martinez ME, Feleszko W, Jones MH, Shen KL, Schaad UB. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol. 2018 Jun;18(3):198-209. doi: 10.1097/ACI.0000000000000433.

  PMID: 29561355 BACKGROUND

• 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.

  PMID: 29575037 BACKGROUND

• Janeczek K, Emeryk A, Rachel M, Duma D, Zimmer L, Poleszak E. Polyvalent Mechanical Bacterial Lysate Administration Improves the Clinical Course of Grass Pollen-Induced Allergic Rhinitis in Children: A Randomized Controlled Trial. J Allergy Clin Immunol Pract. 2021 Jan;9(1):453-462. doi: 10.1016/j.jaip.2020.08.025. Epub 2020 Aug 26.

  PMID: 32858239 RESULT

MeSH Terms

Conditions

Rhinitis, Allergic; Rhinitis, Allergic, Seasonal

Interventions

Broncho-Vaxom

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: April 22, 2018
• Primary Completion: July 20, 2018
• Study Completion: August 12, 2018
• Last Updated: March 17, 2021

Record last verified: 2021-03

Locations

PL (1)