Allergic Rhinitis Due to Grass PollenPhase 3NCT04802616
The Influence of Nonspecific Immunostimulation on Changes in the Concentration of iNKT Cells
A Phase 3 study testing Ismigen in people with Allergic Rhinitis Due to Grass Pollen, run by Medical University of Lublin at 1 site in Poland.
Trial summary
The aim of the study is to assess the effect of polyvalent mechanical bacterial lysate (PMBL, Ismigen) on the clinical course of grass pollen-induced allergic rhinitis (using: total nasal symptom score, visual analogue scale, peak nasal inspiratory flow measurement) in children aged 5 to 17 and to assess changes in… Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Allergic Rhinitis Due to Grass Pollen
- What is being tested?
- Ismigen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 sitePoland
- Study dates
- 22 Mar 2021to 29 Oct 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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 polyvalent mechanical bacterial lysate sublingual tablets.
- Not using drugs to alleviate the symptoms of allergic rhinitis in the last 7 days prior to enrollment in the study: intranasal glucocorticosteroids, intranasal, oral and ophthalmic antihistamines, intranasal and oral alpha-mimetics, intranasal anticholinergics, antileukotrienes and cromones.
- Written informed consent obtained from parents/guardians before any study related procedures are performed.
Who cannot join
- Patient received mechanical bacterial lysate immunostimulation within the previous 12 months before randomisation visit.
- Patient received chemical bacterial lysate immunostimulation within the previous 6 months before randomisation visit.
- Patient received oral/subcutaneous allergen-immunotherapy within the previous 3 years before the start of the study.
- Other chronic conditions of the nose or nasal sinuses.
- Severe nasal septum deviation.
- Acute respiratory infection in the 2 weeks prior to randomization visit.
Show all 10Show fewer
- Treatment with systemic corticosteroids within the last 6 months before the start of the study.
- History of transfusion of blood, blood components or blood products.
- Pregnant or breastfeeding woman.
- Other chronic, uncontrolled diseases of the respiratory tract, gastrointestinal tract, urinary system, hematological diseases, immunodeficiency, cancer, cystic fibrosis.
Trial locations and contacts
1 site in 1 country.
Poland1 site
Department of Pulmonary Diseases and Children Rheumatology, Medical University of Lublin
Lublin, 20-093
About this study
Official title: The Effect of Immunostimulation With Polyvalent Mechanical Bacterial Lysate on Changes in the Concentration of iNKT Cells in Children With Allergic Rhinitis.
The aim of the study is to assess the effect of polyvalent mechanical bacterial lysate (PMBL, Ismigen) on the clinical course of grass pollen-induced allergic rhinitis (using: total nasal symptom score, visual analogue scale, peak nasal inspiratory flow measurement) in children aged 5 to 17 and to assess changes in the concentration of iNKT cells under the influence of the therapy. Half of the 80 participants will receive PMBL while the other half will receive placebo.
Read the detailed description
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, the mechanism of action of these drugs in allergic diseases is still not entirely clear.
iNKT (Invariant Natural Killer T) are a conserved line of T cells with unique features expressing the invariant TCR alpha chain and recognizing glycolipids presented in the context of the non-classical MHC molecule, CD1d. As a result of TCR stimulation, iNKT cells are able to quickly secrete a variety of cytokines, thus stimulating various immune processes and playing an immunoregulatory role. iNKT cells are a small percentage of all T cells, however numerous studies indicate their possible participation in the pathogenesis of allergic diseases.The ambivalence of the activity of iNKT cells may result from the heterogeneity of this subpopulation. iNKT cells, like T lymphocytes, can be divided into further subpopulations: iNKT1, iNKT2, iNKT10, iNKT17 and iNKTreg. Individual subpopulations have a different cytokine profile, and thus may play opposite functions in the pathomechanism of many diseases, including allergic ones.
The main aim of this study is 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) and to assess the impact of PMBL on changes in the concentrations of the iNKT cell subpopulation. The approval of the Bioethics Committee at the Medical University in Lublin was obtained for the study.
Eighty children with SAR will be enrolled to this study and randomly assigned to the PMBL group (n=40) and placebo group (n=40). The study will include six visits, 2 site visits (before the grass pollen season and at the peak of the grass pollen season) and 4 telephone visits.The first site visit will be the randomization visit. The second site visit will take place after the end of the drug intake period. Telephone contact with the patient will take place twice during the period of taking the drug, and twice after the end of this period (follow-up visits).The time frame of the grass pollen season for south-eastern Poland will be determined using the "95%" method on the basis of measurements of grass pollen concentration in the atmospheric air, which will be obtained from the Environmental Allergy Research Centre in Warsaw. Patients will start taking sublingual tablets at the beginning of the April 2021.
Nasal SAR symptoms will be recorded by parents of children in the daily patient diary according to the standard scoring system (TNSS, total nasal symptom score), and their intensity will be also evaluated during six visits using VAS (visual analogue scale). At each site visit, peak nasal inspiratory flow (PNIF) will be also measured.
In order to determine the mechanism responsible for the possible effects of PMBL, blood samples (8 ml) will be taken from patients for additional tests during two site visits. The following iNKT cell subpopulations will be measured in the blood: iNKT1, iNKT2, iNKT10, iNKT17 and iNKTreg.
- Conditions
- Allergic Rhinitis Due to Grass Pollen
- Being tested
- Ismigen, Placebo
- Keywords
- allergic rhinitis, seasonal allergic rhinitis, children, grass pollen season, bacterial lysate, iNKT cells
- Medical subject headings
- Rhinitis, Allergic, Rhinitis, Allergic, Seasonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsmigenDrug
Also called Polyvalent mechanical bacterial lysate (PMBL)
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).
PlaceboDrug
Matched tablets without any active substance.
| Study group | Role | What they receive |
|---|---|---|
| Polyvalent mechanical bacterial lysate | Experimental | Treatment over 3 successive months with one daily sublingual tablet (7 mg of bacterial lysate) over 10 days followed by 20 days of rest. Receives: Drug: Ismigen |
| Placebo | Placebo comparator | Treatment over 3 successive months with one daily sublingual tablet over 10 days followed by 20 days of rest. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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) will be 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 (before the grass pollen season) and obtained 1 month, 2 months, 3 months, 4 months and 5 months after initiating therapy will be used for statistical analysis.
Measured: at baseline, at 1-month, at 2-months, at 3-months, at 4-months and at 5-months
Change in the nasal obstruction using peak nasal inspiratory flow (PNIF)
Assessment of the nasal obstruction during two site visits 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.
Measured: at baseline 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 during six visits (2 site visits and 4 telephone visits) with the use of visual analogue scale.The patient will be asked to indicate the severity of nasal SAR symptoms on a 100 mm visual analogue scale, where 0 is no symptoms and 100 the worst possible symptoms.
Measured: at baseline, at 1-month, at 2-months, at 3-months, at 4-months and at 5-months
iNKT1 cells concentration
To assess the change in the level of iNKT1 cells (T-bet+IFN-γ+) in the blood.
Measured: at baseline and at 3-months
iNKT2 cells concentration
To assess the change in the level of iNKT2 cells (GATA3+IL-4+) in the blood.
Measured: at baseline and at 3-months
iNKT10 cells concentration
To assess the change in the level of iNKT10 cells (E4BP4+IL-10+) in the blood.
Measured: at baseline and at 3-months
iNKT17 cells concentration
To assess the change in the level of iNKT17 cells (RORγt+IL-17+) in the blood.
Measured: at baseline and at 3-months
iNKTreg cells concentration
To assess the change in the level of iNKTreg cells (FoxP3+) in the blood.
Measured: at baseline and at 3-months
Secondary outcomes (8)
Frequency of oral H1-antihistamines use
To assess the mean number of days of oral H1-antihistamines use for the relief of SAR symptoms.
Measured: from baseline, up to the 5-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.
Measured: from baseline, up to the 5-month time point
Incidence of treatment emergent adverse events [safety and tolerability]
Incidence, frequency and severity of treatment emergent adverse events.
Measured: from baseline, up to the 5-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.
Measured: from baseline, up to the 5-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.
Measured: From date of randomization until the date of occurrence of an adverse event leading to discontinuation, assessed up to 5 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.
Measured: at baseline and at 3-months
Incidence of treatment emergent abnormalities in pulse rate [safety and tolerability]
Measure resting pulse rate as beats per minute.
Measured: at baseline and at 3-months
Incidence of treatment emergent abnormalities in blood pressure [safety and tolerability]
Measure systolic and diastolic blood pressure (in mmHg).
Measured: at baseline and at 3-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2021
- Study start22 Mar 2021
- Primary completion30 Sep 2021
- Study completion29 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Allergic Rhinitis Due to Grass PollenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Lublin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kamil Janeczek, Medical University of Lublin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04802616
- Sponsor's protocol ID
- KE-0254/251/2020
- Status last verified
- Aug 2021
- First submitted
- 15 Mar 2021
- Last updated
- 5 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 32858239Janeczek 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.
PubMed 31616231Banche 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.
PubMed 17346436Meng 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.
PubMed 31403136Han 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.
PubMed 24717947Liu 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.
PubMed 28474108Esposito 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.
PubMed 29561355Emeryk 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.
PubMed 29575037Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol. 2005;23:877-900. doi: 10.1146/annurev.immunol.23.021704.115742.
PubMed 15771592Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol. 1999 Nov 1;163(9):4647-50.
PubMed 10528160Oki S, Miyake S. Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases. Allergol Int. 2007 Mar;56(1):7-14. doi: 10.2332/allergolint.R-06-137. Epub 2007 Jan 29.
PubMed 17259804Bennstein SB. Unraveling Natural Killer T-Cells Development. Front Immunol. 2018 Jan 9;8:1950. doi: 10.3389/fimmu.2017.01950. eCollection 2017.
PubMed 29375573Gupta RK, Gupta K, Dwivedi PD. Pathophysiology of IL-33 and IL-17 in allergic disorders. Cytokine Growth Factor Rev. 2017 Dec;38:22-36. doi: 10.1016/j.cytogfr.2017.09.005. Epub 2017 Nov 11.
PubMed 29153708Coomes SM, Kannan Y, Pelly VS, Entwistle LJ, Guidi R, Perez-Lloret J, Nikolov N, Muller W, Wilson MS. CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation. Mucosal Immunol. 2017 Jan;10(1):150-161. doi: 10.1038/mi.2016.47. Epub 2016 May 11.
PubMed 27166557Janeczek K, Kowalska W, Zarobkiewicz M, Suszczyk D, Mikolajczyk M, Markut-Miotla E, Morawska-Michalska I, Bakiera A, Tomczak A, Kaczynska A, Emeryk A, Rolinski J, Piotrowska-Weryszko K. Effect of immunostimulation with bacterial lysate on the clinical course of allergic rhinitis and the level of gammadeltaT, iNKT and cytotoxic T cells in children sensitized to grass pollen allergens: A randomized controlled trial. Front Immunol. 2023 Jan 17;14:1073788. doi: 10.3389/fimmu.2023.1073788. eCollection 2023.
PubMed 36733480
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Immunostimulation With Polyvalent Mechanical Bacterial Lysate on Changes in the Concentration of iNKT Cells in Children With Allergic Rhinitis.
- ClinicalTrials.gov ID
- NCT04802616
- Acronym / sponsor ID
- KE-0254/251/2020
- Conditions
- Allergic Rhinitis Due to Grass Pollen
- Keywords
- allergic rhinitis, seasonal allergic rhinitis, children, grass pollen season, bacterial lysate, iNKT cells
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Medical University of LublinUniversity, hospital or other
- Study start
- 22 Mar 2021 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 29 Oct 2021 (actual)
- First posted
- 17 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to assess the effect of polyvalent mechanical bacterial lysate (PMBL, Ismigen) on the clinical course of grass pollen-induced allergic rhinitis (using: total nasal symptom score, visual analogue scale, peak nasal inspiratory flow measurement) in children aged 5 to 17 and to assess changes in the concentration of iNKT cells under the influence of the therapy. Half of the 80 participants will receive PMBL while the other half will receive placebo.
Detailed description
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, the mechanism of action of these drugs in allergic diseases is still not entirely clear.
iNKT (Invariant Natural Killer T) are a conserved line of T cells with unique features expressing the invariant TCR alpha chain and recognizing glycolipids presented in the context of the non-classical MHC molecule, CD1d. As a result of TCR stimulation, iNKT cells are able to quickly secrete a variety of cytokines, thus stimulating various immune processes and playing an immunoregulatory role. iNKT cells are a small percentage of all T cells, however numerous studies indicate their possible participation in the pathogenesis of allergic diseases.The ambivalence of the activity of iNKT cells may result from the heterogeneity of this subpopulation. iNKT cells, like T lymphocytes, can be divided into further subpopulations: iNKT1, iNKT2, iNKT10, iNKT17 and iNKTreg. Individual subpopulations have a different cytokine profile, and thus may play opposite functions in the pathomechanism of many diseases, including allergic ones.
The main aim of this study is 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) and to assess the impact of PMBL on changes in the concentrations of the iNKT cell subpopulation. The approval of the Bioethics Committee at the Medical University in Lublin was obtained for the study.
Eighty children with SAR will be enrolled to this study and randomly assigned to the PMBL group (n=40) and placebo group (n=40). The study will include six visits, 2 site visits (before the grass pollen season and at the peak of the grass pollen season) and 4 telephone visits.The first site visit will be the randomization visit. The second site visit will take place after the end of the drug intake period. Telephone contact with the patient will take place twice during the period of taking the drug, and twice after the end of this period (follow-up visits).The time frame of the grass pollen season for south-eastern Poland will be determined using the "95%" method on the basis of measurements of grass pollen concentration in the atmospheric air, which will be obtained from the Environmental Allergy Research Centre in Warsaw. Patients will start taking sublingual tablets at the beginning of the April 2021.
Nasal SAR symptoms will be recorded by parents of children in the daily patient diary according to the standard scoring system (TNSS, total nasal symptom score), and their intensity will be also evaluated during six visits using VAS (visual analogue scale). At each site visit, peak nasal inspiratory flow (PNIF) will be also measured.
In order to determine the mechanism responsible for the possible effects of PMBL, blood samples (8 ml) will be taken from patients for additional tests during two site visits. The following iNKT cell subpopulations will be measured in the blood: iNKT1, iNKT2, iNKT10, iNKT17 and iNKTreg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Polyvalent mechanical bacterial lysate | Experimental | Drug: IsmigenTreatment over 3 successive months with one daily sublingual tablet (7 mg of bacterial lysate) over 10 days followed by 20 days of rest. |
| Placebo | Placebo comparator | Drug: PlaceboTreatment over 3 successive months with one daily sublingual tablet over 10 days followed by 20 days of rest. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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 polyvalent mechanical bacterial lysate sublingual tablets.
Key exclusion criteria (10 listed)
- Patient received mechanical bacterial lysate immunostimulation within the previous 12 months before randomisation visit.
- Patient received chemical bacterial lysate immunostimulation within the previous 6 months before randomisation visit.
- Patient received oral/subcutaneous allergen-immunotherapy within the previous 3 years before the start of the study.
- Other chronic conditions of the nose or nasal sinuses.
- Severe nasal septum deviation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsmigenAlso: Polyvalent mechanical bacterial lysate (PMBL)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). | Drug | Polyvalent mechanical bacterial lysate |
| PlaceboMatched tablets without any active substance. | Drug | Placebo |
Primary outcome
Change in the severity of nasal SAR symptoms as assessed by total nasal symptom score (TNSS)
Time frame: at baseline, at 1-month, at 2-months, at 3-months, at 4-months and at 5-months
The severity of nasal SAR symptoms (sneezing, runny nose, itchy nose and nasal congestion) will be 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 (before the grass pollen season) and obtained 1 month, 2 months, 3 months, 4 months and 5 months after initiating therapy will be used for statistical analysis.
Change in the nasal obstruction using peak nasal inspiratory flow (PNIF)
Time frame: at baseline and at 3-months
Assessment of the nasal obstruction during two site visits 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.
Change in the severity of nasal SAR symptoms as assessed by visual analogue scale (VAS)
Time frame: at baseline, at 1-month, at 2-months, at 3-months, at 4-months and at 5-months
Assessment of the severity of nasal SAR symptoms during six visits (2 site visits and 4 telephone visits) with the use of visual analogue scale.The patient will be asked to indicate the severity of nasal SAR symptoms on a 100 mm visual analogue scale, where 0 is no symptoms and 100 the worst possible symptoms.
iNKT1 cells concentration
Time frame: at baseline and at 3-months
To assess the change in the level of iNKT1 cells (T-bet+IFN-γ+) in the blood.
iNKT2 cells concentration
Time frame: at baseline and at 3-months
To assess the change in the level of iNKT2 cells (GATA3+IL-4+) in the blood.
iNKT10 cells concentration
Time frame: at baseline and at 3-months
To assess the change in the level of iNKT10 cells (E4BP4+IL-10+) in the blood.
iNKT17 cells concentration
Time frame: at baseline and at 3-months
To assess the change in the level of iNKT17 cells (RORγt+IL-17+) in the blood.
iNKTreg cells concentration
Time frame: at baseline and at 3-months
To assess the change in the level of iNKTreg cells (FoxP3+) in the blood.
8 secondary outcomes
Frequency of oral H1-antihistamines use
Time frame: from baseline, up to the 5-month time point
Frequency of intranasal corticosteroids use
Time frame: from baseline, up to the 5-month time point
Incidence of treatment emergent adverse events [safety and tolerability]
Time frame: from baseline, up to the 5-month time point
Incidence of treatment emergent adverse events leading to discontinuation [safety and tolerability]
Time frame: from baseline, up to the 5-month time point
Time to discontinuation due to treatment emergent adverse events [safety and tolerability]
Time frame: From date of randomization until the date of occurrence of an adverse event leading to discontinuation, assessed up to 5 months
Incidence of treatment emergent abnormalities in physical examination findings [safety and tolerability]
Time frame: at baseline and at 3-months
Incidence of treatment emergent abnormalities in pulse rate [safety and tolerability]
Time frame: at baseline and at 3-months
Incidence of treatment emergent abnormalities in blood pressure [safety and tolerability]
Time frame: at baseline and at 3-months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2022.
- Background: PubMed 32858239Janeczek 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.
- Background: PubMed 31616231Janeczek 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.
- Background: PubMed 17346436Banche 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.
- Background: PubMed 31403136Meng 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.
- Background: PubMed 24717947Han 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.
- Background: PubMed 28474108Liu 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.
- Background: PubMed 29561355Esposito 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.
- Background: PubMed 29575037Emeryk 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.
- Background: PubMed 15771592Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol. 2005;23:877-900. doi: 10.1146/annurev.immunol.23.021704.115742.
- Background: PubMed 10528160Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol. 1999 Nov 1;163(9):4647-50.
- Background: PubMed 17259804Oki S, Miyake S. Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases. Allergol Int. 2007 Mar;56(1):7-14. doi: 10.2332/allergolint.R-06-137. Epub 2007 Jan 29.
- Background: PubMed 29375573Bennstein SB. Unraveling Natural Killer T-Cells Development. Front Immunol. 2018 Jan 9;8:1950. doi: 10.3389/fimmu.2017.01950. eCollection 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ismigen in people with Allergic Rhinitis Due to Grass Pollen, run by Medical University of Lublin at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the severity of nasal SAR symptoms as assessed by total nasal symptom score (TNSS) (time frame: at baseline, at 1-month, at 2-months, at 3-months, at 4-months and at 5-months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04802616, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2022.