Investigating how epithelial barrier integrity affects treatment response in severe asthma patients with or without nasal polyps.

Role of Epithelial Barrier Integrity in Biologic Treatment Response of Severe Asthmatics With/Out Chronic Rhinosinusitis With Nasal Polyps (CRSwNP). Can Shedding of Epithelial Barrier Proteins be Used as Biomarker in Severe Asthma With/Out CRSwNP Management?

This study is testing how the health of the lung lining affects how well severe asthma patients, with or without nasal polyps, respond to a specific asthma treatment.

Quick facts

• Study type: Observational
• Enrollment: 85 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Crete (Academic / other)
• Drugs / interventions: Mepolizumab
• Locations: 2 sites (Heraklion, Crete and 1 other locations)
• Trial ID: NCT05365841 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the role of epithelial barrier integrity in the treatment response of patients with severe eosinophilic asthma, particularly those with or without chronic rhinosinusitis with nasal polyps (CRSwNP). The researchers hypothesize that the integrity of the bronchial epithelium may influence the pathophysiology of these conditions and the effectiveness of anti-IL5 therapy, specifically mepolizumab. By assessing the relationship between epithelial barrier proteins and treatment outcomes, the study seeks to enhance understanding of asthma severity and management. Participants will include adults who are naïve to anti-IL5 therapies and meet specific diagnostic criteria for asthma and CRSwNP.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with severe eosinophilic asthma, particularly those who are naïve to anti-IL5 therapies and may also have chronic rhinosinusitis with nasal polyps.

Not a fit: Patients with well-controlled asthma who do not have severe eosinophilic asthma or chronic rhinosinusitis with nasal polyps may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for severe asthma patients, enhancing their response to biologic therapies.

How similar studies have performed: While the specific approach of this study may be novel, previous studies have indicated a link between epithelial integrity and asthma severity, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

* Able to provide informed written consent (study participation informed consent form): Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
* Anti-IL5/IL5R naïve
* Confirmed asthma diagnosis and severity and treatment requirements (for severe asthma group see boxes 1-3). For the 2nd control group, patients with CRSwNP must have a diagnosis of mild asthma (GINA steps 1-2) or no asthma by pulmonologist.
* Polyposis must be bilateral, to be considered as CRSwNP
* Triggers and relevant co-morbidity have been assessed and are well controlled Triggers such as active or passive smoking, beta-blockers, aspirin/NSAIDs, allergen exposure;Comorbidities such as rhinitis, obesity, GERD, OSA, VCD, depression/anxiety.
* Age: Adults ≥18 years of age
* Any smoking status
* Any ethnicity
* Be affiliated to or a beneficiary of a social security category and/health insurance.
* Gender: Male and Eligible Female. To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control for the duration of the follow up (and for 4 months after the last injection administration). A serum pregnancy test is required of all females. This test will be performed at the initial screening visit. In addition, a urine pregnancy test can be offered (optional) for all females during each scheduled treatment visit prior to the infusion of biologic product until the 1-year follow-up visit.

Laboratory abnormality: No evidence of clinically significant abnormality (other than those seen in SEA) in the haematological, biochemical or urinalysis screen at Visit 1, as judged by the investigator.

* Asthma Exacerbation: Subjects with an ongoing asthma exacerbation should have their screening and treatment initiation visit delayed until the investigator considers the subject has returned to their baseline asthma status. If the 4-week screening period (visits 1 and 1a) has elapsed, then the subject should be considered a screening failure. An exacerbation is defined as worsening of asthma requiring the use of systemic CS and/or emergency department visit, or hospitalisation. For subjects on maintenance oral corticosteroids, an exacerbation requiring oral CS is defined as the use of oral/systemic corticosteroids at least double the existing dose for at least 3 days.
* Maintenance Asthma Therapy: No changes in the dose or regimen of baseline ICS and/or additional controller medication during the screening period (except for treatment of an exacerbation).
* Maintenance CRSwNP: No changes in the dose or regimen of baseline intranasal CS and/or additional controller medication during the screening period (except for treatment of an exacerbation).
* Subjects with a previous surgery for the removal of nasal polyps are allowed to participate and will be considered as subjects with CRSwNP (with severe asthma or not). However, any subject who had at least one surgery for removal of nasal polyps, even if at study screening he/she is free of nasal polyps, cannot be considered as a subject without CRSwNP.
* Severe asthma patients must meet requirements for biologic therapy with anti-IL5 treatment (Mepolizumab)

Exclusion Criteria:

* Pregnancy
* Current exacerbation at visit 1 (repeat screening when stable). If exacerbation is lasting up until Visit 1a then exclude subject.
* Cognitive impairment preventing completion of data collection forms
* People highly dependent on medical care
* People with significant life limiting co-morbidity
* Other eosinophilic conditions (eosinophilic granulomatosis polyangiitis (Churg-Strauss syndrome), eosinophilic oesophagitis etc)
* Unilateral polyposis
* Primary diagnosis of lung disease other than asthma (chronic obstructive lung disease (COPD), asthma-COPD overlap (ACO), interstitial lung disease, sarcoidosis, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, active tuberculosis, allergic bronchopulmonary aspergillosis (ABPA))
* Current lung cancer or other blood, lymphatic or solid organ malignancy
* Autoimmune diseases of the skin, muscle-skeletal or gastrointestinal system needing systemic corticosteroids, immunosuppressants or biologic treatment as well as individuals with granulomatosis with polyangiitis (Wegener's granulomatosis)
* Inability to attend study and treatment visits
* Inability to understand and speak Greek or English language

Where this trial is running

Heraklion, Crete and 1 other locations

• "PAGNI" University Hospital, Crete — Heraklion, Crete, Greece (Active_not_recruiting)
• Aikaterini Antoniou — Heraklion, Crete, Greece (Recruiting)

Study contacts

• Study coordinator: Nikolaos Tzanakis, Professor

Conditions Severe Eosinophilic Asthma w/wo CRSwNP