Biomarkers of Response to Mepolizumab Treatment in Patients With Nasal Polyps With or Without Bronchial Asthma

ConditionsChronic Rhinosinusitis With Nasal Polyps Asthma

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorAristotle University Of Thessaloniki

About this trial

Mepolizumab is a biologic agent already approved for severe asthma. Recently, there is increasing evidence concerning the benefit of anti-IL5 treatments upon patients with nasal polyposis with or without severe asthma.

The novelty of this project is that no biologic agent has yet been fully investigated to identify any biomarkers of response for patients with nasal polyps with or without asthma including sinonasal tissue remodeling a key element in the resultant histopathological changes of the inflammation. The investigation of airway remodeling of various locations (nose and bronchus) under mepolizumab treatment will be our primary objective on the long-term basis of 156 weeks of treatment.

Endobronchial and nasal biopsies will be performed as routine care for tissue evauation and disease investigation for every patient.

Besides, the united airways will provide better guidance for medical treatment of chronic rhinosinusitis (CRS) patients with nasal polyps (CRSwNP) and asthma.

The initial idea is based on investigating the characteristics that could predict the effectiveness of mepolizumab on patients with nasal polyposis with or without asthma. Patients will receive 39 doses of mepolizumab for 156 weeks. An additional aim of this study is to identify characteristics of non-responders and responders to mepolizumab. Responders will be identified based on airway remodeling status, biomarkers in tissue and secretion samples and on the reduction of the need of surgery through Lund-Kennedy endoscopic score, Lund-Mackay score and patient's clinical status in the 6th, 12th and 36th month after the initiation of treatment.

Regarding the unified airway system, nose and pharyngeal microbiome will be evaluated before and after 52 weeks of mepolizumab treatment in patients with nasal polyps whereas in patients with nasal polyps and asthma bronchus microbiome will also be evaluated. Lung samples will help gain information about the inflammatory profile and local microbiome of CRSwNP patients with asthma through molecular and cellular assays. The human Pharyngeal Microbiome might play a protective role in Respiratory Tract Infections and it has been reported that the microbiome provides critical signals to promote maturation of immune cells and differentiation of the tissue. Thus, we will make an effort to correlate microbiome of various locations with clinical and laboratory characteristics of responders and non-responders to mepolizumab treatment.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult patients > 18 years with bilateral Nasal Polyps

Symptoms VAS scores (for nasal obstruction, hyposmia, post-nasal drip, sneezing, rhinorrhea; 0-10 for each symptom) > 24 in spite of treatment with standard of care treatment.

Patients with bilateral sinonasal polyps with a need for surgery as described by: Lund-Mackay score > 4, Lund Kennedy score > 6, a minimum total Nasal polyp score of 5 out of a maximum score of 8 at screening, ongoing symptoms for at least 12 weeks prior to screening,

Concerning patients with asthmatics with nasal polyps: subjects must have a medical history of asthma as confirmed by asthma related symptoms and by bronchodilator response (BDR) (GINA 2022) or positive methacholine challenge according to ERS guidelines.

Disqualifiers

Pregnant or nursing women, or women of child-bearing potential.

Biologic therapy (eg: Omalizumab, Mepolizumab, Reslizumab, Dupilumab) or previous treatment with Mepolizumab

Allergen immunotherapy in the past 6 months

Systemic corticosteroid treatment for other chronic conditions (i.e.: autoimmune disorders, tumors, etc)

Trial population

Study population The study population will consist of approximately 57 patients with nasal polyposis with or without bronchial asthma receiving mepolizumab for a year aged 18 and above (no children). Clinical evaluation of patients with nasal polyposis with or without asthma will be made according to the European Position Paper on Rhinosinusitis and Nasal Polyps. Besides, standard of care for our patients apart from mepolizumab may include ICS, anti-histamine or LTRAs.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Mepolizumab 100 MG [Nucala]
Drug
subcutaneous injection once a month

Treatment groups

57 Participants

are divided into 2 treatment groups

Group A: chronic rhinosinusitis with nasal polyps with bronchial asthma1 intervention

Group B: chronic rhinosinusitis with nasal polyps without bronchial asthma1 intervention

Trial outcomes

Primary outcomes

Change in Basement Membrane Thickness

The identification of clinical characteristics of non-responders and super-responders. Anwers whether change basement membrane thickness can predict therapeutic response of mepolizumab among patients.

Time frame