The Influence of Mepolizumab on Structural and Inflammatory Cells in Severe Eosinophilic Asthma

NCT05144087 | Active Not Recruiting

• 1 other identifier: RHM MED1765
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The IRIS study aims to investigate the way Mepolizumab affects the structure of the airway cells in patients with Severe Eosinophilic Asthma and how the immune function of these cells changes with treatment. The aim is to take samples of cells from the airways before starting Mepolizumab and after 6 months of treatment. These samples will be taken during a bronchoscopy (a camera test looking into the lungs) and we will analyse these cells in the laboratory. These investigations will allow us to better understand how Mepolizumab affects the cells within the airways.

Conditions

Asthma; Eosinophilic

Keywords

asthma; mepolizumab; eosinophil

Outcome Measures

Primary Outcomes (1)

• To investigate molecular changes in the bronchial epithelium that occurs with mepolizumab treatment using RNA sequencing

  Changes at the level of single cell RNA sequencing will be reported as: 1. Changes in the percentage of cell populations present in the airways 2. Normalised gene counts

  36 months

Secondary Outcomes (8)

• Changes in epithelial barrier integrity using transepithelial resistance

  36 months

• Changes in epithelial antiviral responses using interferon and other antiviral gene measurements

  36 months

• Changes in airway remodelling by assessing fibroblasts isolated from bronchial biopsies using RNA sequencing

  36 months

• Changes in airway remodelling by assessing fibroblasts isolated from bronchial biopsies using immunostaining

  36 months

• Evaluate the impact of Mepolizumab on peripheral airways by obtaining bronchoalveolar lavage for RNA sequencing

  36 months

Other Outcomes (1)

• Evaluation of neural structural changes using immunostaining on biopsy specimens

  36 months

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from University Hospital Southampton (UHS). UHS operates a regional specialist clinical severe asthma service, prescribing biological therapies, including Mepolizumab. Patients will be exclusively recruited from a pool of patients awaiting biological therapies for severe asthma at these centres. Patients are only eligible for Mepolizumab following NICE mandated multidisciplinary team approval reviewing biological eligibility, treatment adherence and satisfaction that other co-morbid conditions have been satisfactorily addressed.

You may qualify if:

• Diagnosis of Severe Eosinophilic Asthma (as per Southampton Severe Asthma MDT and based on ATS/ERS consensus criteria)
• Approved for treatment with Mepolizumab by Southampton Severe Asthma MDT (in accordance with NICE TA 431)
• Blood eosinophil count is ≥0.3 x109cells/L in preceding 12 months
• ≥4 asthma exacerbations needing systemic steroids in the preceding 12 months
• Age ≥18 years
• Able to provide written informed consent

You may not qualify if:

• On maintenance daily oral steroids, asthma immune modulators
• On long-term systemic antibiotics or antifungal treatment
• Current smoker or ex-smoker with \>10 pack year smoking history
• Known clinically significant respiratory disorder such as bronchiectasis, interstitial lung disease, allergic bronchopulmonary aspergillosis
• Currently pregnant or planning pregnancy within the treatment period or breast-feeding
• History of psychiatric, medical or surgical disorders that in the opinion of the chief investigator may interfere with undergoing a bronchoscopy or may compromise study completion or data collection
• Current malignancy
• Alcohol or recreational drug abuse
• Diagnosis of immunodeficiency requiring treatment
• Previous bronchial thermoplasty
• Previous treatment with biological therapy
• Previously unable to tolerate a bronchoscopy
• Current or recent (within the last 12 weeks) infection with SARS-CoV-2
• Unable to provide written informed consent

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• University of Southampton: collaborator
• King's College Hospital NHS Trust: collaborator

Study Sites (1)

NIHR Clinical Research Facility

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

bronchial epithelial cells bronchoalveolar lavage (BAL) peripheral airway brushings blood serum and plasma urinary metabolites

MeSH Terms

Conditions

Pulmonary Eosinophilia; Asthma

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Hitasha Rupani, BM PhD

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: December 3, 2021
• Study Start: May 25, 2022
• Primary Completion: May 30, 2024
• Study Completion (Estimated): November 30, 2027
• Last Updated: February 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)