AzTrials
AzTrials

Asthma; EosinophilicIRISNCT05144087

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

An observational study of Asthma; Eosinophilic, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Asthma; Eosinophilic
How many people
18 participants
Where
1 siteUnited Kingdom
Study dates
25 May 2022to 30 Nov 2027
Phase
Observational
Are there results?
Not yet: the study is under way

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 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • NIHR Clinical Research Facility

    Southampton, Hampshire, SO16 6YD

Other trials in United Kingdom

About this study

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.

Read the detailed description

IRIS is a prospective observational study investigating Mepolizumab in the treatment of severe eosinophilic asthma.

Eosinophilic airway inflammation has been implicated in the pathogenesis of asthma and is particularly relevant in severe eosinophilic asthma (SEA), in which standard asthma therapies fail to adequately control the disease. In severe asthma, there is bronchial epithelial damage and loss of tight junction integrity, goblet cell hyperplasia, enhanced collagen generation within the airway wall and impaired innate immune responses. Mepolizumab has been shown to reduce exacerbations and improve disease control in SEA but there are no studies assessing the impact of Mepolizumab on structural airway cell activity and function and airway remodelling processes.

Primary Objective:

To investigate changes within bronchial epithelial cells following completion of 6 months (7 doses) of Mepolizumab using single cell RNA sequencing (scRNA-seq) and Frac-seq (subcellular fractionation and RNA-sequencing).

Secondary Objectives:

To investigate the following after completing treatment with 6 months of Mepolizumab:

  1. Changes in epithelial barrier integrity using Frac-seq, transepithelial resistance ii) Changes in epithelial antiviral responses fusing Frac-seq in unstimulated and virus-infected cells. iii) Changes in airway remodelling by assessing the profile of fibroblasts isolated from bronchial biopsies employing Frac-seq and immunostaining of bronchial biopsies iv) Evaluate the impact on peripheral airways by obtaining bronchoalveolar lavage (BAL) and peripheral airway brushings for Frac-seq analysis and protein analysis v) Peripheral airway dysfunction using impulse oscillometry vi) Changes in fibroblast profile with stimulation and IL-5 inhibition using a range of molecular, cellular, protein and metabolic techniques

Exploratory Objectives i) Evaluation of neural structural changes using biopsies

Keywords
asthma, mepolizumab, eosinophil
Medical subject headings
Pulmonary Eosinophilia, Asthma

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 36 months

Secondary outcomes (8)

  1. Changes in epithelial barrier integrity using transepithelial resistance

    Transepithelial resistance measures changes in voltage across the epithelial cells

    Measured: 36 months

  2. Changes in epithelial antiviral responses using interferon and other antiviral gene measurements

    Gene expression will be measured using RNA sequencing and reported as gene counts

    Measured: 36 months

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

    RNA sequencing will be reported as gene counts

    Measured: 36 months

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

    Immunostaining will be reported as mean fluorescence intensity and percentage of cells stained

    Measured: 36 months

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

    RNA sequencing will be reported as gene counts

    Measured: 36 months

  6. Evaluate the impact on peripheral airways by obtaining peripheral airway brushings for RNA sequencing

    RNA sequencing will be reported as gene counts

    Measured: 36 months

  7. Peripheral airway dysfunction using impulse oscillometry

    Impulse oscillometry will be measured as resistance and impedance

    Measured: 36 months

  8. Changes in fibroblast profile with stimulation and IL-5 inhibition using a range of molecular, cellular, protein and metabolic techniques

    To study fibroblasts

    Measured: 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2021
  2. Study start25 May 2022
  3. Primary completion30 May 2024
  4. Study completion30 Nov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05144087
Sponsor's protocol ID
RHM MED1765
Acronym
IRIS
Status last verified
Feb 2025
First submitted
3 Sep 2021
Last updated
19 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Researchers and collaborators outside of the study team can submit a request to the PI to access study data at the end of the study for any ethical approved research or external collaborations.

Questions about this trial

What is this clinical trial studying?

An observational study of Asthma; Eosinophilic, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.

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 6 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 19 Feb 2025. 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 United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

To investigate molecular changes in the bronchial epithelium that occurs with mepolizumab treatment using RNA sequencing (time frame: 36 months). 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 NCT05144087.

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 19 Feb 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in