Beyond the Eosinophil: Understanding the Impact of Eosinophil Depletion on T2 Inflammation. (BEUTI)

NCT05847452 | Unknown

• 1 other identifier: 310865
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Benralizumab is a relatively new treatment that is approved by NICE (National Institute for Health and Care Excellence, https://www.nice.org.uk/) for patients with severe asthma who have ongoing eosinophilic inflammation that remains poorly controlled despite high dose inhaled glucocorticosteroid medication. Eosinophils are a type of white blood cell that are linked to allergy and inflammation and are raised in people with severe asthma. Severe asthma is associated with a type-2 (T2) inflammation phenotype characterised by increased T2 cytokines (IL-13, IL-4, IL-5). Increased levels of eosinophils can cause inflammation in the lungs, increasing the risk of asthma attacks. The standard treatment for asthma involves taking inhaled glucocorticosteroid medication which primarily work by suppressing eosinophilic inflammation in the lungs. Benralizumab is a monoclonal antibody that targets a receptor on the surface of eosinophils called interleukin-5 receptor-α (IL-5Rα) leading to the rapid death of these cells and consequently a reduction in airways inflammation. In clinical trials, benralizumab has been shown to reduce both symptoms and the number of asthma attacks suffered by those with severe eosinophilic asthma. However, it remains unclear whether this clinical efficacy relates purely to the removal of the eosinophil, or additionally to the impact of this on other parts of the immune system. The BEUTI study will examine the structure and function of airway cells in patients with severe eosinophilic asthma. Particularly how the immune function of these cells changes with treatment and whether benralizumab leads to a reduction in T2 mediators and/or activation in airway cells. The aim is to take samples of cells from the airways during a bronchoscopy (a camera test looking into the lungs) before starting benralizumab and after 12 weeks of treatment. These investigations will allow us to better understand how benralizumab affects the cells within the airways and the pathways involved.

Conditions

Asthma

Keywords

Asthma; Benralizumab

Outcome Measures

Primary Outcomes (2)

• The change in the number of inflammatory cells in patients with severe eosinophilic asthma at baseline and after 12 weeks of benralizumab treatment.

  To investigate the changes in the number of inflammatory cells in patients with severe eosinophilic asthma at baseline and after 12 weeks of benralizumab treatment.

  12 weeks

• The change in the activation status of Type-2 related cells in patients with severe eosinophilic asthma at baseline and after 12 weeks of benralizumab treatment.

  Activation status will be measured by the relative expression of Type 2 inflammatory cells and gene expression

  12 weeks

Secondary Outcomes (13)

• To investigate changes in epithelial barrier integrity using transepithelial resistance before and after completing treatment with 12 weeks of benralizumab.

  12 weeks

• To investigate changes in epithelial antiviral responses in untreated vs respiratory virus-infected cells including rhinovirus-16 in epithelial cells collected before and after completing 12 weeks of treatment.

  12 weeks

• To investigate changes in antiviral responses of alveolar macrophages to respiratory viruses including rhinovirus-16 in cells collected from the airways before and after completing 12 weeks of treatment.

  12 weeks

• To investigate changes in epithelial responses to pro-inflammatory cytokines/chemokines in cells collected before and after treatment.

  12 weeks

• To investigate changes in Type 2 inflammation in peripheral airways by collecting bronchoalveolar lavage fluid before and after treatment for nucleic acid and protein analyses.

  12 weeks

Study Arms (1)

All participants

All eligible participants will be consented and enrolled into the study and given the IMP as follows: Benzraliziumab 30mcg once a month for 3 months

Drug: Benralizumab

Interventions

Benralizumab DRUG

30mcg ever month for 3 months

All participants

Eligibility Criteria

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

Study Population

Adult patients with poorly-controlled severe eosinophilic asthma who meet NICE criteria to commence biologic therapy with benralizumab.

You may qualify if:

• Informed consent.
• Patients aged 18 and over with a diagnosis of severe eosinophilic asthma for at least the last 6 months
• Eligible for benralizumab based on NICE criteria
• Poorly-controlled (ACQ-6 \>1.5)
• FeNO ≥50ppb at screening despite high dose inhaled corticosteroids (at least 1000mcg BDP equivalent) +/- maintenance prednisolone
• Adult-onset (18+) asthma in a minimum of 50% of the study subjects

You may not qualify if:

• Other severe eosinophilic lung disease including EGPA, chronic eosinophilic pneumonia and ABPA
• Maintenance daily oral corticosteroids (prednisolone)
• Severe bronchiectasis on CT causing daily sputum production
• Inability to give written informed consent
• Current smoking or \>20 pack year smoking history
• Resting oxygen saturations \<94% on air
• Any severe cardiac or other non-asthma related co-morbidity that would make bronchoscopy and/or sedation high risk
• Symptoms suggestive of a respiratory viral / bacterial infection within the last 3 weeks
• Acute exacerbations of asthma requiring high dose prednisolone within the last 3 weeks
• A change in dose of maintenance inhaled and/or oral corticosteroid dose within the last 3 weeks
• Positive strongyloides serology following screening
• Pregnancy or lactation
• Hypersensitivity to benralizumab or any of the excipients

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• King's College London: collaborator

Study Sites (1)

Guy's & St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Serum/ plasma/ cells (blood) Airway samples: Endobronchial biopsy (small lung tissue pieces), bronchial brushings (contains bronchial epithelial cells) bronchoalveolar lavage (fluid and cells collected from the lungs).

MeSH Terms

Conditions

Asthma

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Prof. David Jackson, PhD

  Guy's and St. Thomas NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mathew Clinical Trial Coordinator, MSc

CONTACT

0207 188 5075; mathew.furtado@gstt.nhs.uk

Varsha Clinical Research Scientist, PhD

CONTACT

0207 188 5075; varsha.kanabar@kcl.ac.uk

Study Design

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

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: May 6, 2023
• Study Start: May 22, 2023
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: July 11, 2023

Record last verified: 2023-07

Locations

GB (1)