Effect of mepolizumab on alternative functions of eosinophils in severe eosinophilic asthma

Not Applicable

Completed

• Conditions: Severe asthma; Respiratory - Asthma; Inflammatory and Immune System - Other inflammatory or immune system disorders

• Registration Number: ACTRN12621000113853
• Lead Sponsor: niversity of Newcastle

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-04
• Study Completion: 2023-08-03
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1.Able to provide informed written consent
2.Adults (18 years or older) with doctor diagnosed severe asthma based on Global Initiative For Asthma (GINA) 2019 guidelines and PBS eligibility criteria for initiation of treatment of severe asthma with mepolizumab as follows:
a.Evidence or documented evidence of asthma defined by:
i.Forced expiratory volume (FEV1) reversibility greater than or equal to 12%, and greater than or equal to 200 mL at baseline within 30 minutes after administration of salbutamol (200 to 400 micrograms), OR
ii.Airway hyper-responsiveness defined as a greater than 20% decline in FEV1 during a direct bronchial provocation test or greater than 15% decline during an indirect bronchial provocation test, OR
iii.Peak expiratory flow (PEF) variability of greater than 15% between the two highest and two lowest peak expiratory flow rates during 14 days, OR
iv.Diagnosis of asthma from at least two physicians experienced in the management of patients with severe asthma

b.Asthma is uncontrolled* or not well-controlled^ despite adherence with optimized moderate to high dose inhaled corticosteroid-long-acting beta-2 agonist (ICS-LABA)# therapy and treatment of contributory factors, or that worsens when high dose treatment is decreased.
c.*Uncontrolled asthma includes one or both of the following:
i.Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma)
ii.Exacerbations (1 or more in prior year) requiring oral corticosteroids (OCS), or serious exacerbations (1 or more in prior year) requiring hospitalization
^Not well-controlled asthma is defined by ACQ5 greater than or equal to 1.0 during study screening or at baseline visit (see O’Byrne PM, Reddel HK, Eriksson G et al. Measuring asthma control: a comparison of three classification systems. Eur Resp J. 2010;36:269-276 and Juniper EF, Bousquet J et al. Identifying ‘well-controlled’ and ‘not well-controlled’ asthma using the Asthma Control Questionnaire. Resp Med. 2006;100(4):616-621.)
d.# For GINA definition of moderate to high dose ICS see (https://ginasthma.org/wp-content/uploads/2019/04/GINA-2019-main-Pocket-Guide-wms.pdf)
3.Stable disease, defined by lack of respiratory infection, exacerbation of asthma or alteration of maintenance asthma medication dose in prior 4 weeks to visit.

Exclusion Criteria

- Pregnancy/breastfeeding
- Participants currently receiving or having received in past 6 months treatment with benralizumab or omalizumab.
- No exacerbation of asthma in prior 4 weeks at screening.

Study & Design

• Study Type: Observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparison of blood eosinophil subpopulation number between severe non-eosinophilic asthma, severe eosinophilic asthma, severe eosinophilic asthma.[ Cross-sectional (baseline/initial visit for all participants)];Comparison of blood eosinophil subpopulation proportion between severe non-eosinophilic asthma, severe eosinophilic asthma, severe eosinophilic asthma.[ Cross-sectional (baseline/initial visit for all participants)]

Secondary Outcome Measures

Name	Time	Method
Blood and sputum eosinophil subpopulations.[ Cross-sectional (baseline/initial visit for all participants)];Extracellular trap formation in sputum slides and supernatant[ Cross-sectional (baseline/initial visit for all participants)];Sputum and blood mast cell and basophil measures.[ Cross-sectional (baseline/initial visit for all participants)];Blood and sputum eosinophil subpopulations.[ Longitudinal (participants in group 2 at baseline/initial visit and at >4 weeks and >6 months post commencement of treatment)];Extracellular trap formation in sputum slides and supernatant[ Longitudinal (participants in group 2 at baseline/initial visit and at >4 weeks and >6 months post commencement of treatment)];Sputum and blood mast cell and basophil measures.[ Longitudinal (participants in group 2 at baseline/initial visit and at >4 weeks and >6 months post commencement of treatment)]