Refractory Eosinophilic Asthma.
Conditions
Sponsors
University Hospitals of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Refractory asthma as defined by the American Thoracic Society guidelines. 2. Symptoms and objective evidence of variable airflow obstruction as indicated by one or more of the following: i) >15% increase in FEV1 following 200 micrograms inhaled salbutamol. ii) >20% within day variability in PEF noted on any day following assessment twice daily over 2 weeks. iii) and/or a concentration of metacholine causing 20% fall in FEV1 of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Current smokers or ex smokers with a smoking history of greater than 15 years. 2. Evidence of previous exposure to parasite disease, based on positive parasite serology. 3. History of allergy to antibody therapy. 4. History of an exacerbation or an escalation of treatment in the 2 weeks prior to baseline assessments. Participants can be recruited once they have been stable for at least 2 weeks. 5. History of alcohol or drug abuse. 6. Significant co morbidity pertaining to ischaemic heart disease, severe psychiatric disease and more than two bacterial respiratory tract infections in the last year. 7. Pregnant and lactating females or those women of child bearing potential who do not wish to practice recommended effective contraceptive measures for the duration of the trial period and 100 days after completing the trial. All women of child bearing potential will be required to have a negative pregnancy test prior to study entry. 8. Unexplained abnormal blood tests at screening that are considered a contra indication to proceeding with the trial by the principal investiagtor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether mepolizumab effectively suppresses the presence of eosinophils in sputum and whether this translates into a fall in the frequency of asthma exacerbations in a cohort of refractory asthmatics who otherwise require a high dose of inhaled corticosteroids and, in some cases, regular oral corticosteroids to control their asthma.; Secondary Objective: To assess the effects of mepolizumab on: 1. Long term changes in airway structure and function (airway remodelling) after 12 months treatment using bronchial biopsy material and CT scans. 2. Asthma symptoms and quality of life, analysed using diary cards and validated questionnaires. 3. Exhaled nitric oxide levels. 4. Concentration of methacholine required to cause a fall in FEV1 by 20% from baseline. 5. Hospital admission rates over the 12 months. 6. Obtain blood samples for pharmacogenomic analysis by GSK (N.B. This does not form part of the data collection/analysis of this study). ;Primary end point(s): Severe exacerbation frequency over the 12 month treatment period defined as a decrease in the morning peak expiratory flow to more than 30% below the baseline value on 2 or more consecutive days, or a deterioration in symptoms requiring treatment with rescue oral corticosteroids. | — |
Countries
United Kingdom
Outcome results
None listed