Severe Eosinophilic Asthma MedDRA version: 21.1 Level: LLT Classification code 10068462 Term: Eosinophilic asthma System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Fasenra
Product Name: Fasenra
Product Code: N/A
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: Benralizumab
CAS Number: 1044511-01-4
Concentration
Sponsors
Royal Brompton and Harefield NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: 1. Age 18-75 years 2. Weight =40kg 3. Severe asthma as defined in the 2014 ERS/ATS severe asthma guideline 4. Deemed eligible to commence benralizumab as NHS treatment according to NICE TA565 5. FEV1 = 60% predicted 6. ACQ-6 >1.5. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Exclusion criteria: 1. Significant cardiac disease, e.g. ischaemic heart disease, cardiac failure, permanent pacemaker 2. Pregnant and breastfeeding 3. Significant respiratory disease, other than the condition being studied, e.g. chronic obstructive pulmonary disease, interstitial lung disease, obstructive sleep apnoea requiring treatment. 4. Current malignancy 5. Current smokers (All subjects must be non-smokers or ex-smokers for at least 12 months with 35kg/m2) 7. Rheumatoid arthritis 8. Confounding drugs (anti-asthma immune modulators other than steroids) 9. Treatment with a monoclonal antibody in the last 6 months 10. Known history of allergy or reaction to the study drug formulation, or history of anaphylaxis to any biologic therapy. 11. Long-term systemic antibiotics/ antifungals, or any course(s) of systemic antibiotics/ antifungals within the past 2 weeks. 12. Acute exacerbations of asthma (defined as a clinical episode requiring treatment with systemic corticosteroids, or requiring an increase in the dosage of systemic corticosteroids if the patient is on long term corticosteroid treatment) within the past 2 weeks 13. History of an upper or lower respiratory infection (including common cold) within the past 2 weeks 14. Female subjects who are pregnant/ breastfeeding/ less than 6 weeks post-partum at the time of enrolment, or who fulfil any of these criteria at any point prior to the final investigation (bronchoscopy) 15. Previous bronchial thermoplasty in the last 48 months. 16. Unable to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To measure the change in the numbers of eosinophils (a subtype of white blood cells) in the lung tissue of patients with severe eosinophilic asthma, before and after three injections of 30mg of benralizumab (a newly-approved medicine for asthma that at a higher dose has been shown to markedly reduce the numbers of eosinophils) administered every 4 weeks.;Secondary Objective: - To measure the change in lung function tests in the above patient population - To measure the change in asthma symptom control in the above patient population - To measure the change in Fractional exhaled Nitric Oxide (FeNO, a marker of lung inflammation) in the above patient population - To measure the change in detectable upper and lower airway inflammation and homogeneity of airways ventilation (the distribution of air when it is breathed in and out of the lungs) in the above patient population - To measure the baseline lung and nasal microbiome (i.e. the bacteria and fungi that live in the lungs) in SEA, and the effect of benralizumab on this microbiome - To conduct intensive culture of bronchial brushes pre and post treatment to obtain a bank of bacterial isolates from a subset of patients - To aim to profile relevant epigenetic markers (i.e. markers which tell us whether or not a particular gene is 'switched on' or 'switched off') - To culture and bank primary epithelial cells ;Primary end point(s): Numbers of eosinophils observed in bronchial biopsy after immunohistological staining (cells/mm2);Timepoint(s) of evaluation of this end point: This end point will be evaluated at the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To measure the change in lung function tests in the above patient population - To measure the change in asthma symptom control in the above patient population - To measure the change in Fractional exhaled Nitric Oxide (FeNO, a marker of lung inflammation) in the above patient population - To measure the change in detectable upper and lower airway inflammation and homogeneity of airways ventilation (the distribution of air when it is breathed in and out of the lungs) in the above patient population - To measure the baseline lung and nasal microbiome (i.e. the bacteria and fungi that live in the lungs) in SEA, and the effect of benralizumab on this microbiome - To conduct intensive culture of bronchial brushes pre and post treatment to obtain a bank of bacterial isolates from a subset of patients - To aim to profile relevant epigenetic markers (i.e. markers which tell us whether or not a particular gene is 'switched on' or 'switched off') - To culture and bank primary epithelial cells from bronchial brushes (i.e. grow and store the cells that line the airway) - To measure the change in bronchial biopsy counts of other inflammatory cells in the above patient population Sample Biobank - To establish a sample biobank of biopsies, blood samples (for DNA, RNA and serum), and bacterial isolates and primary epithelial cells pre and post benralizumab administration in a subset of patients - Said Biobank will allow to allow further exploratory studies not limited to but including: *Sequencing of bacterial isolates (i.e. finding out the genetic code of the bacteria that are in the samples) *SNP genotyping (i.e. finding out the differences in genetic code in the samples) *global gene expression of biopsies (i.e. finding out all of the genes that are expressed in the biopsies) *metatranscriptomics of bronchial brushes (i.e. finding out all of the genes that are expressed in the brushes) *co-culture of bacterial isolates with primary epithelial cells ( | — |
Countries
United Kingdom
Outcome results
None listed