In severe prednisone-dependent eosinophilic asthma, Benralizumab would suppress airway eosinophilia that is not suppressed by either Mepolizumab or Reslizumab and this would be associated with greater asthma control
Benralizumab thus targets 'eosinophil biology', by inhibiting the interleukin (IL-5) receptor signalling, and inducing apoptosis in cells with an IL-5receptor. Hence, for patients who remain 'uncontrolled' on anti-IL-5 therapy (with detectable eosinophil activity and IL5-Rα+ cells in the airways), the investigators believe would benefit from a strategy that not only reduces eosinophil proliferation/recruitment/maturation, but also depletes cells capable of inducing downstream IL-5 signalling.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
20
30mg in 1mL pre-filled syringe
Matched placebo (1mL) in pre-filled syringe
Firestone Institute for Respiratory Health, Research - St. Joseph's Healthcare
Hamilton, Ontario, Canada
Sputum eosinophil percentage
Change in Percentage of sputum eosinophils (%)
Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)
Blood eosinophils
Blood eosinophil level (x10\^9/L)
Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)
Forced Expired Volume in 1 second (FEV1)(pre and post bronchodilator)
FEV1 in litres both pre and post bronchodilator
Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)
ACQ-5 (Asthma Control Questionnaire)
Asthma Control Questionnaire score (mean answer of 5 questions on a 7-point scale (0=no impairment, 6= maximum impairment).
Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)
Fraction of exhaled nitric oxide (FeNO)
Exhaled nitric oxide measurement in ppb
Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)
Number of Exacerbations (defined as: ER visit/hospitalization requiring prednisone burst)
Worsening requiring increase in oral steroids/prednisone (30mg x 5 days)
Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)
Sputum and blood ILC2 biology
Measurement of ILC2 biological cells in both blood and sputum
Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)
Sputum autoimmune responses
Measurement of autoimmune markers in sputum: anti-eosinophil peroxidase (EPX) and anti-nuclear antibodies (ANA) - (See last reference PubMed ID: 28751233)
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Time frame: Visit 1 (Week 2) and Visit 10 (Week 38)