Benralizumab in Patients With Inadequate Response to Anti-IL5 Monoclonal Antibody Therapies

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Benralizumab in Patients With Inadequate Response to Anti-IL5 Monoclonal Antibody Therapies

Conditions
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Severe Prednisone Dependent Eosinophilic Asthma

Intervention / Treatment
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* Biological: Benralizumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Prior to the beginning of the study, patients must be willing and fully capable to provide written informed consent. Diagnosed prednisone-dependent eosinophilic asthma Previous treatment with 100 mg mepolizumab administered subcutaneously Q4W or reslizumab 3 mg/kg IV Q4W for at least 6 months Sputum eosinophils >3% ACQ ≥1.5 Age >18 Male or eligible female subjects: To be eligible for entry into the study, females of childbearing potential (premenopausal women who are not permanently sterilized by means of hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) must commit to consistent and correct use of a highly effective method of birth control (true sexual abstinence, a vasectomized sexual partner, Implanon, female tubal occlusion, Intrauterine device (IUD), Depo provera injections, oral contraceptive pills or Nuvaring) for the duration of the trial and for 3 months after the last study drug administration. A serum pregnancy test is required of all females at the initial Baseline Visit (Visit 1). In addition, a urine pregnancy test will be performed for all females prior to enrollment, during each scheduled study visit prior to the injection of investigational product, and during the Follow-up Visit. Male subjects who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of study drug and for 3 months after the last dose of study drug. Exclusion Criteria: Currently receiving another monoclonal antibody Intolerance, hypersensitivity, insensitivity or neutralizing antibody to Mepolizumab and/or Reslizumab Malignancy within the last 5 years Any co-morbidity that the investigator believes is a contraindication. This includes but is not limited to any respiratory, cardiovascular, gastrointestinal, hematological, neurological, immunological, musculoskeletal, renal, infectious, neoplastic or inflammatory condition that may place the safety of the subject at risk during the duration of the study, influence the results of the study or their interpretation, or prevent the patient from completing the entire duration of the study. Current pregnancy or lactation Current smoker or ex-smoker with a smoking history greater than 20 pack years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Benralizumab<br>Benralizumab 30mg in 1mL subcutaneously | Biological: Benralizumab<br>* 30mg in 1mL pre-filled syringe<br>* Other names: MEDI-563;|
| Placebo Comparator: Placebo<br>Matched placebo (1mL) to active Benralizumab subcutaneously | Biological: Placebo<br>* Matched placebo (1mL) in pre-filled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum eosinophil percentage | Change in Percentage of sputum eosinophils (%) | Visit 1 (Week 2) and Visit 10 (Week 38) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood eosinophils | Blood eosinophil level (x10^9/L) | 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 | 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). | Visit 1 (Week 2) and Visit 10 (Week 38) | 
| Fraction of exhaled nitric oxide (FeNO) | Exhaled nitric oxide measurement in ppb | 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) | Visit 1 (Week 2) and Visit 10 (Week 38) | 
| Sputum and blood ILC2 biology | Measurement of ILC2 biological cells in both blood and sputum | 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) | Visit 1 (Week 2) and Visit 10 (Week 38) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eosinophils, asthma, inflammation, prednisone