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| Name | Class |
|---|---|
| St. Joseph's Healthcare Hamilton | OTHER |
| AstraZeneca | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Benralizumab | Active Comparator | Benralizumab 30mg in 1mL subcutaneously |
|
| Placebo | Placebo Comparator | Matched placebo (1mL) to active Benralizumab subcutaneously |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benralizumab | Biological | 30mg in 1mL pre-filled syringe |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sputum eosinophil percentage | Change in Percentage of sputum eosinophils (%) | Visit 1 (Week 2) and Visit 10 (Week 38) |
| 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 |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| Parameswaran Nair, MD, PhD | McMaster University and St. Joseph's Healthcare Hamilton | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Firestone Institute for Respiratory Health, Research - St. Joseph's Healthcare | Hamilton | Ontario | L8N 4A6 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28070196 | Background | Mukherjee M, Lim HF, Thomas S, Miller D, Kjarsgaard M, Tan B, Sehmi R, Khalidi N, Nair P. Airway autoimmune responses in severe eosinophilic asthma following low-dose Mepolizumab therapy. Allergy Asthma Clin Immunol. 2017 Jan 6;13:2. doi: 10.1186/s13223-016-0174-5. eCollection 2017. | |
| 26194544 | Background | Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O'Byrne PM, Gauvreau GM, Boulet LP, Lemiere C, Martin J, Nair P, Sehmi R. Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J Allergy Clin Immunol. 2016 Jan;137(1):75-86.e8. doi: 10.1016/j.jaci.2015.05.037. Epub 2015 Jul 17. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Nov 30, 2023 | |
| Reset | May 17, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Nov 30, 2023 | May 17, 2024 |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C571386 | benralizumab |
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| Placebo | Biological | Matched placebo (1mL) in pre-filled syringe |
|
| 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) |
| 26685004 | Background | Sehmi R, Smith SG, Kjarsgaard M, Radford K, Boulet LP, Lemiere C, Prazma CM, Ortega H, Martin JG, Nair P. Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma. Clin Exp Allergy. 2016 Jun;46(6):793-802. doi: 10.1111/cea.12695. |
| 20513525 | Background | Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall'acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010 Jun;125(6):1344-1353.e2. doi: 10.1016/j.jaci.2010.04.004. |
| 28915080 | Background | Mukherjee M, Aleman Paramo F, Kjarsgaard M, Salter B, Nair G, LaVigne N, Radford K, Sehmi R, Nair P. Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab. Am J Respir Crit Care Med. 2018 Jan 1;197(1):38-46. doi: 10.1164/rccm.201707-1323OC. |
| 28530840 | Background | Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22. |
| 28751233 | Background | Mukherjee M, Bulir DC, Radford K, Kjarsgaard M, Huang CM, Jacobsen EA, Ochkur SI, Catuneanu A, Lamothe-Kipnes H, Mahony J, Lee JJ, Lacy P, Nair PK. Sputum autoantibodies in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2018 Apr;141(4):1269-1279. doi: 10.1016/j.jaci.2017.06.033. Epub 2017 Jul 24. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |