Severe Prednisone Dependent Eosinophilic Asthma Clinical Trial
Official title:
Benralizumab in Patients With Inadequate Response to Anti-IL5 Monoclonal Antibody Therapies
| Verified date | January 2023 |
| Source | McMaster University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | November 30, 2022 |
| Est. primary completion date | June 14, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: 1. Informed consent Prior to the beginning of the study, patients must be willing and fully capable to provide written informed consent. 2. Diagnosed prednisone-dependent eosinophilic asthma 3. Previous treatment with 100 mg mepolizumab administered subcutaneously Q4W or reslizumab 3 mg/kg IV Q4W for at least 6 months 4. Sputum eosinophils >3% 5. ACQ =1.5 6. Age >18 7. 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. 8. 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: 1. Currently receiving another monoclonal antibody 2. Intolerance, hypersensitivity, insensitivity or neutralizing antibody to Mepolizumab and/or Reslizumab 3. Malignancy within the last 5 years 4. 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. 5. Current pregnancy or lactation 6. Current smoker or ex-smoker with a smoking history greater than 20 pack years. |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Firestone Institute for Respiratory Health, Research - St. Joseph's Healthcare | Hamilton | Ontario |
| Lead Sponsor | Collaborator |
|---|---|
| McMaster University | AstraZeneca, St. Joseph's Healthcare Hamilton |
Canada,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Sputum eosinophil percentage | Change in Percentage of sputum eosinophils (%) | Visit 1 (Week 2) and Visit 10 (Week 38) | |
| Secondary | Blood eosinophils | Blood eosinophil level (x10^9/L) | Visit 1 (Week 2) and Visit 10 (Week 38) | |
| Secondary | 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) | |
| Secondary | 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) | |
| Secondary | Fraction of exhaled nitric oxide (FeNO) | Exhaled nitric oxide measurement in ppb | Visit 1 (Week 2) and Visit 10 (Week 38) | |
| Secondary | 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) | |
| Secondary | Sputum and blood ILC2 biology | Measurement of ILC2 biological cells in both blood and sputum | Visit 1 (Week 2) and Visit 10 (Week 38) | |
| Secondary | 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) |