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| Name | Class |
|---|---|
| Teva Canada | UNKNOWN |
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Dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.
Monoclonal antibody therapies targeting the interleukin-5 (IL-5) pathway, critical for maintaining eosinophil homeostasis, have been developed as adjunct therapy for severe asthma with an eosinophilic phenotype. Reslizumab/Cinqair is an approved/marketed product administered monthly by intravenous to severe eosinophilic asthmatics at 3mg/kg. However some patients do exhibit sputum eosinophilia at this dosage. We are investigating whether those that receive 3mg/kg that have persistent sputum eosinophils would benefit at a higher dose of 4mg/kg and those that still exhibit sputum eosinophils at this elevated dose would show improvement at 5mg/kg.
The overall aim of this study is to determine whether dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reslizumab 3 mg/kg | Active Comparator | All patients will initially receive reslizumab 3 mg/kg for at least 16 weeks. |
|
| Reslizumab 4 mg/kg | Active Comparator | Patients who have uncontrolled sputum eosinophilia at 16 weeks will receive an increased dose of 4 mg/kg for the next 16 weeks. The patients with controlled eosinophilia will continue to receive 3 mg/kg. |
|
| Reslizumab 5 mg/kg | Active Comparator | Patients who have uncontrolled sputum eosinophilia who were previously receiving reslizumab at 4 mg/kg at 32 weeks will receive an increased dose of 5 mg/kg for the next 16 weeks. The patients remaining patients will continue on the dose they were receiving (i.e., either 3 mg/kg or 4 mg/kg). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Reslizumab | Biological | Reslizumab 3,4, or 5 mg/kg IV q4 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Sputum eosinophilia | Absolute difference between the mean sputum eosinophil percent | At baseline and at the end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Proportion of patients with sputum eosinophils ≤3% | Number of patients with sputum eosinophils ≤3% | At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| Change in Blood eosinophil count |
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Inclusion Criteria:
Asthma confirmed within the past 2 years by:
a. A ≥12% improvement in forced expiratory volume in 1 second (FEV1) after use of a beta agonist, or a methacholine challenge test showing a ≥20% reduction in FEV1 after a concentration of ≤8 mg/mL of methacholine
Blood eosinophils ≥400 cells/µL and/or sputum eosinophils ≥3% (or presence of moderate-to-many free eosinophil granules) at the time of study enrollment
Treated with an inhaled corticosteroid at a dose of ≥1500 µg of fluticasone propionate (or equivalent) and a long-acting beta agonist with or without oral corticosteroids
Ability to provide informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Parameswaran Nair, MD, PhD | McMaster University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Firestone Institute of Respiratory Health, St Joseph's Hospital | 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. | |
| 32444405 | Background | Mukherjee M, Forero DF, Tran S, Boulay ME, Bertrand M, Bhalla A, Cherukat J, Al-Hayyan H, Ayoub A, Revill SD, Javkar T, Radford K, Kjarsgaard M, Huang C, Dvorkin-Gheva A, Ask K, Olivenstein R, Dendukuri N, Lemiere C, Boulet LP, Martin JG, Nair P. Suboptimal treatment response to anti-IL-5 monoclonal antibodies in severe eosinophilic asthmatics with airway autoimmune phenomena. Eur Respir J. 2020 Oct 8;56(4):2000117. doi: 10.1183/13993003.00117-2020. Print 2020 Oct. |
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| ID | Term |
|---|---|
| D011657 | Pulmonary Eosinophilia |
| D001249 | Asthma |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D017681 | Hypereosinophilic Syndrome |
| D004802 | Eosinophilia |
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| ID | Term |
|---|---|
| C515492 | reslizumab |
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Patients will initially all receive 3 mg/kg of reslizumab. After 16 weeks of treatment, those patients that have uncontrolled sputum eosinophilia will be escalated to 4 mg/kg; the remaining patients will continue on 3 mg/kg. After a further 16 weeks of therapy, those that still have uncontrolled sputum eosinophilia will receive 5 mg/kg; the remaining patients will continue on the dose they were receiving (i.e., either 3 or 4 mg/kg).
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Absolute blood eosinophil count
| At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| Change in ACQ5 score | Mean of 5-question Asthma Control Questionnaire | At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| Change in FEV1 | Forced expired volume in 1 second measured in litres | At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| Change in Number of asthma exacerbations | Number of asthma event that are defined as exacerbation (requiring increase in corticosteroids) | At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| Change in Type of asthma exacerbations (as determined by quantitative sputum cytometry) | Type of exacerbation shown by: neutrophilic, eosinophilic or mixed neutrophilic/eosinophilic bronchitis | At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| Change in Proportion of patients requiring daily oral corticosteroid therapy | Number of patients that require daily oral corticosteroids | At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| Change in Cumulative systemic corticosteroid dose | The total daily dose of oral corticosteroids | At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks |
| 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. |
| 32333684 | Background | Passarell J, Jaworowicz D, Ludwig E, Rabinovich-Guilatt L, Cox DS, Levi M, Garin M, Fiedler-Kelly J, Bond M. Population Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Modeling of Weight-Based Intravenous Reslizumab Dosing. J Clin Pharmacol. 2020 Aug;60(8):1039-1050. doi: 10.1002/jcph.1609. Epub 2020 Apr 25. |
| D007960 |
| Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001982 | Bronchial Diseases |
| D008173 | Lung Diseases, Obstructive |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |