Severe Persistent Asthma Clinical Trial
Official title:
Route of Administration of Anti-IL5 Monoclonal Antibody in Prednisone-dependent Eosinophilic Asthma
The steroid sparing effect of anti interleukin (IL-5) monoclonal antibody has been proven, but the effectiveness of subcutaneous (SC) compared to intravenous (IV) administration of these drugs to suppress airway eosinophilia is still under debate. As part of a previous study, 100mg of mepolizumab were administered subcutaneously to a group of subjects with prednisone-dependent eosinophilic asthma. Despite this intervention, 50% of the subjects (15 patients participated in this study) had persistently elevated sputum eosinophil counts. The same 15 patients will be invited to participate in the current study, and if they provide their informed consent, will receive 2 monthly doses of placebo, followed by 4 monthly doses of IV reslizumab. The primary outcomes are blood and sputum eosinophils, and the secondary outcomes include sputum and blood Innate lymphoid cell-2 (ILC2) cells, cluster of differentiation 4 (CD4+) cells, cluster of differentiation-8 (CD8+) cells, cluster of differentiation-34 (CD34+), Eosinophil-Basophil cluster cells (Eo/B progenitor cells), forced expired volume in 1 second (FEV1), asthma control questionnaire (ACQ) and number of eosinophilic exacerbations. Measurements of the outcomes will be done before placebo, after placebo and after IV reslizumab. This study design will determine whether IV reslizumab is effective in suppressing airway eosinophilia in prednisone-dependent patients.
Study design
Blinded placebo-controlled sequential clinical trial of 4 monthly doses of intravenously
administered reslizumab.
The study will include two periods:
Period 1: After establishing the minimum dose of prednisone to observe sputum eosinophils ≥3%
and blood eosinophils ≥300/µL, all subjects will receive 2 infusions (once monthly) of
matching placebo.
Period 2: All subjects will then receive 4 infusions (once monthly) of reslizumab 3mg/kg.
Methods
15 patients (all of whom had sputum eosinophils ≥3% and blood eosinophils ≥300/µL) who were
previously treated with S/C100 mg mepolizumab for at least 6 months, with the last dose at
least 4 months before entering the study, will be invited to participate in the study.
Since discontinuing mepolizumab, these patients would have been re-established on their
maintenance dose of daily prednisone + high doses of inhaled corticosteroids (ICS) and long
acting beta agonist (LABA).
Baseline measurements of blood and sputum eosinophils, spirometry, symptoms (ACQ), and immune
cells in blood and sputum (ILC2 cells, CD4 + cells, CD8+ cells, CD34+ Eo/B progenitor cells)
will be enumerated by flow cytometry, and measures of local autoimmunity, using our
established protocols at the start of Period 1 (baseline measurement).
They will then receive 2 infusions of placebo at monthly intervals, and measurements will be
repeated at the end of Period 1 (post-placebo measurement).
The subjects will then receive by 4 infusions of 3 mg/kg reslizumab at monthly intervals. At
the end of the 4 months, these measurements will be repeated (post-reslizumab measurement).
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