Anti-Interleukin-5 (IL5) Monoclonal Antibody (MAb) in Prednisone-dependent Eosinophilic Asthma
Condition: Severe Persistent Asthma; Eosinophilic Bronchitis
MeSH terms: Bronchitis; Asthma; Pulmonary Eosinophilia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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.
    

Detailed description: 
      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).
    

Intervention name(s): Reslizumab; Placebo
Intervention type(s): Biological; Drug
Intervention description(s): Reslizumab 3ml/kg once monthly for 4 months; Matching placebo once monthly for 2 months
Other intervention name(s): Anti Il 5 monoclonal antibody; 0.9% normal saline
Intervention MeSH terms: Reslizumab
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Reslizumab; Eosinophils; Asthma; Airway inflammation; Prednisone