NCT02559791

Anti-Interleukin-5 (IL5) Monoclonal Antibody (MAb) in Prednisone-dependent Eosinophilic Asthma

Route of Administration of Anti-IL5 Monoclonal Antibody in Prednisone-dependent Eosinophilic Asthma

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: McMaster University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Severe Persistent Asthma
• Eosinophilic Bronchitis

Interventions

Type	Name	Description
BIOLOGICAL	Reslizumab	Reslizumab 3ml/kg once monthly for 4 months
DRUG	Placebo	Matching placebo once monthly for 2 months

Timeline

• Start date: 2015-10-01
• Primary completion: 2017-04-01
• Completion: 2017-08-01
• First posted: 2015-09-24
• Last updated: 2018-04-04

Locations

1 site across 1 country: Canada