Study design and patients
The two duplicate trials enrolled patients aged 12–75 years with inadequately controlled asthma (Asthma Control Questionnaire-7 [ACQ-7] score ≥ 1.5) on medium-to-high doses of inhaled corticosteroids (ICS), and who had screening EOS ≥ 400 cells/μL, ≥ 1 CAE in the previous year, and FEV1 reversibility of ≥ 12% with albuterol . The selection criteria for FEV1 reversibility were chosen based on National Asthma Education and Prevention Program guidelines available at the time of study design .
Both trials were conducted in accordance with Good Clinical Practice guidelines, the Declaration of Helsinki, and local regulatory requirements. All patients provided written informed consent, and the relevant health authorities and local ethics committees or institutional review boards approved the study protocols.
Following a 2–4-week screening period, patients were randomized (1:1) to receive IV reslizumab (3.0 mg/kg) or matching placebo q4w for 52 weeks. Patients continued their usual asthma treatment during the screening, run-in and treatment periods. Pre-bronchodilator spirometry, Asthma Symptom Utility Index (ASUI), and ACQ-7 were assessed q4w at the scheduled clinic visits, from day of randomization to the end of treatment. Possible cases of CAEs were assessed by questioning of the patient at every scheduled monthly visit. Asthma Quality of Life Questionnaire (AQLQ) score was assessed at baseline and weeks 16, 32, and 52.
FEV1 reversibility at baseline (during screening) was assessed according to EOS category at baseline (day of first dose). Categories for baseline FEV1 reversibility were arbitrarily set at < 14%, 14 to < 16%, 16 to < 20% and ≥ 20%, with baseline EOS categories set arbitrarily at < 150 cells/µL, 150 to < 400 cells/µL, 400 to < 700 cells/µL and ≥ 700 cells/µL. Given that blood eosinophil counts are known to be variable over time, assessment of blood eosinophil count at baseline allowed for selection of patients with persistently elevated blood eosinophils ≥ 400 cells/µL at two timepoints (screening and baseline).
The effect of reslizumab versus placebo on asthma clinical outcomes was also assessed in the subgroup with baseline low FEV1 reversibility (12–14%) and pooled high EOS (≥ 400 cells/µL). Assessment of lung function comprised FEV1, FEV1% predicted, forced vital capacity (FVC) and forced expiratory flow at 25–75% of pulmonary volume (FEF25–75%), and other asthma clinical outcomes assessed were CAEs, ACQ-7, AQLQ and ASUI.
An analysis of covariance was used to model change from baseline at Week 52 in lung function and patient-reported outcomes (ACQ-7, AQLQ and ASUI) with fixed factors for treatment arm, sex, oral corticosteroid use at baseline (Yes or No), region (USA or Other), and a continuous covariate for height.
CAEs counted are those which occurred between the completion of the first dose of study drug and 2 weeks after the end of treatment/early withdrawal visit. CAE rates, CAE rate ratio, and confidence intervals (CIs) and p values are based on a negative binomial regression model adjusted for baseline usage of oral corticosteroid (Yes or No) and region (USA or other).
All analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).