The purpose of this trial is to confirm the safety and clinical benefit of benralizumab administration in asthma patients with mild to moderate persistent asthma in order to gain an understanding of the benefit/risk of benralizumab across the spectrum of asthma disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
211
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12
The FEV1 (L) change from baseline are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect repeated measures (MMRM) analysis with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL), protocol specified visit (Week 4, Week 8, Week 12), region (Europe or North America) and treatment\*visit interaction as fixed effects and baseline pre-bronchodilator FEV1 (L) as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline, Week 4, Week 8 and Week 12
Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
The changes from baseline of weekly average of morning PEF (L/min) are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model for repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL), protocol specified visit, region (Europe or North America) and treatment\*visit interaction as fixed effects and baseline morning PEF (L/min) as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
The changes from baseline of weekly average of evening PEF (L/min) are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model for repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL), protocol specified visit, region (Europe or North America) and treatment\*visit interaction as fixed effects and baseline evening PEF (L/min) as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Research Site
Los Angeles, California, United States
Research Site
Rolling Hills Estates, California, United States
Research Site
Clearwater, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
Blue Island, Illinois, United States
Research Site
Skillman, New Jersey, United States
Research Site
Charlotte, North Carolina, United States
Research Site
Monroe, North Carolina, United States
Research Site
Raleigh, North Carolina, United States
Research Site
Winston-Salem, North Carolina, United States
...and 47 more locations
Change From Baseline in Total Asthma Symptom Score at Week 12
Asthma symptoms were recorded by the patient each morning and evening in the asthma daily diary. Symptoms were recorded using a scale of 0-3, where 0 indicates no asthma symptoms. The daily asthma symptom total score was calculated by taking the sum of the daytime score recorded in the evening and the nighttime score recorded the following morning. The weekly total asthma score was averaged from the daily scores over a 7 day period, with score ranging from 0 to 6, where 0 indicates no asthma symptoms. The changes from baseline of weekly total asthma score are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL), protocol specified visit, region (Europe or North America) and treatment\*visit interaction as fixed effects and baseline total asthma score as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12
The number of rescue medication inhalations and nebulizer treatments taken were recorded by the patient in the asthma daily diary twice daily. The number of inhalations (puffs) per day was calculated as \[number of night inhaler puffs\] + 2 x \[number of night nebulizer times\] + number of day inhaler puffs + 2 x \[number of day nebulizer times\]. The changes from baseline in weekly total asthma rescue medication use (puffs) are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL), protocol specified visit, region (Europe or North America) and treatment\*visit interaction as fixed effects and baseline total asthma rescue medication use (puffs) as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12
Nocturnal awakenings due to asthma symptoms and requiring rescue medication use was recorded by the patient in the asthma daily diary each morning. Proportion of nights with nocturnal awakenings was defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data for awakening due to asthma. The outcome variable for proportion of nights with nocturnal awakenings was the change from baseline at Week 12 in weekly proportion of nights with nocturnal awakenings. The changes are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL), protocol specified visit, region (Europe or North America) and treatment\*visit interaction as fixed effects and baseline proportion of nights with nocturnal awakenings as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Change From Baseline in Mean ACQ-6 Score at Week 12
The asthma control questionnaire, ACQ-6, consists of six questions; all assessed on a 7-point scale from 0 to 6, where 0 represents good control and 6 represents poor control. The overall score is the mean of the responses to each of the six questions. The changes from baseline of ACQ-6 score are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL), protocol specified visit (Week 4, Week 8, Week 12), region (Europe or North America) and treatment\*visit interaction as fixed effects and baseline ACQ-6 score as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline, Week 4, Week 8 and Week 12
Asthma Exacerbations
An asthma exacerbation was defined as a worsening of asthma that led to use of systemic corticosteroids for at least 3 days (a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids) or an emergency room or urgent care visit (defined as evaluation and treatment for \<24 hours in an emergency department or urgent care center) due to asthma that required systemic corticosteroids (as per above) or an inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma. Number of patients experiencing an event included in the definition of asthma exacerbation was presented.
Time frame: Up to Week 12
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
The asthma quality of life questionnaire for 12 years and older, AQLQ(S)+12, consists of 32 questions; all assessed on a 7-point scale from 7 to 1, where 7 represents no impairment and 1 represents severe impairment. The 4 individual domain scores (symptoms, activity limitations, emotional function, and environmental stimuli) are the means of the responses to the questions in each of the domains. The overall score is calculated as the mean response to all questions. The changes from baseline of AQLQ(S)+12 score are compared between benralizumab 30 mg Q4W and placebo by using the analyse of covariance (ANCOVA) with baseline blood eosinophil count (≥300 cells/μL or \<300 cells/μL) and region (Europe or North America) as fixed effects and baseline AQLQ(S)+12 score as a covariate. Changes at Week 12 were calculated based on patients with both baseline and Week 12.
Time frame: Baseline and Week 12
Serum Concentrations (ng/mL)
Blood samples (processed to serum) for pharmacokinetic assessments were collected from all patients at baseline prior to first benralizumab administration at Day 1, at the Week 12 visit or the IP discontinuation visit, and at the Week 20 follow-up visit. Serum concentrations of benralizumab were determined using a validated electrochemiluminescent (ECL) immunoassay.
Time frame: Baseline, Week 12 and Week 20
Peripheral Blood Eosinophil Levels
Peripheral blood eosinophil levels assessments were collected from all patients at baseline prior to first benralizumab administration at Day 1, at the Week 12 visit or the IP discontinuation visit, and at the Week 20 follow-up visit. Changes at Week 12 (respectively at Week 20) were calculated based on patients with both baseline and Week 12 (respectively Week 20).
Time frame: Baseline, Week 12 and Week 20