Study Designs

See the full study descriptions for SIROCCO, CALIMA, ZONDA, Phase 2, BORA, and ANDHI.

01

SIROCCO and CALIMA (Trials 1 and 2)

SIROCCO (48-week) and CALIMA (56-week) were 2 randomized, double-blind, parallel-group, placebo-controlled, multicenter studies comparing FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter; benralizumab 30 mg SC Q4W, and placebo SC. A total of 1204 (SIROCCO) and 1306 (CALIMA) patients aged 12-75 years old with severe asthma uncontrolled on high-dose ICS (SIROCCO) and medium- to high-dose ICS (CALIMA) plus LABA with or without additional controllers were included. Patients had a history of ≥2 exacerbations requiring systemic corticosteroids or temporary increase in usual dosing in the previous year. Patients were stratified by geography, age, and blood eosinophil counts (≥300 cells/μL and <300 cells/μL). The primary endpoint was annual exacerbation rate ratio vs placebo in patients with a blood eosinophil count of ≥300 cells/μL on a high-dose ICS and LABA. Exacerbations were defined as a worsening of asthma that led to use of systemic corticosteroids for ≥3 days, temporary increase in a stable OCS background dose for ≥3 days, emergency/urgent care visit because of asthma that needed systemic corticosteroids, or inpatient hospital stay of ≥24 hours because of asthma. Key secondary endpoints were pre-bronchodilator FEV1 and total asthma symptom score at Week 48 (SIROCCO) and Week 56 (CALIMA) in the same population.1,2

02

ZONDA (Trial 3)

A 28-week, randomized, double-blind, parallel-group, placebo-controlled, multicenter OCS reduction study comparing the efficacy and safety of FASENRA (30 mg SC) Q4W for the first 3 doses, then Q8W thereafter; benralizumab (30 mg SC) Q4W, and placebo (SC) Q4W. A total of 220 adult (18-75 years old) patients with severe asthma on a high-dose ICS plus LABA and daily OCS (7.5 to 40 mg/day), a blood eosinophil count of ≥150 cells/μL, and a history of ≥1 exacerbation in the previous year were included. The primary endpoint was the median percent reduction from baseline in the final daily OCS dose while maintaining asthma control.3

03

Phase 2 Study

A 12-week, phase 2, randomized, double-blind, placebo-controlled, dose-increase study of benralizumab in adults with mild to moderate asthma. Patients were randomized to receive SC administration of benralizumab 25 mg (n=6), benralizumab 100 mg (n=6), benralizumab 200 mg (n=6), or placebo (n=6) Q4W for a total of 3 doses. One objective was to assess the effect of benralizumab on blood eosinophil counts and protein biomarkers. Median blood eosinophil levels at baseline were 400, 200, 120, and 200 cells/μL in the 25, 100, and 200 mg benralizumab and placebo groups, respectively.4

04

BORA (Phase 3 Safety Extension Trial of SIROCCO and CALIMA)

A randomized, double-blind, parallel-group, phase 3 extension study that enrolled patients who completed SIROCCO or CALIMA (n=1576). Patients enrolled in the previous studies were aged 12-75 years and had physician-diagnosed asthma requiring treatment with medium-dosage or high-dosage ICS plus LABA for at least 12 months with or without additional controllers prior to enrollment. Patients originally randomized to FASENRA continued FASENRA 30 mg SC Q8W or benralizumab SC Q4W. Patients previously receiving placebo were re-randomized 1:1 to FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter or benralizumab 30 mg SC Q4W except for adolescent patients in the EU who were randomized to FASENRA 30 mg SC Q8W. Patients were to be maintained on their same dose of ICS/LABA. End of treatment was at Week 56 for adults and Week 108 for adolescents. The primary objective was assessment of safety and tolerability. Secondary objectives included assessments of asthma exacerbations, pre-bronchodilator forced expiratory volume in 1 second (FEV1), and impact of treatment on blood eosinophil levels. Results are at Weeks 68 (adult follow-up) and 56 (adolescents), unless otherwise noted.5

05

ANDHI (Phase 3b Exacerbation Rate Reduction Trial)

ANDHI was a 24-week, randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase 3b study that enrolled patients aged 18-75 years with severe eosinophilic asthma. A total of 660 patients were randomized 2:1 to FASENRA 30 mg SC Q4W for the first 3 doses then Q8W thereafter or matched placebo SC. Patients had a history of ≥2 exacerbations in the prior year despite treatment with medium- to high-dose ICS plus another asthma controller. Patients must have been on high-dose ICS plus another asthma controller for 3 months prior to enrollment. Patients were included in the trial if they had a blood eosinophil count of ≥300 cells/μL or a blood eosinophil count of ≥150 to <300 cells/μL plus ≥1 of the following: maintenance oral corticosteroid (OCS) use at study entry, history of nasal polyps, forced vital capacity (FVC) <65% predicted, ≥3 exacerbations in the previous year, or ≥18 years at asthma diagnosis. Patients were stratified by previous exacerbation count, maintenance OCS use, and region. The primary endpoint was annualized asthma exacerbation rate. The key secondary endpoint was change from baseline to Week 24 in St. George's Respiratory Questionnaire (SGRQ) score. Other secondary endpoints included FEV1, peak expiratory flow, and Asthma Control Questionnaire-6 (ACQ-6).6

IMPORTANT SAFETY INFORMATION