Skip to main content
. 2017 Sep 21;2017(9):CD010834. doi: 10.1002/14651858.CD010834.pub3

FitzGerald 2016

Methods Multicentre, randomised, double‐blind, parallel‐group, placebo‐controlled trial
Participants 1306 participants with moderate‐severe (medium‐high‐dose ICS + LABA, ≥ 2 asthma exacerbations last 12 months, FEV1 < 80% predicted), ACQ‐6 ≥ 1.5 at enrolment

  1. Main inclusion/exclusion criteria:

    1. ≥ 2 exacerbations in the previous 12 months

    2. ACQ‐6 score ≥ 1.5 at enrolment

    3. FEV1 < 80%

    4. maintenance treatment with medium‐ (≥ 250 μg/day FP or equivalent) to high‐dose (≥ 500 μg/day FP or equivalent) ICS/LABA for ≥ 12 months; high‐dose ICS/LABA for ≥ 3 months

  2. Age mean (SD) years: eosinophil ≥ 300 cells per μL benralizumab 30 mg every 4 weeks, 50 (13.1); eosinophil ≥ 300 cells per μL benralizumab 30 mg Q8W. 50 (13.0); eosinophil ≥ 300 cells per μL placebo, 49 (14.1); eosinophil < 300 cells per μL benralizumab 30 mg every four weeks, 52 (12.2); eosinophil < 300 cells per μL benralizumab 30 mg Q8W, 51 (13.8); eosinophil < 300 cells per μL placebo, 52 (14.4)

  3. Males (%): eosinophil ≥ 300 cells per μL benralizumab 30 mg every four weeks, 82 (34); eosinophil ≥ 300 cells per μL benralizumab 30 mg Q8W, 101 (42); eosinophil ≥ 300 cells per μL placebo, 103 (42); eosinophil < 300 cells per μL benralizumab 30 mg every four weeks, 45 (39); eosinophil < 300 cells per μL benralizumab 30 mg Q8W, 38 (30); eosinophil < 300 cells per μL placebo, 46 (38).

  4. Baseline mean (SD) FEV1 % predicted: eosinophil ≥ 300 cells per μL benralizumab 30 mg every four weeks, 59 (13.7); eosinophil ≥ 300 cells per μL benralizumab 30 mg Q8W, 57 (14.2); eosinophil ≥ 300 cells per μL placebo, 58 (13.9); eosinophil < 300 cells per μL benralizumab 30 mg every four weeks, 57 (16.2); eosinophil < 300 cells per μL benralizumab 30 mg Q8W, 57 (15.2); eosinophil < 300 cells per μL placebo, 56 (16.3)

  5. Allocation: eosinophil ≥ 300 cells per μL benralizumab 30 mg every four weeks, 241; eosinophil ≥ 300 cells per μL benralizumab 30 mg Q8W, 239; eosinophil ≥ 300 cells per μL placebo, 248; eosinophil < 300 cells per μL benralizumab 30 mg every four weeks, 116; eosinophil < 300 cells per μL benralizumab 30 mg Q8W, 125; eosinophil < 300 cells per μL placebo, 122
Interventions 56 weeks (final follow‐up at 60 weeks). SC benralizumab 30 mg every 4 weeks for 56 weeks or every 4 weeks for 3 doses then 8 weeks thereafter for 56 weeks
Outcomes Primary outcomes

  1. Annual asthma exacerbations


Secondary outcomes

  1. Pre‐bronchodilator FEV1

  2. Total asthma symptom score

  3. Time to first asthma exacerbation

  4. Annual rate of asthma exacerbations associated with an ED visit, urgent care visit, or admission to hospital

  5. Post‐bronchodilator FEV1

  6. ACQ‐6 score

  7. AQLQ(S)+12 score

  8. EQ‐5D‐5L visual analogue scale (to rate current health status)

  9. Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire

  10. Use of healthcare resources

  11. Participant and clinician assessment of response to treatment

  12. PK parameter and anti‐drug antibodies

  13. Safety and tolerability of intervention
Notes Funding: AstraZeneca and Kyowa Hakko Kirin. 303 clinical research centres in 11 countries
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Participants were assigned to treatment groups using an interactive web‐based voice‐response system. Randomisation was stratified by ICS dosage at enrolment (high or medium), geographic region, age group (adult or adolescent), and peripheral blood eosinophil count at enrolment (< 300 cells per μL or ≥ 300 cells per μL)
Allocation concealment (selection bias) Low risk The study investigator assigned randomisation codes sequentially in each stratum as participants became eligible for randomisation, until each stratum was full
Blinding of participants and personnel (performance bias) All outcomes Low risk To preserve blinding, participants and study centre staff were masked to treatment allocation, placebo solution was visually matched with benralizumab solution, and both placebo and benralizumab were provided in accessorised (needle guards and finger phalanges), prefilled syringes.
Blinding of outcome assessment (detection bias) All outcomes Low risk As above
Incomplete outcome data (attrition bias) All outcomes Low risk The withdrawal rates were relatively low: placebo 11.1% (49/440); benralizumab 30 mg every four weeks 9.6% (41/425); benralizumab 30 mg every eight weeks 13.4% (59/441)
Selective reporting (reporting bias) Low risk Results for all listed primary and secondary outcomes were reported