Conditions: Asthma
Keywords: safety SB-240563 efficacy placebo eosinophils mepolizumab Severe refractory asthma
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 580
Healthy volunteers: no

Brief summary:
This study will evaluate two dose regimens of mepolizumab \[75mg intravenous (i.v.) or 100mg subcutaneous (SC) every 4 weeks\] compared with placebo over a 32 week treatment period in subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be measured by a reduction in the frequency of asthma exacerbations. Additional efficacy assessments will include measurements of lung function, symptom scores, and quality of life. Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse events.

This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588, who meet all eligibility criteria at screening visit, will enter the run-in period. Those subjects that are not able/eligible to be randomised at the end of the 6 week run-in period will be deemed run-in failures. Subjects will remain on their current maintenance therapy throughout the run-in, double-blind treatment administration and follow-up periods. Subjects who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75 miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v. and placebo SC.

Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to participate in the OLE trial.

Detailed description:

Arms:
arm 1: Mepolizumab 75 mg will be administered intravenously approximately every 4 weeks with the last dose at week 32. Subjects in the Mepolizumab IV arm will receive mepolizumab 75 mg intravenously and placebo SC once every 4 weeks with the last dose at Week 28 (total of 8 doses) arm 2: Subjects in the Mepolizumab SC arm will receive mepolizumab 100 mg SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses) arm 3: Subjects in the Placebo arm will receive matching placebo SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)

Interventions: intervention 1: Mepolizumab IV intervention 2: Mepolizumab SC intervention 3: IV Placebo intervention 4: SC Placebo
Intervention descriptions: intervention 1: Mepolizumab 75 mg IV will be administered every 4 weeks with the last dose at Week 28 intervention 2: Mepolizumab 100 mg SC will be administered every 4 weeks with the last dose at Week 28 intervention 3: Normal saline (placebo) will be administered IV every 4 weeks with the last dose at Week 28 intervention 4: Normal saline (placebo) will be administered SC every 4 weeks with the last dose at Week 28

Protocol document: