Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma
Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma
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.
Inclusion Criteria:

 -  Able to give written informed consent prior to participation in the study

 -  At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)

 -  A well-documented requirement for regular treatment with high dose inhaled
 corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance
 oral corticosteroids (OCS)

 -  Current treatment with an additional controller medication, besides ICS, for at least
 3 months or a documented failure in the past 12 months of an additional controller
 medication for at least 3 successive months

 -  Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma

 -  At Visit 1, a pre-bronchodilator FEV1 <80% (for subjects >= 18 years of age), a
 pre-bronchodilator FEV1 <90% or FEV1:FVC ratio <0.8 (for subjects 12-17 years of age).

 -  Previously confirmed history of two or more exacerbations requiring treatment with
 systemic CS

 -  Male or Eligible Female (females of childbearing potential must commit to consistent
 and correct use of an acceptable method of birth control)

 -  French subjects will be included only if either affiliated to or a beneficiary of a
 social security category.

 Exclusion Criteria:

 -  Current smokers or former smokers with a smoking history of >=10 pack years

 -  Presence of a known pre-existing, clinically important lung condition other than
 asthma

 -  A current malignancy or previous history of malignancy in less than 12 months

 -  Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities

 -  Known, pre-existing severe or clinically significant cardiovascular disease

 -  known, pre-existing other concurrent clinically significant medical conditions that
 are uncontrolled with standard treatment

 -  Subjects with any eosinophilic diseases

 -  QTc(F) ≥450msec or QTc(F) ≥480 msec

 -  A history of alcohol/substance abuse

 -  Subject with known immunodeficiency

 -  Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal
 antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of
 Visit 1

 -  Subjects who have received treatment with an investigational drug within the past 30
 days or five terminal phase half-lives of the drug whichever is longer

 -  Subjects with allergy/intolerance to a monoclonal antibody or biologic.

 -  Subjects who are pregnant or breastfeeding

 -  Subjects who have known evidence of lack of adherence to controller medications and/or
 ability to follow physician's recommendations

 -  Previously participated in any study with mepolizumab and received investigational
 product (including placebo)