Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Mepolizumab 750; Mepolizumab 250; Mepolizumab 75; Placebo saline
Intervention description: Mepolizumab 750mg every four weeks by i.v.; Mepolizumab 250mg every four weeks by i.v.; Mepolizumab 75mg every four weeks by i.v.; Placebo saline every four weeks by i.v.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 621.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Dose-ranging; Safety; Pharmacodynamics; eosinophils; SB-240563; Efficacy; Severe refractory asthma; mepolizumab; Placebo

Summary:

      The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously
      (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma
      despite receiving high doses of standard asthma medications. The study will look at different
      doses of mepolizumab in comparison to a placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female

          -  Aged 12 to 65 years inclusive

          -  Minimum weight 45kg

          -  Clinical features of severe refractory asthma

          -  Well documented requirement for high dose inhaled corticosteroids (ICS) [i.e. >=
             880mcg/day fluticasone propionate or equivalent daily] for at least 12 months

          -  Using additional controller medication in addition to high dose ICS for at least 12
             months

          -  Persistent airflow obstruction indicated by a pre-bronchodilator FEV1<80% predicted at
             visit 1 or 2 or peak flow diurnal variability of >20% on 3 or more days during the
             run-in

          -  Airway inflammation which is likely to be eosinophilic in nature demonstrated by
             either raised peripheral blood eosinophils (>=300/microL), sputum eosinophils (>=3%),
             exhaled nitric oxide (>=50ppb) or prompt deterioration of asthma control following a
             <=25% reduction in regular maintenance dose of inhaled or oral corticosteroids (OCS)

          -  History of 2 or more exacerbations requiring systemic corticosteroids in the previous
             12 months

          -  Evidence of asthma documented by airway reversibility, airway hyperresponsiveness or
             airflow variability

          -  ECG assessment demonstrating QTc<450msec or QTc<480msec for patients with bundle
             branch block

          -  Liver function tests demonstrating ALT<2xUpper Limit of Normal (ULN), AST<2xULN, Alk
             Phos <=1.5xULN, bilirubin <=1.5xULN

          -  Female of non-child-bearing potential or child-bearing potential with a negative
             pregnancy test at screening and prepared to agree to an acceptable method of
             contraception

          -  Able to give written informed consent

          -  Able to read, comprehend and write at a sufficient level to complete study materials

        Exclusion Criteria:

          -  Current smokers or smoking history of >=10 pack years

          -  Clinically important lung condition other than asthma

          -  Diagnosis of malignancy or in the process of investigation

          -  Unstable liver disease

          -  Churg-Strauss syndrome

          -  Using methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any
             experimental anti-inflammatory therapy within 3 months of screening

          -  Omalizumab (Xolair) or any other biological for the treatment of inflammatory disease
             within 6 months of Visit 1

          -  Regular use of oral or systemic corticosteroids for diseases other than asthma within
             12 months or any intra-articular, short-acting intramuscular corticosteroid within 1
             month or intramuscular, long-acting depot corticosteroid within 3 months

          -  Allergy/intolerance to the excipients in the mepolizumab formulation

          -  Any investigational drug within 30 days or 5 terminal half-lives, whichever is longer

          -  Pregnant or breastfeeding or planning to become pregnant

          -  Clinically significant disease which is uncontrolled with standard treatment

          -  History of alcohol misuse or substance abuse

          -  Parasitic infestation within previous 6 months

          -  Known immunodeficiency

          -  Unable to follow instructions, use the electronic diary or peak flow meter

          -  Known evidence of lack of adherence to controller medications and/or follow
             physician's recommendations

          -  Previous participation in a study of mepolizumab and received study medication within
             90 days