Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Mepolizumab IV; Mepolizumab SC; IV Placebo; SC Placebo
Intervention description: Mepolizumab 75 mg IV will be administered every 4 weeks with the last dose at Week 28; Mepolizumab 100 mg SC will be administered every 4 weeks with the last dose at Week 28; Normal saline (placebo) will be administered IV every 4 weeks with the last dose at Week 28; Normal saline (placebo) will be administered SC every 4 weeks with the last dose at Week 28
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 580.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: safety; SB-240563; efficacy; placebo; eosinophils; mepolizumab; Severe refractory asthma

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.
    

Eligibility criteria:

        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)