A Phase 3a, Repeat Dose, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects
Condition: Asthma
MeSH terms: Asthma
Intervention: Mepolizumab; SOC
Intervention description: Mepolizumab is a fully humanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks. Mepolizumab will be supplied as a lyophilised cake in sterile vials for individual use.; Standard of Care (SOC) will differ by participant, however it will generally include oral corticosteroids and an inhaled controller medicine (an inhaled corticosteroid plus a long acting beta agonist) and/or short acting beta agonists
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 339.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Severe eosinophilic asthma; Extension study; Expanded access; Safety; Mepolizumab; Eosinophils

Summary:

      This is a multi-center, open-label, long-term study of subcutaneously (SC) administered
      mepolizumab 100mg in addition to standard of care (SOC), in subjects with severe eosinophilic
      asthma. This study will enroll a subset of subjects from Study MEA115661 who have
      demonstrated clear benefit from therapy and who without continuation of mepolizumab therapy
      are individuals at greatest risk of serious deterioration of their health status. In order to
      target individuals at greatest risk for serious deterioration of their health status, only
      subjects from the MEA115661 study with a history of life-threatening or seriously
      debilitating asthma, will be allowed to participate. Subjects meeting all of the eligibility
      criteria for the study will be offered the opportunity to consent for this study of up to 128
      weeks in length (including the Follow-Up Visit). This study will give opportunity to extend
      the collection of clinical data for long-term use and further assess the sustainability of
      efficacy in a population likely to experience significant loss of asthma control and the need
      for higher doses of systemic steroids if returned to SOC only.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed Consent: Prior to commencing any study related activities, subjects must be
             able and willing to provide written informed consent.

          -  Male or Eligible Female Subjects: To be eligible for the study, females of
             child-bearing potential must commit to consistent and correct use of an acceptable
             method of birth control and for 4 months after the last study drug administration. A
             urine pregnancy test is required of all females of childbearing potential at the
             initial Baseline Visit (Visit 1).

          -  French Subjects Only: In France, a subject will be eligible for inclusion in this
             study only if either affiliated to or a beneficiary of a social security category.

          -  MEA115661 Participation: Subjects must have completed Visit 14 of MEA115661.

          -  Current Anti-Asthma Therapy: The subject's asthma has been treated with an ICS
             controller medication for the last 8 months with fluticasone propionate (FP) >=500
             mcg/day (or equivalent).

          -  Disease Severity: Subjects must be assessed as having life-threatening /serious
             debilitating asthma in order to enroll, as defined by the following: Subjects enrolled
             in MEA115588 must meet one of the following criteria: a) Subject has a history of at
             least one intubation during their lifetime; b) >=3 asthma exacerbations in the 12
             months prior to screening for MEA115588; c) >=1 or more hospitalization for asthma
             exacerbation in the 12 months prior to screening for MEA115588. Subjects enrolled in
             MEA115575 must meet one of the following criteria: d) Subject has a history of at
             least one intubation during their lifetime; e) Their optimized dose at randomization
             in MEA115575 was >=10mg of prednisone; f) >=1 or more hospitalization for asthma
             exacerbation in the 12 months prior to screening for MEA115575.

          -  Clinical Benefit: Subjects must have experienced documented clinical benefit to
             enroll. Subjects must meet the following criteria demonstrating clinical benefit:
             Subjects enrolled in MEA115588 who received mepolizumab must meet all of the following
             criteria: a) Subject must have had a reduction in their exacerbation frequency by
             >=50% during MEA115588. The baseline for comparison is the total number of
             exacerbations reported in the 12 months prior to screening for MEA115588. b) The
             investigator response on the "Clinician-Rated Response to Therapy" questionnaire at
             Visit 10 was either: mildly improved, moderately improved or significantly improved.
             Subjects enrolled in MEA115588 who received placebo must meet all of the following
             criteria: c) Subject must have had a reduction in their exacerbation frequency by
             >=50% during the first 8 months of MEA115661. The baseline for comparison is the total
             number of exacerbations reported in the 12 months prior to screening for MEA115588; d)
             The investigator confirms that the subject demonstrated improvement during MEA115661.
             Subjects enrolled in MEA115575 who received mepolizumab must meet all of the following
             criteria: e) Subject must have reduced their oral corticosteroid dose by >=50% during
             MEA115575. The baseline for comparison is the subject's optimized oral corticosteroid
             (OCS) dose at randomization in MEA115575; f) The investigator response on the
             "Clinician-Rated Response to Therapy" questionnaire at Visit 9 was either: mildly
             improved, moderately improved or significantly improved. Subjects enrolled in
             MEA115575 who received placebo must meet all of the following criteria: g) Subject
             must have reduced their oral corticosteroid dose at randomization by >=50% in the
             first 6 months of MEA115661. The baseline for comparison is the subject's optimized
             OCS dose at randomization in MEA115575; h) The investigator confirms that the subject
             demonstrated improvement during MEA115661.

        Exclusion Criteria

          -  Health Status: Clinically significant change in health status during MEA115661 which
             in the opinion of the investigator would make the subject unsuitable for participation
             in this long-term study.

          -  Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled
             if they plan to become pregnanDeart during the time of study participation.

          -  Exacerbation History: Subjects who received placebo in MEA115588 and had NO
             exacerbations during the study.

          -  Oral Corticosteroid Use: Subjects who received placebo in MEA115575 and were able to
             discontinue oral corticosteroid therapy by the end of the study.

          -  Smoking Status: Current smokers

          -  Previous Significant Protocol Deviation: Subjects who were excluded from the per
             protocol analysis due to significant protocol deviations in either study MEA115575 or
             MEA115588.

          -  Electrocardiogram (ECG) Assessment: A clinically significant ECG abnormality at the
             exit visit of MEA115661, as determined by the investigator.