A Phase 3a, Repeat Dose, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects
A Phase 3a, Repeat Dose, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects
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.
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.