Long-term Access Program (LAP) of Mepolizumab for Subjects Who Participated in Study MEA115921

Study Overview
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Brief Summary
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Eosinophilic Granulomatosis with Polyangiitis (EGPA), also referred to as Churg-Strauss syndrome, is a rare hyper-eosinophilic syndrome. Eosinophilia is central to the pathophysiology of EGPA and interleukin-5 (IL-5) is a key cytokine regulating the life-cycle of the eosinophil. Neutralization of IL-5 with mepolizumab, an anti-IL5 monoclonal antibody, therefore offers a potential therapeutic option for EGPA. The objective of study MEA115921 was to investigate the efficacy and safety of mepolizumab compared with placebo wherein the subjects were randomized to receive either: 300 milligram (mg) mepolizumab or Placebo subcutaneous (SC) injection every 4 weeks in addition to their background standard-of-care therapy. Subjects were treated for a period of 52 weeks and then followed up for a further 8 weeks to study completion at Week 60. This is a LAP to support provision of open-label mepolizumab on an individual basis to eligible subjects who participated in clinical study MEA115921 and who require a dose of prednisolone (or equivalent) of >=5 milligrams per day (mg/day) for adequate control of their EGPA. Eligible subjects can initiate mepolizumab under this LAP within a 6-month period starting from completion of study MEA115921 (that is, at Week 60) or, in case of premature discontinuation from study MEA115921, the subjects will initiate mepolizumab at the time point that would have been Week 60 if the subject had completed the study. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks. Eligible subjects will continue to receive mepolizumab under this LAP until mepolizumab is commercially licensed for the treatment of EGPA in the relevant country or until GlaxoSmithKline (GSK) discontinues the program or until the subject meets any of the withdrawal/stopping criteria.

Official Title
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Mepolizumab Long-term Access Programme for Subjects Who Participated in Study MEA115921 (Placebo-controlled Study of Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis in Subjects Receiving Standard-of-care Therapy)

Conditions
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Churg-Strauss Syndrome

Intervention / Treatment
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* Drug: Mepolizumab
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject participated in study MEA115921. Subject has either: a) completed study MEA115921 to Week 60, that is, completion of follow up period, or b) if the subject was withdrawn prematurely from study MEA115921, the subject has reached the date of what would have been the Week 60 if the subject had completed the study, that is, 60 weeks from Baseline (Visit 2). At or up to 6 months after the MEA115921 Week 60 time- point the subject requires a dose of prednisolone (or equivalent) of >=5 mg/day for adequate control of their EGPA. The treating physician requesting mepolizumab under this LAP considers the benefits of treatment with mepolizumab outweigh the risks for the individual subject. To be eligible for mepolizumab treatment under this LAP, females of childbearing potential (FCBP) must commit to consistent and correct use of an acceptable method of birth control, beginning with consent, for the duration of the treatment with mepolizumab and for 4 months after the last mepolizumab administration. The subject consents to receiving treatment with mepolizumab under this LAP. Exclusion Criteria: A current malignancy or history of cancer in remission for less than 12 months (Subjects who had localized carcinoma (that is, basal or squamous cell) of the skin which was resected for cure will not be excluded). Subject has other clinically significant medical conditions uncontrolled with standard of care therapy not associated with EGPA, example, unstable liver disease, uncontrolled cardiovascular disease, ongoing active infectious disease requiring systemic treatment. Subject is pregnant or breastfeeding. Subjects should not be considered for continued treatment if they plan to become pregnant during the course of treatment with mepolizumab. Subject has a known allergy or intolerance to a monoclonal antibody or biologic therapy including mepolizumab. Subject had an adverse event (serious or non-serious) considered related to study treatment whilst participating in study MEA115921 which resulted in permanent withdrawal of study treatment. Subject is receiving treatment with another biological therapy such as a monoclonal antibody therapy or intravenous (IV) immunoglobulin therapy without prior agreement from the GSK Medical Monitor. Subjects who have received treatment with an investigational drug within the past 30 days or 5 terminal phase half-lives of the drug whichever is longer, prior to initiation of mepolizumab treatment under this LAP (this also includes investigational formulations of marketed products). Subject is currently participating in any other interventional clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects who participated in clinical study MEA115921 and require a dose of prednisolone (or equivalent) of >=5 mg/day for adequate control of their EGPA will be included in this study based on the confirmation of their eligibility by GSK Medical Monitor. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects from clinical study MEA115921<br>Subjects who participated in clinical study MEA115921 and who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks. | Drug: Mepolizumab<br>* Mepolizumab will be available as lyophilized powder for injection to be reconstituted with sterile water for injection, prior to use. Subjects will be dosed with mepolizumab at a dose of 300 mg which will be administered as three separate 100 mg SC injections every 4 weeks. The injections will be administered into any of the upper arm, thigh or anterior abdominal wall.<br>Drug: Prednisolone<br>* Subjects who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with corticosteroid use | The use of corticosteroids excluding inhaled and topical steroids will be summarized. | Up to 3 years approximately | 
| Number of subjects with adverse events (AEs) and serious adverse events (SAEs) | An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events based on medical or scientific judgment; and is associated with liver injury and impaired liver function. Additionally, systemic (that is, allergic/hypersensitivity and non-allergic) reactions and local injection site reactions will be recorded throughout the treatment and follow-up period. | Up to 3 years approximately | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eosinophilic Granulomatosis, MEA115921, Polyangiitis, Long-term access program, mepolizumab