A Multi-center, Open-label Extension, Safety Study of Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES) From Study 200622
Condition: Hypereosinophilic Syndrome
MeSH terms: Hypereosinophilic Syndrome; Syndrome
Intervention: Mepolizumab
Intervention description: Mepolizumab will be available as 100 mg vial for injection. Subjects will receive three 100 mg SC injections for every 4 Weeks for a total of 5 doses during 20 Week treatment period.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: hypereosinophilic syndrome; hypereosinophilic syndrome flare; open-label extension study; Mepolizumab; SB240563; Long-term safety

Summary:

      This is an open-label extension study to Study 200622.In this study subjects from Study
      200622 will be continued on 4-weekly dosing with open-label mepolizumab 300 milligram (mg)
      subcutaneously (SC) for an additional 20 Weeks after completing the 32 Week study assessments
      post-randomization, while they continue with their background HES therapy per standard of
      care (SoC). Subjects from study 200622 will participate in this extension study if they had
      completed the 32-Week treatment period in study 200622 or if they were withdrawn from the
      study pre-maturely, but were continued in the study per protocol until 32 Weeks from
      randomization. Data from this study (205203) and 200622 will be combined to provide up to
      52-Week exposure data to further characterize the long-term safety profile of mepolizumab and
      provide additional data on the clinical benefit in HES subjects beyond 32 Weeks. The duration
      of the study participation will be 20 Weeks for subjects who continue with mepolizumab
      treatment via MHE104317/MHE112562 after this open-label extension study; and 28 Weeks for
      subjects who do not continue with MHE104317/MHE112562.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 12 years and older subjects who were enrolled in Study 200622.

          -  To be considered for Study 205203, subjects from study 200622 must have completed
             32-Week treatment period in the study or if the subject was withdrawn from study
             treatment prematurely during the 200622 study, but continued in the study per protocol
             (including HES flare-related assessments) until 32 Weeks from randomization.

          -  Male or female subjects. Female subjects must be either not a woman of childbearing
             potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance at least 30
             days prior to the first dose of study treatment and until 16 weeks after the last dose
             of study treatment.

          -  The treating physician must confirm a positive benefit/risk ratio. The anticipated
             clinical benefit from mepolizumab must outweigh any potential safety or tolerability
             risk in Study 205203.

          -  Capable of giving signed informed consent.

        Exclusion Criteria:

          -  Subjects with any history of hypersensitivity to any monoclonal antibody (including
             mepolizumab).

          -  Subjects with current malignancy or malignancy that developed during Study 200622.

          -  Subjects who is pregnant or breastfeeding.

          -  Subjects who has other clinically significant medical conditions uncontrolled with SoC
             therapy not associated with HES, example (e. g.), unstable liver disease, uncontrolled
             cardiovascular disease, ongoing active infectious disease.

          -  Subjects with QT interval corrected (QTc) greater than 450 millisecond (msec) or QTc
             greater than 480 msec in subjects with bundle branch block based on local
             Electrocardiogram (EGC) reading.

          -  Subjects who discontinue study treatment based on liver chemistry stopping criteria
             during Study 200622.

          -  Current active liver or biliary disease (with the exception of Gilbert's syndrome or
             asymptomatic gallstones or otherwise stable chronic liver disease per investigator
             assessment).

          -  Subjects who have received treatment with an investigational agent (biologic or
             non-biologic) within the past 30 days or 5 drug half-lives whichever is longer, prior
             to the first dose, other than Study 200622 study treatment. The term "investigational"
             applies to any drug not approved for sale for the disease/indication to treat in the
             country in which it is being used or investigational formulations of marketed
             products.

          -  Subjects who are currently participating in any other interventional clinical study.

          -  Subjects had an AE (serious or non-serious) considered related to study treatment
             while participating in Study 200622 which resulted in permanent withdrawal of study
             treatment.