Churg-Strauss Syndrome, Eosinophilic Granulomatosis With Polyangiitis
Conditions
Keywords
Eosinophilic Granulomatosis, MEA115921, Polyangiitis, Long-term access program, mepolizumab
Brief summary
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.
Interventions
DRUGMepolizumab
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.
DRUGPrednisolone
Subjects who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 89 Months | 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 were recorded throughout the treatment and follow-up period. |
Countries
Belgium, Canada, France, Germany, Japan, United Kingdom, United States
Participant flow
Recruitment details
Participants who participated in clinical study MEA115921 and required a dose of prednisolone (or equivalent) of greater than or equal to (\>=) 5 milligrams per day (mg/day) for adequate control of their Eosinophilic Granulomatosis with Polyangiitis (EGPA) were included in this study based on their eligibility. Eligible participants received subcutaneous (SC) injection of mepolizumab 300 milligrams (mg) every 4 weeks.
Pre-assignment details
A total of 100 participants entered the study and received mepolizumab.
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab 300 mg Participants who participated in clinical study MEA115921, who required additional dose of \>=5 milligrams per day (mg/day) prednisolone for adequate control of their Eosinophilic Granulomatosis with Polyangiitis (EGPA) received 300 milligrams (mg) mepolizumab subcutaneous (SC) injection every 4 weeks. | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Physician Decision | 7 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Mepolizumab 300 mg |
|---|---|
| Age, Continuous | 49.6 YEARS STANDARD_DEVIATION 13.9 |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 1 Participants |
| Race/Ethnicity, Customized ASIAN - JAPANESE HERITAGE | 6 Participants |
| Race/Ethnicity, Customized ASIAN - SOUTH EAST ASIAN HERITAGE | 2 Participants |
| Race/Ethnicity, Customized WHITE - ARABIC/NORTH AFRICAN HERITAGE | 1 Participants |
| Race/Ethnicity, Customized WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE | 90 Participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 100 |
| other Total, other adverse events | 97 / 100 |
| serious Total, serious adverse events | 38 / 100 |
Outcome results
Primary
Number of Participants 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 were recorded throughout the treatment and follow-up period.
Time frame: Up to approximately 89 Months
Population: Safety Population consisted of all participants who received at least one dose of open label mepolizumab. On-treatment AEs and on-treatment SAEs are the events occurring on/after the first dose of open-label mepolizumab date and before/on last dose of mepolizumab + 28 days.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mepolizumab 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 98 Participants |
| Mepolizumab 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 38 Participants |