A Phase 3 interventional study of Mepolizumab and Prednisolone in Churg-Strauss Syndrome and Eosinophilic Granulomatosis With Polyangiitis, sponsored by GlaxoSmithKline. Completed at 32 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-12.
Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment
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.
Exclusion Criteria:
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 · Drug: Prednisolone
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.
Subjects who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included.
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
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.
| Milestone | Mepolizumab 300 mg |
|---|---|
| Started | 100 |
| Completed | 73 |
| Not completed | 27 |
| Withdrew: Adverse event | 3 |
| Withdrew: Lack of efficacy | 6 |
| Withdrew: Protocol violation | 1 |
| Withdrew: Physician decision | 7 |
| Withdrew: Withdrawal by subject | 10 |
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.
| Participants | Mepolizumab 300 mg |
|---|---|
| AE | 98 |
| SAE | 38 |
Collected over Up to approximately 89 Months. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Mepolizumab 300 mg | 1/100 (1%) | 38/100 (38%) | 97/100 (97%) |
| Event | Mepolizumab 300 mg |
|---|---|
| AsthmaRespiratory, thoracic and mediastinal disorders | 6/100 |
| Eosinophilic granulomatosis with polyangiitisImmune system disorders | 3/100 |
| PneumoniaInfections and infestations | 3/100 |
| Atrial fibrillationCardiac disorders | 2/100 |
| Myocardial infarctionCardiac disorders | 2/100 |
| BronchitisInfections and infestations | 2/100 |
| CellulitisInfections and infestations | 2/100 |
| GastroenteritisInfections and infestations | 2/100 |
| InfluenzaInfections and infestations | 2/100 |
| SepsisInfections and infestations | 2/100 |
| Event | Mepolizumab 300 mg |
|---|---|
| NasopharyngitisInfections and infestations | 33/100 |
| Upper respiratory tract infectionInfections and infestations | 31/100 |
| SinusitisInfections and infestations | 30/100 |
| BronchitisInfections and infestations | 29/100 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 26/100 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 20/100 |
| Back painMusculoskeletal and connective tissue disorders | 16/100 |
| RashSkin and subcutaneous tissue disorders | 15/100 |
| DiarrhoeaGastrointestinal disorders | 14/100 |
| NauseaGastrointestinal disorders | 14/100 |
| Age, Continuous(YEARS) | Mepolizumab 300 mg |
|---|---|
| Mean | 49.6 ± 13.90 |
| Sex: Female, Male(Participants) | Mepolizumab 300 mg |
|---|---|
| Female | 57 |
| Male | 43 |
| Race/Ethnicity, Customized(Participants) | Mepolizumab 300 mg |
|---|---|
| AMERICAN INDIAN OR ALASKA NATIVE | 1 |
| ASIAN - JAPANESE HERITAGE | 6 |
| ASIAN - SOUTH EAST ASIAN HERITAGE | 2 |
| WHITE - ARABIC/NORTH AFRICAN HERITAGE | 1 |
| WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE | 90 |
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Granulomatosis with Polyangiitis→
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