Treatment of Eosinophilic Granulomatosis with Polyangiitis in Subjects Receiving Standard of Care Therapy. MedDRA version: 17.1 Level: LLT Classification code 10018701 Term: Granulomatous disease System Organ Class: 100000004867 MedDRA version: 17.1 Level: LLT Classification code 10014956 Term: Eosinophilic granuloma System Organ Class: 100000004864 MedDRA version: 17.1 Level: LLT Classification code 10072580 Term: Granulomatous polyangiitis System Organ Class: 100000004866 MedDRA version:
Conditions
Interventions
Product Name: Mepolizumab
Product Code: SB-240563
Pharmaceutical Form: Injection
INN or Proposed INN: Mepolizumab
CAS Number: 196078-29-2
Current Sponsor code: SB-240563
Other descriptive name: Recomb
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials. 2. Age and gender: Male or female subjects age 18 years or older. 3. EGPA diagnosis: subjects who have been diagnosed with EGPA for at least 6 months based on the history or presence of: asthma plus eosinophilia (>1.0x109/L and/or >10% of leucocytes) plus at least two of the following additional features of EGPA. ? a biopsy showing histopathological evidence of eosinophilic vasculitis, or perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation; ? neuropathy, mono or poly (motor deficit or nerve conduction abnormality); ? pulmonary infiltrates, non-fixed; ? sino-nasal abnormality; ? cardiomyopathy (established by echocardiography or MRI); ? glomerulonephritis (haematuria, red cell casts, proteinuria); ? alveolar haemorrhage (by bronchoalveolar lavage); ? palpable purpura; ? ANCA positive (MPO or PR3). 4. History of relapsing OR refractory disease defined as: ? Relapsing disease: Subject must have a past history of at least one confirmed EGPA relapse (i.e., requiring increase in OCS dose, initiation/increased dose of immunosuppressive therapy or hospitalisation) within the past 2 years which occurred at least 12 weeks prior to Screening (Visit 1) whilst receiving a dose of prednisolone (or equivalent) of =7.5 mg/day. ? Japan only definition of Relapsing disease: Subject must have a past history of at least one confirmed EGPA relapse (i.e., requiring increase in OCS dose, initiation of IV prednisolone (or equivalent), initiation/increased dose of immunosuppressive therapy, initiation/increased dose of intravenous immunoglobulin (IVIG) or hospitalisation) within the past 2 years which occurred at least 12 weeks prior to Screening (Visit 1) whilst receiving a dose of prednisolone (or equivalent) of =7.5 mg/day. Refractory disease: ? Either: Failure to attain remission (BVAS=0 and OCS dose =7.5 mg/day prednisolone or equivalent) within the last 6 months following induction treatment with a standard regimen, administered for at least 3 months. Note: a. Subjects who have received a cyclophosphamide (CYC) induction regimen may be included a minimum of 2 weeks after the last dose of daily oral CYC, or 3 weeks after the last dose of pulsed IV CYC prior to Baseline (Visit 2), if their total WBC is =4x109/L (tested at the local laboratory, if necessary) prior to randomisation. b. Subjects who have received a methotrexate, azathioprine, or mycophenolate mofetil induction regimen may be included if on a stable dose for at least 4 weeks prior to Baseline (Visit 2). c. Subjects who have received an induction regimen comprising corticosteroids alone may be included only if they have failed to attain remission after 3 months of treatment AND the corticosteroid dose is =15 mg/day prednisolone or equivalent for the 4 weeks prior to Baseline (Visit 2). ? Or: Within 6 months prior to Screening (Visit 1), recurrence of symptoms of EGPA (not necessarily meeting the protocol definition of relapse) whilst tapering OCS, occurring at any dose level =7.5 mg/day prednisolone or equivalent. 5. Corticosteroid therapy: Subject must be on a stable dose of oral prednisolone or prednisone of =7.5 mg/d
Exclusion criteria
Exclusion criteria: 1. GPA or MPA: Diagnosed with granulomatosis with polyangiitis (GPA; previously known as Wegener’s granulomatosis) or microscopic polyangiitis (MPA). 2. Organ-threatening EGPA: Organ-threatening EGPA as per EULAR criteria, i.e., organ failure due to active vasculitis, creatinine >5.8 g/dL (>513 µmol/L) within 3 months prior to Screening (Visit 1). 3. Life-threatening EGPA: Imminently life-threatening EGPA disease defined as any of the following within 3 months prior to Screening (Visit 1). Please view protocol page 37 for further information. 4. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening (Subjects that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded). 5. Liver disease: Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). 6. Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment including but not limited to: ? Known ejection fraction of 50 mg/day prednisolone/prednisone in the 4-week period prior to Baseline (Visit 2). ? Intravenous or SC corticosteroids in the 4-week period prior to Baseline (Visit 2). ? Omalizumab within 130 days prior to Screening (Visit 1). ? Cyclophosphamide: oral CYC within 2 weeks prior to Baseline (Visit 2) and IV CYC within 3 weeks prior to Baseline (Visit 2), if their total WBC is =4x109/L (measured using the local laboratory if necessary). ? Rituximab within 12 months prior to Screening (Visit 1); in addition, the subject must have shown recovery of peripheral B-cell count to within the normal range. ? IV or SC immunoglobulin within 6 months prior to Screening (Visit 1). ? Interferon_alpha within 6 months prior to Screening (Vis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To investigate the efficacy of mepolizumab plus standard of care compared with placebo plus standard of care on duration of clinical remission, defined as accrued duration in weeks where a subject achieves a BVAS=0 and corticosteroid dose =4 mg/day prednisolone/prednisone, in subjects with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) receiving standard of care therapy including corticosteroid therapy reduction/withdrawal. ? To investigate the durability of response to treatment with mepolizumab plus standard of care compared with placebo plus standard of care, assessed by the proportion of subjects in remission at both Weeks 36 and 48.;Secondary Objective: ? To investigate the efficacy of mepolizumab compared with placebo on time to relapse in subjects with EGPA on background standard of care treatment including corticosteroid therapy reduction/withdrawal. ? To compare the average daily dose of corticosteroid required during the last 4 weeks of the study treatment period. ? To evaluate the proportion of subjects who achieve remission within the first 24 weeks of the study and remain in remission for the remainder of the study treatment period. ? To investigate the safety of mepolizumab compared with placebo in subjects with EGPA on background standard of care treatment. View protocol page 28 for further information.;Primary end point(s): Total accrued duration of remission, i.e., the accrued number of weeks where BVAS=0 plus prednisolone/prednisone dose =4 mg/day over the 52 week study treatment period reported as proportion of subjects achieving remission in the following categories:- Zero; >0 to <12 weeks; - 12 to <24 weeks; - 24 to <36 weeks - =36 weeks. • The proportion of subjects who are in remission at both Weeks 36 and 48 of the study treatment period.;Timepoint(s) of evaluation of this end point: Over the 52 week treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to first confirmed EGPA relapse. •The proportion of subjects with an average daily prednisolone/prednisone dose during the last 4 weeks of the study treatment period (48 through 52) in each of the following categories: ? Zero ? >0 to =4.0 mg ? >4.0 to =7.5 mg ? >7.5 mg ? The proportion of subjects in each treatment group who achieve remission (BVAS=0 and prednisolone/prednisone dose =4 mg/day) within the first 24 weeks of the study and then remain in remission for the remainder of the study treatment period.;Timepoint(s) of evaluation of this end point: As specified in the endpoint. | — |
Countries
Belgium, Canada, France, Germany, Italy, Japan, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials HelpDesk
GlaxoSmithKline Reseacrh & Development Ltd
Outcome results
None listed