Eosinophilic Granulomatosis with Polyangiitis (EGPA)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects age 18 years or older. 2. EGPA diagnosis based on history or presence asthma and eosinophilia (>1.0x10^9/L and/or >10% of leucocytes) and at least 2 of; biopsy with eosinophilic vasculitis or perivascular/granulomatous inflammation; mono-or polyneuropathy, non-fixed pulmonary infiltrates, sino-nasal abnormality; cardiomyopathy; glomerulonephritis; alveolar haemorrhage; palpable purpura; anti neutrophil cytoplasmic anti-body (ANCA) positivity (Myeloperoxidase or proteinease 3). 3. History of relapsing (at least 1 confirmed EGPA relapse within last 2 years and > 12 weeks prior to screening, or refractory (failure to attain remission, defined as BVAS=0 and oral corticosteroid (OCS) dose 50mg/day) for at least 4 weeks prior to randomization. 5. If receiving immunosuppressive therapy (excluding cyclophosphamide) the dose must be stable for the 4 weeks prior to randomization and during the study (dose reductions for safety reasons will be permitted). 6. QTc(F)=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) 2. Organ or life-threatening EGPA 5 years ago, or >1 year ago for basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix 5. An untreated or refractory helminth parasitic infection < 24 weeks prior to screening 6. Unstable liver disease 7. Severe or clinically significant, uncontrolled cardiovascular disease 8. Other concurrent disease that may put the patient at risk, or may influence the results of the study, or the patients’ ability to complete entire duration of the study 9. Chronic or ongoing infectious disease requiring systemic anti-infective treatment 10. Known immunodeficiency disorder or positive HIV test 11. Prior receipt of mepolizumab, reslizumab, dupilumab or benralizumab. Receipt of intravenous/intramuscular/subcutaneous corticosteroids within 4 weeks prior to randomization, receipt of omalizumab within 130 days prior to screenin, rituximab within 6 months prior to screening (or B-cells not recovered), interferon-a or alemtuzumab within 6 months prior to screening, receipt of anti-tumor necrosis factor therapy within 12 weeks prior to screening or an investigational drug within 30 days or 5 terminal phase drug half-lives, whichever is longer, prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the durability of response to treatment with benralizumab compared with mepolizumab in patients with relapsing or refractory EGPA who are receiving Standard of Care Therapy, assessed by the proportion of patients in remission at both Weeks 36 and 48.;Secondary Objective: DB To assess the efficacy of benralizumab compared with mepolizumab on duration of clinical remission To assess the efficacy of benralizumab compared with mepolizumab on time to first relapse To assess the average daily dose of corticosteroid from wk 48 to 52 in benralizumab compared to mepolizumab group To assess the annualized relapse rate in benralizumab compared to mepolizumab group To assess the proportion of patients achieving remission within the first 24 wks and remain in remission for the remainder of the DBperiod in benralizumab compared to mepolizumab groupd To assess additional measures of efficacy and health status/health-related QoL in patients receiving benralizumab compared to mepolizumab To assess the safety,tolerability and immunogenicity of benralizumab compared to mepolizumab To assess the pharmacok of benralizumab OLE To evaluate the effect of benralizumab on remission, relapse and oral OCS use To assess the safety and tolerability of benralizumab;Primary end point(s): Proportion of patients with relapsing or refractory EGPA, achieving remission, defined as BVAS=0 and OCS dose = 4mg/day (Main Remission definition) at both weeks 36 and 48. Supportive endpoint: Proportion of patients who have achieved remission defined by BVAS =0 and OCS dose = 7.5 mg/day (Supportive remission definition) at both weeks 36 and 48.;Timepoint(s) of evaluation of this end point: Both weeks 36&48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Study secondary end point(s) – double-blind period: - Total accrued duration of remission for the following categories: 0 wk, >0 to 0); OR *Active asthma symptoms and/or signs with a corresponding worsening in ACQ-6 score; OR *Active nasal and/or sinus disease, with a corresponding worsening in at least one of the sino-nasal symptom questions warranting any of the following: an increase of OCS therapy (>4mg prednisolone total daily dose or equivalent); an increased dose or addition of an immunosuppressive agent; Hospitalisation related to EGPA worsening. - Proportion of patients in each category of average daily prednisolone/prednisone dose during weeks 48 to 52 using the following categories: 0; >0 to =4 mg; >4 to =7.5 mg and > 7.5 mg - Annualized relapse rate - Proportion of patients who have achieved remission within the first 24 weeks and remained in remission for remainder of the double-blind treatment period. Analysis will be repeated based on main and supportive remission definitions. - BVAS, VDI, pulmonary function testing, asthma symptoms (ACQ-6), sino-nasal symptoms (including SNOT-22 questionnaire), health-related quality of life (SF-36v2), PGIS, WPAI and blood eosinophil counts will be assessed as change from baseline over the 52-week treatment period. PGIC will be assessed as response proportions at each weekly assessment between Visits 2 and 4 - Safety and tolerability will be evaluated based on AEs, Vital signs, physical exam, Clinical laboratory, and electrocardiogram (ECG). Study end point(s) for open label extension (OLE) period: - Remission, relapse (as defined in the secondary endpoints), OCS use -Safety and tolerability will be evaluated based on AEs, Vital signs, physical exam, Clinical laboratory, and ECG . -Serum benralizumab concentrations, Anti-benralizumab antibodies and neutralizing antibodies;Timepoint(s) of evaluation of this end point: Varies depending on the endpoint/objective | — |
Countries
Belgium, Canada, France, Germany, Israel, Italy, Japan, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZenecaAB
Outcome results
None listed