Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. (MANDARA)
ANCA Associated Vasculitis / Posted 1 year ago
This is a randomized, double blind, active-controlled, parallel group, multicenter 52-week Phase 3 study to compare the efficacy and safety of benralizumab 30 mg versus mepolizumab 300 mg administered by subcutaneous (SC) injection in patients with relapsing or refractory EGPA on corticosteroid therapy with or without stable immunosuppressive therapy.
All patients who complete the 52-week double-blind treatment period on IP may be eligible to continue into an open label extension (OLE) period. The OLE period is intended to allow each patient at least 1 year of treatment with open-label benralizumab 30 mg administered SC (earlier enrolled patients may therefore be in the OLE for longer than 1 year).
Inclusion Criteria :
- 1. Male or female subjects age 18 years or older.
- 2. EGPA diagnosis based on history or presence asthma and eosinophilia (greater than 1.0x10^9/L and/or greater than 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. History of relapsing (at least 1 confirmed EGPA relapse within last 2 years and more than 12 weeks prior to screening, or refractory (failure to attain remission, defined as BVAS=0 and oral corticosteroid (OCS) dose less than 7.5 mg/day of prednisolone or equivalent, following standard induction regimen for at least 3 months and within 6 months prior to screening, or recurrence of symptoms upon OCS tapering at any dose of at least 7.5 mg/day prednisolone or equivalent. If induction with glucocorticoidsalone, patient must have failed to attain remission after 3 months and the glucocorticoid dose must be at least 15 mg/day prednisolone or equivalent for the 4 weeks prior to randomization.
- 4. Must be on a stable dose of oral prednisolone or prednisone of at least 7.5 mg/day (but not greater than 50mg/day) for at least 4 weeks prior to randomization. Stable doses of OCS other than prednisolone or prednisone may be acceptable, but must be discussed with the AstraZeneca study physician. 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).
- 5. QTc(F)less than 450 msec or QTc(F)less than 480 msec for patients with bundle branch block.
- 6. Females of childbearing potential must use an acceptable method of birth control from signing the informed consent for at least 12 weeks after the last study drug administration.
Exclusion Criteria :
- 1. Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).
- 2. Organ or life-threatening EGPA less than 3 months prior to screening and through randomisation.
- 3. Currently pregnant or breastfeeding, or planning to become pregnant during study participation.
- 4. Current malignancy or history of malignancy, unless received curative therapy over 5 years ago, or over 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 less than 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&amp;amp;amp;amp;#039; ability to complete entire duration of the study.
- 9. Chronic or ongoing infectious disease requiring systemic antiinfective 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 screening, rituximab within 6 months prior to screening (or B-cells not recovered), interferon-α or alemtuzumab within 6 months prior to screening, receipt of anti-tumor necrosis factor therapy within 12 weeks prior to screening, receipt of of any other marketed or investigational biologic products within 4 months or 5 half-lives prior to screening, whichever is longer . Or receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to screening (V1), whichever is longer, prior to screening.
- Study start date : October 29, 2019
- Study end date : June 9, 2024
- Wales-Based Study Contact : Please speak to your clinician
- Principal Investigator : Michael Wechsler, MD National Jewish Health, 1400 Jackson St Denver, CO 80206