A study of benralizumab in EGPA (also known as Churg-Strauss Syndrome)
Research type
Research Study
Full title
A Randomised, Double-blind, Active-controlled 52-week Study with an Open-label Extension to Evaluate the Efficacy and Safety of Benralizumab Compared to Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA) in Patients Receiving Standard of Care Therapy
IRAS ID
265506
Contact name
David Jackson
Contact email
Sponsor organisation
AstraZeneca AB
Eudract number
2019-001832-77
Duration of Study in the UK
4 years, 0 months, 0 days
Research summary
EGPA (formerly Churg-Strauss syndrome [CSS]) is a rare disease characterised by potentially life-threatening systemic eosinophilic small vessel vasculitis in association with asthma, sinusitis, and pulmonary infiltrates. EGPA and hypereosinophilic syndrome (HES) have distinct, but partly overlapping clinical and histologic features, including target organs. Because eosinophilia is central to the pathophysiology of EGPA it is hypothesized that direct or indirect depletion of eosinophils could also treat EGPA.
Benralizumab (FASENRA™) is a humanized, afucosylated, monoclonal antibody (IgG1,
IgGκ) that binds to the human interleukin-5 receptor alpha subunit (IL-5Rα) with high affinity and specificity. The IL-5 receptor (IL-5R) is specifically expressed on the surface of eosinophils and basophils. The absence of fucose in the Fc domain of benralizumab results in high affinity for FcγRIII receptors on immune effector cells such as natural killer (NK) cells leading to depletion by apoptosis of eosinophils and basophils through enhanced antibodydependent cell-mediated cytotoxicity (ADCC). The direct eosinophil-depleting ability of benralizumab has been shown to be effective in eosinophilic asthma and in steroid-dependent asthma. Benralizumab has also shown potential for benefit in HES, a group of diseases with
persistent blood eosinophilia and evidence of eosinophil-mediated end-organ damage.This Phase 3 study in patients with relapsing or refractory EGPA on corticosteroid therapy with or without stable immunosuppressive therapy includes a 52-week double-blind period in which the efficacy and safety of benralizumab will be compared with an active comparator, mepolizumab, that has regulatory approval in several markets for use in patients with EGPA.
The study also includes an open-label extension (OLE) period intended to allow each patient at least 1 further year of treatment with open-label benralizumab which will provide an opportunity to assess long-term safety and tolerability of benralizumab in this patient population.REC name
South West - Central Bristol Research Ethics Committee
REC reference
19/SW/0140
Date of REC Opinion
20 Aug 2019
REC opinion
Further Information Favourable Opinion