Active, not recruiting
Phase 3
Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab.
Condition(s) studied
Eosinophilic Granulomatous Vasculitis
Investigational drug(s) / intervention(s)
BenralizumabMepolizumabPlacebo to MepolizumabPlacebo to Benralizumab
Benralizumab: 30 mg/mL solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC)
Mepolizumab: 3x100 mg vials of powder for solution for injection reconstituted into 3 separate 1 mL syringes for administration on each dosing occasion. Injection volume per syringe is 1 mL. Mepolizumab active solution will be administered subcutaneously (SC)
Placebo to Mepolizumab: Matching placebo: 0.9% sodium chloride, solutions for injection in 1mL syringes (3 syringes will be used on each dosing occasion). Injection volume per syringe is 1mL. Placebo to Mepolizumban will be administered subcutaneously (SC)
Placebo to Benralizumab: Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC)
Study summary
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).
Eligibility
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 \<=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 ≥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 ≥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 ≥7.5 mg/day (but not \>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)\<450 msec or QTc(F)\<480 msec for patients with bundle branch block.
7. Females of childbearing potential must use an acceptable method of birth control from randomization 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 \< 3 months prior to screening
3. Currently pregnant or breastfeeding, or planning to become pregnant during study participation.
4. Current malignancy or history of malignancy, unless received curative therapy \>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 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 or an investigational non-biologic product within 30 days or 5 half-lives prior to screening, whichever is longer. Receipt of any other marketed or investigational biologic products within 4 months or 5 half-lives prior to screening, whichever is longer.
Primary outcome measure(s)
- Number of Subjects Who Achieved Main Remission at Both Weeks 36 and 48 — Week 36 and Week 48
Percentage of patients with relapsing or refractory EGPA, achieving remission, defined as BVAS = 0 and OCS dose ≤ 4 mg/day (main remission definition) at both Weeks 36 and 48.
- Supportive Endpoint: Proportion of Subjects Who Achieved Supportive Remission at Both Weeks 36 and 48 — Week 36 and Week 48
Supportive endpoint: Proportion of patients with relapsing or refractory EGPA, achieving remission, defined as BVAS = 0 and OCS dose ≤ 7.5 mg/day (supportive remission definition) at both Weeks 36 and 48.
Trial sites (50)
| Facility | City | Region | Status |
| Research Site |
Denver |
Colorado |
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| Research Site |
Ann Arbor |
Michigan |
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| Research Site |
Rochester |
Minnesota |
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| Research Site |
Albuquerque |
New Mexico |
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| Research Site |
Great Neck |
New York |
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| Research Site |
New York |
New York |
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| Research Site |
Philadelphia |
Pennsylvania |
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| Research Site |
Denison |
Texas |
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| Research Site |
Seattle |
Washington |
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| Research Site |
Brussels |
Belgium |
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| Research Site |
Brussels |
Belgium |
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| Research Site |
Calgary |
Alberta |
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| Research Site |
Hamilton |
Ontario |
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| Research Site |
Toronto |
Ontario |
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| Research Site |
Toronto |
Ontario |
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| Research Site |
Dijon |
France |
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| Research Site |
Marseille |
France |
|
| Research Site |
Montpellier |
France |
|
| Research Site |
Nantes |
France |
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| Research Site |
Paris |
France |
|
| Research Site |
Paris |
France |
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| Research Site |
Suresnes |
France |
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| Research Site |
Toulouse |
France |
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| Research Site |
Bamberg |
Germany |
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| Research Site |
Freiburg im Breisgau |
Germany |
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| Research Site |
Hamburg |
Germany |
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| Research Site |
Kirchheim |
Germany |
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| Research Site |
Lübeck |
Germany |
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| Research Site |
Ashkelon |
Israel |
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| Research Site |
Beersheba |
Israel |
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| Research Site |
Jerusalem |
Israel |
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| Research Site |
Ramat Gan |
Israel |
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| Research Site |
Rehovot |
Israel |
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| Research Site |
Tel Aviv |
Israel |
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| Research Site |
Cuneo |
Italy |
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| Research Site |
Florence |
Italy |
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| Research Site |
Milan |
Italy |
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| Research Site |
Milan |
Italy |
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| Research Site |
Naples |
Italy |
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| Research Site |
Roma |
Italy |
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+ 10 more sites — see the full list on the official registry below.
More AstraZeneca trials in the UK