Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab.

NCT ID: NCT04157348

Last Updated: 2026-02-03

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-29

Study Completion Date

2026-03-31

Brief Summary

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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).

Detailed Description

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Conditions

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Eosinophilic Granulomatous Vasculitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Benralizumab arm

1x benralizumab SC injection + 3x placebo to mepolizumab SC injections

Group Type EXPERIMENTAL

Benralizumab

Intervention Type BIOLOGICAL

30 mg/mL solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC)

Placebo to Mepolizumab

Intervention Type BIOLOGICAL

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)

Mepolizumab arm

3x mepolizumab SC injections + 1x placebo to benralizumab SC injection

Group Type ACTIVE_COMPARATOR

Mepolizumab

Intervention Type BIOLOGICAL

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 Benralizumab

Intervention Type BIOLOGICAL

Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC)

Interventions

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Benralizumab

30 mg/mL solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC)

Intervention Type BIOLOGICAL

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)

Intervention Type BIOLOGICAL

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)

Intervention Type BIOLOGICAL

Placebo to Benralizumab

Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC)

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Wechsler, MD

Role: PRINCIPAL_INVESTIGATOR

National Jewish Health, 1400 Jackson St Denver, CO 80206

Locations

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Research Site

Denver, Colorado, United States

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Ann Arbor, Michigan, United States

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Rochester, Minnesota, United States

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Albuquerque, New Mexico, United States

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Great Neck, New York, United States

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New York, New York, United States

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Philadelphia, Pennsylvania, United States

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Denison, Texas, United States

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Seattle, Washington, United States

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Brussels, , Belgium

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Brussels, , Belgium

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Calgary, Alberta, Canada

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Dijon, , France

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Marseille, , France

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Suresnes, , France

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Toulouse, , France

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Bamberg, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Kirchheim, , Germany

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Lübeck, , Germany

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Ashkelon, , Israel

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Beersheba, , Israel

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Rehovot, , Israel

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Tel Aviv, , Israel

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Cuneo, , Italy

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Florence, , Italy

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Milan, , Italy

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Milan, , Italy

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Napoli, , Italy

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Roma, , Italy

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Torino, , Italy

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Chiba, , Japan

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Kita-gun, , Japan

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Sagamihara-shi, , Japan

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Sendai, , Japan

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Shinjuku-ku, , Japan

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Cambridge, , United Kingdom

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Leicester, , United Kingdom

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London, , United Kingdom

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Portsmouth, , United Kingdom

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Countries

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United States Belgium Canada France Germany Israel Italy Japan United Kingdom

References

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Wechsler ME, Nair P, Terrier B, Walz B, Bourdin A, Jayne DRW, Jackson DJ, Roufosse F, Borjesson Sjo L, Fan Y, Jison M, McCrae C, Necander S, Shavit A, Walton C, Merkel PA; MANDARA Study Group. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024 Mar 7;390(10):911-921. doi: 10.1056/NEJMoa2311155. Epub 2024 Feb 23.

Reference Type DERIVED
PMID: 38393328 (View on PubMed)

Serling-Boyd N, Wallace ZS. Management of primary vasculitides with biologic and novel small molecule medications. Curr Opin Rheumatol. 2021 Jan;33(1):8-14. doi: 10.1097/BOR.0000000000000756.

Reference Type DERIVED
PMID: 33164993 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2023-510248-19-00

Identifier Type: OTHER

Identifier Source: secondary_id

2019-001832-77

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D3253C00001

Identifier Type: -

Identifier Source: org_study_id

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