Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab.
MANDARA
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 (MANDARA Study)
3 other identifiers
interventional
140
9 countries
50
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Oct 2019
Longer than P75 for phase_3
50 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 29, 2019
CompletedStudy Start
First participant enrolled
October 29, 2019
CompletedFirst Posted
Study publicly available on registry
November 8, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 10, 2023
CompletedResults Posted
Study results publicly available
January 14, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2026
CompletedFebruary 3, 2026
January 1, 2026
3.8 years
September 29, 2019
July 16, 2024
January 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Subjects Who Achieved Main Remission at Both Weeks 36 and 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.
Week 36 and Week 48
Supportive Endpoint: Proportion of Subjects Who Achieved Supportive Remission at Both Weeks 36 and 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.
Week 36 and Week 48
Secondary Outcomes (30)
Total Accrued Duration of Remission During DB Treatment Period
from baseline to end of DB period, 52 Weeks.
Total Accrued Duration of Sustained Remission During DB Treatment Period
from baseline to end of DB period, 52 Weeks
Time From Randomization to First Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse
from baseline to end of DB period, 52 Weeks
Annualized Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse Rate
from baseline to end of DB period, 52 Weeks
Average Daily Dose of Prednisolone/Prednisone and Change From Baseline During Week 48 Through 52
last 4 weeks of DB period
- +25 more secondary outcomes
Study Arms (2)
Benralizumab arm
EXPERIMENTAL1x benralizumab SC injection + 3x placebo to mepolizumab SC injections
Mepolizumab arm
ACTIVE COMPARATOR3x mepolizumab SC injections + 1x placebo to benralizumab SC injection
Interventions
30 mg/mL solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC)
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)
Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC)
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)
Eligibility Criteria
You may qualify if:
- Male or female subjects age 18 years or older.
- 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).
- 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.
- 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.
- 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).
- QTc(F)\<450 msec or QTc(F)\<480 msec for patients with bundle branch block.
- 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.
You may not qualify if:
- Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
- Organ or life-threatening EGPA \< 3 months prior to screening
- Currently pregnant or breastfeeding, or planning to become pregnant during study participation.
- 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
- An untreated or refractory helminth parasitic infection \< 24 weeks prior to screening
- Unstable liver disease
- Severe or clinically significant, uncontrolled cardiovascular disease
- 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
- Chronic or ongoing infectious disease requiring systemic anti-infective treatment
- Known immunodeficiency disorder or positive HIV test
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (50)
Research Site
Denver, Colorado, 80206, United States
Research Site
Ann Arbor, Michigan, 48109, United States
Research Site
Rochester, Minnesota, 55905-0001, United States
Research Site
Albuquerque, New Mexico, 87106, United States
Research Site
Great Neck, New York, 11021, United States
Research Site
New York, New York, 10021, United States
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Philadelphia, Pennsylvania, 19104, United States
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Denison, Texas, 75020, United States
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Seattle, Washington, 98115, United States
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Brussels, 1070, Belgium
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Brussels, 1090, Belgium
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Calgary, Alberta, T2N 4Z6, Canada
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Hamilton, Ontario, L8N 4A6, Canada
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Toronto, Ontario, M5G 1E2, Canada
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Toronto, Ontario, M5T 3A9, Canada
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Dijon, 21079, France
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Marseille, 13915, France
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Montpellier, 34090, France
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Nantes, 44093, France
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Paris, 75014, France
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Paris, 75877, France
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Suresnes, 92151, France
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Toulouse, 31059, France
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Bamberg, 96049, Germany
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Freiburg im Breisgau, 79106, Germany
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Hamburg, 20251, Germany
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Kirchheim, 73230, Germany
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Lübeck, 23538, Germany
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Ashkelon, 7830604, Israel
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Beersheba, 84101, Israel
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Jerusalem, 91120, Israel
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Ramat Gan, 52621, Israel
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Rehovot, 7661041, Israel
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Tel Aviv, 6423906, Israel
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Cuneo, 12100, Italy
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Florence, 50141, Italy
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Milan, 20132, Italy
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Milan, 20162, Italy
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Naples, 80131, Italy
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Roma, 00168, Italy
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Torino, 10128, Italy
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Chiba, 260-0877, Japan
Research Site
Kita-gun, 761-0793, Japan
Research Site
Sagamihara-shi, 228-0815, Japan
Research Site
Sendai, 980-8574, Japan
Research Site
Shinjuku-ku, 162-8666, Japan
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Cambridge, CB2 0QQ, United Kingdom
Research Site
Leicester, LE3 9QP, United Kingdom
Research Site
London, SE19RT, United Kingdom
Research Site
Portsmouth, PO6 3LY, United Kingdom
Related Publications (2)
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.
PMID: 38393328DERIVEDSerling-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.
PMID: 33164993DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Head
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Wechsler, MD
National Jewish Health, 1400 Jackson St Denver, CO 80206
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 29, 2019
First Posted
November 8, 2019
Study Start
October 29, 2019
Primary Completion
August 10, 2023
Study Completion
March 31, 2026
Last Updated
February 3, 2026
Results First Posted
January 14, 2025
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.