Eosinophilic Granulomatous VasculitisPhase 3MANDARANCT04157348
Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab.
A Phase 3 study testing Benralizumab and Mepolizumab in people with Eosinophilic Granulomatous Vasculitis, run by AstraZeneca at 50 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Eosinophilic Granulomatous Vasculitis
- What is being tested?
- Benralizumab and Mepolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 50 sitesin 9 countries
- Study dates
- 29 Oct 2019to 30 Nov 2026
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
50 sites in 9 countries.
50 sites in 9 countries
United States9 sites
Research Site
Albuquerque, New Mexico, 87106
Research Site
Ann Arbor, Michigan, 48109
Research Site
Denison, Texas, 75020
Research Site
Denver, Colorado, 80206
Research Site
Great Neck, New York, 11021
Research Site
New York, New York, 10021
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Rochester, Minnesota, 55905-0001
Research Site
Seattle, Washington, 98115
France8 sites
Research Site
Dijon, 21079
Research Site
Marseille, 13915
Research Site
Montpellier, 34090
Research Site
Nantes, 44093
Research Site
Paris, 75014
Research Site
Paris, 75877
Research Site
Suresnes, 92151
Research Site
Toulouse, 31059
Italy7 sites
Research Site
Cuneo, 12100
Research Site
Florence, 50141
Research Site
Milan, 20132
Research Site
Milan, 20162
Research Site
Naples, 80131
Research Site
Roma, 00168
Research Site
Torino, 10128
Israel6 sites
Research Site
Ashkelon, 7830604
Research Site
Beersheba, 84101
Research Site
Jerusalem, 91120
Research Site
Ramat Gan, 52621
Research Site
Rehovot, 7661041
Research Site
Tel Aviv, 6423906
Germany5 sites
Research Site
Bamberg, 96049
Research Site
Freiburg im Breisgau, 79106
Research Site
Hamburg, 20251
Research Site
Kirchheim, 73230
Research Site
Lübeck, 23538
Japan5 sites
Research Site
Chiba, 260-0877
Research Site
Kita-gun, 761-0793
Research Site
Sagamihara-shi, 228-0815
Research Site
Sendai, 980-8574
Research Site
Shinjuku-ku, 162-8666
Canada4 sites
Research Site
Calgary, Alberta, T2N 4Z6
Research Site
Hamilton, Ontario, L8N 4A6
Research Site
Toronto, Ontario, M5G 1E2
Research Site
Toronto, Ontario, M5T 3A9
United Kingdom4 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Leicester, LE3 9QP
Research Site
London, SE19RT
Research Site
Portsmouth, PO6 3LY
About this study
Official 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 (MANDARA Study)
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).
- Conditions
- Eosinophilic Granulomatous Vasculitis
- Being tested
- Benralizumab, Mepolizumab, Placebo to Mepolizumab, Placebo to Benralizumab
- Keywords
- Benralizumab, Inhaled corticosteroids, Eosinophilic Granulomatous Vasculitis
- Medical subject headings
- Churg-Strauss Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenralizumabBiological
30 mg/mL solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC)
MepolizumabBiological
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 MepolizumabBiological
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 BenralizumabBiological
Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC)
| Study group | Role | What they receive |
|---|---|---|
| Benralizumab arm | Experimental | 1x benralizumab SC injection + 3x placebo to mepolizumab SC injections Receives: Biological: Benralizumab; Biological: Placebo to Mepolizumab |
| Mepolizumab arm | Active comparator | 3x mepolizumab SC injections + 1x placebo to benralizumab SC injection Receives: Biological: Mepolizumab; Biological: Placebo to Benralizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Week 36 and Week 48
Secondary outcomes (30)
Total Accrued Duration of Remission During DB Treatment Period
Total accrued duration of remission for the following categories: 0 week, > 0 to < 12 week, 12 to < 24 week, 24 to < 36 week, ≥ 36 week.
Measured: from baseline to end of DB period, 52 Weeks.
Total Accrued Duration of Sustained Remission During DB Treatment Period
Total accrued duration of sustained remission for the following categories: 0 week, > 0 to < 12 week, 12 to < 24 week, 24 to < 36 week, ≥ 36 week.
Measured: from baseline to end of DB period, 52 Weeks
Time From Randomization to First Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse
Time from randomization to first Eosinophilic Granulomatosis with Polyangiitis (EGPA) relapse, where relapse is defined as any of the following:
- Active vasculitis (BVAS > 0); OR
- Active asthma symptoms and/or signs with a corresponding worsening in ACQ-6 score; OR
- Active nasal and/or sinus disease, with a corresponding worsening in at least one of the sino-nasal symptom questions; warranting any of the following:
- An increased dose of OCS therapy to > 4 mg/day prednisolone total daily dose; OR
- An increased dose or addition of immunosuppressive therapy; OR
- Hospitalization related to EGPA worsening Calculated using the Kaplan-Meier technique.
Measured: from baseline to end of DB period, 52 Weeks
Annualized Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse Rate
Annualized Eosinophilic Granulomatosis with Polyangiitis (EGPA) relapse rate through end of DB treatment period. The estimate of annualized relapse rate (relapses per year) and the corresponding 95% CIs were calculated using a negative binomial model. The response variable in the model is the number of relapses experienced by a subject up to Week 52. The logarithm of the subject's corresponding follow-up time up to Week 52 was used as an offset variable to adjust for subjects having different follow-up times during which the events occur. The covariates in the model include treatment arm, baseline dose of prednisone, baseline BVAS and region.
Measured: from baseline to end of DB period, 52 Weeks
Average Daily Dose of Prednisolone/Prednisone and Change From Baseline During Week 48 Through 52
Average daily dose of prednisolone/prednisone and change from baseline during Week 48 through 52, or last 28 days prior to last double-blind assessment for those that withdrew
Measured: last 4 weeks of DB period
Proportion of Patients With Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52
Proportion of patients with average daily dose of prednisolone/prednisone during Week 48 through 52 in each category: 0 mg; >0 to ≤ 4 mg; > 4 to ≤ 7.5 mg and > 7.5 mg
Measured: last 4 weeks of DB period
Percentage Reduction From Baseline in Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52
Percentage reduction from baseline in average daily dose of prednisolone/prednisone during Week 48 through 52 in each category: no reduction or withdrawal from treatment; < 25% reduction; 25 to < 50% reduction; 50 to <75% reduction; 75 to < 100% reduction; 100% reduction.
Measured: last 4 weeks of DB period
Proportion of Subjects With Reduction From Baseline in Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52
Proportion of subjects with reduction from baseline in average daily dose of prednisolone/prednisone during Week 48 through 52 in each category: >= 50% reduction; 100% reduction; OCS dose <= 4 mg/day.
Measured: last 4 weeks of DB period
Proportion of Subjects Who Achieve Clinical Benefit
Proportion of subjects who achieved any clinical benefit definition 1 (defined as any of the following:
- Main remission at any time in DB period
- >= 50% reduction in OCS dose in Weeks 48 to 52
- EGPA relapse free in DB period) and subjects who achieved complete response definition 1 (defined as meeting all the definition 1 criteria above.)
Measured: from baseline to end of DB period, 52 Weeks
Proportion of Patients Who Have Achieved Remission Within the First 24 Weeks and Remained in Remission for Remainder of the Double-blind Treatment Period
Proportion of patients who have achieved remission within the first 24 weeks and remained in remission for remainder of the double-blind treatment period
Measured: from baseline to end of DB period, 52 Weeks
Change From Baseline in Birmingham Vasculitis Activity Score (BVAS)
Birmingham Vasculitis Activity Score (BVAS) change from baseline by timepoint up to week 52. The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The total score on all 9 organ systems gives an indication of the disease activity of each patient at the time of scoring. Total scores range from 0 to 63, with higher scores indicating more active vasculitis.
Measured: from baseline to end of DB period, 52 Weeks
Spirometry Change From Baseline by Timepoint up to Week 52: Pre-BD FEV1 (L)
Pre-bronchodilator (BD) Forced Expiratory Volume during first second (FEV1) change from baseline by timepoint up to week 52
Measured: from baseline to end of DB period, 52 Weeks
Spirometry Change From Baseline by Timepoint up to Week 52: Pre-BD FVC (L)
Pre-bronchodilator (BD) Forced vital capacity (FVC) change from baseline by timepoint up to week 52
Measured: from baseline to end of DB period, 52 Weeks
Change From Baseline in Vasculitis Damage Index (VDI)
Vasculitis Damage Index (VDI) change from baseline by timepoint up to week 52. The VDI is divided into 11 organ systems and records items of damage, due to vasculitis, treatment or unrelated, that have occurred since the onset of vasculitis. Completion of the form provides a numerical score, ranging from 0 to 64, with a higher score indicating more damage.
Measured: from baseline to end of DB period, 52 Weeks
Change From Baseline in Asthma Control Questionnaire (6-item Version) (ACQ-6)
Asthma Control Questionnaire (6-item version) (ACQ-6) change from baseline by timepoint up to week 52. The ACQ-6 score is calculated by taking the mean of 6 equally weighted domains, with a range of 0 (well controlled) to 6 (extremely poorly controlled).
Measured: from baseline to end of DB period, 52 Weeks
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) Component: Physical Component Summary (PCS)
Short Form 36-item health survey (version 2, acute recall) (SF-36v2) component Physical Component Summary (PCS) change from baseline by timepoint up to week 52. PCS score ranges from 10.8 to 75.5, where a higher score indicates better health.
Measured: from baseline to end of DB period, 52 Weeks
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) Component: Mental Component Summary (MCS)
Short Form 36-item health survey (version 2, acute recall) (SF-36v2) component Mental Component Summary (MCS) change from baseline by timepoint up to week 52. MCS score ranges from 5.6 to 69.7, where a higher score indicates better health.
Measured: from baseline to end of DB period, 52 Weeks
Change From Baseline in Sino-nasal Outcome Test-22 (SNOT-22) Total Score
Sino-nasal Outcome Test-22 (SNOT-22) total score change from baseline by timepoint up to week 52. Patient reported symptom severity and symptom impact over the previous 2 weeks on 22 items are captured via a 6-point scale (0 = no problem to 5 = problem as bad as it can be). The total score is the sum of item scores and ranges from 0 to 110 (higher scores indicate poorer outcomes).
Measured: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Runny Nose
Sino-nasal Symptoms Questionnaire (SSQ) scores : symptom runny nose by timepoint. For the SSQ, participants rate each symptom against the following categories: very severe, severe, moderate, mild, none. Higher scores indicate greater severity (0 = none to 4 = very severe).
Measured: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Post-nasal Discharge
Sino-nasal Symptoms Questionnaire (SSQ) scores : symptom Post-nasal discharge by timepoint. For the SSQ, participants rate each symptom against the following categories: very severe, severe, moderate, mild, none. Higher scores indicate greater severity (0 = none to 4 = very severe).
Measured: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Facial Pain/Pressure
Sino-nasal Symptoms Questionnaire (SSQ) scores: symptom Facial pain/pressure by timepoint. For the SSQ, participants rate each symptom against the following categories: very severe, severe, moderate, mild, none. Higher scores indicate greater severity (0 = none to 4 = very severe).
Measured: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Loss or Reduction in Sense of Taste/Smell
Sino-nasal Symptoms Questionnaire (SSQ) scores: symptom Loss or reduction in sense of taste/smell by timepoint. For the SSQ, participants rate each symptom against the following categories: very severe, severe, moderate, mild, none. Higher scores indicate greater severity (0 = none to 4 = very severe).
Measured: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Blockage/Congestion of Nose
Sino-nasal Symptoms Questionnaire (SSQ) scores: symptom Blockage/congestion of nose by timepoint. For the SSQ, participants rate each symptom against the following categories: very severe, severe, moderate, mild, none. Higher scores indicate greater severity (0 = none to 4 = very severe).
Measured: from baseline to end of DB period, 52 Weeks
Patient Global Impression of Severity (PGIS) Category
Patient Global Impression of Severity (PGIS) category by timepoint
Measured: from baseline to end of DB period, 52 Weeks
Patient Global Impression of Change (PGIC) Category
Patient Global Impression of Change (PGIC) category by timepoint
Measured: from baseline to week 4
WPAI-GH Endpoint, Change From Baseline by Timepoint: Absenteeism (%)
The Work Productivity and Activity Impairment questionnaire (WPAI-GH) has 6 questions which address absenteeism, presenteeism (reduced effectiveness while working), overall work productivity loss (absenteeism plus presenteeism), and activity impairment for the 7 days prior to the assessment. WPAI outcomes are presented as impairment percentages (a higher percentage indicating greater impairment and less productivity). Subscale: Absenteeism (work time missed) (%) score, range 0-100.
Measured: from baseline to end of DB period, 52 Weeks
WPAI-GH Endpoint, Change From Baseline by Timepoint up to Week 52: Subscale: Presenteeism (Impairment at Work) (%), Range 0-100.
The Work Productivity and Activity Impairment questionnaire (WPAI-GH) has 6 questions which address absenteeism, presenteeism (reduced effectiveness while working), overall work productivity loss (absenteeism plus presenteeism), and activity impairment for the 7 days prior to the assessment. WPAI outcomes are presented as impairment percentages (a higher percentage indicating greater impairment and less productivity). Presenteeism (%) score.
Measured: from baseline to end of DB period, 52 Weeks
WPAI-GH Endpoint, Change From Baseline by Timepoint: Work Productivity Loss (%)
The Work Productivity and Activity Impairment questionnaire (WPAI-GH) has 6 questions which address absenteeism, presenteeism (reduced effectiveness while working), overall work productivity loss (absenteeism plus presenteeism), and activity impairment for the 7 days prior to the assessment. WPAI outcomes are presented as impairment percentages (a higher percentage indicating greater impairment and less productivity). Work productivity loss (%) score, range 0-100.
Measured: from baseline to end of DB period, 52 Weeks
WPAI-GH Endpoint, Change From Baseline by Timepoint: Activity Impairment (%)
The Work Productivity and Activity Impairment questionnaire (WPAI-GH) has 6 questions which address absenteeism, presenteeism (reduced effectiveness while working), overall work productivity loss (absenteeism plus presenteeism), and activity impairment for the 7 days prior to the assessment. WPAI outcomes are presented as impairment percentages (a higher percentage indicating greater impairment and less productivity). Activity impairment (%) score, range 0-100.
Measured: from baseline to end of DB period, 52 Weeks
Absolute Eosinophil Count, Change From Baseline
Absolute eosinophil count, change from baseline by timepoint up to week 52
Measured: from baseline to end of DB period, 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study start29 Oct 2019
- Primary completion10 Aug 2023
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Eosinophilic Granulomatous VasculitisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Wechsler, MD, Principal investigator, National Jewish Health, 1400 Jackson St Denver, CO 80206
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04157348
- Sponsor's protocol ID
- D3253C00001
- Other IDs
- 2023-510248-19-00, 2019-001832-77, 2019, 2023
- Acronym
- MANDARA
- Status last verified
- Jul 2026
- First submitted
- 29 Sep 2019
- Last updated
- 12 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Nair PK, Hellmich B, Bourdin A, Jayne DRW, Roufosse F, Khalidi N, Borjesson Sjo L, Fan Y, McCrae C, Necander S, Rodriguez-Suarez E, Shavit A, Walton C, Merkel PA, Wechsler ME. The Effect of Benralizumab and Mepolizumab on Use of Oral Glucocorticoids in Patients With Eosinophilic Granulomatosis With Polyangiitis. Arthritis Rheumatol. 2026 Mar;78(3):695-704. doi: 10.1002/art.43398. Epub 2025 Nov 30.
PubMed 40977418Wechsler 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.
PubMed 38393328Serling-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.
PubMed 33164993
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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 (MANDARA Study)
- ClinicalTrials.gov ID
- NCT04157348
- Acronym / sponsor ID
- MANDARA / D3253C00001
- Conditions
- Eosinophilic Granulomatous Vasculitis
- Keywords
- Benralizumab, Inhaled corticosteroids, Eosinophilic Granulomatous Vasculitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 140 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 29 Oct 2019 (actual)
- Primary completion
- 10 Aug 2023 (actual)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 8 Nov 2019 (actual)
- Results
- Posted 14 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Benralizumab arm | Experimental | Biological: Benralizumab, Biological: Placebo to Mepolizumab1x benralizumab SC injection + 3x placebo to mepolizumab SC injections |
| Mepolizumab arm | Active comparator | Biological: Mepolizumab, Biological: Placebo to Benralizumab3x mepolizumab SC injections + 1x placebo to benralizumab SC injection |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Benralizumab30 mg/mL solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC) | Biological | Benralizumab arm |
| Mepolizumab3x100 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) | Biological | Mepolizumab arm |
| Placebo to MepolizumabMatching 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) | Biological | Benralizumab arm |
| Placebo to BenralizumabMatching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC) | Biological | Mepolizumab arm |
Primary outcome
Number of Subjects Who Achieved Main Remission at Both Weeks 36 and 48
Time frame: 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
Time frame: 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.
30 secondary outcomes
Total Accrued Duration of Remission During DB Treatment Period
Time frame: from baseline to end of DB period, 52 Weeks.
Total Accrued Duration of Sustained Remission During DB Treatment Period
Time frame: from baseline to end of DB period, 52 Weeks
Time From Randomization to First Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse
Time frame: from baseline to end of DB period, 52 Weeks
Annualized Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse Rate
Time frame: from baseline to end of DB period, 52 Weeks
Average Daily Dose of Prednisolone/Prednisone and Change From Baseline During Week 48 Through 52
Time frame: last 4 weeks of DB period
Proportion of Patients With Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52
Time frame: last 4 weeks of DB period
Percentage Reduction From Baseline in Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52
Time frame: last 4 weeks of DB period
Proportion of Subjects With Reduction From Baseline in Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52
Time frame: last 4 weeks of DB period
Proportion of Subjects Who Achieve Clinical Benefit
Time frame: from baseline to end of DB period, 52 Weeks
Proportion of Patients Who Have Achieved Remission Within the First 24 Weeks and Remained in Remission for Remainder of the Double-blind Treatment Period
Time frame: from baseline to end of DB period, 52 Weeks
Change From Baseline in Birmingham Vasculitis Activity Score (BVAS)
Time frame: from baseline to end of DB period, 52 Weeks
Spirometry Change From Baseline by Timepoint up to Week 52: Pre-BD FEV1 (L)
Time frame: from baseline to end of DB period, 52 Weeks
Spirometry Change From Baseline by Timepoint up to Week 52: Pre-BD FVC (L)
Time frame: from baseline to end of DB period, 52 Weeks
Change From Baseline in Vasculitis Damage Index (VDI)
Time frame: from baseline to end of DB period, 52 Weeks
Change From Baseline in Asthma Control Questionnaire (6-item Version) (ACQ-6)
Time frame: from baseline to end of DB period, 52 Weeks
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) Component: Physical Component Summary (PCS)
Time frame: from baseline to end of DB period, 52 Weeks
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) Component: Mental Component Summary (MCS)
Time frame: from baseline to end of DB period, 52 Weeks
Change From Baseline in Sino-nasal Outcome Test-22 (SNOT-22) Total Score
Time frame: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Runny Nose
Time frame: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Post-nasal Discharge
Time frame: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Facial Pain/Pressure
Time frame: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Loss or Reduction in Sense of Taste/Smell
Time frame: from baseline to end of DB period, 52 Weeks
Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Blockage/Congestion of Nose
Time frame: from baseline to end of DB period, 52 Weeks
Patient Global Impression of Severity (PGIS) Category
Time frame: from baseline to end of DB period, 52 Weeks
Patient Global Impression of Change (PGIC) Category
Time frame: from baseline to week 4
WPAI-GH Endpoint, Change From Baseline by Timepoint: Absenteeism (%)
Time frame: from baseline to end of DB period, 52 Weeks
WPAI-GH Endpoint, Change From Baseline by Timepoint up to Week 52: Subscale: Presenteeism (Impairment at Work) (%), Range 0-100.
Time frame: from baseline to end of DB period, 52 Weeks
WPAI-GH Endpoint, Change From Baseline by Timepoint: Work Productivity Loss (%)
Time frame: from baseline to end of DB period, 52 Weeks
WPAI-GH Endpoint, Change From Baseline by Timepoint: Activity Impairment (%)
Time frame: from baseline to end of DB period, 52 Weeks
Absolute Eosinophil Count, Change From Baseline
Time frame: from baseline to end of DB period, 52 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40977418Nair PK, Hellmich B, Bourdin A, Jayne DRW, Roufosse F, Khalidi N, Borjesson Sjo L, Fan Y, McCrae C, Necander S, Rodriguez-Suarez E, Shavit A, Walton C, Merkel PA, Wechsler ME. The Effect of Benralizumab and Mepolizumab on Use of Oral Glucocorticoids in Patients With Eosinophilic Granulomatosis With Polyangiitis. Arthritis Rheumatol. 2026 Mar;78(3):695-704. doi: 10.1002/art.43398. Epub 2025 Nov 30.
- Derived from this study: PubMed 38393328Wechsler 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.
- Derived from this study: PubMed 33164993Serling-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.
- This is a poster.Link provided by the sponsor.
- A website on the Mandara study. The website was active until the end of the recruitment process.Link provided by the sponsor.
- CSR SynopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Wechsler, MD principal investigator
National Jewish Health, 1400 Jackson St Denver, CO 80206
50 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Benralizumab and Mepolizumab in people with Eosinophilic Granulomatous Vasculitis, run by AstraZeneca at 50 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, France, Italy, Israel, Germany and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Who Achieved Main Remission at Both Weeks 36 and 48 (time frame: Week 36 and Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04157348, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.