Efficacy and Safety of Benralizumab in EGPA compared to mepolizumab.  (MANDARA)

Recruitment Status:
Recruiting

Sponsor:
AstraZeneca

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT04157348

Verification:
Verified 01 May 2021   by AstraZeneca

History of Changes:
ClinicalTrials.gov

Purpose

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).

Official Title:A Randomized, 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
Study Type:Interventional
Overall Recruitment Status:Recruiting
Study Start Date:29 October 2019
Study Start Date Type:Actual
Primary Completion Date:30 December 2022
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
ConditionInterventionPhase
Eosinophilic Granulomatous Vasculitis
Biological/Vaccine: Benralizumab
Biological/Vaccine: Mepolizumab
Biological/Vaccine: Placebo to Mepolizumab
Biological/Vaccine: Placebo to Benralizumab
Phase 3
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

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. Stable doses of OCS
other than prednisolone or prednisone may be acceptable, but must be discussed with the AstraZeneca study physician.
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 signing the informed consent 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 and through
randomisation.
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 antiinfective 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, receipt of of any other marketed or investigational biologic products within 4 months or 5 half-lives prior to screening, whichever is longer . Or receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to screening (V1), whichever is longer, prior to screening.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    information.center@astrazeneca.com  

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: Michael  Wechsler , MD   National Jewish Health, 1400 Jackson St Denver, CO 80206

Locations

CountryLocationFacilityContactStatus
GermanyResearch Site Bamberg, Germany, 96049Recruiting
GermanyResearch Site Berlin, Germany, 10117Withdrawn
GermanyResearch Site Dresden, Germany, 01067Not Yet Recruiting
GermanyResearch Site Freiburg, Germany, 79106Recruiting
GermanyResearch Site Hamburg, Germany, 20251Suspended
GermanyResearch Site Jena, Germany, 07747Suspended
GermanyResearch Site Kirchheim, Germany, 73230Recruiting
GermanyResearch Site Lübeck, Germany, 23538Not Yet Recruiting
GermanyResearch Site München, Germany, 80336Recruiting
United KingdomResearch Site Cambridge, United Kingdom, CB2 0QQRecruiting
United KingdomResearch Site Leicester, United Kingdom, LE3 9QPSuspended
United KingdomResearch Site London, United Kingdom, SE19RTRecruiting
United KingdomResearch Site London, United Kingdom, W12 0HSSuspended
United KingdomResearch Site Portsmouth, United Kingdom, PO6 3LYRecruiting
Canada , ONResearch Site Hamilton, ON, Canada, L8N 4A6Recruiting
Canada , ONResearch Site Toronto, ON, Canada, M5T 3A9Recruiting
Canada , ONResearch Site Toronto, ON, Canada, M5G 1E2Recruiting
JapanResearch Site Chiba-shi, Japan, 260-0877Recruiting
JapanResearch Site Sagamihara-shi, Japan, 228-0815Recruiting
JapanResearch Site Sendai-shi, Japan, 980-8574Recruiting
JapanResearch Site Shinjuku-ku, Japan, 162-8666Recruiting
BelgiumResearch Site Brussel, Belgium, 1090Recruiting
BelgiumResearch Site Brussels, Belgium, 1070Recruiting
United States of America , PAResearch Site Philadelphia, PA, United States of America, 19104Recruiting
United States of America , PAResearch Site Pittsburgh, PA, United States of America, 15213Not Yet Recruiting
FranceResearch Site Dijon Cedex, France, 21079Not Yet Recruiting
FranceResearch Site LILLE CEDEX, France, 59037Recruiting
FranceResearch Site Marseille, France, 13915Recruiting
FranceResearch Site Montpellier, France, 34090Recruiting
FranceResearch Site Nantes Cedex 1, France, 44093Recruiting
FranceResearch Site PARIS, France, 75014Recruiting
FranceResearch Site PARIS cedex 18, France, 75877Recruiting
FranceResearch Site SURESNES CEDEX, France, 92151Recruiting
FranceResearch Site Toulouse, France, 31059Recruiting
ItalyResearch Site Cuneo, Italy, 12100Recruiting
ItalyResearch Site Firenze, Italy, 50141Recruiting
ItalyResearch Site Milano, Italy, 20132Not yet recruiting
ItalyResearch Site MILANO, Italy, 20162Recruiting
ItalyResearch Site NAPOLI, Italy, 80131Recruiting
ItalyResearch Site Roma, Italy, 00168Recruiting
ItalyResearch Site Torino, Italy, 10128Not Yet Recruiting
United States of America , NMResearch Site Albuquerque, NM, United States of America, 87131Recruiting
United States of America , NCResearch Site Chapel Hill, NC, United States of America, 27599Recruiting
United States of America , GAResearch Site Atlanta, GA, United States of America, 30322Recruiting
United States of America , MNResearch Site Rochester, MN, United States of America, 55905-0001Recruiting
United States of America , MAResearch Site Boston, MA, United States of America, 02215Not Yet Recruiting
United States of America , KSResearch Site Kansas City, KS, United States of America, 66160Recruiting
United States of America , CAResearch Site La Jolla, CA, United States of America, 92037Recruiting
United States of America , VAResearch Site Norfolk, VA, United States of America, 23507Recruiting
United States of America , VAResearch Site Richmond, VA, United States of America, 23298Recruiting
United States of America , TXResearch Site Denison, TX, United States of America, 75020Recruiting
United States of America , FLResearch Site Jacksonville, FL, United States of America, 32224Not Yet Recruiting
United States of America , TNResearch Site Nashville, TN, United States of America, 37232Recruiting
IsraelResearch Site Ashkelon, Israel, 7830604Recruiting
IsraelResearch Site Beer Sheva, Israel, 84101Recruiting
IsraelResearch Site Jerusalem, Israel, 91120Suspended
IsraelResearch Site Ramat Gan, Israel, Recruiting
IsraelResearch Site Rehovot, Israel, 7661041Recruiting
IsraelResearch Site Tel Aviv, Israel, 6423906Recruiting
United States of America , MIResearch Site Ann Arbor, MI, United States of America, 48109Recruiting
United States of America , KYResearch Site Lexington, KY, United States of America, 40502Recruiting
United States of America , NYResearch Site Great Neck, NY, United States of America, 11021Not Yet Recruiting
United States of America , NYResearch Site New York, NY, United States of America, 10021Recruiting
United States of America , ORResearch Site Portland, OR, United States of America, 97239Not Yet Recruiting
United States of America , OHResearch Site Cleveland, OH, United States of America, 44195Not Yet Recruiting
United States of America , OHResearch Site Columbus, OH, United States of America, 43210Recruiting
United States of America , WAResearch Site Seattle, WA, United States of America, 98115Recruiting
United States of America , WAResearch Site Spokane, WA, United States of America, 99204Not Yet Recruiting
United States of America , COResearch Site Denver, CO, United States of America, 80206Recruiting
United States of America , CTResearch Site New Haven, CT, United States of America, 06510Withdrawn
Canada , ABResearch Site Calgary, AB, Canada, T2N 4Z6Suspended
United States of America , OKResearch Site Oklahoma City, OK, United States of America, 73104Not Yet Recruiting
United States of America , UTResearch Site Salt Lake City, UT, United States of America, 84108Not Yet Recruiting

No attachments posted.

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Purpose

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).

Official Title:A Randomized, 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
Study Type:Interventional
Overall Recruitment Status:Recruiting
Study Start Date:29 October 2019
Study Start Date Type:Actual
Primary Completion Date:30 December 2022
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
ConditionInterventionPhase
Eosinophilic Granulomatous Vasculitis
Biological/Vaccine: Benralizumab
Biological/Vaccine: Mepolizumab
Biological/Vaccine: Placebo to Mepolizumab
Biological/Vaccine: Placebo to Benralizumab
Phase 3
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

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. Stable doses of OCS
other than prednisolone or prednisone may be acceptable, but must be discussed with the AstraZeneca study physician.
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 signing the informed consent 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 and through
randomisation.
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 antiinfective 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, receipt of of any other marketed or investigational biologic products within 4 months or 5 half-lives prior to screening, whichever is longer . Or receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to screening (V1), whichever is longer, prior to screening.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    information.center@astrazeneca.com  

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: Michael  Wechsler , MD   National Jewish Health, 1400 Jackson St Denver, CO 80206

Locations

CountryLocationFacilityContactStatus
GermanyResearch Site Bamberg, Germany, 96049Recruiting
GermanyResearch Site Berlin, Germany, 10117Withdrawn
GermanyResearch Site Dresden, Germany, 01067Not Yet Recruiting
GermanyResearch Site Freiburg, Germany, 79106Recruiting
GermanyResearch Site Hamburg, Germany, 20251Suspended
GermanyResearch Site Jena, Germany, 07747Suspended
GermanyResearch Site Kirchheim, Germany, 73230Recruiting
GermanyResearch Site Lübeck, Germany, 23538Not Yet Recruiting
GermanyResearch Site München, Germany, 80336Recruiting
United KingdomResearch Site Cambridge, United Kingdom, CB2 0QQRecruiting
United KingdomResearch Site Leicester, United Kingdom, LE3 9QPSuspended
United KingdomResearch Site London, United Kingdom, SE19RTRecruiting
United KingdomResearch Site London, United Kingdom, W12 0HSSuspended
United KingdomResearch Site Portsmouth, United Kingdom, PO6 3LYRecruiting
Canada , ONResearch Site Hamilton, ON, Canada, L8N 4A6Recruiting
Canada , ONResearch Site Toronto, ON, Canada, M5T 3A9Recruiting
Canada , ONResearch Site Toronto, ON, Canada, M5G 1E2Recruiting
JapanResearch Site Chiba-shi, Japan, 260-0877Recruiting
JapanResearch Site Sagamihara-shi, Japan, 228-0815Recruiting
JapanResearch Site Sendai-shi, Japan, 980-8574Recruiting
JapanResearch Site Shinjuku-ku, Japan, 162-8666Recruiting
BelgiumResearch Site Brussel, Belgium, 1090Recruiting
BelgiumResearch Site Brussels, Belgium, 1070Recruiting
United States of America , PAResearch Site Philadelphia, PA, United States of America, 19104Recruiting
United States of America , PAResearch Site Pittsburgh, PA, United States of America, 15213Not Yet Recruiting
FranceResearch Site Dijon Cedex, France, 21079Not Yet Recruiting
FranceResearch Site LILLE CEDEX, France, 59037Recruiting
FranceResearch Site Marseille, France, 13915Recruiting
FranceResearch Site Montpellier, France, 34090Recruiting
FranceResearch Site Nantes Cedex 1, France, 44093Recruiting
FranceResearch Site PARIS, France, 75014Recruiting
FranceResearch Site PARIS cedex 18, France, 75877Recruiting
FranceResearch Site SURESNES CEDEX, France, 92151Recruiting
FranceResearch Site Toulouse, France, 31059Recruiting
ItalyResearch Site Cuneo, Italy, 12100Recruiting
ItalyResearch Site Firenze, Italy, 50141Recruiting
ItalyResearch Site Milano, Italy, 20132Not yet recruiting
ItalyResearch Site MILANO, Italy, 20162Recruiting
ItalyResearch Site NAPOLI, Italy, 80131Recruiting
ItalyResearch Site Roma, Italy, 00168Recruiting
ItalyResearch Site Torino, Italy, 10128Not Yet Recruiting
United States of America , NMResearch Site Albuquerque, NM, United States of America, 87131Recruiting
United States of America , NCResearch Site Chapel Hill, NC, United States of America, 27599Recruiting
United States of America , GAResearch Site Atlanta, GA, United States of America, 30322Recruiting
United States of America , MNResearch Site Rochester, MN, United States of America, 55905-0001Recruiting
United States of America , MAResearch Site Boston, MA, United States of America, 02215Not Yet Recruiting
United States of America , KSResearch Site Kansas City, KS, United States of America, 66160Recruiting
United States of America , CAResearch Site La Jolla, CA, United States of America, 92037Recruiting
United States of America , VAResearch Site Norfolk, VA, United States of America, 23507Recruiting
United States of America , VAResearch Site Richmond, VA, United States of America, 23298Recruiting
United States of America , TXResearch Site Denison, TX, United States of America, 75020Recruiting
United States of America , FLResearch Site Jacksonville, FL, United States of America, 32224Not Yet Recruiting
United States of America , TNResearch Site Nashville, TN, United States of America, 37232Recruiting
IsraelResearch Site Ashkelon, Israel, 7830604Recruiting
IsraelResearch Site Beer Sheva, Israel, 84101Recruiting
IsraelResearch Site Jerusalem, Israel, 91120Suspended
IsraelResearch Site Ramat Gan, Israel, Recruiting
IsraelResearch Site Rehovot, Israel, 7661041Recruiting
IsraelResearch Site Tel Aviv, Israel, 6423906Recruiting
United States of America , MIResearch Site Ann Arbor, MI, United States of America, 48109Recruiting
United States of America , KYResearch Site Lexington, KY, United States of America, 40502Recruiting
United States of America , NYResearch Site Great Neck, NY, United States of America, 11021Not Yet Recruiting
United States of America , NYResearch Site New York, NY, United States of America, 10021Recruiting
United States of America , ORResearch Site Portland, OR, United States of America, 97239Not Yet Recruiting
United States of America , OHResearch Site Cleveland, OH, United States of America, 44195Not Yet Recruiting
United States of America , OHResearch Site Columbus, OH, United States of America, 43210Recruiting
United States of America , WAResearch Site Seattle, WA, United States of America, 98115Recruiting
United States of America , WAResearch Site Spokane, WA, United States of America, 99204Not Yet Recruiting
United States of America , COResearch Site Denver, CO, United States of America, 80206Recruiting
United States of America , CTResearch Site New Haven, CT, United States of America, 06510Withdrawn
Canada , ABResearch Site Calgary, AB, Canada, T2N 4Z6Suspended
United States of America , OKResearch Site Oklahoma City, OK, United States of America, 73104Not Yet Recruiting
United States of America , UTResearch Site Salt Lake City, UT, United States of America, 84108Not Yet Recruiting

Oversight


Is IND/IDE protocol: Yes 
IND/IDE Grantor: CDER 
IND/IDE Number: 100237 
Has Expanded Access: No 
U.S. FDA-regulated Drug: Yes 
U.S. FDA-regulated Device: No 

More Information


No publications provided

Responsible Party:AstraZeneca
ClinicalTrials.gov Identifier:NCT04157348
Other Study ID Numbers:D3253C00001, 2019-001832-77

Keywords provided by AstraZeneca
Benralizumab
Inhaled corticosteroids
Eosinophilic Granulomatous Vasculitis

Additional Relevant MeSH terms:
Eosinophilic Granulomatous Vasculitis

Primary Outcome Measures:

  • Proportion of patients who are in remission at both weeks 36 and 48 [ Time Frame: 36 and 48 weeks ] [ Designated as safety issue:  ]
    Patients must be in remission at both of these timepoints of weeks 36 and 48.

    Main definition: Remission is defined as BVAS=0 and OCS dose ≤ 4mg/day.
    Supportive definition: Remission is defined by BVAS =0 and OCS dose ≤ 7.5 mg/day.
    Analysis will be repeated based on main and supportive remission definitions.

Secondary Outcome Measures:

  • Number of patients in each category of accrued duration of remission [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    The categories of accrued duration of remission are: 0 wk, >0 to <12 wk, 12 to <24 wk, 24 to <36 wk, ≥36 wk. Analysis will be repeated based on main and supportive remission definitions.

  • Time from randomisation to first EGPA relapse [ Time Frame: During first 52 weeks ] [ Designated as safety issue:  ]
    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 increase of OCS therapy (>4mg prednisolone total daily dose or equivalent);
    -an increased dose or addition of an immunosuppressive agent;
    -Hospitalisation related to EGPA worsening.

  • Number of patients in each category of average daily prednisolone/prednisone dose during weeks 48 through 52 [ Time Frame: 48 through 52 weeks ] [ Designated as safety issue:  ]
    The categories of average daily prednisolone/prednisone dose are: 0; >0 to ≤4 mg; >4 to ≤7.5 mg and > 7.5 mg.

  • Annualized relapse rate [ Time Frame: Over first 52 weeks ] [ Designated as safety issue:  ]

  • 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: Up to 52 weeks ] [ Designated as safety issue:  ]
    Analysis will be repeated based on main and supportive remission definitions.

  • Change from baseline in VDI [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Vasculitis Damage Index (VDI)

    Vasculitis Damage Index measures accrued damage across 11 organ systems since diagnosis. Total score is sum of all systems and ranges from 0 to 64 with higher scores indicating more damage.

  • Change from baseline in BVAS [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Birmingham Vasculitis Activity Score (BVAS)

    Birmingham Vasculitis Activity Score (BVAS) measures vasculitis disease activity across 9 organ systems. Total score is sum of the weighted organ scores and ranges from 0 to 63 with higher scores indicating higher disease activity.

  • Change from baseline in pulmonary function [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    As measured by Forced vital capacity (FVC), unit L

  • Change from baseline in pulmonary function [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    As measured by Forced Expiratory Volume during first second (FEV1), unit L

  • Change from baseline in ACQ-6 [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Asthma Control Questionnaire (6-item version) (ACQ-6 )

    The 6 items in ACQ-6 have a 7-point scale ranging from 0=no impairment to 6=maximum impairment. The ACQ-6 score is calculated by taking the mean of the 6 equally weighted items ranging from 0=well controlled to 6=extremely well controlled. Higher scores indicate worse disease control.

  • Change from baseline in sino-nasal symptoms (SSQ) [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Sino-nasal Symptoms Questionnaire (SSQ)

    SSQ captures 5 different sino-nasal symptoms over the previous week as scored as none, mild, moderate, severe, or very severe. Higher scores indicate greater severity.

  • Change from baseline in SNOT-22 [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Sino-nasal Outcome Test-22 (SNOT-22)

    The 22 items in SNOT-22 have a 6-point scale ranging from 0=no problem to 5=problem as bad as it can be. The total score is the sum of item scores and has a range from 0 to 110. Higher scores indicate poorer outcomes.

  • Change from baseline in SF-36v2 [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Short Form 36-item health survey (version 2, acute recall) (SF-36v2)

    The short form 36-item health survey, version 2 (SF-36v2) is a 36-item, self-report survey of functional health and well-being. The assessment yields 8-domain profile consisting of the following: Physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). Psychometrically-based physical and mental health component summary scores (PCS and MCS, respectively) are computed from subscale scores to give a broader metric of physical and mental health-related quality of life. The score range is 0 to 100 with higher scores indicating better health status.

  • Change from baseline in PGIS [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Patient Global Impression of Severity (PGIS)

    PGIS is a 6-point categorical response scale ranging from 0=no symptoms to 6= very severe symptoms. Higher scores indicate worse severity.

  • Change from baseline in WPAI [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Work productivity and Activity Impairment Questionnaire (WPAI)

    WPAI consists of 6 questions regarding absenteeism, presenteeism (reduced effectiveness while working), overall work productivity loss (absenteeism plus presenteeism), and activity impairment. WPAI outcomes are scored as impairment percentages, with a higher percentage indicating greater impairment and less productivity.

  • Change from baseline in blood eosinophil counts [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]

  • Proportion of PGIC responders at each weekly assessment [ Time Frame: Up to 4 weeks ] [ Designated as safety issue:  ]
    Patient Global Impression of Change (PGIC)

    Patient Global Impression of Change (PGIC) measures the patient´s overall impression of response to treatment since the initial dose using a 7-point scale ranging from “much better”, “about the same” to “much worse”. Lower scores indicate better health status.

Other Pre-specified Outcome Measures:

  • Numbers of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]

  • Change from baseline in systolic and diastolic blood pressure [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]

  • Change from baseline in pulse rate [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]

  • Change from baseline in hematology parameters of hemoglobin, leukocytes, lymphocytes, monocytes, basophils, eosinophils, neutrophils, and platelets [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]

  • Change from baseline in clinical chemistry parameters of Alanine Aminotransferase (ALT), alkaline phosphatase, Aspartate Aminotransferase (AST), creatinine kinase, indirect and total bilirubin, creatinine and glucose [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]

  • Change from baseline in QT Interval Corrected by Fridericia's Method (QTcF) [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]
    Triplicate measurements of 12-lead electrocardiograms recorded at rest.

  • Serum benralizumab concentration as a measure of pharmacokinetics [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]

  • Anti-drug antibodies (ADA) titers as measure of immunogenicity [ Time Frame: Minimum of 52 weeks ] [ Designated as safety issue:  ]

  • Cumulative OCS use [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]
    Total OCS use (measured in mg) as measured by sum of all daily doses during the 52-week double-blind period.

  • Number of EGPA related hospitalisations [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]

  • Length of hospital stay [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]

  • ICU (Intensive Care Unit) days [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]

  • Number of EGPA related ER visits [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]

  • Number of EGPA related outpatient visits [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]

  • Number of EGPA related procedures/tests (by specific procedure/test) [ Time Frame: Up to 52 weeks ] [ Designated as safety issue:  ]

ArmsAssigned Interventions
Experimental: Benralizumab arm
1x benralizumab SC injection + 3x placebo to mepolizumab SC injections
Biological/Vaccine: Benralizumab
30 mg/mL solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC)
Biological/Vaccine: 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)
 
Active Comparator: Mepolizumab arm
3x mepolizumab SC injections + 1x placebo to benralizumab SC injection
Biological/Vaccine: 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)
Biological/Vaccine: Placebo to Benralizumab
Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC)