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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 16 February 2021
Main ID:  NCT04157348
Date of registration: 29/09/2019
Prospective Registration: Yes
Primary sponsor: AstraZeneca
Public title: Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. MANDARA
Scientific 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
Date of first enrolment: October 29, 2019
Target sample size: 140
Recruitment status: Recruiting
URL:  https://clinicaltrials.gov/show/NCT04157348
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).  
Phase:  Phase 3
Countries of recruitment
Belgium Canada France Germany Israel Italy Japan United Kingdom
United States
Contacts
Name:     AstraZeneca Clinical Study Information Center
Address: 
Telephone: 1-877-240-9479
Email: information.center@astrazeneca.com
Affiliation: 
Name:     Michael Wechsler, MD
Address: 
Telephone:
Email:
Affiliation:  National Jewish Health, 1400 Jackson St Denver, CO 80206
Key inclusion & exclusion 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-a 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.



Age minimum: 18 Years
Age maximum: 130 Years
Gender: All
Health Condition(s) or Problem(s) studied
Eosinophilic Granulomatous Vasculitis
Intervention(s)
Biological: Benralizumab
Biological: Mepolizumab
Biological: Placebo to Benralizumab
Biological: Placebo to Mepolizumab
Primary Outcome(s)
Proportion of patients who are in remission at both weeks 36 and 48 [Time Frame: 36 and 48 weeks]
Secondary Outcome(s)
Annualized relapse rate [Time Frame: Over first 52 weeks]
Change from baseline in ACQ-6 [Time Frame: Up to 52 weeks]
Change from baseline in blood eosinophil counts [Time Frame: Up to 52 weeks]
Change from baseline in BVAS [Time Frame: Up to 52 weeks]
Change from baseline in PGIS [Time Frame: Up to 52 weeks]
Change from baseline in pulmonary function [Time Frame: Up to 52 weeks]
Change from baseline in SF-36v2 [Time Frame: Up to 52 weeks]
Change from baseline in sino-nasal symptoms (SSQ) [Time Frame: Up to 52 weeks]
Change from baseline in SNOT-22 [Time Frame: Up to 52 weeks]
Change from baseline in VDI [Time Frame: Up to 52 weeks]
Change from baseline in WPAI [Time Frame: Up to 52 weeks]
Number of patients in each category of accrued duration of remission [Time Frame: Up to 52 weeks]
Number of patients in each category of average daily prednisolone/prednisone dose during weeks 48 through 52 [Time Frame: 48 through 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: Up to 52 weeks]
Proportion of PGIC responders at each weekly assessment [Time Frame: Up to 4 weeks]
Time from randomisation to first EGPA relapse [Time Frame: During first 52 weeks]
Secondary ID(s)
2019-001832-77
D3253C00001
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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