Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab.

Study 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).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More 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-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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04157348
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	AstraZeneca
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Michael Wechsler, MD
Principal Investigator Affiliation	National Jewish Health, 1400 Jackson St Denver, CO 80206
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Belgium, Canada, France, Germany, Israel, Italy, Japan, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Eosinophilic Granulomatous Vasculitis
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: Benralizumab arm

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

Active Comparator: Mepolizumab arm

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

Interventions

Biological: - Benralizumab

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

Biological: - Mepolizumab

3x100 mg vials of powder for solution for injection reconstituted into 3 separate 1 mL syringes for administration on each dosing occasion. Injection volume per syringe is 1 mL. Mepolizumab active solution will be administered subcutaneously (SC)

Biological: - Placebo to Mepolizumab

Matching placebo: 0.9% sodium chloride, solutions for injection in 1mL syringes (3 syringes will be used on each dosing occasion). Injection volume per syringe is 1mL. Placebo to Mepolizumban will be administered subcutaneously (SC)

Biological: - Placebo to Benralizumab

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

Contact a Trial Team

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Research Site, La Jolla, California

Status

Recruiting

Address

Research Site

La Jolla, California, 92037

Site Contact

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