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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: EUCTR
Last refreshed on: 13 October 2020
Main ID:  EUCTR2019-001832-77-DE
Date of registration: 21/08/2019
Prospective Registration: Yes
Primary sponsor: AstraZeneca AB
Public title: Efficacy and Safety of Benralizumab in EGPA compared to mepolizumab.
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: 15/01/2020
Target sample size: 140
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001832-77
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Belgium Canada France Germany Israel Italy Japan United Kingdom
United States
Contacts
Name: Information Center   
Address:  N/A SE-151 85 Södertälje Sweden
Telephone:
Email: information.center@astrazeneca.com
Affiliation:  AstraZenecaAB
Name: Information Center   
Address:  N/A SE-151 85 Södertälje Sweden
Telephone:
Email: information.center@astrazeneca.com
Affiliation:  AstraZenecaAB
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.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1. Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
2. Organ or life-threatening EGPA < 3 months prior to screening
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 anti-infective 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 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Eosinophilic Granulomatosis with Polyangiitis (EGPA)
MedDRA version: 20.1 Level: LLT Classification code 10014957 Term: Eosinophilic granulomatous vasculitis System Organ Class: 100000004870
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Intervention(s)

Product Name: benralizumab
Product Code: MEDI-563
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: benralizumab
CAS Number: 1044511-01-4
Current Sponsor code: MEDI-563
Other descriptive name: Benralizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Nucala 100 mg powder for solution for injection
Product Name: mepolizumab
Product Code: L04AC06
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Mepolizumab
CAS Number: 0196078-29-2
Current Sponsor code: Mepolizumab
Other descriptive name: Nucala
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)
Main Objective: To assess the durability of response to treatment with benralizumab compared with mepolizumab in patients with relapsing or refractory EGPA who are receiving Standard of Care Therapy, assessed by the proportion of patients in remission at both Weeks 36 and 48.
Primary end point(s): Proportion of patients with relapsing or refractory EGPA, achieving remission, defined as BVAS=0 and OCS dose = 4mg/day (Main Remission definition) at both weeks 36 and 48.

Supportive endpoint: Proportion of patients who have achieved remission defined by BVAS =0 and OCS dose = 7.5 mg/day (Supportive remission definition) at both weeks 36 and 48.
Secondary Objective: DB
To assess the efficacy of benralizumab compared with mepolizumab on duration of clinical remission
To assess the efficacy of benralizumab compared with mepolizumab on time to first relapse
To assess the average daily dose of corticosteroid from wk 48 to 52 in benralizumab compared to mepolizumab group
To assess the annualized relapse rate in benralizumab compared to mepolizumab group
To assess the proportion of patients achieving remission within the first 24 wks and remain in remission for the remainder of the DBperiod in benralizumab compared to mepolizumab groupd
To assess additional measures of efficacy and health status/health-related quality of life in patients receiving benralizumab compared to mepolizumab
Assess the safety,tolerability and immunogeniccity of benralizumab compared to mepolizumab
Assess the pharmacokinetics of benralizumab
OLE
Evaluate the effect of benralizumab on remission, relapse and OCS use
Assess the safety and tolerability of benralizumab
Timepoint(s) of evaluation of this end point: Both weeks 36&48
Secondary Outcome(s)
Secondary end point(s): Study secondary end point(s) – double-blind period:
- Total accrued duration of remission for the following categories: 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, 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 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.

- Proportion of patients in each category of average daily prednisolone/prednisone dose during weeks 48 to 52 using the following categories: 0; >0 to =4 mg; >4 to =7.5 mg and > 7.5 mg
- Annualized relapse rate

- Proportion of patients who have achieved remission within the first 24 weeks and remained in remission for remainder of the double-blind treatment period. Analysis will be repeated based on main and supportive remission definitions.

- BVAS, VDI, pulmonary function testing, asthma symptoms (ACQ-6), SNOT-22 questionnaire, health-related quality of life (SF-36v2), WPAI and blood eosinophil counts will be assessed as change from baseline over the 52-week treatment period.
PGIC will be assessed as response proportions at each weekly assessment between Visits 2 and 4

- Safety and tolerability will be evaluated based on AEs, Vital signs, physical exam, Clinical laboratory, and electrocardiogram (ECG).


Study end point(s) for open label extension (OLE) period:
- Remission, relapse (as defined in the secondary endpoints), OCS use

-Safety and tolerability will be evaluated based on AEs, Vital signs, physical exam, Clinical laboratory, and ECG .

-Serum benralizumab concentrations, Anti-benralizumab antibodies and neutralizing antibodies
Timepoint(s) of evaluation of this end point: Varies depending on the endpoint/objective
Secondary ID(s)
2019-001832-77-FR
D3253C00001
Source(s) of Monetary Support
AstraZenecaAB
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 15/01/2020
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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