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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: 26 October 2020
Main ID:  EUCTR2019-001832-77-GB
Date of registration: 22/10/2020
Prospective Registration: No
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: 20/08/2019
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 Sodertalje Sweden
Telephone:
Email: information.center@astrazeneca.com
Affiliation:  AstraZeneca AB
Name: Information Center   
Address:  N/A SE-151 85 Sodertalje Sweden
Telephone:
Email: information.center@astrazeneca.com
Affiliation:  AstraZeneca AB
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: 0
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 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 screenin, 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)
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: Dose 1-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: NUCALA
Product Name: NUCALA
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 endpoint: Proportion of patients with relapsing or refractory EGPA, achieving
remission, defined as BVAS=0 (BVAS is a physician completed score based on disease activity in multiple parts of the body) and OCS (Oral corticosteroid) dose less or equal to 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 less or equal to 7.5 mg/day (Supportive remission definition) 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: Double blind period Objectives
1. To assess the efficacy of benralizumab compared with mepolizumab on duration of clinical remission, defined as accrued duration in weeks where a patient achieves remission 2. To assess the efficacy of benralizumab compared with mepolizumab on time to first relapse. 3. To assess the average daily dose of corticosteroid required during weeks 48 to 52 in patients receiving benralizumab compared to mepolizumab
4. To assess the annualized relapse rate in patients receiving benralizumab compared to mepolizumab. 5. To assess the proportion of patients who achieve remission within the first 24 weeks and remain in remission for the remainder of the double-blind period in patients receiving benralizumab compared to mepolizumab 6. To assess additional measures of the efficacy and health status/health-related quality of life in patients receiving benralizumab compared to mepolizumab.
7. To assess the safety and tolerability of benralizumab compared to mepolizum
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. Descriptive statistics will be provided for PGIS and WPAI to assess change from baseline over the 52 week double-blind 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
AstraZeneca AB
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 20/08/2019
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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