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    Summary
    EudraCT Number:2013-002523-42
    Sponsor's Protocol Code Number:D3250C00020
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-09-18
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBulgarian Drug Agency
    A.2EudraCT number2013-002523-42
    A.3Full title of the trial
    A multicenter, randomized, double-blind, parallel group, placebo-controlled, Phase 3 efficacy and safety study of benralizumab (MEDI-563) to reduce oral corticosteroid use in patients with uncontrolled asthma on high dose inhaled corticosteroid plus long acting beta2 agonist and chronic oral corticosteroid therapy (ZONDA)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy and safety study of Benralizumab to reduce OCS use in patients with uncontrolled asthma on high dose inhaled corticosteroid plus LABA and chronic OCS therapy
    A.3.2Name or abbreviated title of the trial where available
    ZONDA
    A.4.1Sponsor's protocol code numberD3250C00020
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02075255
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation PlanP/018/2015
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointClinical Trial Transparency
    B.5.3 Address:
    B.5.3.1Street AddressVastra Malarehamnen 9
    B.5.3.2Town/ citySodertalje
    B.5.3.3Post code151 85
    B.5.3.4CountrySweden
    B.5.4Telephone number46855326000
    B.5.5Fax number46855329000
    B.5.6E-mailClinicalTrialTransparency@astrazeneca.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namebenralizumab
    D.3.2Product code MEDI-563
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNbenralizumab
    D.3.9.1CAS number 1044511-01-4
    D.3.9.2Current sponsor codeMEDI-563
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Asthma
    E.1.1.1Medical condition in easily understood language
    Asthma (an illness that causes breathing difficulty) that is not fully controlled, so that episodes of breathing difficulty are still occuring despite the use of other available treatments
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10003553
    E.1.2Term Asthma
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the effect of 2 dosing regimens of benralizumab on percentage reduction of oral corticosteroid (OCS) dose in adult patients with uncontrolled asthma
    E.2.2Secondary objectives of the trial
    To assess the effect of 2 dosing regimens of benralizumab on:
    - OCS dose in adult patients with uncontrolled asthma
    - parameters associated with asthma exacerbations
    - pulmonary function
    - asthma symptoms and other asthma control metrics
    - asthma related health-related quality of life
    - blood eosinophil levels
    - lung function as assessed through body plethysmography (subset of patients)
    To evaluate the pharmacokinetics (PK) and immunogenicity of 2 dosing regimens of benralizumab


    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Provision of informed consent prior to any study specific procedures
    2. Female and male aged from 18 to 75 years, inclusively
    3. History of physician-diagnosed asthma requiring treatment with medium to high dose ICS and a LABA
    4. Elevated level of peripheral blood eosinophil
    5. Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
    6. Chronic oral corticosteroid therapy for at least 6 continuous months directly preceding Visit 1. Subjects must be on doses equivalent to 7.5 – 40 mg/day of prednisolone/prednisone at Visit 1 and be on a stable dose for at least 2 weeks prior to randomization.
    7.Patients with documented failures of OCS reduction within 6 months prior to Visit 1 will not be required to proceed through the dose optimization phase during run-in.
    8. Morning pre-bronchodilator (Pre-BD) FEV1 of <80% predicted
    9. Evidence of asthma as documented by either: - Airway reversibility (FEV1 ≥12% and 200 mL) demonstrated at Visit 1, Visit 2, or Visit 3 using the Maximum Post-bronchodilator Procedure OR - Documented reversibility in the previous 24 months prior to Visit 1 OR - Airway hyperresponsiveness (PC20 FEV1 methacholine concentration ≤8mg/mL) documented in the previous 12 months prior to planned date of randomization OR - Airflow variability in clinic FEV1 ≥20% between 2 consecutive clinic visits documented in the 12 months prior to the planned date of randomization (FEV1 recorded during an exacerbation should not be considered for this criterion).
    10. At least 1 documented asthma exacerbation in the previous 12 months prior to the date informed consent is obtained.
    11. Optimized OCS dose reached at least 2 weeks prior to randomization
    12. Additional asthma controller medication must not have been initiated during run in/optimization period (not applicable for management of exacerbations during screening/ run in optimization phase).
    13. At least 70% compliance with OCS use.
    14. At least 70% compliance with usual asthma controller ICS-LABA.
    15. Minimum 70% (ie. 10 of 14 days) compliance with asthma daily diary (morning and evening diary) between each study Visit from 1 to 6.
    E.4Principal exclusion criteria
    1. Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
    2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological,musculoskeletal, infectious, endocrine, metabolic,hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: − Affect the safety of the patient throughout the study − Influence the findings of the studies or their interpretations − Impede the patient’s ability to complete the entire duration of study.
    3. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period.
    4. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient’s ability to complete entire duration of the study.
    5. History of life-threatening asthma.
    6. Asthma control reached at an OCS dose of ≤5mg during run-in/OCS optimization phase.
    7. Qualifies for 3 consecutive dose reductions at Visits 2-4 and continues to meet OCS dose reduction criteria at Visit 5.
    8. Receipt of oral corticosteroids, other than prednisone or prednisolone, as the maintenance oral steroid controller for asthma symptoms from Visit 1 and throughout the study.
    E.5 End points
    E.5.1Primary end point(s)
    Percentage reduction in final OCS dose compared with baseline (Week 0, Visit 6), while maintaining asthma control
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 28
    E.5.2Secondary end point(s)
    The effect of 2 dosing regimens of benralizumab on:
    -OCS dose in terms of proportion of patients with ≥50% reduction in average daily OCS dose at week 28 compared with dose at week 0 while maintaining asthma control.
    -Proportion of patients with 100% reduction in average daily OCS dose at week 28 compared with baseline dose at week 0, while maintaining asthma control.
    -Proportion of patients with average final OCS dose ≤5.0 mg daily at week 28, while maintaining asthma control.
    -Proportion of patients with ≤5.0 mg reduction on daily OCS dose at week 28 compared with dose at week 0, while maintaining asthma control.
    -Proportion of patients with ≥1 asthma exacerbation after randomization.
    -Annual rate of asthma exacerbations after randomization.
    -Time to the first asthma exacerbation after randomization.
    -Time to first exacerbation requiring hospitalization.
    -Time to first exacerbation requiring hospitalization or emergency department (ED) visit,
    -Number of days in hospital due to asthma.
    -Mean number of days with oral corticosteroids taken for exacerbations
    -Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization after randomization.
    -Pulmonary function in terms of change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1).
    -Asthma symptoms and other asthma control metrics in the terms of change from week 0 in asthma symptom score (total, daytime, and night time) and in rescue medication use.
    -Asthma symptoms and other asthma control metrics in the terms of change from week 0 in home lung function (morning and evening peak expiratory flow – PEF).
    -Asthma symptoms and other asthma control metrics in the terms of change from week 0 in the number of nights with awakening due to asthma requiring rescue medication.
    -Asthma symptoms and other asthma control metrics in the terms of change from week 0 in Asthma Control Questionnaire 6 (ACQ-6).
    -Asthma related health related quality of life in the terms of change from week 0 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12).
    -The pharmacokinetics (PK) in the terms of PK parameters.
    -The immunogenicity in the terms of Anti-drug antibodies (ADA) presence or absence.
    -The safety and tolerability in terms of Adverse Event (AE)/Serious Adverse Event (SAE).
    -The safety and tolerability in terms of laboratory variables.
    -The safety and tolerability in terms of electrocardiogram (ECG) evaluation.
    -The safety and tolerability in terms of physical examination results.
    -Blood eosinophils count.
    -Lung function as assessed by body plethysmography (subset of patients) in terms of Total lung capacity (TLC), Residual volume (RV), Vital capacity (VC), Inspiratory capacity (IC), Functional residual capacity (FRC).
    E.5.2.1Timepoint(s) of evaluation of this end point
    week 28
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA43
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Bulgaria
    Canada
    Chile
    France
    Germany
    Korea, Democratic People's Republic of
    Poland
    Spain
    Turkey
    Ukraine
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 189
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 21
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 102
    F.4.2.2In the whole clinical trial 210
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects may be eligible to enrol in the follow-on extension study
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-10-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-25
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-07-06
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