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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43715   clinical trials with a EudraCT protocol, of which   7255   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    EudraCT Number:2016-002094-36
    Sponsor's Protocol Code Number:D3250C00038
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-10-13
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2016-002094-36
    A.3Full title of the trial
    A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3b Study to Evaluate the Onset of Effect and Time Course of Change in Lung Function with Benralizumab in Severe, Uncontrolled Asthma Patients with Eosinophilic Inflammation
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate the Onset of Effect and Time Course of Change in Lung Function with Benralizumab in Severe, Uncontrolled Asthma Patients with Eosinophilic Inflammation
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberD3250C00038
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1185-6625
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    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.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.5.4Telephone number46855326000
    B.5.5Fax number46855329000
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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 Yes
    D. medicinal product typemonoclonal antibody
    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
    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 20.0
    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 determine the effect of benralizumab on the time course of change on lung function
    E.2.2Secondary objectives of the trial
    1.To determine time course of effect of benralizumab on blood eosinophils and correlate changes in eosinophil depletion with lung function
    2. To determine the effect of benralizumab on the time course of change and maintenance on lung function
    3. To determine the time course of the effect of benralizumab on asthma control metrics
    4. To determine the time course of effect of benralizumab on health related quality of life
    5. To determine the effect of benralizumab on the time course of change in exhaled nitric oxide (FeNO)
    6. To evaluate the pharmacokinetics and immunogenicity of benralizumab
    7. To assess the safety and tolerability of benralizumab
    8. To evaluate patient impression of overall asthma severity and overall change from baseline as reported by the patient and clinician
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Body plethysmography sub-study. No separate title defined in the main protocol body.

    Primary objective: effect of benralizumab on the time course of change in lung function as assessed through body plethysmography. Outcome measure: Residual volume (RV)
    Secondary objective: effect of benralizumab on the time course of change in lung function as assessed through body plethysmography. Outcome measures: Total lung capacity (TLC), RV/TLC ratio, Inspiratory capacity (IC), Functional residual capacity (FRC), Vital capacity (VC), Specific airway resistance (SGaw), Airway resistance (Raw)
    E.3Principal inclusion criteria
    1. Written informed consent for study participation obtained prior to any study related procedures being performed and according to international guidelines

    2. Female and male patients aged 18 to 75 years, inclusively at Visit 1.

    3. Documented history of current treatment with ICS and LABA for at least 30 days before Visit 1

    4. History of at least 2 asthma exacerbation that required treatment with systemic corticosteroids in the 12 months prior to Visit 1.

    5. Pre-bronchodilator (pre-BD) FEV1 of < 80% predicted at Visit 2 or Visit 3

    6. ACQ-6 score≥ 1.5 at Visit 1

    7. Evidence of asthma as documented by airway reversibility (FEV1 ≥12% and 200 ml) demonstrated at Visit 1, Visit 2 or Visit 3. For patients in the body plethysmography substudy, reversibility to be demonstrated at Visit 1 or at Visit 2 only

    8. Peripheral blood eosinophil count of ≥300 cells/μL assessed by central lab at Visit 1

    9. Women of childbearing potential (WOCBP) must use an effective form of birth control

    10. All sexually active male patients must agree to use a barrier method of contraception from the first dose of IP until 16 weeks after their last dose

    11. Weight of ≥40 kg

    Inclusion criteria at randomization Visit 4:
    1. At least one of the following within 7 days prior to randomization:
    - Daytime or nighttime asthma symptom for 2 or more days;
    - Rescue SABA use on at least 2 days
    - Nighttime awakenings due to asthma at least 1 night during the 7-day period
    2. ACQ >0.75 at Visit 4 prior to randomisation
    3. A negative urine pregnancy test in WOCBP prior to administration of IP

    Additional inclusion criteria applicable for the Body Plethysmography substudy:
    1. Residual volume ≥125% of predicted at Visit 3

    E.4Principal exclusion criteria
    1. Clinically important pulmonary disease other than asthma (e.g. active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome)

    2. Life-threatening asthma within the 12 months prior to Visit 1

    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. An upper respiratory tract infection or an asthma exacerbation that required treatment with systemic corticosteroids or an increase in regular maintenance dose of OCS during the screening/run-in period prior to randomisation Visit 4

    5. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, 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 or impede the patient’s ability to complete the entire duration of study

    6. Known history of allergy or reaction to any component of the investigational product formulation

    7. History of anaphylaxis to any biologic therapy

    8. History of Guillain-Barré syndrome

    9. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy

    10. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening 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

    11. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which in the opinion of the Investigator may put the patient at risk or interfere with study assessments

    12. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained

    13. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol

    14. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test

    15. Current smokers or former smokers with a smoking history of ≥10 pack years

    16. Current malignancy, or history of malignancy, except for:
    - Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
    - Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained

    17. Use of immunosuppressive medication within 3 months prior to the date informed consent

    18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥1.5 times the upper limit of normal (ULN) confirmed during screening period.

    19. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained

    20. Receipt of any marketed (eg, omalizumab, mepolizumab etc.) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer

    21. Receipt of live attenuated vaccines 30 days prior to the date of randomization.

    22. Receipt of any investigational medication within 30 days or 5 half-lives prior to randomization, whichever is longer

    Exclusion criteria at randomization Visit 4
    1. Greater than/equal to 20% change in mean Pre BD FEV1 value (mean of the Pre BD FEV1 taken 30 min (+/- 10 min) and 60 min (+/- 10 min) prior to dosing) at randomization Visit 4 from the mean pre BD FEV1 calculated from the pre BD FEV1 recorded at Visit 2 and Visit 3
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline to end of treatment between benralizumab and placebo in pre-BD FEV1.

    Body plethysmograpfy sub-group primary endpoint:
    1. Change from baseline to end of treatment in Residual volume (RV) compared to placebo
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 84 (Visit 10)
    E.5.2Secondary end point(s)
    1. Change from baseline in blood eosinophils (from hematology) to end of treatment
    2. Change from baseline in pre-BD FEV1 at all clinic visits compared to placebo
    3. Change from baseline in pre-BD forced vital capacity (FVC) at all clinic visits compared to placebo
    4. Change from baseline in ACQ-6 score at all post-baseline assessment timepoints
    5. Change from baseline in SGRQ score at all postbaseline assessment timepoints
    6. FeNO (ppb)
    7. Serum PK and anti-drug antibodies
    8. AEs, SAEs, laboratory variables, physical examination
    9. CGIC, PGI-S and PGIC assessments

    Body plethysmograpfy sub-group secondary endpoints:
    1. Change from baseline to end of treatment in the following measures compared to placebo :
    -Total lung capacity (TLC)
    -RV/TLC ratio
    -Inspiratory capacity (IC)
    -Functional residual capacity (FRC)
    -Vital capacity (VC)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 84 (Visit 10)
    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 No
    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. 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 trial2
    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.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    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
    Korea, Republic of
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    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) No
    F.1.2.1Number of subjects for this age range: 210
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 85
    F.4.2.2In the whole clinical trial 230
    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)
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-02-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-12-23
    P. End of Trial
    P.End of Trial StatusCompleted
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