Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.

    The EU Clinical Trials Register currently displays   35503   clinical trials with a EudraCT protocol, of which   5838   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).
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools

    < Back to search results

    Print Download

    EudraCT Number:2010-020126-17
    Sponsor's Protocol Code Number:MI-CP220/D3250L00001
    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:2011-04-14
    Trial results View results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBulgarian Drug Agency
    A.2EudraCT number2010-020126-17
    A.3Full title of the trial
    A Phase 2b, dose-ranging study to evaluate the efficacy and safety of MEDI-563 in adults with uncontrolled asthma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    This is a clinical study designed to explore the safety, effectiveness and optimum dose of the medicine MED-563 in adult patients who suffer from asthma that is not fully controlled by other treatments
    A.4.1Sponsor's protocol code numberMI-CP220/D3250L00001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01238861
    A.5.4Other Identifiers
    Name:not applicableNumber:N/A
    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 support
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointInformation
    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 nameMEDI-563
    D.3.2Product code MEDI-563
    D.3.4Pharmaceutical form Powder for solution for injection
    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.3.9.1CAS number 1044511-01-4
    D.3.9.2Current sponsor codeMEDI-563
    D.3.9.3Other descriptive namebenralizumab
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 No
    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
    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
    Uncontrolled 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 14.0
    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
    The primary objective of this study is to evaluate the effect of multiple-dose SC administration of MEDI-563 on the annual asthma exacerbation rate in adult subjects with uncontrolled, suspected eosinophilic asthma.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are:
    1. To evaluate the safety and tolerability of MEDI-563.
    2. To determine the optimal dose of MEDI-563 to be used in Phase 3 studies.
    3. To describe the immunogenicity (IM) and pharmacokinetics (PK) of MEDI-563.
    4. To assess the effect of MEDI-563 on other assessments of clinical activity (i.e. asthma control and pulmonary function).
    5. To assess the effect of MEDI-563 on health-related quality of life.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 18 through 75 years at the time informed consent is obtained.
    2. Written informed consent and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluatons.
    3. Female subjects of childbearing potential who are sexually active with non-sterilized male partner must use adequate contraception from the date informed consent is obtained through the end of the study. An acceptable method of contraception is defined as one that has no higher than a 1% failure rate. In this study, where medications and devices containing hormones are included, the recommended methods of contraception are described in Table 4.2.1-1 of the protocol. Sustained abstinence is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
    4. Non-sterilized males who are sexually active with a female of child-bearing potential must use adequate contraception from the date informed consent is obtained through the end of the study.
    5. Females or female partners not of childbearing potential must have been surgically sterilized (eg, hysteroctomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as at least 1 year since last regular menses) and follicle stimulating hormone (FSH) > 23 IU/L according to a central laboratory.
    6. Sterilized males must be at least 1 year post vasectomy.
    7. Weight of > 45 kg but equal to or less than 150 kg (>100 lb but equal to or less than 330 lb).
    8. History of physician-diagnosed asthma for at least 12 months prior to the date informed consent is obtained.
    9. Morning pre-bronchodilator forced expiratory volume in 1 second (FEV1) value of more than or equal to 40% and <90% predicted during the screening/run-in period.
    10. Meeting any one of the following criteria: a) Proof of post-bronchodilator reversibility of airflow obstruction more than or equal to 12% documented within 36 months prior to randomization or proof of a positive response [PC20 less than or equal to 8 mg/mL (ATS, 2000)] to a methacholine challenge documented within 36 months prior to randomization; OR b) A post-bronchodilator increase in FEV1 greater than or equal to 12% and greater than or equal to 200ml at Week -3 screening visit: OR c) If a) and b) are not met and all other inclusion/exclusion criteria are met, subjects with a FEV1 of more than or equal to 1.5 L and more than or equal to 60% predicted on the Week -2 screening visit will be eligible to undergo a methacholine challenge at the Week -2 screening visit at sites where methacholine testing is available. If the subject achieves a positive response to this methacholine challenge (PC20 less than or equal to 8 mg/mL), then this inclusion criterion is met.
    11. Physician prescribed daily use of medium-dose or high-dose ICS (as defined in GINA Report 2009) plus LABA or any combination of sequential dosing of either medium dose or high dose ICS/LABA for at least 12 months prior to the date informed consent is obtained. Dose must be stable for at least 30 days prior to the date informed consent is obtained and during the screening/run-in period.
    12. Willingness to switch to an ICS/LABA combination product if using individual ICS and LABA inhalers prior to the date informed consent is obtained.
    13. Dose of other asthma controller medications (leukotriene modifiers, theophylline, or cromones) must be stable for at least 30 days prior to the date informed consent is obtained).
    14. At least 2, but not more than 6, documented asthma exacerbations in the 12 months prior to the date informed consent is obtained that required use of a systemic corticosteroid burst.
    15. An Asthma Control Questionnaire (ACQ) score of more than or equal to 1.5 at least twice during the screening/run-in period .
    16. For subjects 65 years of age or older, a chest x-ray (CXR) or chest computed tomography (CT) that is normal for an asthmatic population and excludes alternative diagnosis per the investigator during screening/run-in or within 12 months prior to the date informed consent is obtained.
    17. Ability and willingness to complete the study to Week 66, and if needed to Week 92 for additional follow-up of peripheral blood eosinophil counts, as required by protocol.
    E.4Principal exclusion criteria
    1. Any condition that, in the opinion of the investigator or medical monitor, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
    2. Concurrent enrolment in another clinical study.
    3. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
    4. Known history of allergy or reaction to any component of the investigational product formulation.
    5. History of anaphylaxis to any biologic therapy.
    6. Unexplained abdominal discomfort, nausea, vomiting, decreased appetite, and/or diarrhea within 30 days prior to the date informed consent is obtained & during the 3-week screening/run-in period; diagnosis of helminth parasitic infection resulting from positive stool sample during the 3-week screening/run-in period that has not been treated with, or has failed to respond to, standard of care therapy; or positive serology or stool sample for S stercoralis in subjects with chronic oral corticosteroid-dependent asthma during the 3-week screening/run-in period.
    7. Use of immunosuppressive medication (eg methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained. Chronic oral prednisone or equivalent up to 10 mg daily or 20 mg every other day for asthma is allowed.
    8. Oral corticosteroid burst or short-acting systemic corticosteroid within 30 days prior to the date informed consent is obtained or during the screening/run-in period.
    9. Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 30 days prior to the the date informed consent is obtained or during the screening/run-in period.
    10. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
    11. Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained. whichever is longer. Receipt of vaccinations (eg rubella, measles, chicken pox, vaccinations for travel abroad) is allowed providing administration was not within 3 weeks prior to any study visit.
    12. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
    13. Previously received MEDI-563.
    14. Any clinically relevant 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 subject at risk because of his/her participation in study, or may influence the results of the study, or the subject's ability to participate in the study.
    15. Past history of clinically significant cardiac disease or any ECG abnormality obtained during the screening/run-in period, which in the opinion of the Investigator may put the subject at risk or interfere with study assessments.
    16. Breastfeeding or lactating women.
    17. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
    18. History of any known primary immunodeficiency disorder excluding asymptomatic selective IgA or IgG subclass deficiency.
    19. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccinations without history of hepatitis B are allowed to enrol.
    20. A positive HIV test or subject taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
    21. History of cigarette smoking more or equal to 10 pack-years or smoking within 12 months prior to the date informed consent is obtained.
    22. Evidence of any systemic disease upon physical examination.
    23. Known exposure to inhaled occupational agents or fumes with an established diagnosis of occupational asthma.
    24. History of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy more than 12 months prior to the date informed consent is obtained or other malignancies treated with apparent success with curative therapy more than 5 years prior to the date informed consent is obtained.
    25. Planned surgical procedures during the conduct of the study.
    26. Stable dose of allergy vaccinations regimen (immunotherapy) for less than 30 days prior to the date informed consent is obtained.
    27. Subjects unable to demonstrate acceptable inhaler, peak flow meter, & spirometry techniques.
    28. Current use of any oral or ophthalmic β-adrenergic antagonist (eg, propranolol).
    E.5 End points
    E.5.1Primary end point(s)
    The primary objective of this study is to evaluate the effect of multiple-dose SC administration of MEDI-563 on the annual exacerbation rate in eosinophilic-positive adult subjects with uncontrolled asthma requiring medium-dose or high-dose ICS plus LABA and having a history of more than or equal to 2 but less than or equal to 6 documented asthma exacerbations in the 12 months prior to the date informed consent is obtained that required use of a systemic corticosteroid burst. The primary endpoint is the annual exacerbation rate during the study (Week 1 (Day 1) to Week 52) for eosinophilic-positive subjects only, where annual exacerbation rate is defined as the number of exacerbations from Week 1 (Day 1) to Week 52. If a subject discontinues before the Week 52 visit, the annual exacerbation rate for this subject will be calculated/observed Days x 364. The primary endpoint analysis will be conducted using the mITT Population at the 0.05 significant level without multiplicity adjustment this analysis will also be conducted on the PP population as a secondary analysis. The primary endpoint will be assessed by Cochran-Mantel-Haenszel (CMH) row mean score test (Van Elteren test) with baseline (Day 1) ICS use (approximately 60% of subjects on medium-dose vs. at leat 40% of subjects on high dose) as a stratification factor.
    The comparison between the combined MEDI-563 groups (100 mg) from both eosinophilic-positive and eosinophilic-negative subjects versus combined placebo groups will be assessed as part of the exploratory analyses with baseline (Day 1) ICS use (approximately 60% of subjects on medium-dose vs. at least 40% subjects on high-dose) and eosinophilic phenotype (eosinophilic-positive vs. eosinophilic-negative) as stratification factors.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 1 [Day 1] to Week 52
    E.5.2Secondary end point(s)
    Safety and Tolerability: This will be assessed by summarizing AEs and SAEs using the safety population. The occurrence of AEs and SAEs will be described by system organ class (SOC), preferred term, severity, and relationship to the investigational product. Other variables used for the safety assessments include but not limited to ECG, vital signs, and routine laboratory assessments, which will be evaluated in the MEDI-563 and placebo groups as changes from baseline. These variables as well as their changes from baseline will be summarized descriptively. Neutrophil counts and CPK will be summarized separately with absolute value and change from baseline for each study visit. In addition, if warranted, shift tables will be included.

    Dose Response: A dose-response model will be evaluated based on mITT population. The details of the dose-response analysis will be described in the statistical analysis plan.

    Pharmacokinetics and Immunogenicity: MEDI-563 concentration data will be tabulated by treatment group together with descriptive statistics. Serum MEDI-563 concentration-time profiles by treatment group will be generated and included in the report. Population modeling will be performed to better characterize the PK of MEDI-563 given by SC injection in asthmatic subjects. The incidence rate of positive serum antibodies to MEDI-563 will be described by treatment group.

    Asthma Control: Asthma control will be evaluated by ACQ, TNSS-3, and asthma symptom diary. The change from baseline in mean ACQ and TNSS-3 will be summarized by treatment and visit. The β2 agonist use and Asthma Symptom Diary will also be summarized weekly by treatment. Change from baseline in mean ACQ at various visits may be analyzed by ANCOVA with treatment and baseline values as possible covariates.

    Pulmonary Function: Pulmonary function as measured by changes of airflow obstruction (FEV1 and FVC at the site and PEF and FEV1 at home) during the study will be assessed. The measurements, along with change from baseline at various time points will be summarized using descriptive statistics. ANCOVA with treatment arm and baseline value as possible covariates may be used to compare the changes from baseline in FEV1 and PEF between the individual MEDI 563 group and the placebo group, respectively.

    Health-related Quality of Life: Health-related quality of life will be evaluated using the AQLQ(S) and EQ-5D. The overall score and the 4 domain scores from the AQLQ(S) responses, along with their respective changes from baseline will be summarized by treatment group and visit using descriptive statistics. The EQ-5D will be summarized by treatment and visit for each dimension.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The secondary enpoints will be evaluated via periodic assessments over the entire course of the study.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 trial4
    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 concerned11
    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
    Russian Federation
    South Africa
    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
    The end of the study is defined as the date of the last protocol-specified visit/ assessment (including telephone contact) for the last subject in the study.
    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 months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    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: 432
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 482
    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 (including those who are who are discontinued from receiving test product before completion of treatment) will be followed for safety through the full study period (through the Week 66 visit), including the collection of any protocol-specified samples, unless consent is withdrawn, lost to follow-up, or enrolled in another clinical study.

    After the end of the study period, subjects will continue to receive normal treatment for their asthma, as determined by their own doctor/s.
    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 Decision2011-01-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-01-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-08-15
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice