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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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

    Summary
    EudraCT Number:2014-003701-15
    Sponsor's Protocol Code Number:20101228
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2015-04-29
    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 ConcernedUK - MHRA
    A.2EudraCT number2014-003701-15
    A.3Full title of the trial
    A Randomized, Double-blind, Placebo-controlled Study With an Open Label Extension to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Axial Spondyloarthritis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and Efficacy of Brodalumab in Subjects With Axial Spondyloarthritis
    A.4.1Sponsor's protocol code number20101228
    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 SponsorAmgen Inc.
    B.1.3.4CountryUnited States
    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 supportAmgen Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen (EUROPE) GmbH
    B.5.2Functional name of contact pointIHQ Medical Info - Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZug
    B.5.3.3Post codeCH-6300
    B.5.3.4CountrySwitzerland
    B.5.6E-mailMedinfoInternational@amgen.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 namebrodalumab (140mg/ml)
    D.3.2Product code AMG 827
    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 INNbrodalumab
    D.3.9.1CAS number 1174395-19-7
    D.3.9.2Current sponsor codeAMG 827
    D.3.9.3Other descriptive nameBRODALUMAB
    D.3.9.4EV Substance CodeSUB31188
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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 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 No
    D.IMP: 2
    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 namebrodalumab (70mg/0.5ml)
    D.3.2Product code AMG 827
    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 INNbrodalumab
    D.3.9.1CAS number 1174395-19-7
    D.3.9.2Current sponsor codeAMG 827
    D.3.9.3Other descriptive nameBRODALUMAB
    D.3.9.4EV Substance CodeSUB31188
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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 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 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
    D.8 Placebo: 2
    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
    Axial Spondyloarthritis
    E.1.1.1Medical condition in easily understood language
    Axial Spondyloarthritis
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10051265
    E.1.2Term Spondyloarthropathy
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue 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 evaluate the efficacy of brodalumab in ankylosing spondylitis (AS) compared to placebo, as measured by the proportion of AS subjects achieving an Assessment of SpondyloArthritis international Society (ASAS) 20 response at week 16.
    E.2.2Secondary objectives of the trial
    • To evaluate the efficacy of brodalumab in AS subjects on Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) change from baseline at week 16
    • To evaluate the efficacy of brodalumab in the pooled population (AS and non-radiographic axial spondyloarthritis [nr-axSpA] subjects) on ASAS 20 at week 16
    • To evaluate the efficacy of brodalumab in AS subjects as measured by ASAS 40 at week 16
    • To evaluate the efficacy of brodalumab in the anti-TNF-experienced and anti-TNF-naïve subgroups as measured by ASAS 20 at week 16
    • To describe the effect of brodalumab in subjects with nr-axSpA as measured by ASAS 20 at week 16
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    • Pharmacokinetic substudy:
    To better characterize the pharmacokinetics of brodalumab in AS subjects following subcutaneous administration, additional pharmacokinetic samples will be collected with sparse sampling to determine the steady-state PK area under the concentration-time profile (AUC) in a small subset of subjects (n= 28).

    • Longitudinal MRI substudy of the axial spine will be assessed in approximately 40 AS subjects at baseline and week 16.

    • Biomarker Development:
    Blood samples are to be assessed for biomarker development. A cell pellet from the blood plasma tube may be utilized to assess the impact of brodalumab on circulating immune cells via DNA methylation analysis, a pharmacodynamics assessment of methylation patterns of relevant genes.

    • Pharmacogenetic Studies:
    Focus on inherited genetic variations to evaluate their possible correlation to the disease and/or responsiveness to the therapies used in this study. The goals of the optional studies include the use of genetic markers to help in the investigation of inflammatory disease and/or to identify subjects who may have positive or negative responses to brodalumab.
    E.3Principal inclusion criteria
    Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
    Subject is ≥ 18 years of age at time of screening

    Disease Related
    - Subject fulfills the ASAS classification criteria of axial spondyloarthritis (with the exception of the Crohn's disease criterion) for > 3 months with age of onset < 45 years of age
    AS subjects: Subject has radiographic evidence of sacroiliitis grade ≥ 2 bilaterally or grade 3 to 4 unilaterally (image must have been obtained ≤ 4 years from time of screening; centrally read)
    OR
    nr-axSpA subjects: Subject does not have radiographic evidence of sacroiliitis grade ≥ 2 bilaterally or grade 3 to 4 unilaterally (image must have been obtained ≤ 6 months from time of screening; centrally read)
    AND
    presence of inflammatory lesions of sacroiliac joint by MRI of Spondyloarthritis Research Consortium of Canada (SPARCC) level ≥ 2 (confirmed by a central
    imaging reader)
    - Subject has Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 at screening and baseline
    - Subject has spinal pain score (BASDAI question #2) ≥ 4 at screening and baseline
    - Subject has had adequate therapeutic trial (at least 4 weeks) of ≥ 2 non-steroidal anti-inflammatory drugs (NSAIDs) at the maximum recommended dose unless contraindicated or subject is intolerant.
    - For subjects receiving non-biologic DMARDs (eg, methotrexate not to exceed 25 mg per week; sulfasalazine not to exceed 3000 mg per day) subject has
    received treatment for ≥ 3 months, with a stable dose for ≥ 4 weeks prior to initiation of IMP.
    - For subject receiving oral corticosteroids: the subject must be on a stable dose (not to exceed the equivalent of 10 mg of prednisone per day) for ≥ 4 weeks prior to initiation of IMP.
    E.4Principal exclusion criteria
    Disease Related: Complete ankylosis of the spine
    Other Medical Conditions
    - Subject has known history of active tuberculosis (TB)
    - .Subject has a positive test for tuberculosis during screening
    . Subjects with a positive purified protein derivative (PPD) and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test.
    . Subjects with a positive PPD test or subjects with a positive or indeterminate Quantiferon test are allowed if they have ALL of the following:
    • no symptoms per tuberculosis worksheet provided by Amgen
    • documented history of a completed course of adequate prophylaxis per local standard of care prior to the start of IMP
    • no known exposure to a case of active tuberculosis after most recent prophylaxis
    • no evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of IMP
    - Subject has a planned surgical intervention between baseline and week 16
    - Subject has an active infection or history of infections as follows:
    • any active infection for which systemic anti-infectives were used within 28 days prior to the first IMP dose
    • a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to the first IMP dose recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject
    - Subject has any systemic disease considered by the investigator to be clinically significant and uncontrolled.
    - Subject has positive hepatitis B surface antigen, hepatitis B core antibody or hepatitis C virus antibody serology
    - Subject had myocardial infarction, unstable angina pectoris or stroke within the past 12 months prior to the first IMP dose
    - Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
    - Subject has history of malignancy within the last 5 years EXCEPT treated and considered cured cutaneous basal or squamous cell carcinoma, in situ cervical cancer or in situ breast ductal carcinoma
    - Subject has active Crohn's disease or a history of Crohn's disease
    - Subject has active ulcerative colitis requiring daily use of immunosuppressive therapy
    - Subject has had active fibromyalgia within the past 12 months
    Laboratory Abnormalities
    - Subject has any of the following laboratory abnormalities at screening:
    • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN)
    • serum direct bilirubin ≥ 1.5 mg/dL (25.7 μmol/L)
    • white blood cell (WBC) count < 3.00 x 109/L
    • absolute neutrophil count (ANC) < 2.00 x 109/L
    - Subject has any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
    Washouts or Other Treatments
    - Subject has a prior history of >1 anti-TNF therapy for ankylosing spondylitis
    - Subject has used commercially available or investigational biologic therapies for ankylosing spondylitis
    General
    - Subject has a history or evidence of suicidal ideation (severity of 4 or 5) or any suicidal behavior based on an assessment with the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) at screening or at baseline
    - Subject has a history or evidence of a psychiatric disorder or substance abuse or any other mental health disorder that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
    - Subject has severe depression based on a total score of ≥ 15 on the Patient Health Questionnaire-8 (PHQ-8) at screening or baseline (note: subjects with a
    total score of 10 to 14 on the PHQ-8 should be referred to a mental health care professional).
    - Women who are pregnant or planning to become pregnant while on study through 8 weeks after the last dose of Amgen study drug.
    - Women with a positive pregnancy test; women who have had a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy or are post-menopausal per section 7.2.2.6 are not required to have pregnancy tests.
    - Women of reproductive potential who are not willing to use an acceptable form of birth control during the study and for an additional 8 weeks after the last dose of study drug.
    - Women who are lactating/breastfeeding or planning to breastfeed during the study and for an additional 8 weeks after the last dose of Amgen study drug.

    For full detail, please refer to section 4.2 of the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    ASAS 20 in AS subjects at week 16
    E.5.1.1Timepoint(s) of evaluation of this end point
    at week 16
    E.5.2Secondary end point(s)
    • ASDAS-CRP change from baseline in AS subjects at week 16
    • ASAS 20 at week 16 in the pooled population (AS and nr-axSpA subjects)
    • ASAS 40 at week 16 in AS subjects
    • ASAS 20 at week 16 in anti-TNF-naïve AS subjects
    • ASAS 20 at week 16 in anti-TNF-experienced AS subjects
    • ASAS 20 at week 16 in nr-axSpA subjects
    E.5.2.1Timepoint(s) of evaluation of this end point
    at week 16
    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 Yes
    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.7.1.3.1Other 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 Yes
    E.8.1.7.1Other trial design description
    16-week double-blind treatment period plus an open-label treatment period of up to 290 weeks
    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.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Canada
    Czech Republic
    France
    Germany
    Japan
    Poland
    Russian Federation
    Spain
    United Kingdom
    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
    LSLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    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: 170
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 61
    F.4.2.2In the whole clinical trial 180
    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)
    Plans for treatment of care after the subject has ended participation are not different from the expected normal treatment for this 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 Decision2015-05-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-04-21
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2015-05-28
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 02:11:42 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA