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   35898   clinical trials with a EudraCT protocol, of which   5892   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

    Summary
    EudraCT Number:2007-000872-18
    Sponsor's Protocol Code Number:WA18221
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2008-03-21
    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 ConcernedGreece - EOF
    A.2EudraCT number2007-000872-18
    A.3Full title of the trial
    A 12- week randomized, double blind, placebo - controlled, parallel group, 2- arm study to evaluate the efficacy and safety of tocilizumab in patients with active systemic juvenile idiopathic arthritis (sJIA); with a 92- week single arm open- label extension to examine the long term use of tocilizumab
    A.4.1Sponsor's protocol code numberWA18221
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorF. Hoffmann-La Roche Ltd.
    B.1.3.4CountrySwitzerland
    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.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameTocilizumab Roche
    D.3.2Product code RO4877533 (TCZ)
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTocilizumab
    D.3.9.2Current sponsor codeRO4877533
    D.3.9.3Other descriptive nameMRA (Actemra)
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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.3.11.13.1Other medicinal product typeMonoclonal antibody, inhibitor of interleukin-6 receptor (IL-6 inhibitor)
    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 placeboConcentrate for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Systemic Juvenile Idiopathic Arthritis (sJIA)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10059176
    E.1.2Term Juvenile idiopathic arthritis
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part I: Primary Objectives:
    1. To assess the efficacy of tocilizumab versus placebo in
    combination with stable ongoing therapy at 12 weeks, with
    regard to signs and symptoms in sJIA patients with persistent
    activity and an inadequate response to NSAIDs and systemic
    corticosteroids.
    2. To evaluate the short term safety of tocilizumab versus
    placebo in combination with stable ongoing therapy at 12
    weeks, with regard to adverse events and laboratory
    assessments in patients with sJIA with persistent activity and
    an inadequate response to NSAIDs and corticosteroids.
    Part II: Primary Objectives:
    1. To evaluate the safety of tocilizumab in chronic
    administration;
    2. To assess the effect of tocilizumab to enable the reduction or
    elimination of corticosteroids.
    E.2.2Secondary objectives of the trial
    Part I
    To assess the efficacy in combination with stable ongoing therapy, with regard to
    common systemic features in sJIA patients with persistent activity and an inadequate response to NSAIDs and corticost;
    To assess the efficacy of treatment to permit concomitant corticosteroid reduction;
    To explore the immunogenicity and PD properties;
    To investigate, by a population analysis approach, the PK including the influence of covariates. ALSO IN PART II.
    Part II
    To assess the durability and magnitude of the tocilizumab efficacy response in patients with sJIA including meeting the definition of inactive disease and clinical remission.
    To assess the efficacy of treatment to permit concomitant medication reductions.
    To assess the clinical implications of HAHA in relationship to the occurrence of drug hypersensitivity and loss of efficacy in comparison to assays for IgE isotype antibodies and HAHA including neutralizing antibodies, respectively.

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 2 up to and including 17 years at screening into trial;
    2. Systemic Juvenile Idiopathic Arthritis according to ILAR classification (2001);
    3. More than 6 months of persistent sJIA activity prior to screening including an
    inadequate response to NSAIDs and corticosteroids due to toxicity or lack of efficacy.
    4. Presence of active disease as determined by the presence of :
    • ≥ 5 active joints, or
    • ≥ 2 active joints and fever >38°C for at least 5 out of any 14 consecutive days
    during screening and receiving prednisone or equivalent at a stable dose at no more than 0.5 mg/kg/day or 30 mg/day, whichever is less. During this same time
    period the corticosteroid dose continues unchanged.
    5. hsCRP > 4.3 mg/L or 0.43 mg/dl (1.5 x ULN (ULN= 0.28 mg/dl));
    6. Recovered from any symptomatic serositis for at least one month prior to the
    screening visit, and requiring dose of corticosteroids ≤ than 30 mg/day at baseline
    7. Fertility:
    • Female not of child-bearing potential, or
    • Female of child-bearing potential practicing effective contraceptive measures,
    having a negative urine pregnancy test within three weeks prior to randomization;,
    or
    • Sterile male, or
    • Non sterile male practicing effective contraceptive measures with female partner
    of child-bearing potential.
    [Females of childbearing potential must be using a reliable means of contraception
    (abstinence being a possible option) throughout the study and up to 12 weeks after the last infusion of study drug].
    8. Must meet one of the following:
    • not receiving MTX, or discontinued MTX at least 4 weeks prior to baseline visit,
    -or-
    • taking MTX for at least 12 weeks immediately prior to the baseline visit and on a
    stable dose of ≤20 mg/m2 for at least 8 weeks prior to the baseline visit, together
    with either folic acid or folinic acid according to local standard of care.
    9. Never treated with biologics or, if previously treated with biologics, discontinued
    etanercept ≥ 2 weeks, infliximab or adalimumab ≥ 8 weeks, anakinra ≥1 week, or
    abatacept ≥ 12 weeks prior to the baseline visit;
    10. Not currently receiving oral corticosteroids, or taking oral corticosteroids at a stable
    dose for a minimum of 2 weeks prior to the baseline visit at no more than 30 mg/day
    or 0.5 mg/kg/day whichever is less;
    11. Not taking NSAIDs, or taking no more than 1 type of NSAID at a stable dose for a
    minimum of 2 weeks prior to the baseline visit and is less than or equal to the
    maximum recommended daily dose;
    12. Written informed consent for study participation obtained from parents or legal
    guardian, with assent as appropriate by the patient, depending on the level of the
    patient’s understanding;
    13. Parental or guardian written agreement to comply with the requirements of the study protocol.
    E.4Principal exclusion criteria
    General
    1. Wheelchair or bedridden;
    2. Any other auto-immune, rheumatic disease or overlap syndrome other than sJIA;
    3. Not fully recovered from recent surgery or less than six weeks since surgery, at the
    time of screening visit; or planned surgery during the initial 12 weeks of the study;
    4. Lack of peripheral venous access;
    General Safety
    1. Pregnant, lactating, or intending to become pregnant during study conduct and up to
    12 weeks after the last administration of study drug;
    2. Any significant concurrent medical or surgical condition which would jeopardize the
    patient’s safety or ability to complete the trial;
    3. History of significant allergic or infusion reactions to prior biologic therapy;
    4. Inborn conditions characterized by a compromised immune system;
    5. Known HIV infection or other acquired forms of immune compromise;
    6. History of alcohol, drug or chemical abuse within 6 months of screening;
    7. Evidence of serious uncontrolled concomitant diseases including but not limited to
    the nervous system, renal, hepatic or endocrine;
    8. Asthma for which the patient has required the use of oral or parenteral corticosteroids
    for ≥ 2 weeks within 6 months prior to the baseline visit;
    9. Any active acute, subacute, chronic or recurrent bacterial, viral or systemic fungal
    infection including but not limited to:
    a) acute or chronic renal / bladder infections,
    b) acute or chronic pulmonary infections;
    10. History of atypical tuberculosis;
    11. Active TB requiring treatment within 2 years prior to screening visit;
    12. Positive PPD at screen, unless treated with anti-tuberculosis therapy for at least 4 weeks prior to receiving study medication and chest radiograph is negative for active tuberculosis;
    13. Any major episode of infection requiring hospitalization or treatment during
    screening or treatment with IV antibiotics completing within 4 weeks of the screening
    visit or oral antibiotics completing within 2 weeks of the screening visit;
    14. History of reactivation or new onset of a systemic infection such as herpes zoster or Epstein Bar virus within 2 months of the screening visit;
    15. Hepatitis B surface Ag or hepatitis C Ab positive;
    16. Chronic hepatitis – viral or autoimmune;
    17. Significant cardiac [e.g. congenital heart disease, valvular heart disease, constrictive pericarditis (unrelated to systemic JIA), myocarditis] or pulmonary disease, (e.g. asthma, cystic fibrosis);
    18. History or concurrent serious gastrointestinal disorders such as ulcer or inflammatory bowel disease, Crohn’s disease, ulcerative colitis or other symptomatic lower gastrointestinal conditions, including ulcer and perforation;
    19. History of or current cancer or lymphoma;
    20. Uncontrolled diabetes mellitus defined as Hgb A1c > 8.8 mg/dL;
    21. History of macrophage activation syndrome within 3 months prior to the screening visit;

    Excluded Previous or Concomitant Therapy
    1. Participation in another interventional clinical trial within the past thirty days or five
    serum half-lives or the pharmacodynamic effect of the investigative medication,
    whichever is longer;
    2. Previous treatment with tocilizumab;
    3. Intra-articular, intramuscular, intravenous or long-acting (such as dexamethasone)
    corticosteroids within 4 weeks prior to the baseline visit;
    4. Treatment with DMARDs (other than MTX) or immunosuppressants, including but
    not limited to: hydroxychloroquine, chloroquine, gold, azathioprine, D-penicillamine,
    sulfasalazine, cyclosporine or thalidomide within 6 weeks prior to the baseline visit;
    5. Treatment with leflunomide which was not followed by standardized cholestyramine
    washout and documented to be below the limit of detection prior to the baseline visit;
    6. Treatment with cyclophosphamide within 3 months prior to the baseline visit;
    7. Treatment with etoposide (VP16) within 3 months prior to the baseline visit;
    8. Treatment with growth hormone within 4 weeks prior to the baseline visit;
    9. Treatment with androgens (e.g. testosterone) within 4 weeks prior to the baseline
    visit;
    10. Treatment with a statin within 3 months prior to the baseline visit;
    11. Administration of intravenous immunoglobulin within 4 weeks prior to the baseline
    visit;
    12. Previous treatment with any cell depleting therapies, including investigational agents
    (e.g. anti-CD19 and anti-CD20);
    13. Prior stem cell transplant at any time;
    14. Live or attenuated vaccines within 4 weeks prior to the baseline visit, or intending to receive while on study medication or 12 weeks following the last dose of study medication;
    For additional Exclusion criteria please refer to the Protocol.
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoint:
    The proportion of patients with at least 30% improvement in JIA
    core set (JIA ACR30 response) at week 12 (JIA Core Set assessed
    in comparison to baseline) and absence of fever*
    *Absence of fever is defined as no temperature measurement ≥ 37.5° C.
    in the preceding seven days
    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 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.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.8.3 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA26
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Yes
    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 years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    The study will recruit paediatric patients form the age of 2 years old. Written informed consent for study participation will be obtained from parents or legal guardian depending on the level of the patient’s understanding.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 108
    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 Decision2008-05-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-09-09
    P. End of Trial
    P.End of Trial StatusOngoing
    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
    EMA HMA