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    The EU Clinical Trials Register currently displays   37733   clinical trials with a EudraCT protocol, of which   6184   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2009-012218-30
    Sponsor's Protocol Code Number:ML22648
    National Competent Authority:Portugal - INFARMED
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-08-12
    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 ConcernedPortugal - INFARMED
    A.2EudraCT number2009-012218-30
    A.3Full title of the trial
    A randomized, double-blind, placebo-controlled study to assess the efficacy of tocilizumab (TCZ) + non-biological DMARD in reducing synovitis as measured by magnetic resonance imaging (MRI) at 12 weeks after initiation of treatment in patients with moderate to severe rheumatoid arthritis (RA) with inadequate response to non-biological DMARDs
    A.3.2Name or abbreviated title of the trial where available
    PORTRAIT
    A.4.1Sponsor's protocol code numberML22648
    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 SponsorRoche Farmacêutica Química, Lda.
    B.1.3.4CountryPortugal
    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 Yes
    D.2.1.1.1Trade name RoActemra
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited, UK
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.4Pharmaceutical 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.3.11 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 typeIL6 receptor inhibitor, humanised monoclonal antibody
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Men and women > 18 years of age with RA who are currently experiencing an inadequate clinical response to a stable dose of non-biologic DMARDs (at least 12 weeks) and with MRI documented synovitis of dominant hand.
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of TCZ on synovitis as measured by MRI compared to placebo at 12 weeks after initiation of therapy in patients with RA
    E.2.2Secondary objectives of the trial
    Evaluate the changes in individual components and in global OMERACT-RAMRIS score as well as in DCE-MRI EER at 12 and 24 weeks after initiation of TCZ compared to placebo
    Evaluate the positive and negative predictive value of MRI response at 12 weeks, as an estimator of clinical response, assessed by DAS28, at 24 weeks of treatment with TCZ
    Evaluate the positive and negative predictive value of MRI response at 12 weeks, as an estimator of MRI changes at 24 weeks of treatment with TCZ
    Evaluate the effect of TCZ on global DAS28 score and its individual components (swollen and tender joint count, VAS and ESR) and CRP at 24 weeks
    Evaluate the effect of TCZ on disability measured by HAQ-DI at 24 weeks
    Assess the safety and tolerability of tocilizumab in combination with non-biologic DMARDs
    Investigate the potential of steroid hormone status to predict clinical response to tocilizumab
    Assess the impact of IL-6 blockade upon endogenous steroid hormone secretion and neuropeptide Y.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male or non-pregnant, non-nursing female
    • ≥ 18 years of age
    • Diagnosis of RA of ≥6 months duration and moderate to severe disease activity defined as a DAS28 > 3.2 at screening
    • Synovitis in the wrist of the dominant hand (defined as the presence of swollen and tender wrist joint and confirmed by MRI screening)
    • Receiving treatment on an outpatient basis
    • Patients on ≥ 1 non-biologic DMARDs at a stable dose for a period ≥ 12 weeks prior to treatment (baseline)
    • If patients are receiving an oral corticosteroid, the dose must have been stable for at least 25 out of 28 days prior to treatment (baseline)
    • Able and willing to give written informed consent and comply with the requirements of the study protocol
    E.4Principal exclusion criteria
    • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment
    • Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g. vasculitis, pulmonary fibrosis or Felty’s syndrome)
    • Functional class IV as defined by the ACR Classification of Functional Status in RA (largely or wholly incapacitated with patient bedridden or confined to wheel chair, permitting little or no self-care)
    • Prior history of or current inflammatory joint disease other than RA (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease)
    • Patient with interstitial pulmonary fibrosis and still able to tolerate MTX therapy are allowed
    • Sjögren’s Syndrome with RA is allowed
    • Treatment with any investigational agent or with anakinra, calcineurin inhibitors (e.g. tacrolimus or cyclosporine), mycophenolate mofetil or mycophenolic acid sodium within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening
    • Previous treatment with any cell-depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20)
    • Previous treatment with abatacept
    • Previous treatment with anti-TNF
    • Treatment with leflunomide in combination with MTX
    • Treatment with IV gammaglobulin, plasmapheresis or Prosorba® column within 6 months before baseline
    • Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
    • Intraarticular corticosteroids on dominant hand to be imaged within 6 months prior to baseline
    • Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
    • Previous treatment with TCZ (an exception to this criterion may be granted for single-dose exposure upon application to the sponsor on a case by case basis)
    • Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation
    • Any previous treatment with a biologic agent for RA

    E.5 End points
    E.5.1Primary end point(s)
    • Change in MRI-assessed synovial volume in the wrist and/or 2nd to 5th MCP joints of the dominant hand at 12 weeks after treatment initiation
    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 No
    E.6.7Pharmacodynamic No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Saline infusion bags
    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 No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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
    Date of last visit of the last patient (LPLV; week 24)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months0
    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.1.3Elderly (>=65 years) Yes
    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 state55
    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)
    Provided in the protocol.
    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 Decision2009-10-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-10-02
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-09-30
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