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    The EU Clinical Trials Register currently displays   44043   clinical trials with a EudraCT protocol, of which   7319   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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    Summary
    EudraCT Number:2004-003733-14
    Sponsor's Protocol Code Number:WA17823
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2004-12-07
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2004-003733-14
    A.3Full title of the trial
    A randomized, double-blind, parallel group study of the safety
    and prevention of structural joint damage during treatment with
    MRA versus placebo, in combination with methotrexate, in
    patients with moderate to severe active rheumatoid arthritis.
    A.4.1Sponsor's protocol code numberWA17823
    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 Yes
    D.2.1.1.1Trade name RoActemra®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    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.3.1Product nameTocilizumab Roche
    D.3.2Product code RO4877533
    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 Roche
    D.3.9.1CAS number 375823-41-9
    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
    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 injection
    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
    Rheumatoid arthritis
    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
    Primary Objectives:
    To assess the efficacy of treatment with MRA versus placebo, in
    combination with methotrexate (MTX), with regard to the
    following three primary endpoints in patients with moderate to
    severe active rheumatoid arthritis (RA) who have had an
    inadequate response to MTX:
    􀂾 Reduction in signs and symptoms over 6 months,
    􀂾 Prevention of structural joint damage over 12 months
    (with confirmation at 24 months), and
    􀂾 Improvement in physical function over 12 months (with
    confirmation at 24 months).
    To assess the safety of MRA versus placebo, in combination with
    Methotrexate (MTX), with regard to adverse events and
    laboratory assessments.
    E.2.2Secondary objectives of the trial
    Secondary Objectives:
    􀂾 To explore the pharmacokinetics, immunogenicity and
    pharmacodynamic parameters of MRA in this patient
    population
    􀂾 To assess long-term safety and efficacy of MRA
    administration in the defined patient population
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able and willing to give written informed consent and comply with the
    requirements of the study protocol.
    2. Patients with rheumatoid arthritis of ≥6 months duration, diagnosed according to
    the revised 1987 American College of Rheumatology (ACR; formerly American
    Rheumatism Association) criteria
    3. Receiving treatment on an outpatient basis.
    4. Prior to randomization, will have discontinued etanercept for ≥2 weeks, infliximab
    or adalimumab for ≥8 weeks (see exclusion #5), anakinra for ≥1 week,
    leflunomide for ≥12 weeks (or ≥4 weeks after 11 days of standard cholestyramine
    washout).
    5. Have received methotrexate for at least 12 weeks immediately prior to baseline, of
    which the last 8 weeks must have been at a stable dose of between 10 and
    25 mg/week (p.o. or parenteral).
    6. All DMARDs, other than MTX, withdrawn prior to baseline.
    7. Swollen joint count (SJC) ≥6 (66 joint count) and tender joint count (TJC) ≥8 (68
    joint count) at screening and baseline.
    8. At screening either CRP ≥1 mg/dL (10 mg/L) or ESR ≥28 mm/hr
    9. Radiographic evidence of at least one joint with a definite erosion attributable to
    rheumatoid arthritis, as determined by the central reading site. Any joint of the
    hands, wrist, or feet can be considered with the exception of the DIP joints of the
    hands.
    10. Age ≥18 years.
    11. Oral corticosteroids (≤10 mg/day prednisone or equivalent) and NSAIDs (up to
    the maximum recommended dose) are permitted if the dose has been stable for at
    least 6 weeks prior to baseline.
    12. Females of child-bearing potential and males with female partners of childbearing
    potential may participate in this trial only if using a reliable means of
    contraception (e.g. physical barrier (patient and partner), contraceptive pill or
    patch, spermicide and barrier, or IUD).
    13. Must be willing to receive oral folate.
    14. If female and of childbearing potential, the patient must have a negative urine
    pregnancy test within three weeks prior to baseline.
    E.4Principal exclusion criteria
    General:
    1. Major surgery (including joint surgery) within eight weeks prior to screening or
    planned major surgery within six months following randomization.
    2. Rheumatic autoimmune disease other than RA, including SLE, MCTD,
    scleroderma, polymyositis or significant systemic involvement secondary to RA
    (e.g., vasculitis, pulmonary fibrosis or Felty’s syndrome). Sjögren’s Syndrome
    with RA is allowable.
    3. Functional class IV as defined by the ACR Classification of Functional Status in
    Rheumatoid Arthritis.
    4. Prior history of or current inflammatory joint disease other than RA (e.g., gout,
    reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme
    disease).
    Excluded Previous or Concomitant Therapy
    5. Unsuccessful treatment with an anti-TNF agent (i.e. significant safety issues or
    lack of efficacy. Patients who terminated previous anti-TNF treatment due to cost
    or discomfort with the subcutaneous injections, may participate in this study) (see
    Inclusion #4 for anti-TNF agent washouts).
    6. Treatment with any investigational agent within four weeks (or five half-lives of
    the investigational drug, whichever is longer) of screening.
    7. Previous treatment with any cell depleting therapies, including investigational
    agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-
    CD20).
    8. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba ™
    column within six months of baseline.
    9. Intra-articular or parenteral corticosteroids within six weeks prior to baseline.
    10. Immunization with a live/attenuated vaccine within four weeks prior to baseline.
    11. Previous treatment with MRA. (An exemption to this exclusion may be granted
    for single dose exposure upon application to the sponsor on a case by case basis.)
    12. Any previous treatment with alkylating agents such as cyclophosphamide or
    chlorambucil or with total lymphoid irradiation.
    Exclusions for General Safety
    13. History of severe allergic or anaphylactic reactions to human, humanized or
    murine monoclonal antibodies.
    14. Evidence of serious uncontrolled concomitant cardiovascular, nervous system,
    pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine
    (including uncontrolled diabetes mellitus) or gastrointestinal disease.
    15. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel
    disease, where flares are commonly treated with oral or parenteral corticosteroids.
    15a History of diverticulitis, diverticulosis requiring antibiotic treatment or chronic
    ulcerative lower GI disease such as Crohn’s disease, ulcerative colitis or other
    symptomatic lower GI conditions that might predispose to perforations.
    16. Current liver disease as determined by principal investigator. (Patients with prior
    history of ALT elevation will not be excluded.)
    17. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
    or other infections (including but not limited to tuberculosis and atypical
    mycobacterial disease, clinically significant abnormalities on chest X-ray as
    determined by the investigator, Hepatitis B and C, and herpes zoster, but
    excluding fungal infections of nail beds) or any major episode of infection
    requiring hospitalization or treatment with IV antibiotics within four weeks of
    screening or oral antibiotics within two weeks prior to screening.
    18. Primary or secondary immunodeficiency (history of or currently active).
    19. Evidence of active malignant disease, malignancies diagnosed within the previous
    10 years (including hematologic malignancies and solid tumors, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed
    within the previous 20 years.
    20. Pregnant women or nursing (breast feeding) mothers.
    21. History of alcohol, drug or chemical abuse within the six months prior to
    screening.
    22. Neuropathies or other painful conditions that might interfere with pain evaluation.
    23. Patients with lack of peripheral venous access.
    24. Body weight >150 kg.

    For Laboratory Exclusion criteria (at screening) please refer to section 4.3 of the Protocol
    E.5 End points
    E.5.1Primary end point(s)
    Primary:
    1. At Week 24 (6 months):
    Proportion of patients with ACR20 response
    2. At Week 52 (12 months):
    (a) Change from baseline* in modified Sharp total
    radiographic score
    (b) Change in physical function as measured by the area
    under the curve for the change from baseline in the Health
    Assessment Questionnaire (HAQ) Disability Index
    3. At Week 104 (24 months):
    (a) Change from baseline* in modified (Genant) Sharp total
    radiographic score (confirmation of week 52 result)
    (b) Change in physical function as measured by the area
    under the curve for the change from baseline in the Health
    Assessment Questionnaire (HAQ) Disability Index
    * assessment taken prior to receiving first dose of study
    medication is considered baseline
    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 Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of Life
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA56
    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 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 trial will occur when the last participating patient completes the last scheduled visit of the extension period, or when the sponsor decides to discontinue the development program.

    All patients, including those who withdraw from the study, must return for a follow-up assessment 4, 8 and 12 weeks after last dose of study medication.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    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 years7
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    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 Information not present in EudraCT
    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 state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 392
    F.4.2.2In the whole clinical trial 1170
    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 Decision2005-01-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2004-12-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-02-24
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    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.

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