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    The EU Clinical Trials Register currently displays   41472   clinical trials with a EudraCT protocol, of which   6816   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2006-005330-20
    Sponsor's Protocol Code Number:WA20495
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-04-10
    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 ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2006-005330-20
    A.3Full title of the trial
    A randomized, double-blind, parallel group, international study to
    evaluate the safety and efficacy of ocrelizumab compared to
    placebo in patients with active rheumatoid arthritis who have an
    inadequate response to at least one anti-TNF-α therapy.
    A.4.1Sponsor's protocol code numberWA20495
    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 nameocrelizumab
    D.3.2Product code RO 496-4913
    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 INNocrelizumab
    D.3.9.2Current sponsor codeRO 496-4913
    D.3.9.3Other descriptive nameRhuMAb 2H7
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 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
    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
    To determine the efficacy and safety of ocrelizumab versus
    placebo in reducing signs and symptoms of rheumatoid arthritis (RA), when used in
    combination with methotrexate (MTX) or leflunomide given either alone or in
    combination with other non-biologic Disease Modifying Anti-Rheumatic Drugs (DMARD) in patients with active RA who have an inadequate response to at least
    one anti-TNF-α therapy.
    E.2.2Secondary objectives of the trial
    • To assess the efficacy of ocrelizumab to slow or inhibit
    structural damage
    • To assess the effect of ocrelizumab on physical function
    • To investigate the pharmacokinetics and pharmacodynamics
    of ocrelizumab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Target population
    Patients with active rheumatoid arthritis who have experienced an inadequate response to previous or current treatment with at least one anti-TNF-α-agent, such as etanercept, infliximab or adalimumab because of toxicity or inadequate efficacy.

    Inclusion Criteria
    Patients must meet the following criteria to be eligible for study entry:
    1. Ability and willingness to provide written informed consent and to comply with the requirements of the protocol

    2. Age ≥18 years

    3. Have active disease defined as:
    a) Diagnosis of RA of at least 3 months duration using the ACR criteria for the classification of RA.
    b) Swollen joint count (SJC) ≥4 (66 joint count) and tender joint count (TJC) ≥ (68 joint count) at screening and baseline.
    c) CRP ≥0.6 mg/dL using a high-sensitivity assay.
    d) Positive rheumatoid factor or positive anti-CCP antibody or both.

    4. Previous and current treatments:
    a) Current treatment for RA on an outpatient basis.
    b) Experienced an inadequate response to previous or current treatment with at least one anti-TNF-α-agent, such as
    etanercept, infliximab or adalimumab because of toxicity or inadequate efficacy. An adequate trial of therapy (to define inadequate efficacy) is defined as follows:
    •Etanercept dose: 25 mg twice weekly or 50 mg once weekly for ≥3 months
    •Infliximab dose: ≥3 mg/kg for at least 3 infusions
    •Adalimumab dose: 40 mg every other week or 20 mg weekly for ≥3 months
    Etanercept therapy should be discontinued at least 4 weeks prior to the baseline visit, while infliximab and
    adalimumab therapy should be discontinued at least 8 weeks prior to baseline.
    c) Patients must be receiving either
    •Leflunomide at a dose of 10-20 mg once daily for at least 12 weeks, with the last 4 weeks, prior to baseline at a stable dose, or
    •Methotrexate at a dose of 7.5-25 mg/week (p.o or parenteral) for at least 12 weeks, with the last 4 weeks, prior to baseline at a stable dose,
    •Patients receiving both methotrexate and leflunomide must discontinue one of the two prior to baseline.
    Under this circumstance methotrexate should be discontinued for at least 4 weeks prior to baseline and leflunomide should be discontinued for 12 weeks or 4 weeks after 11 days of standard cholestyramine or activated charcoal drug removal prior to baseline.
    d) If receiving other non-biologic DMARDs, these agents should have been administered for at least 12 weeks, with the last 4 weeks, prior to baseline at a stable dose.
    e) If receiving non-anti-TNF-α biologic DMARDs (such as abatacept, anakinra) these agents should be washed out at least four weeks prior to baseline.
    f) If receiving current treatment with corticosteroids, the dose must not exceed 10 mg/day prednisolone or equivalent and during the four weeks prior to baseline it must be at a stable dose.
    g) If receiving current treatment with NSAIDs, the patient must be on a stable dose for the 4 weeks prior to baseline.
    h) Patients receiving methotrexate must be willing to receive oral folic acid or equivalent.

    5. Other:
    a) For patients of reproductive potential (males and females), a reliable means of contraception must be used for the duration of the study (e.g., hormonal contraceptive, intrauterine device, physical barrier) according to local guidelines.
    b) Female patients of childbearing age must have a negative urine pregnancy test.

    E.4Principal exclusion criteria
    Exclusion Criteria Related to Rheumatoid Arthritis
    1. Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty’s syndrome). Patients with secondary Sjögren’s syndrome or secondary limited cutaneous vasculitis with RA are eligible.
    2. Functional Class IV as defined by the ACR Classification of Functional Status in RA
    3. History of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome).

    Exclusions Related to General Health
    4. Any surgical procedure, including bone or joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to or planned within 48 weeks after baseline.
    5. Sepsis in a prosthetic joint within the last 48 weeks or indefinitely if the prosthesis concerned remains in situ.
    6. Lack of peripheral venous access.
    7. Pregnancy or lactation.
    8. Known significant cardiac disease (NYHA Class III and IV)
    9. Known severe chronic obstructive pulmonary disease
    (COPD) (FEV1 < 50% predicted or functional dyspnoea ≥Grade 3 on the MRC Dyspnoea Scale)
    10. Evidence of significant uncontrolled concomitant diseases such as nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the investigator’s opinion, would preclude patient participation.
    11. Any neurological (congenital or acquired), psychiatric, vascular or systemic disorder which could affect any of the efficacy assessments, in particular, joint pain and swelling (e.g. Parkinson’s disease, cerebral palsy, diabetic neuropathy, chronic fatigue syndrome, chronic remitting anemia of unknown origin or requiring transfusion).
    12. Uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids.
    13. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
    14. Known active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with iv anti-infectives within 4 weeks of baseline or oral anti-infectives within 2 weeks prior to baseline.
    15. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis, septic arthritis of a native joint) within 48 weeks of baseline.
    16. Evidence of chronic active hepatitis B or C
    17. Evidence of active tuberculosis (patients receiving chemoprophylaxis for latent tuberculosis infection are eligible for the study)
    18. History of serious recurrent or chronic infections not specified above.
    19. History of cancer within the last 10 years, including solid tumors and hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and cured).
    20. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline.

    Exclusion Criteria Related to Medications
    21. History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of ocrelizumab infusion
    22. Treatment with any investigational agent 12 weeks or five half-lives of the investigational drug (whichever is longer) prior to baseline.
    23. Previous treatment with any cell-depleting therapies, including investigational agents (e.g., CAMPATH, anti-CD3, anti-CD4, anti-CD5, anti-CD11a, anti-CD19, anti-CD22, anti-BLys/BAFF, and anti-CD20).
    24. Treatment with iv γ-globulin or Prosorba® column within
    24 weeks prior to baseline.
    25. Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline.
    26. Receipt of any vaccine within 6 weeks prior to baseline (it is recommended that a patient’s vaccination record and the need for immunization prior to receiving ocrelizumab should be carefully investigated)
    27. Intolerance or contraindications to iv methylprednisolone.

    Exclusions Related to Laboratory Values at Screening
    28. Positive urine pregnancy test.
    29. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal.

    E.5 End points
    E.5.1Primary end point(s)
    Co-Primary Endpoints
    •Proportion of patients with ACR20 responses at 24 weeks
    •Proportion of patients with ACR20 responses at 48 weeks.
    ACR= American College of Rheumatology
    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.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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA68
    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
    Please refer to Section 3.1.4 in the Protocol.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    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 years5
    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 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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 239
    F.4.2.2In the whole clinical trial 800
    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)
    Standard of Care
    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 Decision2007-08-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-09-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-05-17
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