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    The EU Clinical Trials Register currently displays   41207   clinical trials with a EudraCT protocol, of which   6750   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2007-001754-11
    Sponsor's Protocol Code Number:ML 21081
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-07-02
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2007-001754-11
    A.3Full title of the trial
    Pilot study to evaluate the effect of Rituximab in combination with MTX in the inhibition of progression of synovitis, bone marrow edema, and erosions evaluated by magnetic resonance imaging (MRI) in the hand of patients with rheumatoid arthritis.
    A.3.2Name or abbreviated title of the trial where available
    ND
    A.4.1Sponsor's protocol code numberML 21081
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberND
    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
    B.1.3.4CountryItaly
    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 Mabthera
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRituximab
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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 No
    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
    Rheumatoid arthritis
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate modifications of the synovial membrane enhancement, the extent of bone marrow oedema, and the number and extent of erosions in the wrist and metacarpophlangeal joints of RA patients after a single course (two infusions 15 days apart) of Rituximab. MRI will be performed on a low field extremity-dedicated system (Artoscan, ESAOTE) using the RAMRIS scoring system developed by OMERACT and dynamic gadolinium-enhanced MRI of the wrist, a new MRI technique devised to evaluate inflammatory synovial neoangiogenesis.
    E.2.2Secondary objectives of the trial
    not planned
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    1. Patients capable of understanding and signing the informed consent and of respecting the procedures involved in the study

    2. Patients with rheumatoid arthritis diagnosed for at least 3 months according to the 1987 criteria of the American College of Rheumatology (ACR)

    3. Patients experiencing inadequate response to MTX at a dose of 12.5 25 mg/week (p.o. or parenteral) for at least 12 weeks, with the last 4 weeks prior to baseline maintained at a stable dose. A MTX dose of 7.5 or 10 mg/week is permitted only in case of documented intolerance to higher doses .

    4. Disease duration <= 10 years

    5. Anti-CCP and / or RF positive

    6. Patients with a DAS 28-CRP > 3.2

    7. At screening: C reactive protein (CRP) > 0.6 mg/dL (6 mg/L) or ESR > 28 mm/h.

    8. Age: 18-75 years.

    9. Evidence of erosive disease and/or clinical synovitis in a signal (MRI) joint (metacarpophalangeal and/or wrist)

    10. RA duration > 1 year: at least one erosion evaluated by a radiograph at the X-ray and evidence of clinical synovitis

    11. RA duration < 1 year: evidence of clinical synovitis&#61482;

    12. The use of glucocorticoids (< 10 mg/day prednisolone or equivalent) is allowed, providing they have been taken at a stable dosage for at least 4 weeks before baseline.

    13. The use of NSAIDs is allowed providing they have been taken at a stable dosage for at least 4 weeks before baseline.

    14. Potentially fertile women may participate in the study only if during the course of the study and for at least a year after treatment, they do not become pregnant.
    E.4Principal exclusion criteria
    Exclusion criteria related to rheumatoid arthritis

    1. Autoimmune rheumatic diseases other than RA. A past or present medical record reporting inflammatory joint diseases other than RA (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or any other systemic autoimmune disease (e.g. SLE, inflammatory intestinal disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or any other concomitant syndrome).General exclusion criteria

    2. Surgical operations (including synovectomy) on bones/joints (including fusion or joint replacements) in the 12 weeks prior to the baseline visit or, in the case of scheduled surgery, within 48 weeks of randomization.

    3. Absence of peripheral venous access.

    4. Women who are pregnant or breast-feeding.

    5. Significant heart disease (NYHA class III - IV) or lung disease, the latter unrelated to the pathology (including obstructive lung disease).

    6. Evidence of a serious concomitant and uncontrolled disease concerning the nervous system, kidney, liver, endocrine glands or gastrointestinal tract, which, in the doctor's opinion, would preclude the participation of the patient.

    7. Primary or secondary immunodeficiency (previous or currently active), including a history of HIV infection.

    8. Active infections of any kind (excluding mycotic infections of the nail bed), or any important episode requiring hospitalisation or intravenous therapy with anti-infective agents in the 4 weeks prior to baseline or oral anti-infective agents in the 2 weeks prior to baseline.

    9. A history of deep tissue infections (e.g. fasciitis, abscesses, osteomyelitis) within 52 weeks of selection.

    10. A history of serious recurrent or chronic infections (to verify the presence of chest infections a chest x-ray will be performed at screening, if not already performed in the 12 weeks prior to screening).

    11. Uncontrolled high or low blood pressure.

    12. A history of neoplasia, including solid tumours, haematological neoplasia and carcinoma in situ in the previous 10 years (except for basal cell and squamous cell skin cancer already removed and healed).

    13. Neurological disorders (congenital or acquired), vascular or systemic diseases that could interfere with the evaluation of efficacy, particularly with joint pain and swelling (e.g. Parkinson's disease, cerebral palsy, diabetic neuropathy).

    14. Alcohol or drug abuse or a history of alcoholism or drugaddiction in the 24 weeks prior to baseline.

    Exclusion criteria related to MRI

    15. Impossibility to perform MRI due to known allergy to Gadoteridol or presence of metallic implants in the area to be examined.

    Exclusion criteria related to therapy

    16. Confirmed hypersensitivity to any component of Rituximab or to murine proteins.

    17. Concomitant treatment with biological agents.

    18. Previous treatment with more than one biological agent approved for RA.

    19. Previous treatment with cell-depleting therapies, including experimental agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD11a, anti-CD22, anti-BLys/ BAFF, and anti-CD20).

    20. Previous treatment with any experimental agent within 28 days of baseline or within a period equal to five times the half-life of the experimental drug (whichever time is longest).

    21. Administration of any vaccine within 28 days prior to baseline (it is recommended that a patient's vaccination record and the need for immunization prior to receiving rituximab should be carefully investigated).
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the study is to test whether low field MRI can detect Rituximab-induced changes of synovitis and bone damage in a small group of RA patients within 6 months from the infusion. These changes will be compared with those observed in a cohort of patients from another study who underwent high field MRI evaluation.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Information not present in EudraCT
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    open pilot study
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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 Information not present in EudraCT
    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 years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2007-07-02. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state10
    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 Decision2007-08-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-06-22
    P. End of Trial
    P.End of Trial StatusCompleted
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