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    Summary
    EudraCT Number:2007-001585-33
    Sponsor's Protocol Code Number:MA21056
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-09-13
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2007-001585-33
    A.3Full title of the trial
    Estudio clínico multicéntrico, aleatorizado y controlado con placebo para investigar la eficacia de rituximab (MabThera/Rituxan) en la inhibición del daño estructural articular valorado por resonancia magnética nuclear en pacientes con artritis reumatoide y una respuesta inadecuada al metotrexato - estudio SCORE.
    A.3.2Name or abbreviated title of the trial where available
    SCORE
    A.4.1Sponsor's protocol code numberMA21056
    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. Hoffman-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 MabThera 500mg
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Ltd.
    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.3.9.1CAS number 174722-31
    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 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 Information not present in EudraCT
    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 placeboIntravenous 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
    Artritis reumatoide (AR)

    Rheumatoid arthritis (RA)
    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
    1. To investigate the efficacy of rituximab (1000 mg x 2) in the inhibition of joint structural damage progression assessed by using MRI in patients with an inadequate clinical response to MTX
    2. To investigate the efficacy of rituximab (1000 mg x 2) in the improvement of synovitis and osteitis measured by MRI in patients with an inadequate clinical response to MTX
    3. To explore the efficacy of rituximab (500 mg x 2) in the inhibition of joint structural damage progression and in the improvement of synovitis and osteitis assessed by using MRI in patients with an inadequate clinical response to MTX
    4. To investigate the efficacy and safety of repeated courses of rituximab
    5. To evaluate additional exploratory endpoints, including those relating to MRI of targeted joints and surrounding structures.
    E.2.2Secondary objectives of the trial
    N/A
    E.2.3Trial contains a sub-study No
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    N/A
    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 active RA for at least 3 months diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of RA
    3. Disease duration ≤ 10 years
    4. Either anti-cyclic citrullinated peptide (anti-CCP) (≥ 20 Units) or rheumatoid factor positive (≥20 IU/mL) or both
    5. Active disease as defined by DAS28-CRP ≥ 3.2
    6. Evidence of erosive disease and/or clinical synovitis in a signal (MRI) joint (metacarpophalangeal and/or wrist)
    • RA duration > 1 year: at least one erosion evaluated by a radiograph at the X-ray screening visit and evidence of clinical synovitis
    • RA duration ≤ 1 year: evidence of clinical synovitis*
    7. Age ≥ 18 and ≤ 80 years
    8. Glucocorticoids ≤10 mg/day prednisolone or equivalent permitted if stable for at least 4 weeks prior to baseline
    9. Use of non-steroidal anti inflammatory drugs is permitted if stable for at least 4 weeks prior to baseline
    10. For patients of reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, intrauterine device, physical barrier) throughout study participation
    11. 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. Minimal MTX doses of 7.5 or 10 mg/week are permitted only in case of documented intolerance to higher doses.

    *In the event that clinical synovitis is not confirmed by MRI assessment at baseline, the patient will be excluded from the study
    E.4Principal exclusion criteria
    Exclusion criteria related to RA:
    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). Secondary Sjögren’s syndrome or secondary limited cutaneous vasculitis with RA is permitted
    2. Bed-bound or wheelchair bound patients
    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 any overlap syndrome)
    4. Diagnosis of juvenile idiopathic arthritis, also known as juvenile RA and/or RA before age 16.

    Exclusion criteria related to general health:
    1. Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of randomization
    2. Lack of peripheral venous access
    3. Pregnancy or breast feeding
    4. Significant cardiac or pulmonary disease, including obstructive pulmonary disease
    5. Evidence of significant, uncontrolled, concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the investigator’s opinion, would preclude patient participation
    6. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection
    7. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti infectives within 4 weeks prior to baseline or completion of oral anti-infectives within 2 weeks prior to baseline
    8. History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline
    9. History of serious recurrent or chronic infection (patients will be screened for chest infections using a chest radiograph at screening if not previously performed within the 12 weeks prior to screening)
    10. History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell or squamous cell carcinoma of the skin that has been excised and cured)
    11. Any neurological (congenital or acquired), 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)
    12. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline.

    Exclusion criteria related to medications:
    1. History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins
    2. Previous treatment with any approved or investigational biologic agent for RA
    3. Previous treatment with an anti-alpha 4 integrin antibody or co stimulation modulator
    4. Previous treatment with any B cell modulating or cell depleting therapies, including investigational agents (e.g., CAMPATH, anti CD4, anti-CD5, anti CD3, anti CD19, anti-CD11a, anti-CD22, anti BLys/BAFF, and anti-CD20)
    5. Treatment with any investigational agent within 28 days of baseline or five half lives of the investigational drug (whichever is the longer)
    6. Receipt 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 study drug be carefully investigated
    7. Intra-articular or parenteral glucocorticoids within 4 weeks prior to baseline
    8. Intolerance or contraindications to i.v. glucocorticoids.

    Exclusion criteria related to MRI:
    1. Patients who have a metal device affected by MRI (e.g., any type of electronic, mechanical, or magnetic implant; cardiac pacemaker; aneurysm clip[s]; implanted cardiac defibrillator) or have history of orbit trauma by a potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects) for which they have sought medical attention
    2. Allergy or other contraindications to an i.v. injection of gadolinium diethylenetriamine pentaacetic acid
    3. Severe active or dominant hand joint subluxations and/or contractures
    4. Claustrophobia sufficient to interfere with the patient undergoing the MRI scan.

    Exclusion criteria related to laboratory findings:
    1. Positive serum human chorionic gonadotropin measured prior to the first infusion of study drug
    2. Positive test for HBsAg or for hepatitis C serology
    3. Positive HBcAb associated with positive HBV detection (> 29 IU/L or > 169 copies/mL)
    4. Hemoglobin < 8.0 g/dL
    5. Absolute neutrophil count < 1.5 x 10 to the power of 3 micrograms per litre
    6. Concentration of serum IgG and/or IgM below 5.0 and 0.40 mg/mL, respectively.
    E.5 End points
    E.5.1Primary end point(s)
    The change in the MRI bone erosion score (assessed using RAMRIS) between baseline and week 24 in patients receiving rituximab 1000 mg i.v. x 2 compared to those receiving placebo i.v. x 2.
    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 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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA38
    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
    Week 52 is defined as the end of 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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    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 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 2007-09-13. Yes
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 130
    F.4.2.2In the whole clinical trial 180
    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 Decision2007-11-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-10-10
    P. End of Trial
    P.End of Trial StatusCompleted
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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
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