A Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: MabThera/Rituxan; Methotrexate; Placebo
Intervention description: 1; 2; 3
Intervention MeSH terms: Methotrexate; Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 520.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This study will assess the safety and efficacy of rituximab combined with MTX in participants
      with active rheumatoid arthritis (RA) who have had an inadequate response to anti-Tumor
      Necrosis (TNF) alpha therapy. The anticipated time in the study is up to 2 years and the
      target sample size is 500 participants. Eligible participants may receive re-treatment with
      rituximab under a separate protocol WA17531.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants 18-80 years of age with active RA for at least 6 months;

          -  Received treatment for RA on an outpatient basis and experienced an inadequate
             response or intolerance to treatment with at least 1 anti-TNF alpha therapy
             (etanercept, infliximab or adalimumab);

          -  Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to
             screening at a stable dose;

          -  Participants with swollen joint count (SJC) and tender joint count (TJC) of at least 8
             joints at screening and at randomization;

          -  Radiographic evidence of at least 1 joint with a definite erosion due to RA;

          -  Participants of reproductive potential must be using reliable contraceptive methods.

        Exclusion Criteria:

          -  Bone or joint surgery within 8 weeks prior to screening or joint surgery planned
             within 24 weeks of randomization;

          -  Class IV functional status of RA;

          -  Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba
             column;

          -  Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit;

          -  With a live vaccine within 4 weeks prior to randomization;

          -  Previous treatment with rituximab or other cell-depleting therapies;

          -  Concurrent treatment with any disease-modifying anti-rheumatic drug (except for MTX)
             or any anti-TNF alfa factor or other biologic therapy;

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies;

          -  Evidence of significant uncontrolled concomitant diseases such as cardiovascular
             disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal
             disorders;

          -  Known contraindications to receiving rituximab;

          -  Known active bacterial, viral, fungal, mycobacterial or other infection;

          -  History of recurrent significant infection or history of recurrent bacterial
             infections;

          -  Primary or secondary immunodeficiency (history of, or currently active);

          -  History of cancer, including solid tumors and hematologic malignancies (except basal
             cell or squamous cell carcinoma of the skin that have been excised and cured);

          -  Women who are pregnant or breast-feeding;

          -  History of alcohol, drug or chemical abuse within 6 months prior to screening;

          -  Neuropathies and neurovasculopathies which might interfere with pain evaluation;

          -  Participants with poor peripheral venous access;

          -  Intolerance or contraindications to oral or intravenous corticosteroids.