A Study of Retreatment With Rituximab in Patients With Rheumatoid Arthritis Receiving Background Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: placebo; rituximab; methotrexate; folate
Intervention description: Intravenous repeating dose; Intravenous repeating dose; Oral or parenteral repeating dose; Intravenous repeating dose
Intervention MeSH terms: Rituximab; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 559.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study
      evaluating the efficacy of retreatment with rituximab in subjects with active rheumatoid
      arthritis (RA) who are receiving Methotrexate (MTX).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent form

          -  Ability and willingness to comply with the requirements of the study protocol

          -  Age 18-80 years

          -  Diagnosis of RA for at least 6 months

          -  Receiving treatment for RA on an outpatient basis

          -  Documented moderate to severe active RA activity at screening and Day 1

          -  Documented inadequate response to previous or current treatment with one or more of
             the following: etanercept, infliximab, and/or adalimumab because of toxicity or
             inadequate efficacy

          -  Use of MTX 10-25 mg/wk for ≥ 12 weeks prior to Day 1 at a stable dose for ≥ 4 weeks

          -  Willingness to receive oral folic acid

          -  If taking a background corticosteroid, use of the corticosteroid must be at a stable
             dose during the 4 weeks prior to Day 1

          -  Use of one NSAID is permitted if the dose is stable for ≥ 2 weeks prior to Day 1

          -  For men and women of reproductive potential, willingness to use a reliable means of
             contraception for ≥ 30 days prior to Day 1 and for the study duration or the duration
             that the subject's peripheral CD19 B cells are depleted, whichever is longer

        Exclusion Criteria:

          -  Rheumatic autoimmune disease other than RA or significant systemic involvement
             secondary to RA; Secondary Sjogren's syndrome with RA is permitted.

          -  History of or current inflammatory joint disease other than RA or other systemic
             rheumatic disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease,
             scleroderma, inflammatory myopathy, or overlap syndrome)

          -  History of deep space/tissue infection within 52 weeks prior to Day 1

          -  Diagnosis of juvenile idiopathic arthritis (JIA), juvenile rheumatoid arthritis (JRA),
             and/or RA before age 16

          -  Functional Class IV, as defined by the ACR Classification of Functional Status in
             Rheumatoid Arthritis

          -  Any surgical procedure, including bone/joint surgery/synovectomy (including joint
             fusion or replacement), within 12 weeks prior to Day 1 or planned within 48 weeks
             after Day 1

          -  Known hypersensitivity to any component of a humanized or murine monoclonal antibody

          -  Receipt of any vaccination within 4 weeks prior to Day 1

          -  Significant cardiac or pulmonary disease, including obstructive pulmonary disease

          -  Evidence of significant uncontrolled concomitant disease, such as, but not limited to
             nervous system, renal, hepatic, endocrine, or gastrointestinal disorders

          -  Known active bacterial, viral, fungal, mycobacterial, or other infection (including
             tuberculosis or atypical mycobacterial disease but excluding fungal infections of the
             nail beds) or any major episode of infection requiring hospitalization or treatment
             with IV antibiotics within 4 weeks of Day 1 or oral antibiotics within 2 weeks of Day
             1

          -  History of serious recurrent or chronic infection (a chest X-ray will be performed at
             screening if one has not been performed within 12 weeks of screening that showed no
             clinically significant abnormality)

          -  History of or currently active primary or secondary immunodeficiency, including HIV
             infection

          -  History of cancer, including solid tumors and hematologic malignancies (except basal
             cell or squamous cell carcinoma of the skin that has been excised and cured)

          -  History of significant cytopenias or other bone marrow disorders

          -  History of alcohol, drug, or chemical abuse within 24 weeks prior to Day 1

          -  Pregnancy or lactation

          -  Neuropathies and neurovasculopathies that might interfere with pain evaluation

          -  Poor peripheral venous access

          -  Intolerance or contraindications to oral or IV corticosteroids

          -  Positive hepatitis B surface antigen or hepatitis C antibody serology

          -  For women of childbearing potential (including those who have had a tubal ligation), a
             positive serum pregnancy test at screening

          -  Current use of any DMARD other than MTX

          -  Concurrent treatment with any biologic agent

          -  Treatment with any investigational agent within 4 weeks prior to Day 1 or five
             half-lives of the investigational drug (whichever is longer)

          -  Any previous treatment with rituximab or other cell-depleting therapies, including
             CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD11a, anti-CD22, anti-BLys/
             BAFF, and other anti-CD20 agents

          -  Previous treatment with a co-stimulation blocking agent, including abatacept

          -  Previous treatment with an anti-<alpha> 4 integrin agent, including natalizumab

          -  Previous treatment within 6 months of screening with IV & globulin or the Prosorba(R)
             Column

          -  Intra-articular or parenteral corticosteroids within 4 weeks prior to Day 1