A Study of Subcutaneous RoActemra/Actemra (Tocilizumab) as Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Patients With Active Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: DMARD; methotrexate; tocilizumab [RoActemra/Actemra]; tocilizumab [RoActemra/Actemra]; tocilizumab [RoActemra/Actemra]
Intervention description: non-biological disease-modifying antirheumatic drugs at stable dose; stable dose; 162 mg subcutaneously (SC) qw, Weeks 1-24; 162 mg SC qw or q2w, Weeks 24-48; 162 mg SC qw, Weeks 24-48
Intervention MeSH terms: Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 401.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This multicenter, open-label study will evaluate the efficacy and safety of subcutaneously
      administered RoActemra/Actemra (tocilizumab) as monotherapy or in combination with
      methotrexate or other non-biologic DMARDs in patients with active rheumatoid arthritis and an
      inadequate response to non-biologic DMARDs or to one anti-TNF. In Phase 1, all patients will
      receive RoActemra/Actemra 162 mg subcutaneously (sc) weekly for Weeks 1 to 24, with or
      without methotrexate or other non-biologic DMARDs. For Part 2, patients who achieve sustained
      clinical DAS28-ESR remission at Weeks 20 and 24 will be randomized to receive
      RoActemra/Actemra 162 mg sc either weekly or every 2 weeks for Weeks 24 to 48, with or
      without methotrexate or other non-biologic DMARDs. Patients who do not achieve sustained
      clinical remission but achieve low disease activity (DAS-ESR </= 3.2) will continue the
      initial treatment of RoActemra/Actemra 162 mg sc weekly for Weeks 24 to 48, with or without
      methotrexate or other non-biologic DMARDs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult patients, >/= 18 years of age

          -  Active rheumatoid arthritis (DAS28-ESR > 3.2), according to the revised (1987) ACR
             criteria or EULAR/ACR (2010) criteria of > 6 months duration

          -  Patients with intolerance or inadequate response to methotrexate or other non-biologic
             DMRADs or inadequate response to a first ant-TNF agent

          -  Oral corticosteroids (</= 10 mg/day prednisone or equivalent) and non-steroidal
             anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if
             on a stable dose regimen for >/= 4 weeks prior to baseline

          -  Permitted non-biologic DMRAD is allowed if at stable dose for at least 4 weeks prior
             to baseline

          -  Females of childbearing potential and males with female partners of childbearing
             potential must be using a reliable means of contraception as defined by protocol
             during the study and for at least 3 months following the last dose of
             RoActemra/Actemra

          -  Patients with intolerance or inadequate response to methotrexate or other non-biologic
             DMARDs or inadequate response to first anti-TNF agent

        Exclusion Criteria:

          -  Major surgery (including joint surgery) within 8 weeks prior to screening or planned
             major surgery within 6 months following baseline

          -  Rheumatic autoimmune disease other than RA or significant systemic involvement
             secondary to RA; secondary Sjögren's syndrome with RA is permitted

          -  Functional Class IV as defined by the ACR Classification of Functional Status in
             Rheumatoid Arthritis

          -  Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of
             16

          -  Prior history of current inflammatory joint disease other than RA

          -  Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline

          -  Treatment with any investigational agent with four weeks (or five-half lives of the
             investigational drug, whichever is longer) of screening

          -  Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline

          -  Previous treatment with Abatacept

          -  History of severe allergic of anaphylactic reactions to human, humanized, or murine
             monoclonal antibodies

          -  Evidence of serious uncontrolled concomitant cardiovascular, nervous system,
             pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disease

          -  History of diverticulitis, diverticulitis requiring antibiotic treatment, or chronic
             ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other
             symptomatic lower GI conditions that might predispose to perforation

          -  Known active current or history of recurrent bacterial, viral, fungal, mycobacterial,
             or other infections (including but not limited to tuberculosis [TB] and atypical
             mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal
             infections or nail beds)

          -  Any major episode of infection requiring hospitalization or treatment with IV
             antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of
             screening

          -  Active TB requiring treatment within the previous 3 years

          -  Positive hepatitis B or hepatitis C

          -  Primary or secondary immunodeficiency (history of or currently active)

          -  Evidence of active malignant disease, malignancies diagnosed with the previous 10
             years (including hematological malignancies and solid tumors, except basal of squamous
             cell carcinoma of the skin diagnosed within the previous 20 years

          -  Pregnant and lactating women

          -  History of alcohol, drug, or chemical abuse within 1 year prior to screening

          -  Neuropathies or other conditions that might interfere with pain evaluation

          -  Inadequate hematological, real of liver function