A Study of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Azathioprine; Chloroquine; Hydroxychloroquine; Leflunomide; Methotrexate; Sulfasalazine; Tocilizumab
Intervention description: Participants may receive azathioprine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.; Participants may receive chloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.; Participants may receive hydroxychloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.; Participants may receive leflunomide as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.; Participants may receive methotrexate as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.; Participants may receive sulfasalazine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.; Participants will receive tocilizumab at a fixed dose of 162 mg SC QW either as monotherapy or in combination with non-biologic DMARDs.
Intervention MeSH terms: Hydroxychloroquine; Chloroquine; Sulfasalazine; Methotrexate; Azathioprine; Leflunomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This Phase IIIb, multicenter, open label, single arm study will evaluate the safety and
      efficacy of subcutaneous (SC) tocilizumab as monotherapy or in combination with methotrexate
      or other non-biologic DMARDs in participants with active rheumatoid arthritis who are either
      naïve to or have an inadequate response to prior non-biologic or/and biologic DMARDs. The
      anticipated time on study treatment is 52 weeks. Those participants who will complete the
      60-week study period and have achieved Disease Activity Score 28 (DAS28) remission or a good
      European League Against Rheumatism (EULAR) response at 52 weeks will be eligible to enter the
      extension phase until tocilizumab is commercially available and reimbursed in Greece.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria
             or EULAR/ACR (2010) criteria

          -  Oral corticosteroids (less than or equal to [</=] 10 milligrams per day [mg/day]
             prednisolone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to
             the maximum recommended dose) are permitted if on a stable dose regimen for greater
             than or equal to [>/=] 4 weeks prior to baseline

          -  Permitted non biologic DMARDs are allowed if a stable dose for at least 4 weeks prior
             to baseline

          -  Receiving treatment on an outpatient basis, not including tocilizumab

          -  Females of childbearing potential and males with female partners of childbearing
             potential must agree to use a reliable means of contraception during the study;
             females of childbearing potential must use a reliable means of contraception for at
             least 3 month following the last dose of tocilizumab

        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 rheumatoid arthritis; secondary Sjögren's
             syndrome with rheumatoid arthritis is permitted

          -  Functional Class 4 as defined by the ACR Classification of Functional Status in
             Rheumatoid Arthritis

          -  Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or
             rheumatoid arthritis before the age of 16

          -  Prior history of or current inflammatory joint disease other than rheumatoid arthritis

          -  Participants with lack of peripheral venous access

          -  Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline

          -  Treatment with any investigational agent within 4 weeks (or five half-lives of the
             investigational drug, whichever is longer) of screening

          -  Previous treatment with any cell-depending therapies

          -  Treatment with IV gamma globulin, plasmapheresis within 6 months of baseline

          -  Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline

          -  Immunization with a live/attenuated vaccine within 4 weeks prior to baseline

          -  Any previous treatment with alkylating agents such as chlorambucil, or with total
             lymphoid irradiation

          -  History of severe allergic or anaphylactic reactions to human, humanized, or murine
             monoclonal antibodies

          -  Evidence of serious uncontrolled concomitant cardiovascular, nervous system,
             pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or
             gastrointestinal disease

          -  Known active current or history of recurrent bacterial, viral, fungal, mycobacterial,
             or other infections

          -  Any major episode of infection requiring hospitalization of treatment with IV
             antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of
             screening

          -  Active tuberculosis (TB) requiring treatment within the previous 3 years

          -  Positive for hepatitis B surface antigen or hepatitis C antibody

          -  Primary or secondary immunodeficiency (history of or currently active)

          -  Evidence of active malignant disease, malignancies diagnosed within the previous 10
             years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ
             of the cervix uteri that has been excised and cured), or breast cancer diagnosed
             within the previous 20 years

          -  Pregnant or breast feeding women

          -  History of alcohol, drug or chemical abuse within 1 year prior to screening

          -  Neuropathies or other conditions that interfere with pain evaluation