A Study of the Impact of Methotrexate (MTX) Discontinuation on the Efficacy of Subcutaneous (SC) Tocilizumab (TCZ) With MTX
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Tocilizumab (TCZ); Methotrexate (MTX); Placebo (PBO)
Intervention description: TCZ will be administered at a dose of 162 milligrams (mg) via SC injection weekly (if body weight is greater than or equal to [>/=] 100 kilograms [kg]) or every 2 weeks (if body weight was less than [<] 100 kg).; MTX will be administered at a stable dose (15 mg to 25 mg per week) orally.; PBO matching to MTX will be administered orally.
Intervention MeSH terms: Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 718.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized, multicenter, double-blind, parallel group study will evaluate the impact of
      MTX discontinuation on the efficacy of SC TCZ in participants with moderate to severe active
      rheumatoid arthritis who have an inadequate response to current MTX therapy. Participants
      will initiate treatment with TCZ weekly or every 2 weeks along with MTX at a stable dose
      orally in an open-label manner for 24 weeks. Participants with a disease activity score based
      on 28 joints (DAS28) less than or equal to (</=) 3.2 at Week 24, will be randomized to either
      continue receiving a stable dose of MTX or to switch to matching placebo up to Week 52.
      Participants without a DAS28 score </=3.2 at Week 24, will continue the same treatment in a
      non-randomized open-label manner up to Week 52.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body weight </=150 kg

          -  Active moderate to severe rheumatoid arthritis (DAS28 >/=4.4) according to the revised
             1987 ACR criteria at screening and baseline (prior to treatment on Day 1)

          -  Currently receiving oral MTX for at least 24 weeks and on a stable oral dose of at
             least 15 mg/week for at least 6 weeks prior to treatment (Day 1), with the following
             exception: a stable dose of at least 10 mg/week is allowed for participants with a
             body weight <50 kg or calculated glomerular filtration rate (or creatinine clearance)
             <60 milliliters per minute (mL/min)

          -  History of parenteral (SC or intramuscular [IM]) MTX is allowed, but not within 6
             weeks prior to treatment (Day 1). Participants must not have a documented, clinically
             significant intolerance to oral MTX and must be receiving oral MTX at a dose of 15
             mg/week for at least 6 weeks prior to treatment (Day 1)

          -  Participants who have received one prior anti-tumor necrosis factor (TNF) must have
             discontinued etanercept, infliximab, certolizumab, adalimumab, or golimumab for at
             least 6 months prior to screening

          -  Oral corticosteroids must have been </=10 mg/day prednisone (or equivalent) and stable
             for at least 25 out of 28 days prior to treatment (Day 1)

          -  Participants receiving treatment on an outpatient basis

        Exclusion Criteria:

          -  Documented medical history of significant intolerance to oral MTX >/=15 mg/week

          -  Participants receiving other (non-MTX) disease modifying anti-rheumatic drugs (DMARDs)
             within 8 weeks of screening

          -  Previous treatment with abatacept, rituximab, tofacitinib, or anakinra

          -  Treatment with parenteral corticosteroids within 4 weeks prior to treatment

          -  Previous treatment with cell-depleting therapies or alkylating agents

          -  Previous treatment with TCZ

          -  Major surgery (including joint surgery) within 8 weeks prior to screening or planned
             major surgery during the study

          -  Rheumatic autoimmune disease other than rheumatoid arthritis

          -  Non-rheumatic active autoimmune diseases (for example, inflammatory bowel diseases,
             psoriasis, multiple sclerosis)

          -  Prior history of or current inflammatory joint disease other than rheumatoid arthritis

          -  Functional Class IV according to the revised (1987) ACR criteria for rheumatoid
             arthritis

          -  History of severe allergic or anaphylactic reactions to human, humanized, or murine
             monoclonal antibodies

          -  Evidence of significant uncontrolled concomitant diseases; uncontrolled disease states
             where flares are commonly treated with oral or parenteral corticosteroids

          -  Active current or history of recurrent infection, or any major episode of infection
             requiring hospitalization or treatment with intravenous antibiotics within 4 weeks
             prior to screening or oral antibiotics within 2 weeks prior to screening

          -  Active tuberculosis requiring treatment within the previous 3 years

          -  History of or currently active primary or secondary immunodeficiency

          -  Pregnant or breast-feeding women

          -  Positive for hepatitis B or hepatitis C infection

          -  For potential MRI substudy participants: the presence of any metal-containing device
             or object in the body