Evaluation of the Effectiveness and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease

Inclusion Criteria

Subjects may be enrolled in the study only if they meet all of the following criteria:

• Subjects willing and able to sign informed consent
• Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 12 weeks prior to Screening.
• Inadequate response to treatment with MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if intolerant to higher doses).
• The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.
• Subjects must be willing to take folic acid or equivalent throughout the study
• Subjects must have moderately to severely active RA disease as defined by all of the following:
• ≥6 tender joints (68 joint count) at Screening and baseline; and
• ≥6 swollen joints (66 joint count) at Screening and baseline; and
• CRP above ULN at Screening based on the central laboratory results.

Exclusion Criteria

• Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). However, subjects could have secondary Sjogren's syndrome or hypothyroidism
• Subjects who were Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
• Prior exposure to any licensed or investigational compound directly or indirectly targeting IL-6 or IL-6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase [SYK] inhibitors)
• Prior treatment with cell-depleting therapies, including anti-CD20 or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, and anti-CD19)
• Prior use of bDMARDs, with the following exception:
• Subjects who discontinued TNFi therapy due to a reason other than lack of efficacy were allowed to enter the study (TNFi therapy was not to be discontinued to facilitate a subject's participation in the study but should instead have been previously discontinued as part of a subject's medical management of RA). The use of TNFi therapy within the following windows prior to baseline was exclusionary:
• 4 weeks for etanercept
• 8 weeks for infliximab
• 10 weeks for adalimumab, certolizumab, and golimumab
• Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline
• Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent), or change in dosage within 2 weeks prior to baseline
• Prior documented history of no response to hydroxychloroquine and sulfasalazine
• Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs were not to be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):
• 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline
• 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours
• 24 weeks for cyclophosphamide
• Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study
• Participation in any other investigational drug study within 30 days or 5 times the terminal half-life of the investigational drug, whichever is longer, prior to baseline
• Other treatments for RA (e.g., Prosorba Device/Column) within 6 months prior to baseline
• Use of intra-articular hyaluronic acid injections within 4 weeks prior to baseline
• Use of non-steroidal anti-inflammatory drugs (NSAIDs) on unstable dose or switching of NSA