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

Inclusion Criteria:

• Subjects willing and able to sign informed consent
• Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revisedclassification criteria for RA for at least 12 weeks prior to Screening. (If thesubject was diagnosed according to ACR 1987 criteria previously, the Investigator mayclassify the subject per ACR 2010 retrospectively, using available source data)
• Inadequate response to treatment with oral, SC, or intramuscular MTX (defined as asubject with at least 12 weeks of exposure prior to Screening and with either absenceof any documented clinically significant response, or documented initial clinicalresponse with subsequent loss of that response or partial response) for at least 12weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if intolerantto higher doses). The dose and route of administering MTX had to have been stable forat least 6 weeks prior to Screening. A lower dose of MTX (≥7.5 mg/week) was permittedfor subjects enrolled in the Republic of Korea, consistent with local clinicalpractice.
• 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 thefollowing:
• ≥6 tender joints (68 joint count) at Screening and baseline; and
• ≥6 swollen joints (66 joint count) at Screening and baseline; and
• CRP above the normal range (ULN) at Screening based on the central laboratoryresults.

Exclusion Criteria:

• Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (eg, gout,psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathicarthritis, or systemic lupus erythematosus). However, subjects could have secondarySjogren's syndrome or hypothyroidism.
• Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely orwholly bed-ridden or confined to a wheelchair, with little or no self-care)
• Prior exposure to any licensed or investigational compound directly or indirectlytargeting IL 6 or IL 6R (including tofacitinib or other Janus kinases and spleentyrosine kinase [SYK] inhibitors)
• Prior treatment with cell depleting therapies including anti CD20 or investigationalagents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19)
• Prior use of bDMARDs
• Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior tobaseline
• Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) orchange 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 should not be discontinued to facilitate a subject's participation in thestudy, but should instead have been previously discontinued as part of a subject'smedical management of RA):

1. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine,chloroquine, gold, penicillamine, minocycline, or doxycycline
2. 12 weeks for leflunomide unless the subject has completed the followingelimination procedure at least 4 weeks prior to baseline: Cholestyramine at adosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at adosage of 50 grams 4 times daily for at least 24 hours
3. 24 weeks for cyclophosphamide

• Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccinationwith live vaccines during the study
• Participation in any other investigational drug study within 30 days or 5 times theterminal 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 tobaseline
• 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 ofNSAIDs within 2 weeks prior to baseline
• Previous participation in this study (randomized) or another study of OKZ
• Subjects with concurrent acute or chronic viral hepatitis B or C infection as detectedby blood tests at Screening(e.g., positive for hepatitis B surface antigen [HBsAg],total hepatitis B core antibody [anti-HBc], or hepatitis C virus antibody [HCV Ab]).Subjects who are are positive for hepatitis B surface antibodies (anti-HBs), butnegative for HBsAg and anti-HBc, will be eligible
• Subjects with human immunodeficiency virus (HIV) infection
• Subjects with:

1. Suspected or confirmed current active TB disease or a history of active TBdisease
2. Close contact (i.e., sharing the same household or other enclosed environment,such as a social gathering place, workplace, or facility, for extended periodsduring the day) with an individual with active TB within 1.5 years prior toScreening

• Concurrent malignancy or a history of malignancy within the last 5 years (with theexception of successfully treated carcinoma of the cervix in situ and successfullytreated basal cell carcinoma and squamous cell carcinoma not less than 1 year prior toScreening [and no more than 3 excised skin cancers within the last 5 years prior toScreening])
• Subjects with any infection requiring oral antibiotic or antiviral therapy in the 2weeks prior to Screening or at baseline, injectable anti-infective therapy in the last 4 weeks prior to baseline, or serious or recurrent infection with history ofhospitalization in the 6 months prior to baseline
• Subjects with evidence of disseminated herpes zoster infection, zoster encephalitis,meningitis, or other non-self-limited herpes zoster infections in the 6 months priorto baseline
• Subjects with planned surgery during the study or surgery ≤ 4 weeks prior to Screeningand from which the subject has not fully recovered, as judged by the Investigator
• Subjects with diverticulitis or other symptomatic GI conditions that might predisposethe subject to perforations, including subjects with history of such predisposingconditions (e.g., diverticulitis, GI perforation, or ulcerative colitis)
• Pre-existing central nervous system demyelinating disorders (e.g., multiple sclerosisand optic neuritis)
• History of chronic alcohol or drug abuse as judged by the Investigator
• Female subjects who are pregnant, currently lactating, have lactated within the last 12 weeks, or who are planning to become pregnant during the study or within 6 monthsof last dose of study treatment
• Female subjects of childbearing potential (unless permanent cessation of menstrualperiods, determined retrospectively after a woman has experienced 12 months of naturalamenorrhea as defined by the amenorrhea with underlying status (e.g., correlative age)or 6 months of natural amenorrhea with documented serum follicle-stimulating hormonelevels >40 mIU/mL and estradiol <20 pg/mL) who are not willing to use a highlyeffective method of contraception during the study and for at least 6 months after thelast administration of study treatment OR Male subjects with partners of childbearingpotential not willing to use a highly effective method of contraception during thestudy and for at least 3 months after the last administration of study treatment.
• Subjects with a known hypersensitivity to any component of the OKZ drug product,adalimumab, or placebo
• Subjects with a known hypersensitivity or contraindication to any component of therescue medication
• History of severe allergic or anaphylactic reactions to human, humanized, or murinemonoclonal antibodies The above information was not intended to contain all considerations relevant to aparticipant's potential participation in a clinical trial.