A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists

Inclusion Criteria

Inclusion criteria: Diagnosis of rheumatoid arthritis ≥6 months duration, according to the
American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010
Rheumatoid Arthritis Classification Criteria (1). ACR Class I-III functional status,
based on 1991 revised criteria (2). Anti-TNF therapy failures, defined by the
investigator as patients with an inadequate clinical response, after being treated for at
least 3 consecutive months, and/or intolerance to at least 1 anti-TNF blocker(s),
resulting in or requiring their discontinuation: TNF-blockers may include, but are
not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab.
Moderate-to-severely active rheumatoid arthritis. Continuous treatment with one or a
combination of DMARDs (except for simultaneous combination use of leflunomide and
methotrexate) for at least 12 weeks prior to baseline and on a stable dose(s) for at
least 6 weeks prior to screening: Methotrexate - 6 to 25 mg/wk orally or parenterally
Leflunomide - 10 to 20 mg orally daily Sulfasalazine - 1000 to 3000 mg orally daily
Hydroxychloroquine - 200 to 400 mg orally daily. Exclusion criteria: Patients <18 years
of age or legal adult age Past history of, or current, autoimmune or inflammatory
systemic or localized joint disease(s) other than RA. History of juvenile idiopathic
arthritis or arthritis onset prior to age 16. Severe active systemic RA, including but not
limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome. Treatment with
anti-TNF agents, as follows: o Within 28 days prior to the baseline visit - etanercept
o Within 42 days prior to the baseline visit - infliximab, adalimumab, golimumab,
certolizumab pegol Treatment with previous RA-directed biologic agents with other than
TNF antagonist mechanisms: o Within 28 days prior to the randomization (baseline) visit
- anakinra o Within 42 days prior to the randomization (baseline) visit - abatacept
Within 6 months prior to the randomization (baseline) visit - any cell depleting agents
including but not limited to rituximab without a normal lymphocyte and CD 19+ lymphocyte
count. Treatment with any DMARD other than those allowed per protocol and limited to the
maximum specified dosage within 12 weeks prior to baseline. Treatment with prednisone >10
mg or equivalent per day, or change in dosage within 4 weeks prior to baseline visit. Any
parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline.
Prior treatment with anti-IL-6 or IL-6R antagonist therapies, including tocilizumab or
sarilumab, participation in a prior study of sarilumab, irrespective of treatment arm.
Prior treatment with a Janus kinase inhibitor (such as tofacitinib). New treatment or
dose-adjustment to ongoing medication for dyslipidemia within 6 weeks prior to
randomization, ie, stable dose for at least 6 weeks prior to randomization. Participation
in any clinical research study evaluating another investigational drug or therapy within 5
half-lives or 60 days of first investigational medicinal product (IMP) administration,
whichever is longer. History of alcohol or drug abuse within 5 years prior to the
screening visit. Patients with a history of malignancy other than adequately-treated
carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of
the skin, within 5 years prior to the randomization (baseline) visit. Nonmalignant
lymphoproliferative disorders are also excluded. Patients with active tuberculosis or
latent tuberculosis infection. The above information is not intended to contain all
considerations relevant to a patient's potential participation in a clinical trial.