The current study is designed to evaluate the safety and efficacy, including MRI imaging, across a range of VX-509 doses in subjects with active rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs).

VX-509 is an oral, selective Janus kinase 3 (JAK3) inhibitor being developed by Vertex. In autoimmune diseases, JAK3 is an essential component of the immune signaling cascade. This cascade ultimately contributes to abnormal immune response that results in chronic inflammation and, in the case of rheumatoid arthritis (RA), irreversible damage to cartilage and bones. Selective inhibition of JAK3 offers a new disease modifying approach to the treatment of RA, and a broad range of other autoimmune diseases.

Inclusion Criteria:

• Male and female subjects 18 to 65 years of age (inclusive)
• Diagnosis of RA
• Swollen joint count of ≥6 out of 66 joints and tender joint count of ≥6 out of 68 joints
• Seropositivity based on either a positive rheumatoid factor or anti cyclic citrullinated peptide antibody at screening -OR- known erosive disease based on previous X-ray report or erosions detected on screening hand and foot X-ray
• Baseline CRP level or Westergren erythrocyte sedimentation rate ≥1.2 × upper limit of normal
• Receiving stable therapy with 1 of the following DMARDs: methotrexate, sulfasalazine, leflunomide, anti-malarial drug, or penicillamine
• Palpable 2+ synovitis of the wrist or ≥2 MCPs in the MRI-designated hand

Exclusion Criteria:

• History or presence of a clinically significant medical disorder other than RA that, in the opinion of the investigator and medical monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• Inflammatory, rheumatological disorders other than RA, where arthritis may be a prominent feature
• Planned surgery during the study
• History of alcohol or drug abuse, or excessive alcohol consumption
• History of tuberculosis (TB) infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.
• Pregnant or nursing an infant or with a life partner who is pregnant, nursing, or planning to become pregnant