The primary objective of this study is to determine the safety of LX3305 in a dose escalation compared with placebo over 12 weeks in subjects with active rheumatoid arthritis (RA).

Inclusion Criteria:

• Adult subjects, aged 18 to 75 years
• Active rheumatoid arthritis (RA), class I to III (defined by the American College of Rheumatology), diagnosed at least 3 months prior to Screening
• Minimum of 4 swollen joints (at Screening and Day 1), minimum of 4 tender joints (at Screening and Day 1), and serum C-reactive protein (CRP) level >1.2x the upper limit of normal and/or elevated erythrocyte sedimentation rate (ESR)
• If receiving methotrexate (7.5 mg to 25 mg/week), subject must have been treated for at least 6 weeks prior to Screening and currently receiving a stable dose of methotrexate (MTX) with a stable route of administration, and have no plans to change MTX dose during the study
• Ability to give written informed consent

Exclusion Criteria:

• Women who are pregnant or nursing
• RA diagnosis prior to 16 years of age (juvenile RA)
• Intra-articular and/or parenteral corticosteroids within 4 weeks of study Day 1
• Receipt of live vaccine within 4 weeks prior to Day 1
• Major surgical procedure within 8 weeks prior to Day 1
• Blood donation within 4 weeks prior to Day 1
• Any systemic inflammatory condition
• History of bleeding diathesis
• History of medically significant opportunistic infection
• History of drug or alcohol abuse within 3 years prior to Day 1
• History of cancer within 5 years prior to Day 1
• Presence of hepatic or biliary disease
• History of tuberculosis
• History of human immunodeficiency virus (HIV)
• Any clinically significant laboratory test results, in the opinion of the investigator
• Use of any investigational agent or participation in an investigative trial within 30 days of Day 1
• Concurrent use of any biologic agent for the treatment of RA or concomitant disease modifying antirheumatoid drugs (other than MTX, hydroxychloroquine, leflunomide, and sulfasalazine - at stables doses for 8 weeks)