• The primary objective of this study is to assess the efficacy of R788 100 mg PO bid compared with placebo, as determined by ACR20 responder rates at Month 3. [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  

• To assess the response rate of R788 100 mg PO bid as determined by ACR50, ACR70, ACRn, DAS28-CRP, and DAS28-ESR at Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  
• To assess the rapidity of onset of clinical effect of R788 100 mg PO bid compared with placebo as determined by ACR20 response rates at Weeks 1 and 2 [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  
• To assess the radiologic response of R788 100 mg PO bid compared with placebo as determined by Magnetic Resonance Imaging (MRI) using the modified RAMRIS scoring system of hands and wrists at baseline and Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  
• To assess and compare the safety profiles of R788 100 mg PO bid dose with placebo for effects on liver function tests, clinically significant reduction in peripheral neutrophil counts, G-I side effects and other adverse effects as they may appear. [ Time Frame: Study ] [ Designated as safety issue: Yes ]
  

Inclusion Criteria:

• Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
• Males and females, 18 years of age or older, with active RA for at least 12 months prior to Day 1 dosing
• Are currently receiving or previously had received a biologic therapy with an inhibitor of TNF, rituximab, abatacept, or anakinra at an approved labeled dose for ≥3 months prior to Day 1 dosing and are designated as biologic therapy failures for lack of efficacy, safety, or tolerability.
• Patients may receive stable doses of methotrexate (MTX), azathioprine (not in combination with MTX), leflunomide (not in combination with MTX), sulfasalazine, chloroquine, hydroxychloroquine, gold, NSAIDs (including COX2 inhibitors), minocycline, or doxycycline. The dose must have been stable for at least 30 days prior to Day 1 dosing and must not be changed during the washout, screening and treatment periods, unless dictated by tolerability requirements. Patients who are taking MTX must have been receiving weekly MTX doses (7.5-25 mg/week) for a minimum of 3 months prior to Day 1 dosing and must be receiving a stable MTX dose, with no change in route, for the previous 6 weeks prior to Day 1 dosing. Patients who are receiving MTX must also be receiving folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing.
• Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
• The patient must otherwise be in good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period. See exclusion criteria for specific exclusions.
• In the Investigator's opinion, the patient has the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol.

Exclusion Criteria:

• The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator's opinion, could affect the conduct of the study. Specifically, excluded are patients with the following:

  1. uncontrolled or poorly controlled hypertension;
  2. other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder) or arthritis syndromes (gout, Lyme disease, Reiter's syndrome);
  3. recent serious surgery or infectious disease;
  4. recent history ( of, or treatment for, a malignancy other than nonmelanomatous skin cancer, or any history of lymphoma;
  5. Hepatitis B;
  6. Hepatitis C;
  7. interstitial pneumonitis or active pulmonary infection on chest x-ray
  8. Tuberculosis (TB)
  9. known laboratory abnormalities
• The patient has a history of substance abuse, drug addiction or alcoholism. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled spirits= 1.5 oz or 44 mL.
• The patient has been treated previously treated with R788 under a different protocol.
• The patient has a pacemaker, aneurysm clip or other contraindication to MRI.