A randomized, double blind, placebo-controlled, phase 2a study of the efficacy, safety and pharmacokinetics of MLN3897 in patients with rheumatoid arthritis taking methotrexate.

1. Age 18-70;

2. Meeting ACR criteria for RA;

3. RA Global Functional Class I,II or III;

4. Taking MTX for a minimum of 6 months before screening, dose stable 3 months;

5. No more than 10 mg/day prednisone/equivalent;

6. Stable use (if on) NSAIDs, at least 2 weeks;

7. Willing/able to comply to the protocol;

8. Female of childbearing potential must not be pregnant, or breastfeeding;

9. Females of childbearing potential and all males must use two accepted forms of contraception for the duration of the study;

10. Have at least 6 tender and 6 swollen joints plus two of the following: morning stiffness >45 minutes, ESR >28 mm/hr, CRP >1.5 mg/dl.

1. Use of any other DMARDS than MTX concomitantly or within one month prior to enrollment (in case of leflunomide, 3 months prior to enrollment or washout with cholestyramine);

2. Currently being treated with TNF-antagonists or other biologicals (washout period 8 weeks);

3. TB infection;

4. Have received investigational drug one month prior to day1;

5. Have received intra-articular or systemic injection with corticosteroids within one month prior to screening;
6-26 summary: have any other condition or increased risk of a condition or concomitant use of medication incompatible with the study (including infections, liver and kidney diseases, cardiac conditions/arrythmia, etc.) or have a history of cancer, except for distant history of cured ca. in situ of the cervix or BCC.