A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY OF THE EFFICACY AND SAFETY OF TOFACITINIB IN SUBJECTS WITH ACTIVE ANKYLOSING SPONDYLITIS (AS)

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. ;2. Subjects who are willing and able to comply with scheduled visits, treatment plan,laboratory tests, and other study procedures.;3. Subject is at least 18 years old (20 years old for subjects in Taiwan) at the Screening Visit. ;4. The subject has a diagnosis of AS based on the Modified New York Criteria for Ankylosing Spondylitis (1984). ;5. Subject has active AS at the Screening and Baseline (Day 1) visits defined as:;• BASDAI score of >=4; and;• Back pain score (BASDAI Question 2) of >=4.;6. Subject has active disease despite nonsteroidal anti-inflammatory drug (NSAID) therapy or is intolerant to NSAIDs as defined by either:;- Subject must have had an adequate trial of at least 2 different oral NSAIDs taken over a total period of 4 weeks. ;or;- Intolerance to NSAID therapy. Intolerance is defined as the subject must have discontinued NSAID treatment due to a related adverse event (eg, allergic reaction, gastrointestinal symptoms or signs, hypertension, etc).;7. Subjects may be receiving the following non-biologic DMARDs at the time of the Screening visit. These medications should be continued throughout the entire study and doses should remain unchanged. Any other DMARDs require discussion prior to enrollment with the sponsor for washout timeframe.;• Methotrexate: Maximum dose of 20 mg/week. Minimum duration of therapy 4 months and dose stable for 4 weeks prior to first dose of study drug. Subjects on methotrexate should be on an adequate and stable dose of folate supplementation (eg, not less than 5 mg weekly based on folic acid, unless such doses would violate the local label guidelines or standard of care) for at least 4 weeks prior to the first dose of study drug. Subject must not have had previous serious toxicity while on;methotrexate and not be expected to require evaluation for possible methotrexate toxicity (eg, require a liver biopsy for methotrexate toxicity) during the study; • Sulfasalazine (Azulfidine, Salazpyrin): Maximum dose of 3 gm/day. Minimum duration of therapy 2 months and dose stable for 4 weeks prior to first dose of study drug.;8. Subjects who are already taking oral corticosteroids (not injectables) may participate in the study:;• Oral corticosteroids: Subjects who are already receiving oral corticosteroids must be;on a stable dose of <=10 mg/day of prednisone or equivalent for 4 weeks prior to the first dose of study medication;;• Injected (eg, intraarticular, intramuscular, epidural or intravenous) corticosteroids;must be discontinued 4 weeks prior to the first dose of study medication;;• Topical and intra-rectal corticosteroids will be allowed during the study.;9. Subject has discontinued all disallowed concomitant medication for the required time prior to the first dose of study medication and is taking only those concomitant medications in doses and frequency allowed by the protocol.;10. Subjects who are receiving any investigational or marketed treatment for AS, arthritis or back pain not mentioned elsewhere must have that treatment discontinued for 4 weeks or 5 half-lives, whichever is longer.;11. Subjects receiving non-prohibited concomitant medications for any reason must be willing to stay on a stable regimen as defined in the protocol. ;12. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined in protocol. ;13. Women of childbearing potential must test negative for pregnancy prior to enrollment in this study. ;15. Female subjects who are not of childbearing potential (ie, meet at least one of the following criteria): • Have undergone hysterectomy or bilateral oophorectomy; • Have medically confirmed ovarian failure; • Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause); laboratory confirmation of FSH level indicative of post menopausal according to the central laboratory may be indicated per investigator*s determination.

1. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial. ;2. Participation in other interventional studies within 4 weeks before the current study begins and/or during study participation (excluding noninterventional follow-up during the screening period). ;3. Subjects receiving any other DMARDs (other than those allowed), thalidomide (including previous use).;4. Subjects currently receiving or previous use of a TNF inhibitor or other biological agent. ;5. Blood dyscrasias at screening or within 3 months prior to the first dose of study drug including confirmed:;a. Hemoglobin <= g/dL;;b. Absolute white blood cell count (WBC) <=3.0 x 10 9/L (<=3000 mm3);;c. Absolute neutrophil count (ANC) <=1.2 x 10 9/L (<= 1200 mm3);;d. Absolute lymphocyte count <= 1.0 x 10 9/L (<= 1000/mm3);;e. Platelet count <=100 x 10 9/L (<=100,000/mm3).;One re-testing of a laboratory-acceptable specimen (eg, appropriately labeled within stability parameters, not hemolyzed, appripriate type (tube and reagent) and volume) is allowed of any above parameters if the abnormal lab(s) was an uncharacteristic result(s). Documentation in the source of the typical results to allow a repeat lab is required.;Re-test must be completed within the screening period.;6. Estimated Creatinine Clearance <=40 mL/min based on Cockcroft Gault equation at Screening visit. ;7. Total bilirubin, AST or ALT more than 1.5 times the upper limit of normal at screening visit. (One re-testing with an uncompromised sample is allowed if the abnormal lab result was an uncharacteristic result and must be completed within the screening period. Documentation in the source of the typical results to allow a repeat lab is required).;8. History of any other autoimmune rheumatic disease (eg, systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, polymositis) or known diagnosis of fibromyalgia, without approval by Sponsor. ;9. History of an infected joint prosthesis at any time, with the prosthesis still in situ. ;10. History of any lymphoproliferative disorder, such as Epstein Barr Virus related;lymphoproliferative disorder (EBV-LPD), history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.;11. History of recurrent (more than one episode) herpes zoster or disseminated/multi-dermatomal (a single episode) herpes zoster or disseminated (a single episode) herpes simplex. ;12. History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study medication.;13. History of infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study medication. ;14. Any prior treatment with alkylating agents (eg, cyclophosphamide or chlorambucil), total lymphoid irradiation, etc. 15. Any subject who has been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study medication or is to be vaccinate with these vaccines at any time during treatment or within 6 weeks after last dose of study drug.;16. A subject with any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary. 17. History of alcohol or drug abuse unless in full remission for greater than 6 months prior to first dose of study medication.;18. Body weight or body habitus greater than what can be accommodated by the site*s MRI scanner table weight limits or MRI scanner bore.;19. Any contraindication to MRI that in the judgment of the investigator and MRI center poses a safety risk to the subject such as, but not limited to, cardiac pacemaker; implanted cardiac defibrillator; aneurysm clips; carotid artery vascular clamp; neurostimulator; insulin or infusion pumps; bone growth/fusion stimulator; cochlear, otologic, and ear implants. ;20. Subjects with passive implants that may be weakly ferromagnetic in the vicinity of the RF coil that may cause image artifacts in the spine and SI joints. ;For exclusion criteria 21-30 see protocol.