A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs

Inclusion Criteria:

• Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of Rheumatology/European League againstRheumatism (ACR/EULAR) criteria

• Subject who did not receive the following drugs, or received the drugs with stabledosage for at least 28 days prior to the baseline (start of treatment) for RAtreatment:

• Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations),oral morphine or equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, ororal corticosteroids (≤ 10 mg/day in prednisolone equivalent)

• At screening subject has active RA as evidenced by both of the following:

• ≥ 6 tender/painful joints (using 68-joint assessment)

• ≥ 6 swollen joints (using 66-joint assessment)

• CRP > 0.50 mg/dL at screening

• Subject meets the ACR 1991 Revised Criteria for the Classification of GlobalFunctional Status in RA Class I, II or, III at screening.

• Inadequate responder to (including subjects who were intolerant of) at least oneDMARD administered for at least 90 days prior to screening

Exclusion Criteria:

• Subject has received a biologic DMARD within the specified period

• Subject has received etanercept

• Inadequate responder to at least 3 biologic DMARDs as determined byinvestigator/sub-investigator

• Subject has received intra-articular, intravenous, intramuscular or endorectal (excluding suppositories for anal diseases) corticosteroid within 28 days prior tobaseline

• Subject has participated in any study of ASP015K and has received ASP015K or placebo

• Subject has received other investigational drugs within 90 days or within 5half-lives, whichever is longer, prior to baseline

• Subject has received plasma exchange therapy within 60 days prior to baseline

• Subject has undergone joint drainage, has received local anesthesia and nerve block,or has received articular cartilage protectant at the assessed joint within 28 daysprior to baseline

• Subject has undergone surgery and has residual effects in the assessed joints at thediscretion of investigator/sub-investigator, or is scheduled to undergo surgery thatmay affect the study evaluation of the assessed joints at the discretion ofinvestigator/sub-investigator

• A diagnosis of inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis,SLE, sarcoidosis, etc.) other than RA

• Any of the following laboratory values at screening:

• Hemoglobin < 9.0 g/dL

• Absolute neutrophil count < 1000/μL

• Absolute lymphocyte count < 800/μL

• Platelet count < 75000/μL

• ALT ≥ 2 ×ULN

• AST ≥ 2 × ULN

• Total bilirubin (TBL) ≥ 1.5 × ULN

• Estimated GFR ≤ 40 mL/min as measured by the MDRD method

• β-D-glucan > ULN [in case of Japan: ≥ 11 pg/mL]

• Positive HBs antigen, HBc antibody, HBs antibody or HBV-DNA quantitation (However, subject with negative HBs antigen and HBV-DNA quantitation, andpositive HBc antibody and/or HBs antibody is eligible if HBV-DNA is monitoredby HBV-DNA quantitation at every scheduled visit after initiation of study drugor reference drug administration.)

• Positive HCV antibody

• Subject has a history of or concurrent active tuberculosis (TB)

• Subject has a history of or concurrent interstitial pneumonia andinvestigator/sub-investigator judges that it is inappropriate for the subject toparticipate in this study

• Subject has a history of or concurrent malignant tumor (except for successfullytreated basal cell carcinoma)

• Subject has received live or live attenuated virus vaccination within 56 days priorto baseline. (Inactivated vaccines including influenza and pneumococcal vaccines areallowed.)

• Subject has a history of or concurrent demyelinating disorders

• Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic,hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac,neurological, infectious, or autoimmune disease except for RA (excluding Sjogren'ssyndrome and chronic thyroiditis), or any ongoing illness which would make thesubject unsuitable for the study as determined by the investigator/sub-investigator

• Subject has a history of clinically significant allergy. (Clinically significantallergy includes allergies such as systemic urticaria induced by specific antigensand drugs, anaphylaxis, and allergy associated with shock necessitating hospitalizedtreatment.)

• Subject has concurrent cardiac failure, defined as NYHA classification Class III orhigher, or a history of it

• Subject has concurrent prolonged QT syndrome or a history of it. Subject hasprolonged QT interval (defined as QTc ≥ 500 msec. Subject has QTc ≥ 500 msec atretest will be excluded) at screening

• Subject has a history of positive HIV infection

• Subject has congenital short QT syndrome or a history of it. Subject has shortenedQT interval (defined as QTc < 330 msec. Subject has QTc < 330 msec at retest will beexcluded) at screening.