A Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis Subjects Who Have Had an Inadequate Response to Methotrexate

• Percentage of subjects achieving American College of Rheumatology Criteria 20 (ACR 20) response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Trough plasma concentration of ASP015K and metabolite(s) [ Time Frame: up to Week 12 ] [ Designated as safety issue: No ]

• Percentage of subjects achieving ACR 50 response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Percentage of subjects achieving ACR 70 response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Change from baseline in Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the safety and efficacy of ASP015K in moderate to severe rheumatoid arthritis subjects who are methotrexate-inadequate responders (MTX-IR).

Subjects in each treatment group will continue to take their concomitant oral weekly dose of methotrexate (MTX) in addition to daily ASP015K or matching placebo, taken orally with food, daily for 12 weeks after randomization.

• Drug: ASP015K
  oral
• Drug: Placebo
  oral

• Experimental: ASP015K lowest dose
  ASP015K lowest dose daily in addition to concomitant weekly oral methotrexate
  Intervention: Drug: ASP015K
• Experimental: ASP015K low dose
  ASP015K low dose daily in addition to concomitant weekly oral methotrexate
  Intervention: Drug: ASP015K
• Experimental: ASP015K medium dose
  ASP015K medium dose daily in addition to concomitant weekly oral methotrexate
  Intervention: Drug: ASP015K
• Experimental: ASP015K high dose
  ASP015K high dose daily in addition to concomitant weekly oral methotrexate
  Intervention: Drug: ASP015K
• Placebo Comparator: Placebo
  Placebo daily in addition to concomitant weekly oral methotrexate
  Intervention: Drug: Placebo

Inclusion Criteria:

• Subject has rheumatoid arthritis (RA) diagnosed according to the 1987 revised ACR criteria for at least 6 months prior to Screening
• Subject has been treated with oral methotrexate (MTX) for a minimum of 90 days and at a stable dose for 28 days prior to the first dose of study drug
• ≥6 tender/painful joints; ≥6 swollen joints
• Subject meets the ACR 1991 Revised Criteria for Global Functional Status in RA Class I, II or III
• Subject's other medication taken for treatment of RA must be stable for at least 28 days prior to start of the study
• Male and female subjects must be willing to comply with contraception requirements

Exclusion Criteria:

• Positive tuberculin (TB) test within 90 days of Screening
• Abnormal chest x-ray indicative of an acute or chronic infectious process or malignancy
• Receipt of live or live attenuated virus vaccination within 30 days prior to the first dose of study drug
• Known history of positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody or history of a positive test for human immunodeficiency virus (HIV) infection
• History of any other autoimmune rheumatic disease, other than Sjogren's syndrome
• Previous history of clinically significant infections or illness (requiring hospitalization or requiring parenteral therapy) within 90 days of the Screening visit, or a history of any illness that would preclude participation in the study
• History of any malignancy, except for successfully treated basal or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix
• Does not meet specified washout criteria for the following RA medications: gold, penicillamine, etanercept, certolizumab, adalimumab, golimumab, infliximab, cyclophosphamide, and leflunomide
• Subject has previously used a non anti-TNF biologic disease-modifying antirheumatic drug (DMARD) (e.g., anakinra, abatacept, rituximab, tocilizumab)
• Previous intolerance to Janus kinase (JAK) inhibitors
• Receipt of intra-articular or parenteral corticosteroid within 28 days prior to the first dose of study drug
• Receipt of plasma exchange therapy within 60 days prior to the start of study drug
• Receipt of any investigational agent within 30 days or 5 half-lives, whichever is longer, prior to first dose of study drug
• Receipt of medications that are CYP3A substrates with narrow therapeutic range within 14 days prior to first dose of study drug
• History of heart failure, defined as New York Heart Association (NYHA) grade 3 or greater
• History of long QT syndrome or prolonged QT interval
• Any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, or infectious disease, or any ongoing illness which would make the subject unsuitable for the study
• Subject has any condition possibly affecting oral absorption (e.g., gastrectomy or clinically significant diabetic gastroenteropathy)