A Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis

Subjects will take ASP015K or matching placebo orally with food for 12 weeks after
randomization. Potential subjects who have previously used disease-modifying antirheumatic
drugs (DMARDs) and/or biologic agents may be eligible to participate after completing a
washout period. Subjects who complete the 12-week dosing period in this study may be
eligible to participate in a long-term, open-label Extension Study.

Inclusion Criteria:

- ≥ 6 tender/painful joints; ≥ 6 swollen joints

- C-Reactive Protein (CRP) of ≥ 0.8 mg/dL or Erythrocyte Sedimentation Rate (ESR) of ≥
28 mm/hr

- Subject meets the ACR 1991 Revised Criteria for Global Functional Status in RA Class
I, II or III at Screening and Baseline

- Use of non-steroidal anti-inflammatory drugs [NSAIDs], cyclooxygenase-2 (COX-2)
inhibitors, or oral corticosteroids for the 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 as
well as restrictions regarding egg and sperm donation

- Female subject must not be breastfeeding at Screening or during the study period, and
for 60 days after the final study drug administration

- Subject agrees not to participate in another interventional study while on treatment

Exclusion Criteria:

- Positive Mycobacterium tuberculosis (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 Baseline
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,
azathioprine, minocycline, penicillamine, etanercept, certolizumab, adalimumab,
golimumab, infliximab, cyclophosphamide, and leflunomide

- 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 or is currently taking > 30 mg oral morphine (or narcotic
equivalent) per day

- 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,
other malabsorption syndromes, or clinically significant diabetic gastroenteropathy)