A Study Investigating the Efficacy and Safety of Upadacitinib (ABT-494) Given With Methotrexate (MTX) in Adults With Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone

Inclusion Criteria: 1. Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European League against Rheumatism (EULAR) criteria for ≥ 3 months. 2. Have active RA as defined by the following minimum disease activity criteria: * ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits. * ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. * high-sensitivity C-reactive protein (hsCRP) \> upper limit of normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (CCP) at Screening. 3. Subjects must have been receiving oral or parenteral methotrexate therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to Baseline Visit. Subjects should continue with their stable doses of methotrexate and folic acid throughout the study. 4. Except for MTX, subjects must have discontinued all oral disease-modifying anti-rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer: * ≥ 4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide * ≥ 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal) 5. Subject has a negative tuberculosis (TB) Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of TB prophylaxis, prior to Baseline Visit. 6. Subjects can be taking non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg), or inhaled corticosteroids at a stable dose for at least 4 weeks prior to Baseline Visit for stable medical conditions and should be kept at a stable dose throughout the study. NSAIDs, acetaminophen, tramadol, codeine, hydrocodone and propoxyphene taken as needed are allowed but may not be taken 24 hours prior to any study visit. Oral and inhaled corticosteroids taken as needed are allowed but may not be taken 24 hours prior to any study visit. 7. Subjects must have discontinued high potency opiates including (but not limited to): oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, methadone, hydromorphone, and morphine at least 4 weeks prior to Baseline Visit. Exclusion Criteria: 1. Female who is pregnant or breastfeeding. 2. Prior exposure to Janus activated kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib). 3. Prior exposure to any investigational or approved biologic RA therapy. 4. Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to Week 0 Visit. 5. Current or expected need of other immunosuppressant medications, except methotrexate. Use of oral intake of \> 10 mg prednisone/day or equivalent corticosteroid therapy (see inclusion criterion 7). 6. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit. 7. Screening laboratory values meeting the following criteria: * Serum aspartate transaminase (AST) or alanine transaminase (ALT) \> 1.5 × ULN * Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula \< 40 mL/min/1.73 m² * Total white blood cell count (WBC) \< 3,000/µL * Absolute neutrophil count (ANC) \< 1,200/µL * Platelet count \< 100,000/µL * Absolute lymphocytes count \< 750/ µL * Hemoglobin \< 9 gm/dL