A Study To Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of ASP2408 After Multiple Dose Subcutaneous Injections in Patients With Rheumatoid Arthritis on Methotrexate

Inclusion Criteria:

• Subject weighs at least 50 kg.
• Subject has a body mass index (BMI) of ≤ 35 kg/m2.
• Subject's 12-lead electrocardiogram (ECG) results are normal at Screening and Day 1 prior to study drug dosing or, if abnormal, the abnormality is not clinically significant as determined by the Investigator.
• Subject has Rheumatoid Arthritis (RA) that was diagnosed according to the 1987 revised criteria of the American College of Rheumatology (ACR) ≥ 6 months prior to Screening.
• Subject meets the ACR 1991 revised criteria for Global Functional Status in RA, Class I, II or III at Screening.

• Subject MUST be on concomitant methotrexate (MTX):

  • for ≥ 3 months prior to Day 1, AND
  • at a stable dose (10 - 25 mg/week) for ≥ 28 days prior to Day 1 and throughout the study.

• Subject's other related medications taken for the treatment of RA at the time of Screening must meet the noted stability requirements and remain on a stable regimen, as follows:

  • Non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxy-genase-2 (COX-2) inhibitors, oral corticosteroids (≤ 10 mg of prednisone, or equivalent, daily) or low dose opioids (≤ 30 mg of oral morphine, or equivalent, daily) must be stable for ≥ 28 days prior to Screening and remain so throughout the Treatment and Observation Period.
• Hydroxychloroquine (Plaquenil®) and sulfasalazine must have started ≥ 2 months, and be stable for ≥ 28 days, prior to Day 1.

Exclusion Criteria:

• Subject has an ongoing infection or has had an infection requiring intravenous antibiotics within 1 month prior to Day 1.
• Subject has a past history of serious opportunistic infection.
• Subject has a positive Mantoux tuberculin skin or QuantiFERON-TB Gold test within 90 days of, or at Screening, and has not completed an adequate course of antimicrobial therapy per CDC guidelines.
• Subject received any live or live-attenuated vaccine within 30 days prior to Day 1.

• Subject received any of the following:

  • Anakinra (Kineret®), etanercept (Enbrel®), or adalimumab (Humira®) within 60 days prior to Day 1.
  • Rituximab (Rituxan®) or any other anti-CD20 antibody within 180 days prior to Day 1.
  • Leflunomide (Arava®) within 60 days prior to drug dosing on Day 1, unless the subject has undergone cholestyramine washout at least 30 days prior to Day 1.
  • Oral or injectable gold, azathioprine, penicillamine, cyclosporine, or tacrolimus within 30 days prior to Day 1.
  • Cyclophosphamide within 180 days prior to Day 1.
• Subject has received any CTLA4-Ig molecule (including, but not limited to abatacept [Orencia®] and belatacept [Nulojix]).
• Subject has participated in a previous clinical study with treatment with ASP2408 or ASP2409 or has participated in another dose cohort of the current trial.
• Subject has previously participated in any interventional clinical study, or has received an experimental agent within 56 days or 5 half-lives, whichever is longer, prior to Day 1.
• Subject has a history of prolonged QT syndrome.