A Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose 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 -1or, if abnormal, the abnormality is not clinically significant

• Female subject must be either:

• Of non-childbearing potential:

1. post-menopausal (defined as at least 1 year without any menses) prior toScreening, or

2. documented surgically sterile or status post hysterectomy (at least 1 monthprior to Screening).

• Or, if of childbearing potential:

1. must have a negative serum pregnancy test at Screening and a negative urinepregnancy test on Day -1.

2. must use two forms of birth control (at least one of which must be a barriermethod) starting at Screening and throughout the Treatment and ObservationPeriod, and for ≥ 120 days after final study drug administration.

3. Acceptable forms include:

4. Established use or oral, injected or implanted hormonal methods ofcontraception.

5. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

6. Barrier methods of contraception: condom or occlusive cap (diaphragm orcervical/vault cap) with spermicidal foam/gel/film/ cream/suppository.

• Female subject must not be breastfeeding at Screening or during the Treatment andObservation period and for ≥ 120 days after final study drug administration.

• Female subject must not donate ova starting at Screening and throughout the Treatmentand Observation period and for ≥ 120 days after final study drug administration.

• Male subject must not donate sperm starting at Screening and throughout the Treatmentand Observation period and for at least ≥ 120 days after final study drugadministration.

• Male subject and their female spouse/partners who are of childbearing potential mustbe using highly effective contraception consisting of two forms of birth control (oneof which must be a barrier method) starting at Screening and continue throughout theTreatment and Observation period and for ≥ 120 days after final study drugadministration.

• Subject has Rheumatoid Arthritis (RA) that was diagnosed according to the 1987 revisedcriteria 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, ClassI, II or III at Screening.

• Subject MUST be on concomitant methotrexate (MTX):

• for ≥ 3 months prior to study drug infusion, AND

• at a stable dose (10 - 25 mg/week) for ≥ 28 days prior to study drug infusion andthroughout the study.

• Subjects on the following medications must remain on a stable regimen: non-steroidalanti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors,hydroxychloroquine (Plaquenil®), sulfasalazine, oral corticosteroids (≤ 10 mg ofprednisone, or equivalent, daily) or low dose opioids (≤ 30 mg of oral morphine, orequivalent, daily) for

≥ 28 days prior to Screening and remain so throughout the Treatment and ObservationPeriod. (The start of Plaquenil and sulfasalazine must be ≥ 2 months prior to studydrug infusion.)

• Subject is highly likely to comply with the protocol and complete the study.

Exclusion Criteria:

• Subject has an ongoing clinically significant systemic disease such as uncompensatedheart failure, uncontrolled diabetes mellitus, severe hepatic failure or severepulmonary disease.

• Subject has a history of any malignancy except for adequately-treated, non-melanomaskin cancer and adequately-treated in-situ cervical cancer.

• Subject has a history of severe allergic or anaphylactic reactions.

• Subject has a history of consuming more than 14 units of alcoholic beverages per weekor has a history of alcoholism or drug/chemical/substance abuse within past 6 monthsprior to Screening (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce ofspirits).

• Subject has a positive test for alcohol or drugs of abuse (excluding drugs prescribedto subject) at Screening or Day -1.

• Subject has/had a viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to Day -1.

• Subject has a past history of serious opportunistic infection.

• Subject is known positive for human immunodeficiency virus (HIV) antibody.

• Subject has a positive tuberculosis (TB) skin test or Quantiferon Gold test atScreening.

• Subject has a positive test for hepatitis C antibody, or positive test for hepatitis Bsurface antigen (HBsAg), or positive hepatitis B core antibody at Screening.

• Subject's laboratory test results at Screening:

• alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), are ˃ 2times the upper limit of normal, AND/OR

• are outside the normal limits and considered by the Investigator to be clinicallysignificant with regard to the remaining per-protocol laboratory tests.

• Subject received any live or live attenuated vaccine within 30 days prior to studydrug infusion.

• Subject received any systemic immunosuppressant agent, other than (MTX) or stablesteroid regimen, within 2 months prior to study drug infusion.

• Subject has previously received any antibody or therapeutic biologic product within 56days or 5 half-lives, whichever is longer, prior to study drug infusion.

• Subject has previously participated in any interventional clinical study or hasreceived an experimental agent within 56 days or 5 half-lives, whichever is longer,prior to study drug infusion.

• Subject is participating in another clinical trial or has participated in another dosegroup of the current trial.

• Subject has had any significant blood loss, donated one unit (450 mL) of blood ormore, or received a transfusion of any blood or blood products within 60 days ordonated plasma within 7 days prior to clinic admission on Day -1.

• Subject has taken Orencia® (abatacept), Nulojix® (belatacept) or any other CTLA4-Igmolecule.

• Subject has any other condition which precludes the subject's participation in thetrial.

• Subject has a history of prolonged QT syndrome.