Study to Evaluate the Safety, Tolerability, and Action of AMG 357 in Females With Rheumatoid Arthritis

Inclusion Criteria:

- Subject provided informed consent.

- Rheumatoid arthritis present for ≥ 3 months.

- Global functional class I, II, or III.

- History of or positive for, Rheumatoid Arthritis

- Taking methotrexate consecutively for ≥ 12 weeks and on a stable dose at 10-25 mg
weekly.

- Subjects currently taking NSAIDs or oral corticosteroids.

- Normal ECG values

- Immunizations up to date.

Exclusion Criteria:

- Positive Hepatitis B, Hepatitis C, Positive HIV

- Sensitivity to any of the products or components to be administered.

- Malignancy within 3 years

- Presence of recurrent or chronic infections

- Evidence of infections within the 30 days prior to randomization

- Presence of a serious infection

- Prosthetic joint infection within 3 years or native joint infection within 1 year

- History of exposure to tuberculosis without a history of prophylactic treatment

- Class IV RA.

- Felty's syndrome

- Chronic pelvic pain or hemorrhagic ovarian cyst within 3 years

- Any bleeding disorder that is clinically significant

- Low white blood cell or neutrophil count

- Elevated serum creatinine clearance

- Low hemoglobin and platelet count

- Received live vaccines within 3 months of first dose

- Alcohol and/or substance abuse within past 12 months

- Blood donation within 60 days

- Positive urine screen for drugs of abuse

- Any prior use of rituximab in the last 6 months (or other B cell depleting agents)
and CD19 levels < lower limits of normal

- Use of a weekly or bimonthly biologic within 2 weeks or monthly biologic agents
within 4 weeks

- Corticosteroid injections for acute RA flare within 4 weeks

- Grapefruit juice or grapefruit containing products within 7 days of first dose.

- All herbal medicines, vitamins, and supplements within the 30 days

- The use of any experimental/investigational biologic DMARD unless off agent for 3
months; or off for 6 months for B cell depleting agents

- Known GI disease or GI procedures

- Women of reproductive potential who are unwilling to practice birth control

- Women who are pregnant/lactating/breastfeeding

- Subject with IgG levels < lower limit of normal at screening