A Phase 2 Study to Evaluate the Safety, Tolerability, and Activity of Fontolizumab in Subjects With Active Rheumatoid Arthritis

Inclusion Criteria:

- Male or female, at least 18 years of age

- A diagnosis of RA according to ACR criteria (Appendix D, American College of
Rheumatology Clinical Classification Criteria for Rheumatoid Arthritis)

- RA functional class I, II, or III (Appendix E, ACR Revised Criteria for
Classification of Functional Status in Rheumatoid Arthritis ) for at least 6 months

- Active RA with ≥ 6 tender joints and ≥ 6 swollen joints within one week of dosing or
on Day 0, before dosing

- Serum CRP ≥ 1.0 mg/dL (10 mg/L) or ≥ 45 minutes of morning stiffness

- On stable doses for at least 30 days before receiving study drug of at least one, but
not more than two, of the following disease-modifying antirheumatic drugs (DMARDs):
hydroxychloroquine, leflunomide, methotrexate (leflunomide-methotrexate combination
is unacceptable), or sulfasalazine. If being treated with nonsteroidal
anti-inflammatory drugs (NSAIDs) or low-dose prednisone (≤ 10 mg/day), must be on
stable regimen for at least 14 days before receiving study drug

- Women of childbearing potential with a negative serum pregnancy test at screening

- Subjects with reproductive potential agree to use a double-barrier method of
contraception during the study and for 3 months after receiving last dose of study
drug

- Must provide a signed and dated informed consent and an authorization to use
protected health information, have the ability to understand the study requirements,
and comply with study procedures, including required study visits

Exclusion Criteria:

- Significant involvement of secondary RA (eg, Felty's syndrome, pulmonary fibrosis,
Sjogren's syndrome, vasculitis (keratoconjunctivitis sicca is not exclusionary)

- Received a live vaccine within 30 days of receiving fontolizumab

- Received an investigational agent within 30 days or five half-lives of the agent,
whichever is longer, of receiving fontolizumab

- Received a corticosteroid injection into any joint, or has been treated with > 10
mg/day of a corticosteroid within 30 days of receiving fontolizumab

- Received etanercept or anakinra within 30 days of receiving fontolizumab

- Received gold salts, infliximab, or adalimumab within 60 days of receiving
fontolizumab

- Received IV gamma-globulin or Prosorba column therapy within 90 days of receiving
fontolizumab

- Received rituximab or cyclophosphamide within 6 months of receiving fontolizumab

- Failed B cell recovery after exposure to rituximab

- History of hypersensitivity to glycine, histidine, or Polysorbate 80

- Pregnant women or nursing mothers

- Malignancy within 5 years (excluding basal or squamous cell carcinoma of the skin or
adequately treated cervical carcinoma in situ)

- Known chronic viral infections with HIV, hepatitis B, or hepatitis C

- Clinical, PPD, or clear radiographic evidence of prior TB

- Infection requiring hospitalization or parenteral medication, such as an antibiotic,
antiviral, antifungal, or antiparasitic agent, within 90 days of receiving
fontolizumab

- History of inflammatory joint disease (eg, gout, Lyme disease, psoriatic arthritis,
reactive arthritis, seronegative spondyloarthropathy) or chronic inflammatory
diseases (eg, inflammatory bowel disease, inflammatory myopathy, multiple sclerosis,
overlap syndrome, scleroderma, systemic lupus erythematosus) other than RA

- Clinically significant unstable or poorly controlled acute or chronic diseases, such
as myocardial infarction within 6 months, unstable angina, poorly controlled diabetes
or hypertension

- ALT > 1.5 × the upper limit of normal; AST > 1.5 × the upper limit of normal;
creatinine 1.5 × the upper limit of normal; absolute neutrophil count (ANC) <
1000/mm3; platelet count < 50,000/mm3

- History of any other medical disease, laboratory abnormalities, or psychological
conditions that would make the subject (based upon the principal investigator's
judgment) unsuitable for study enrollment

- Current abuse of alcohol or drugs (based upon investigator's assessment)

- Major surgery within 3 months prior to or planned elective surgery during or within 3
months after last dose of study drug