This study is to assess the safety, tolerability, and pharmacokinetics (PK) of multiple infusions of GS-5745 in adults with rheumatoid arthritis (RA). Participants will be randomized in a 4:1 ratio to receive 1 intravenous (IV) infusion of GS-5745 or placebo every 2 weeks, for a total of 3 IV infusions.

Inclusion Criteria:

• 18 to 70 years of age, inclusive, at time of screening
• Weight: ≥ 45 to < 120 kg
• Males or non-pregnant, non-lactating females
• Diagnosis of RA according to the 1987 revised American College of Rheumatology (ACR) for the classification of RA
• Active disease, defined as a mean high sensitivity C-reactive protein (hsCRP) value from Visits 1 & 2 of ≥ 8 mg/L
• Individuals taking chronic Disease-Modifying Antirheumatic Drugs (DMARDs) should be on a stable dose for at least 45 days prior to randomization
• Chronic use of systemic corticosteroids up to a maximum of 10 mg/day of prednisone or equivalent is allowed if dose is stable for at least 30 days prior to randomization
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs) or other analgesics are allowed if doses are stable for at least 30 days prior to randomization

Exclusion Criteria:

• Have a document medical history of anaphylaxis
• Positive HIV antibody during screening
• Positive hepatitis B surface antigen (HBsAg), or positive hepatitis B core antigen (HBcAg), followed by a positive hepatitis B virus (HBV) DNA by quantitative polymerase chain reaction (PCR) during screening
• Positive hepatitis C virus (HCV) antibody followed by a positive HCV viral RNA during screening
• A positive QuantiFERON-tuberculosis (TB) GOLD test during screening
• History of malignancy within the last 5 years except for individuals who have been treated locally for non-melanoma skin cancer or cervical carcinoma in situ
• Severe dementia or Alzheimer's disease, chronic medical or psychiatric problem, or alcohol or drug abuse, that in the judgment of the investigator may interfere with individual's ability to comply with study procedures
• Any serious cardiac event such as myocardial infarction, unstable or life-threatening arrhythmia, hospitalization for cardiac failure within 6 months prior to randomization or any significant or new ECG finding at Visit 1 as judged by the investigator
• History of significant systemic involvement secondary to RA such as vasculitis, pulmonary fibrosis, or Felty's syndrome
• History of or current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease
• History of or current autoimmune or rheumatic disorders, other than RA, such as systemic lupus erythematosus, inflammatory bowel disease, fibromyalgia, polymyalgia rheumatic, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome
• Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) that, in the judgment of the investigator, would make the individual unsuitable for the study or would prevent compliance with the study protocol
• Treatment with antibiotics for a clinical infection or other medical condition within 30 days prior to randomization
• Treatment with azathioprine or cyclosporine 90 days prior to randomization
• Treatment with infliximab, golimumab, adalimumab, abatacept, tocilizumab within 90 days; and etanercept or anakinra within 30 days of randomization
• Treatment with rituximab or any B-cell depleting agent within 12 months of randomization
• Treatment with any other marketed or investigational biologic within 5 half-lives of the molecule or if unknown within 90 days of randomization
• Administration of any investigational drug or use of any investigational device within 30 days prior to randomization