A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Participants With Rheumatoid Arthritis (MK-8457-010 AM3)

This study consists of a 24-week base study in which participants will receive MK-8457 100
mg twice daily or matching placebo, and a 76-week safety extension in which participants
will received MK-8457 100 mg twice daily.

Country-Specific Amendments: Amendments 1 and 2 (Brazil); Amendment 3 (Sweden)

Inclusion Criteria:

- Diagnosis of rheumatoid arthritis for at least 6 months prior to screening

- Active rheumatoid arthritis as defined by the presence of >= 6 swollen joints (of 66
count) and >= 6 tender joints (of 68 joint count)

- C-reactive protein blood level >0.9 mg/dL

- Anti-citrullinated protein antibody positive and/or rheumatoid factor positive at
screening

- American College of Rheumatology Functional Class I, II, or III

- Received methotrexate for a minimum of 3 months prior to screening with a regionally
appropriate stable weekly dose for at least 4 weeks prior to screening. The dose of
methotrexate must remain stable through Week 24 of the study.

- Failed treatment with 1 or 2 anti-tumor necrosis factor alpha (anti-TNF-α) therapies
or was intolerant to anti-TNF-α therapy prior to screening

- If using non-steroidal anti-inflammatory drugs or other analgesics, participant must
be on a stable dose

- No history of either untreated latent or active tuberculosis prior to baseline

- Participants of reproductive potential must agree to remain abstinent or use 2
acceptable methods of birth control

Exclusion Criteria:

- Presence of inflammatory disease other than rheumatoid arthritis, including but not
limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus,
or Lyme disease

- Hospitalization due to an acute cardiovascular event, cardiovascular illness, or
cardiovascular surgery within 6 months of screening

- Participant has a transplanted organ, excluding corneal transplant, performed > 3
months prior to the first dose of trial medication

- History of, or current ongoing ,chronic or recurrent infectious disease

- Positive hepatitis B surface antigen or hepatitis C test result

- Human immunodeficiency virus positive

- User of recreational or illicit drugs or has had a history (within the previous 2
years) of drug or alcohol abuse or dependence

- Prior exposure to fostamatinib or other spleen tyrosine kinase inhibitors

- Prior exposure to 3 or more anti-TNF therapeutic agents

- Prior exposure to any biological agents other than anti-TNF therapeutic agents

- Currently participating in another interventional clinical trial or has participated
in an interventional clinical trial within 4 weeks prior to screening