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)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: MK-8457 100 mg; Methotrexate; Dose-match placebo
Intervention description: MK-8457 100 mg dosed orally BID; MTX dosed at the stable dose received upon study entry; Dose-matched placebo dosed orally BID
Intervention MeSH terms: Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the safety and efficacy of MK-8457 + Methotrexate
      (MTX) in participants with active rheumatoid arthritis (RA) and an inadequate response or
      intolerance to anti-tumor necrosis factor α (anti-TNF-α) therapy. The primary hypothesis of
      this study is that among participants with active RA, MK-8457 100 mg twice daily (BID) + MTX
      will be superior to placebo + MTX as measured by the change in Disease Activity Score 28
      C-Reactive Protein (DAS28-CRP) after 12 weeks of treatment.
    

Eligibility criteria:

        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 or an elevated erythrocyte sedimentation
             rate (ESR) >28 mm/hr and evidence of synovitis on imaging

          -  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 (TB) 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 (HIV) 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

          -  Has been treated for RA with a marketed biologic agent (other than anti-TNF
             therapeutic agents) and failed the agent due to lack of efficacy

          -  Currently participating in another interventional clinical trial or has participated
             in an interventional clinical trial within 4 weeks prior to screening

          -  Severe opportunistic infection within the 6 months prior to screening