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)

• Status: Terminated
• Trial end date: 2013-10-08
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Methotrexate

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