A Phase 3 Study Comparing 2 Doses of CP-690,550 vs. Placebo for Treatment of Rheumatoid Arthritis

• Drug: CP-690,550
  
  5mg CP-690,550 BID PO for 6 months
• Drug: CP-690,550
  
  10 mg CP-690,550 BID PO for 6 months
• Drug: Placebo
  
  Placebo patients advance to 5mg CP-690,550 BID at Month 3 visit
• Drug: Placebo
  
  Placebo patients advance to 10mg CP-690,550 BID at Month 3 visit

• Experimental: Active 5mg
  
  Intervention: Drug: CP-690,550
• Experimental: Active 10 mg
  
  Intervention: Drug: CP-690,550
• Placebo Comparator: Placebo Sequence 1
  
  Intervention: Drug: Placebo
• Placebo Comparator: Placebo Sequence 2
  
  Intervention: Drug: Placebo

• Strand V, Kremer J, Wallenstein G, Kanik KS, Connell C, Gruben D, Zwillich SH, Fleischmann R. Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs. Arthritis Res Ther. 2015 Nov 4;17:307. doi: 10.1186/s13075-015-0825-9.
• Charles-Schoeman C, Burmester G, Nash P, Zerbini CA, Soma K, Kwok K, Hendrikx T, Bananis E, Fleischmann R. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14. Erratum in: Ann Rheum Dis. 2017 Mar;76(3):611.
• Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
• Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, Gruben D, Wallenstein GV, Zwillich SH, Kanik KS; ORAL Solo Investigators. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012 Aug 9;367(6):495-507. doi: 10.1056/NEJMoa1109071.

Inclusion Criteria:

• The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria.
• The patient has active disease at both Screening and Baseline, as defined by both: ?6 joints tender or painful on motion; and ?6 joints swollen; and fulfills 1 of the following 2 criteria at Screening: 1.ESR (Westergren method) >28 mm in the local laboratory. 2. CRP >7 mg/L in the central laboratory
• Patient had an inadequate response to at least one DMARD (traditional or biologic) due to lack of efficacy or toxicity.
• No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis.
• Patient has washed out of all DMARDs other that antimalarials

Exclusion Criteria:

• Blood dyscrasias including confirmed: 1. Hemoglobin <9 g/dL or Hematocrit <30%; 2. White blood cell count <3.0 x 109/L; 3. Absolute neutrophil count <1.2 x 109/L; 4. Platelet count <100 x 109/L
• History of any other autoimmune rheumatic disease other than Sjogren's syndrome
• No malignancy or history of malignancy.
• History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug