A Phase 3 Study Comparing 2 Doses Of CP-690,550 And The Active Comparator, Humira (Adalimumab) Vs. Placebo For Treatment Of Rheumatoid Arthritis

• Drug: CP 690,550
  
  tablets 5 mg BID PO plus q2 week placebo SC injections for 12 months
• Drug: CP-690,550
  
  tablets 10 mg BID PO plus q2 week placebo SC injections for 12 months
• Other: Placebo
  
  placebo tablets BID PO advance to 5mg CP 690,550 BID at Month 3 or 6 visit plus q2 week placebo SC injections for 12 months
• Other: Placebo
  
  tablets BID PO advance tablets to10mg CP 690,550 BID at Month 3 or 6 visit plus q2 week placebo SC injections for 12 months
• Biological: Biologic TNFi
  
  placebo tablets BID PO plus adalimumab 40 mg q2 week SC injections for 12 months
  Other Name: Humira (Adalimumab)

• Experimental: 5mg
  
  Intervention: Drug: CP 690,550
• Experimental: 10 mg
  
  Intervention: Drug: CP-690,550
• Placebo Comparator: Placebo Sequence 1
  
  Intervention: Other: Placebo
• Placebo Comparator: Placebo Sequence 2
  
  Intervention: Other: Placebo
• Active Comparator: adalimumab
  
  Intervention: Biological: Biologic TNFi

• 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.
• van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, García Meijide JA, Wagner S, Forejtova S, Zwillich SH, Gruben D, Koncz T, Wallenstein GV, Krishnaswami S, Bradley JD, Wilkinson B; ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012 Aug 9;367(6):508-19. doi: 10.1056/NEJMoa1112072. Erratum in: N Engl J Med. 2013 Jul 18;369(3):293.

Inclusion Criteria:

• The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria.
• The patient must have had an inadequate response to methotrexate and have active disease, 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.
• No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis.
• The patient must have been on a stable dose of 7.5 mg to 25 mg weekly of methotrexate and washed out of all other DMARDs.

Exclusion Criteria:

• Blood dyscrasias including confirmed: 1. Hemoglobin <9 g/dL or Hematocrit <30%; 2. White blood cell count <3,000 cu.mm. Absolute neutrophil count <1,200 cu.mm; 4. Platelet count <100,000/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
• Patients who have failed any TNFi for either lack of efficacy or a TNFi mechanism related adverse event.
• Patients who have previously received adalimumab therapy for any reason.
• Patients who are contraindicated for treatment with adalimumab in accordance with the approved local label.
• Patients meeting the New York Heart Association Class III and Class IV Congestive Heart failure