A Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Study to Ev aluate the Efficacy and Safety of PF-04236921 in Subjects with Crohn's Disease Who are Anti-TNF Inadequate Responsers

INTERVENTION: Product Name: Not Applicable Product Code: PF‐04236921 Pharmaceutical Form: Powder for injection INN or Proposed INN: Not Applicable Current Sponsor code: PF‐04236921 Other descriptive name: The investigational medicinal product (IMP) may be labelled as either “PF‐04236921 106 mg/vial, Clonal SC lyophilized form” or “PF‐04236921 Powder for Injection, 106 mg/vial”. Supplies labelled with either nomenclature are equivalent. Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 106‐ Pharmaceutical form of the placebo: Powder for injection Route of administration of the placebo: Subcutaneous use CONDITION: Crohn's Disease (active moderate to severe) ; MedDRA version: 17.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 ‐ Gastrointestinal disorders Therapeutic area: Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective: The primary objectives of this study are to demonstrate clinical activity of PF 04236921 that will induce a clinical response and remission in subjects with Crohn’s Disease (CD) via the Crohn’s Disease Activity Index (CDAI) and to select dose(s) for future clinical studies. Primary end point(s): The CDAI 70 response rate at Week 8 or Week 12 Secondary Objective: The secondary objectives include:; • Evaluate safety, tolerability, and immunogenicty of PF‐04236921.; • Characterize PK of PF‐04236921 in subjects with CD.; ; Exploratory Objectives; • Explore the relationship between PK/PD and CDAI score and biomarkers.; • Characterize PD and other biomarkers; • Assess health outcome measures in IBDQ and EQ 5D™.; Timepoint(s) of evaluation of this end point: Week 8 or Week 12 SECONDARY OUTCOME: Secondary end point(s): • Percent of subjects with a CDAI remission (CDAI <150), CDAI 70 and CDAI 100 responses Weeks 2 through 12 (Day 14 to Day 84). ; • Mean change from baseline for CDAI score Weeks 2 through 12 (Day 14 to Day 84). ; • Safety and tolerability of PF‐04236921 dose levels versus placebo: the frequency of on treatment adverse events, withdrawals due to adverse events, and SAEs will be reported. Any subject who receives at least 1 dose of investigational product will be included in the evaluation for safety. ; • Percent of subjects that develop ADAs and NAbs, if observed, measured at baseline, and Weeks 4, 8, 12, 16, 24, 32 and 40 will be reported. ; • Serum concentrations of PF‐04236921 measured at baseline and every two weeks up to Week 12 and monthly through Week 40 will be reported. ; Timepoint(s) of evaluation of this end point: The timepoints are defined with the seconday endpoints INCLUSION CRITERIA: 1. Evidence of personally signed & dated informed consent document indicating. 2. Subjects willing & able to comply with scheduled visits, & other study procedures. 3. Subjects between ages of =18 &=75 years. 4. Subjects must have failed or are intolerant to anti TNFs; Relapsed after at least 1 anti TNF; Primary non‐responder to at least 1 anti TNF ; Intolerant to at least 1 anti TNF; Other – Discontinued at least 1 anti TNF regimen for other reasons. 5. Active moderate to severe ileal (terminal ileum), ileocolic or colonic CD (CDAI scores =220 to =450), despite previous or current use of conventional therapies including mesalamine (5 ASAs), oral steroids and/or immunosupressants (AZA, 6 MP, & MTX) (May continue use of 5 ASAs, AZA, MTX, 6 MP and oral steroids in this trial; dose should be stable 2 weeks prior to randomization). (Note: current use of immunosuppressant therapy type (AZA, 6MP, MTX or none) is another stratification factor in this s