Phase IIB Rheumatoid Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to Methotrexate

• Proportion of subjects with ACR 20 response [ Time Frame: At weeks 24 ] [ Designated as safety issue: No ]
• Proportion of subjects achieving ACR 50 response rate [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
• Proportion of subjects achieving ACR 70 response rate [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in disease activity as measured by Disease Activity Score 28 C-reactive protein (DAS28-CRP) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
• Proportion of subjects with remission by DAS28-CRP [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in Clinical Disease Activity Index (CDAI) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
• Proportion of subjects with remission by CDAI [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in Simplified Disease Activity Index (SDAI) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
• Proportion of subjects with remission by SDAI [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
• Proportion of subjects with remission rate by Boolean definition [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in Health Assessment Questionnaire (HAQ) disability Index [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in Short Form 36 (SF-36) as measured by physical and mental components as well as 8 individual domain scores [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in fatigue severity (VAS) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) as measured by 4 domain scores [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in radiographic progression of synovitis, osteitis (bone marrow edema), bone erosion and cartilage loss (joint-space narrowing) (MRI) [ Time Frame: Baseline (Day 1) and To weeks 12 ] [ Designated as safety issue: No ]
• Mean change from baseline in radiographic progression of joint damage as measured by modified Sharp/van der Heijide scores (X-ray) [ Time Frame: Baseline (Day 1) and To weeks 24 ] [ Designated as safety issue: No ]
• Safety will be measured by adverse events, clinically significant changes in vital signs, physical exams and ECG, laboratory test abnormality and immunogenicity changes from baseline [ Time Frame: Upto double-blind period (48 weeks) ] [ Designated as safety issue: Yes ]

• To assess additional efficacy outcomes of BMS-945429 SC at 12 weeks as measured by ACR50 and 70 response rates, DAS28-CRP, CDAI, SDAI, remission, physical function and health-related quality of life outcomes. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • ACR20 - 20% American College of Rheumatology (ACR) response
  • ACR50 - 50% American College of Rheumatology (ACR) response
  • ACR70 - 70% American College of Rheumatology (ACR) response
  • DAS28-CRP - Disease Activity Score 28 - C-reactive protein
  • CDAI - Clinical Disease Activity Index
  • SDAI - Simplified Disease Activity Index
• To assess efficacy of BMS-945429 SC at 24 weeks as measured by ACR 20, 50 and 70 response rates, DAS28-CRP, CDAI, SDAI, remission, physical function and health-related quality of life outcomes. [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
• To assess radiographic progression of joint damage by imaging studies: Magnetic resonance imaging (MRI) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• To assess radiographic progression of joint damage by imaging studies: x-ray [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
• To assess safety and tolerability including immunogenicity rates by the number of adverse events and serious adverse events, laboratory values, physical exams and vital signs, and electrocardiogram (ECG). [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
• To assess safety and tolerability including immunogenicity rates by the number of adverse events and serious adverse events, laboratory values, physical exams and vital signs, and electrocardiogram (ECG). [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]

The purpose of this study is to determine the effective dose of BMS-945429 in subjects with inadequate response to Methotrexate in the treatment of moderate to severe Rheumatoid Arthritis.

• Drug: BMS-945429 Placebo
  Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only
• Biological: BMS-945429
  Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only
• Biological: BMS-945429
  Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks
• Biological: BMS-945429
  Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48
• Biological: BMS-945429
  Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks
• Drug: Methotrexate
  Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only
• Drug: Methotrexate
  Tablets, Oral, 15 mg, Weekly, 48 weeks
• Drug: Methotrexate Placebo
  Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only
• Drug: Methotrexate
  Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only
• Drug: Adalimumab Placebo
  Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
• Drug: Adalimumab
  Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

• Placebo Comparator: Arm 1
  BMS-945429 Placebo/BMS-945429+Methotrexate+Adalimumab Placebo
  Interventions:

  • Drug: BMS-945429 Placebo
  • Biological: BMS-945429
  • Drug: Methotrexate
  • Drug: Adalimumab Placebo
• Experimental: Arm 2
  BMS-945429 + Methotrexate + Adalimumab Placebo
  Interventions:

  • Biological: BMS-945429
  • Drug: Methotrexate
  • Drug: Adalimumab Placebo
• Experimental: Arm 3
  BMS-945429 + Methotrexate + Adalimumab Placebo
  Interventions:

  • Biological: BMS-945429
  • Drug: Methotrexate
  • Drug: Adalimumab Placebo
• Experimental: Arm 4
  BMS-945429 + Methotrexate + Adalimumab Placebo
  Interventions:

  • Biological: BMS-945429
  • Biological: BMS-945429
  • Drug: Methotrexate
  • Drug: Adalimumab Placebo
• Experimental: Arm 5
  BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo
  Interventions:

  • Biological: BMS-945429
  • Drug: Methotrexate Placebo
  • Drug: Methotrexate
  • Drug: Adalimumab Placebo
• Experimental: Arm 6
  BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo
  Interventions:

  • Biological: BMS-945429
  • Drug: Methotrexate Placebo
  • Drug: Methotrexate
  • Drug: Adalimumab Placebo
• Active Comparator: Arm 7
  Adalimumab + Methotrexate
  Interventions:

  • Drug: Methotrexate
  • Drug: Adalimumab

Inclusion Criteria:

• Inadequate response to Methotrexate
• Must have been taking Methotrexate for at least 3 months at a minimal weekly dose of at least 15 mg and stable dose for 4 weeks prior to randomization
• American College of Rheumatology (ACR) global function status class 1-3
• Minimum of 6 swollen and 6 tender joints with evidence of synovitis in at least 1 hand or wrist
• High sensitivity C-reactive protein (hsCRP) ≥ 0.8 mg/dL

Exclusion Criteria:

• Previously received or currently receiving concomitant biologic therapy