A Dose Range Finding Study of JNJ-38518168 in Patients With Active Rheumatoid Arthritis in Spite of Treatment With Methotrexate

• Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Patient's Global Assessment of Disease Activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.
  
  

• Change from baseline in DAS28 (CRP) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  
• Change from baseline in DAS28 (erythrocyte sedimentation rate [ESR]) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• DAS28 (CRP) response rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• DAS28 (ESR) response rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• DAS28 (CRP) remission rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• DAS28 (ESR) remission rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• American College of Rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  An ACR 20/50/70 response is defined as a greater than or equal to 20/50/70 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).
  
  
• Hybrid ACR response at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  The hybrid ACR response is a continuous variable that is limited to an overall score of -100 (maximal worsening) to +100 (maximal improvement).
  
  
• ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]

  According to the ACR/EULAR provisional definition, a patients RA can be defined as being in remission based on either of 2 definitions:

  when scores on the tender joint count, swollen joint count, CRP (in mg/dL), and patient global assessment (0-10 scale) are all less than or equal to 1 OR when the score on the simplified disease activity index (SDAI) is less than or equal to 3.3 Analyses based on each definition will be performed.

  
  
• Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  The SDAI is the numerical sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28‐joint assessment, patient global assessment of disease activity (PGA VAS in cm), physician global assessment of disease activity (MDGA VAS in cm) and C‐reactive protein (CRP in mg/dL).
  
  
• Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  The CDAI is the numerical sum of 5 outcome parameters: TJC and SJC based on a 28‐joint assessment, PGA, and MDGA.
  
  
• Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
  The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area).
  
  
• Change from baseline in HAQ-DI score at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• Percent change from baseline in ESR levels at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• Percent change from baseline in ACR components at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ] [ Designated as safety issue: No ]
  
• Number of patients with adverse events [ Time Frame: Up to Week 28 ] [ Designated as safety issue: Yes ]
  

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), multicenter, placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each group of patients will be treated at the same time), dose range finding study of JNJ-38518168 in patients with active RA despite concomitant MTX therapy. The study will consist a screening period, a 24-week placebo-controlled period and a 4-week follow-up period between the last dose and the last visit. The duration of participation in the study for an individual patient will be up to 34 weeks (including screening). The patients will be assigned to 1 of 4 treatment groups in a 1:1:1:1 ratio to placebo and JNJ-38518168 (3 mg or 10 mg or 30 mg). Safety assessments and evaluations to determine the efficacy of JNJ-38518168 to reduce the signs and symptoms of RA will be performed at study visits. Safety will be monitored throughout the study.