A Study in Patients With Rheumatoid Arthritis (FLEX V)

• Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Mean percent improvement in ACR-N [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Tender Joint Count (68 joint count) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Swollen Joint Count (66 joint count) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Patient's Assessment of Pain (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Patient's Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Physician's Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Disease Activity Score-C-Reactive Protein (DAS28-CRP) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain and summary scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Brief Fatigue Inventory (BFI) individual items and impact scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in duration of morning stiffness (minutes) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Time to ACR20 response [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in absolute B cell counts [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
• Change from baseline to 24 weeks in serum immunoglobulin (Ig) levels [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
• Population Pharmacokinetics (PK) [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: No ]
• Percentage of patients developing anti-LY2127399 antibodies [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: Yes ]
• Change from baseline to 24 weeks in CRP [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]

• Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Mean percent improvement in ACR-N [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Tender Joint Count (68 joint count) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Swollen Joint Count (66 joint count) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Patient's Assessment of Pain (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Patient's Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Physician's Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Disease Activity Score-C-Reactive Protein (DAS28-CRP) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain and summary scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Brief Fatigue Inventory (BFI) individual items and impact scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in duration of morning stiffness (minutes) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
• Time to ACR20 response [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24 weeks in absolute B cell counts [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
• Change from baseline to 24 weeks in serum immunoglobulin (Ig) levels [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
• Population Pharmacokinetics (PK) [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: No ]
• Percentage of patients developing anti-LY2127399 antibodies [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: Yes ]

The primary purpose of this study is to help answer if LY2127399 is safe and effective in the treatment of rheumatoid arthritis in patients with an inadequate response to one or more Tumor necrosis factor-alpha (TNF α) inhibitors.

This study is comprised of 2 periods:

Period 1 - 24 week blinded treatment

Period 2 - 48 week post treatment follow up

• Drug: LY2127399
  Administered Subcutaneously
• Drug: Placebo every 4 weeks
  Administered Subcutaneously
• Drug: Placebo every 2 weeks
  Administered Subcutaneously

• Experimental: 120 mg LY2127399

  Given every 4 weeks for 24 weeks. Patients receive a 240mg loading dose when initiating treatment.

  During the Treatment Period, for blinding purposes, patients will alternate injections of LY2127399 and injections of placebo every 2 weeks.

  After 16 weeks, non-responders will receive 90 mg every 2 weeks.

  Interventions:

  • Drug: LY2127399
  • Drug: Placebo every 4 weeks
• Experimental: 90 mg LY2127399

  Given every 2 weeks for 24 weeks. Patients receive a 180 mg loading dose when initiating treatment.

  After 16 weeks, non-responders will continue to receive 90 mg every 2 weeks.

  Intervention: Drug: LY2127399
• Placebo Comparator: Placebo

  Given every 2 weeks for 24 weeks, and then patients are randomized to receive one of the 2 doses of LY2127399.

  After 16 weeks, non-responders will receive 90 mg every 2 weeks.

  Interventions:

  • Drug: LY2127399
  • Drug: Placebo every 2 weeks

Inclusion Criteria:

• Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years
• At least 8 tender and swollen joints
• An abnormally high C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR)
• Positive for Rheumatoid Factor (RF) or Anti-cyclic citrullinated peptide (CCP) antibody
• Previously treated with biologic TNF-α inhibitor therapy (infliximab, certolizumab, golimumab, etanercept, adalimumab) and stopped treatment due to insufficient efficacy or intolerance
• Regular use of at least one conventional disease-modifying anti-rheumatic drug (DMARD), with a stable dose for at least 8 weeks prior to study start
• Woman must not be pregnant, breastfeeding, or become pregnant during the study

Exclusion Criteria:

• Use of unstable doses of non-steroidal inflammatory drugs (NSAIDS) in the past 6 weeks
• Steroid injection or intravenous (IV) infusion in the last 6 weeks
• Use of more than 10 mg/day of oral steroids in the last 6 weeks
• History of a serious reaction to other biological DMARDs
• Use of an oral calcineurin inhibitor (e.g., cyclosporin or tacrolimus) in the last 8 weeks
• Surgery on a joint or other major surgery less than 2 months ago, or plans to have joint surgery or major surgery during the study
• Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA
• Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years
• Received a live vaccine received within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines)
• Hepatitis or human immunodeficiency virus (HIV)
• A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months
• Symptoms of herpes zoster or herpes simplex within the last month
• Active or latent tuberculosis (TB)
• Current symptoms of a serious disorder or illness
• Use of an investigational drug within the last month