The primary purpose of the study is to help answer the following research questions, and not to provide treatment for Rheumatoid Arthritis (RA):

• The safety of LY2439821 and any side effects that might be associated with it.
• Whether LY2439821 can help patients with active RA.
• How much LY2439821 should be given to patients.

Study I1F-MC-RHAK is a multicenter study in patients with active rheumatoid arthritis on concomitant conventional disease modifying anti-rheumatic drug (DMARD) therapy. The study is a Phase 2 study with 2 parts. Part A is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging design and Part B is an optional, open-label extension design. Two patient populations will be evaluated in this study: biologic disease modifying anti-rheumatic drug [bDMARD]-naive patients and tumor necrosis factor alpha-inadequate responder [TNFα-IR] patients. Patients in Part A receive multiple subcutaneous (SC) injections of LY2439821 (bDMARD-naive patients: 0 [placebo], 3, 10, 30, 80, or 180 mg; TNFα-IR patients: 0 [placebo], 80 or 180 mg) at Weeks 0, 1, 2, 4, 6, 8, and 10. Patients in Part B receive SC injections of LY2439821 160 mg at Weeks 16, 18, and 20, and every 4 weeks thereafter through Week 60. Patients who complete both Part A and B have a total study participation of up to approximately 72 to 84 weeks.

• Biological: LY2439821
  subcutaneous
  Other Name: LY2439821
• Drug: Placebo
  subcutaneous
  Other Name: Placebo

• 3mg LY2439821 [bDMARD-naive population]: Experimental
  3 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Biological: LY2439821
• 10mg LY2439821 [bDMARD-naive population]: Experimental
  10mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Biological: LY2439821
• 30mg LY2349821 [bDMARD-naive population]: Experimental
  30mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Biological: LY2439821
• 80mg LY2439821 [bDMARD-naive population]: Experimental
  80mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Biological: LY2439821
• 180mg LY2439821[bDMARD-naive population]: Experimental
  180mg at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Biological: LY2439821
• 80mg LY2439821 [TNFa-IR population]: Experimental
  80mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Biological: LY2439821
• 180mg LY2439821 [TNFa-IR population]: Experimental
  180mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Biological: LY2439821
• Placebo [bDMARD-naive population]: Placebo Comparator
  Placebo at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Drug: Placebo
• Placebo [TNFa-IR population]: Placebo Comparator
  Placebo at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
  Intervention: Drug: Placebo

Inclusion Criteria:

• You must be between the ages of 18 and 75
• You must have active RA

Qualifications Specific to the bDMARD-naive Population:

You must be regularly using methotrexate (MTX) for at least 12 weeks before your participation in this study

Qualifications Specific to the TNFα-IR Population:

• You must have been treated with at least 1 biologic TNFα inhibitor therapy and either had an insufficient response to at least 3 months of treatment OR have been intolerant of such treatment
• You must be regularly using at least 1 conventional DMARD in a stable treatment regimen

Exclusion Criteria:

• You are concomitantly using non-steroidal anti-inflammatory drugs (NSAIDS), unless you are on a stable dose within the last 2 weeks
• You are a woman who is lactating or breast feeding
• You have donated more than 300 mL of blood within the last month
• You have received glucocorticoid administered by intra-articular, intramuscular, or intravenous (IV) injection or oral corticosteroids at an average daily dose of greater than 10 mg per day of prednisone or its equivalent within the last 4 weeks
• You had surgery on a joint that is to be assessed in the study within 2 months of study enrollment, or will require such during the study
• You have another serious disorder or illness
• You suffered a serious bacterial infection (for example, pneumonia, cellulitis, or bone or joint infections) within the last 3 months
• You have a history of uncontrolled high blood pressure
• You have clinical laboratory test results at entry that are outside the normal reference range
• You are an employee of the clinic or you are an immediate family member of an employee of the clinic. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
• You are currently participating in or were discontinued within the last 30 days from another clinical trial involving an investigational drug
• If you are a woman and you could become pregnant during this study, you must talk to the study doctor about the birth control that you will use to avoid getting pregnant during the study.
• If you are a post menopausal woman, you must be at least 45 years of age and have not menstruated for the last 12 months
• If you are a woman between 40 and 45 years of age, test negative for pregnancy, and have not menstruated during the last 12 months only, you must have an additional blood test to see if you can participate.
• If you are male, you must agree to reduce the risk of your female partner becoming pregnant during the study.

Exclusions Specific to the bDMARD-naive Population:

• You have received any prior biologic DMARD therapy such as TNFα, IL-1, IL-6, T-cell, or B-cell targeted therapies
• You have had an inadequate response to a minimum of 3 months of treatment with 5 or more conventional DMARDs (such as leflunomide, azathioprine, cyclosporine, etc)
• You have used DMARDs other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks
• You have used leflunomide within the last 12 weeks and have not received cholestyramine to speed up the elimination of leflunomide from your body.

Exclusions Specific to the TNFα-IR Population:

• You are currently using or recently used a biologic DMARD or a biologic TNFα inhibitor therapy within specified periods
• You have had a serious reaction to other biologic DMARDs that, in the study doctor's opinion, puts you at serious risk
• You have used cyclosporine or any other immunosuppressive in the 8 weeks before your participation in this study