A Study in Patients With Rheumatoid Arthritis

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 participants with active RA.
* How much LY2439821 should be given to participants.

Study I1F-MC-RHAK is a multicenter study in participants with active RA on concomitant conventional 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 participant populations will be evaluated in this study: bDMARD-naive participants and TNFα-IR participants. Participants in Part A receive multiple subcutaneous injections of LY2439821 \[bDMARD-naive participants: 0 (placebo), 3, 10, 30, 80, or 180 mg; TNFα-IR participants: 0 (placebo), 80 or 180 mg\] at Weeks 0, 1, 2, 4, 6, 8, and 10. Participants in Part B receive subcutaneous injections of LY2439821 160 mg at Weeks 16, 18, and 20, and every 4 weeks thereafter through Week 60. Participants who complete both Part A and B have a total study participation of up to approximately 72 to 84 weeks.

Eligibility Criteria:
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 milliliters (mL) of blood within the last month
* You have received glucocorticoid administered by intra-articular, intramuscular, or intravenous 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 post-menopausal 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 bDMARD therapy such as TNFα, Interleukin (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 \[such as leflunomide, azathioprine, cyclosporine, etcetera (etc.)\]
* 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 bDMARD 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