An Open Label Study for Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The primary purpose of this study is to help answer if LY2127399 is safe and effective during long-term treatment in participants with Rheumatoid Arthritis. This study is comprised of 2 periods: Period 1: Unblinded treatment for up to 240 weeks for participants who enroll from Study H9B-MC-BCDO (BCDO) (NCT01202760) or Study H9B-MC-BCDV (BCDV) (NCT01202773) or up to 168 weeks for participants who enroll from Study H9B-MC-BCDM (BCDM) (NCT01198002). Period 2: 48-week post-treatment follow-up

Detailed Description
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Week 16 non-responders (NR) are participants with <20% improvement from baseline in both tender and swollen joint counts when assessed at Week 16 of Studies BCDO, BCDV and BCDM.

Official Title
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A Phase 3b, Multicenter, Open-Label Study to Evaluate the Long-Term Safety and Efficacy of LY2127399 in Patients With Rheumatoid Arthritis (RA)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: LY2127399


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have completed 24 weeks of participation in Study H9B-MC-BCDO or Study H9B-MC-BCDV, or have completed 100 weeks of participation in Study H9B-MC-BCDM Woman must not be pregnant, breastfeeding, or become pregnant during the study Exclusion Criteria: Current presence of a serious disorder or illness

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 120 milligrams (mg) of LY2127399<br>Given every 4 weeks for 240 weeks for those participants from Study BCDO or Study BCDV. Participants who had been receiving placebo immediately prior to enrollment will receive a 240 mg loading dose when initiating treatment. Or Given every 4 weeks for 168 weeks for those participants from Study BCDM. | Drug: LY2127399<br>* Administered Subcutaneously<br>* Other names: Tabalumab;|
| Experimental: 90 mg LY2127399<br>Given every 2 weeks for 240 weeks for those participants from Study BCDO or Study BCDV. Participants who had been receiving placebo immediately prior to enrollment will receive a 180 mg loading dose when initiating treatment. Or Given every 2 weeks for 168 weeks for those participants from Study BCDM. | Drug: LY2127399<br>* Administered Subcutaneously<br>* Other names: Tabalumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | A TEAE was defined as an event that first occurred or worsened in severity on or after the date of the first injection and prior to study termination. AESI are infection, injection site reactions, malignancy, major adverse cardiovascular events (MACE), allergy and hypersensitivity, depression, suicide/self-injury and pregnancy. MACE were defined as 1 of the adjudicated events: cardiovascular death, Myocardial infarction (MI), stroke, hospitalization for unstable angina, hospitalization for heart failure, coronary revascularization procedure, peripheral revascularization procedure, cardiogenic shock due to MI, resuscitated sudden death, serious arrhythmia, hospitalization for hypertension, peripheral arterial event. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | up to 84.4 weeks during treatment period | 
| Percentage of Participants Developing Anti-LY2127399 Antibodies | Participants with treatment-emergent anti-LY2127399 antibodies were participants who had any samples from baseline up to and through Week 72 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants with anti-LY2127399 antibodies=(number of participants with treatment-emergent anti-LY2127399 antibodies / number of participants assessed)*100. | Baseline through Weeks 4, 24, 48 and 72 | 
| Change From Baseline in Absolute B Cell Counts | Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B cell count is the average of the values on or prior to the date of first injection of study treatment in preceding studies, including unscheduled visits. A positive or negative change indicated an increase or decrease, respectively, in B cell count. | Baseline, Week 48 | 
| Change From Baseline in Serum Immunoglobulin (Ig) Levels | Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. | Baseline, Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | ACR Responder Index is a Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responders: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants achieving ACR20 response=(number of ACR20 responders / number of participants treated) * 100. All participants who discontinue study treatment for any reason were defined as NR at that time point and going forward. | Baseline through Weeks 12, 24 and 48 | 
| Change From Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) |  | Baseline, 240 weeks | 
| Percentage of Participants With DAS28-Based European League Against Rheumatism (EULAR-28) Response |  | Baseline through 240 weeks | 
| Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores |  | Baseline, 240 weeks | 
| Change From Baseline in Tender Joint Count (68 Joint Count) |  | Baseline, 240 weeks | 
| Change From Baseline in Swollen Joint Count (66 Joint Count) |  | Baseline, 240 weeks | 
| Change From Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)] |  | Baseline, 240 weeks | 
| Change From Baseline in Participants Global Assessment of Disease Activity (VAS) |  | Baseline, 240 weeks | 
| Change From Baseline in Physicians Global Assessment of Disease Activity (VAS) |  | Baseline, 240 weeks | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) |  | Baseline, 240 weeks | 
| Change From Baseline in CRP |  | Baseline, 240 weeks | 
| American College of Rheumatology Percent Improvement (ACR-N) |  | Baseline through 240 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis