A Study for Japanese Participants With Rheumatoid Arthritis (RA)

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of multiple doses of LY2127399 (tabalumab) in Japanese participants with RA. The study consists of a 20-week treatment period. All participants will be followed for up to 12 weeks after the last study drug administration.

Official Title
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Multiple-Dose, Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY2127399 in Japanese Patients With Rheumatoid Arthritis Treated With Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: LY2127399 (Tabalumab)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have given written informed consent Women must not be pregnant, breastfeeding or be at risk to become pregnant during study participation Diagnosis of RA Active RA Current, regular use of Methotrexate, at a stable dose Body weight between 40 and 105 kilograms (kg), inclusive Exclusion Criteria: Use of excluded medications (reviewed by study doctor) Have medical findings which, in the opinion of the study doctor, put participant at an unacceptable risk for participation in the study Have had recent or ongoing infection which, in the opinion of the study doctor put participant at an unacceptable risk for participation Evidence of tuberculosis Have systemic inflammatory condition other than RA

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30 milligrams (mg) Tabalumab<br>30 mg tabalumab every 4 weeks (Q4W) for 20 weeks (6 doses of study drug) | Drug: LY2127399 (Tabalumab)<br>* Administered subcutaneously<br>* Other names: Tabalumab;|
| Experimental: 60 mg Tabalumab<br>60 mg tabalumab Q4W for 20 weeks (6 doses of study drug) | Drug: LY2127399 (Tabalumab)<br>* Administered subcutaneously<br>* Other names: Tabalumab;|
| Experimental: 120 mg Tabalumab<br>120 mg tabalumab Q4W for 20 weeks (6 doses of study drug) | Drug: LY2127399 (Tabalumab)<br>* Administered subcutaneously<br>* Other names: Tabalumab;|
| Placebo Comparator: Placebo Q4W<br>Q4W for 20 weeks | Drug: Placebo<br>* Administered subcutaneously<br>|
| Experimental: 120 mg once every 2 weeks (Q2W) Tabalumab<br>Initial loading dose of 240 mg tabalumab followed by 120 mg Q2W for 20 weeks (10 doses of study drug) | Drug: LY2127399 (Tabalumab)<br>* Administered subcutaneously<br>* Other names: Tabalumab;|
| Placebo Comparator: Placebo Q2W<br>Q2W for 20 weeks | Drug: Placebo<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) [Clinically Significant Effects] | Clinically significant effects are defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Baseline through study completion (up to Week 32 plus up to 12 weeks for B cell monitoring) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Tabalumab: Area Under the Concentration Time Curve (AUC) | The following parameters are reported for the first SC injection of tabalumab: AUC(0-tlast) defined as AUC from time 0 to time t, where t is the time at the end of the dosing interval; AUC(0-2W) defined as AUC from time 0 to Week 2; and AUC(0-tau) defined as AUC during 1 dosing interval at steady state. | Week 0: Day 1 [predose and 1 hour (h), 3 h, and 6 h postdose], Days 2, 3, and 5, and Weeks 1, 2, 3, and 4 postdose | 
| PK of Tabalumab: Maximum Observed Drug Concentration (Cmax) | Cmax for the first SC injection of tabalumab is reported. | Week 0: Day 1 Predose, 1 h, 3 h, and 6 h postdose | 
| Percent Change From Baseline in B Cell [Cluster Designation 20+ (CD20+)] Counts | B-lymphocyte antigen, CD20+, is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Percent change from baseline in B cell counts=[(post-baseline CD20+ B cell count-baseline CD20+ B cell count)/(baseline CD20+ B cell count)]*100. A negative change indicates a decrease in cell count. | Baseline, Week 0 (Day 2), Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, and 32 | 
| Change From Baseline in Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody [Inova Enzyme-Linked Immunosorbent Assay (ELISA) Method] | During the analysis of anti-CCP, the analytical method was changed from the Inova ELISA method to the Roche Cobas 6000 method due to the discontinuation of a reagent used in the Inova ELISA method. The anti-CCP data are summarized separately for samples collected before and after the method change. No post-baseline samples from the 120 mg tabalumab Q4W and Q2W cohorts were analyzed using the Inova ELISA method. For both methods, a decrease in anti-CCP antibodies indicated an improvement in the participant's condition. | Baseline, Week 24 | 
| Change From Baseline in Anti-CCP Antibody (Roche Cobas 6000 Method) | During the analysis of anti-CCP, the analytical method was changed from the Inova ELISA method to the Roche Cobas 6000 method due to the discontinuation of a reagent used in the Inova ELISA method. The anti-CCP data are summarized separately for samples collected before and after the method change. No baseline samples from the 30 mg, 60 mg, and 120 mg tabalumab Q4W cohorts were analyzed using the Roche Cobas 6000 method. For both methods, a decrease in anti-CCP antibodies indicated an improvement in the participant's condition. | Baseline, Week 24 | 
| Change From Baseline in Rheumatoid Factor (RF) | RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis (RA). Higher RF levels indicate an aggressive RA and a higher risk of joint damage. A decrease in RF levels indicate an improvement in the participant's condition. | Baseline, Week 24 | 
| Change From Baseline in Serum Immunoglobulins (IgG, IgM, IgA) | Immunoglobulins, 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 G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) levels are reported. A negative change indicates a decrease in immunoglobulin levels. | Baseline, Weeks 4, 16, 24, and 32 | 
| Percent Change From Baseline in CRP | CRP is an indicator of inflammation. The percent change from baseline in CRP=[(post-baseline CRP- baseline CRP)/(baseline CRP)]*100. A negative change indicates an improvement in the participant's condition. | Baseline, Weeks 4, 8, 16, and 24 | 
| Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Reference ranges are gender-specific and can vary slightly among laboratories. The normal range is approximately ≤10 millimeters per hour (mm/h) for males and ≤20 mm/h for females. Higher scores indicate greater inflammation. The percent change from baseline in ESR=[(post-baseline ESR- baseline ESR)/(baseline ESR)]*100. A decrease in ESR indicates an improvement in the participant's condition. | Baseline, Weeks 4, 8, 16, and 24 |