Evaluation of Tabalumab Using Auto-Injector or Prefilled Syringe in Participants With Rheumatoid Arthritis (RA)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the serum concentration of tabalumab after the administration using either prefilled syringe or auto-injector after the initial loading dose and after 12 weeks of treatment. Treatment period is followed by 40 weeks optional safety extension.

Official Title
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Pharmacokinetic Evaluations of Tabalumab Following Subcutaneous Administration by Prefilled Syringe or Auto Injector in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tabalumab Auto-Injector
* Drug: Tabalumab Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory males or females ≥18 years of age Diagnosis of adult-onset RA Active RA (at least 8/68 tender and at least 8/66 swollen joints) Screening C-reactive protein (CRP) >1.2 times the upper limit of normal (ULN) or a screening erythrocyte sedimentation rate (ESR) >28 millimeters per hour (mm/hr) Documented history of, or current, positive rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (anti-CCP Ab) test Regular use of methotrexate (MTX) for at least 12 weeks and stable dose (10 to 25 mg/week) for at least 8 weeks prior to baseline American College of Rheumatology (ACR) functional class I, II, or III Able and willing to inject tabalumab by themselves (or have an assistant who will inject tabalumab) and able and willing to complete all study procedures Able and willing to have blood drawn for pharmacokinetic (PK) sampling Exclusion Criteria: Use of oral corticosteroids at average daily doses of >10 milligrams per day (mg/day) of prednisone or its equivalent within 6 weeks prior to baseline Injection of any parenteral (including intraarticular) corticosteroid within 6 weeks of baseline Have previously discontinued treatment with a biologic disease-modifying antirheumatic drug (DMARD) or a novel drug that interrupts cytokine signaling [for example, Janus kinase (JAK) inhibitors] due to insufficient efficacy Participants who had discontinued biologic DMARDS for reasons other than efficacy will not be excluded but must have done so prior to baseline Participants who discontinued a JAK inhibitor for lack of efficacy Participants who discontinued a JAK inhibitor for reasons other than efficacy will not be excluded, but must have done so prior to baseline for 21 days Previous severe reaction to any biologic therapy that, in the opinion of the Investigator, would pose an unacceptable risk to the participant if participating in the study Have had an inadequate response to treatment with 3 or more of the following DMARDs prescribed alone or in combination at approved doses for a minimum of 90 days: leflunomide, azathioprine, cyclosporine, and/or sulfasalazine Use of other DMARDs (for example, gold salts, cyclosporin, azathioprine, or any other immunosuppressives) other than MTX, hydroxychloroquine, chloroquine, or sulfasalazine, or the use of a JAK inhibitor in the 8 weeks prior to baseline

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: Tabalumab Auto-Injector<br>Tabalumab 180 milligram (mg) loading dose administered using auto-injectors at Week 0 as 2 subcutaneous (SC) injections (90 mg each), followed by a 90 mg SC injection every 2 weeks (Q2W) up to Week 12. | Drug: Tabalumab Auto-Injector<br>* Administered SC by auto-injector<br>* Other names: LY2127399;|
| Experimental: Tabalumab Prefilled Syringe<br>Tabalumab 180 mg loading dose administered using prefilled syringes at Week 0 as 2 SC injections (90 mg each), followed by a 90 mg SC injection Q2W up to Week 12. | Drug: Tabalumab Prefilled Syringe<br>* Administered SC by prefilled syringe<br>* Other names: LY2127399;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Tabalumab After Loading Dose |  | Days 4, 7, 9, 11, and 14 after loading dose administered | 
| PK: Area Under the Concentration Time Curve From Time 0 to 14 Days [AUC(0-14)] |  | Days 4, 7, 9, 11, and 14 after loading dose administered | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12-Week Endpoint in Achieving American College of Rheumatology (ACR) Core Set |  | Baseline, Week 12 | 
| Percentage of Participants Achieving ACR Response |  | Week 12 | 
| Percent Change From Baseline to 12-Week Endpoint in American College of Rheumatology (ACR-N) Index |  | Baseline, Week 12 | 
| Change From Baseline to 12-Week Endpoint in Disease Activity Score Based on a 28-Joint Count and C-Reactive Protein (DAS28-CRP) Level |  | Baseline, Week 12 | 
| Percentage of Participants Achieving European League Against Rheumatism Responder Index Based on the 28-Joint Count (EULAR-28) |  | Week 12 | 
| Number of Participants Developing Anti-Tabalumab Antibodies |  | Week 12 | 
| Number of Operation Failures |  | Week 12 | 
| Change From Baseline Score in Subcutaneous Administration Assessment Questionnaire (SQAAQ) |  | Baseline, Weeks 4 and 8 |