A Study of Tabalumab (LY2127399) Using Two Different Injection Methods in Participants With Lupus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the amount of tabalumab in the blood after it is given by two different injection methods - A traditional syringe or a spring loaded syringe for 12 weeks. Participants may continue to receive study drug for up to 52 weeks.

Official Title
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Pharmacokinetic Evaluations of Tabalumab Following Subcutaneous Administration by Prefilled Syringe or Auto Injector in Patients With Systemic Lupus Erythematosus

Conditions
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Lupus Erythematosus, Systemic

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: Diagnosis of Lupus. Able and willing to have blood drawn for PK sampling. Exclusion Criteria: Have severe active lupus nephritis. Have severe active central nervous system (CNS) or peripheral neurologic disease or other severe neurologic involvement requiring treatment within approximately 3 months prior to screening. Have received high dose corticosteroid within approximately 1 month prior to baseline. Have initiated or adjusted treatment with immunosuppressant drugs within approximately 1 month prior to baseline. Have received plasmapheresis within approximately 3 months prior to baseline. Have previously received approved or experimental B cell targeted therapies within the last year. Have received any biologic or non-biologic therapy within approximately 3 months or 5 half-lives (whichever is longer). Have a history of severe reaction to any biologic therapy. Have an active or recent infection within approximately 1 month prior to Week 0. Have had a serious infection within approximately 3 month or serious bone/joint infection within approximately 6 months prior to baseline. Have evidence of or test positive for active hepatitis B or are positive for hepatitis C or human immunodeficiency virus (HIV). Have evidence of active or latent tuberculosis. Have significant hematological abnormalities.

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 given Week 0 as a loading dose of 240 milligram (mg) given as two subcutaneous (SC) injections each of 120 mg followed by 120 mg SC injection every two weeks for 12 weeks. Participants may continue on this treatment regimen for 52 weeks. | Drug: Tabalumab Auto-Injector<br>* Administered SC<br>* Other names: LY2127399;|
| Experimental: Tabalumab Prefilled Syringe<br>Tabalumab given Week 0 as a loading dose of 240 mg given as two SC injections each of 120 mg followed by 120 mg SC injections every two weeks for 12 weeks. Participants may continue to on this treatment regimen for 52 weeks. | Drug: Tabalumab Prefilled Syringe<br>* Administered SC<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 Concentration (Cmax) of Tabalumab After Loading Dose | Maximum serum concentration of tabalumab, after the loading dose, assessed over the 14-day dosing interval, stratified by device.PK samples taken during the first dosing interval, days 4, 7, 9, 11, 14, were analyzed using noncompartmental analysis (NCA) methods to calculate the geometric mean. | Day 4, 7, 9, 11, 14: collected at approximately the same time of day as the administration of the Week 0 injection of tabalumab | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time 0 to 14 Days (AUC 0-14) of Tabalumab After Loading Dose | Area under the concentration time curve after the loading dose, assessed over the 14-day dosing interval, stratified by device.PK samples taken during the first dosing interval, days 4, 7, 9, 11, 14, were analyzed using NCA methods to calculate the geometric mean. | Day 4, 7, 9, 11, 14: collected at approximately the same time of day as the administration of the Week 0 injection of tabalumab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Cmax of Tabalumab Based on Body Weight | Maximum serum concentration of tabalumab, after the loading dose, assessed over the 14-day dosing interval , stratified by body weight (low <60 kilograms (kg), medium 60kg- 100kg, high >100kg).PK samples taken during the first dosing interval, days 4, 7, 9, 11, 14, were analyzed using NCA methods to calculate the geometric mean. | Day 4, 7, 9, 11, 14: collected at approximately the same time of day as the administration of the Week 0 injection of tabalumab | 
| Pharmacokinetics (PK): AUC 0-14 of Tabalumab Based on Body Weight | Area under the concentration time curve after the loading dose, assessed over the 14-day dosing interval, stratified by body weight (low <60 kilograms (kg), medium 60kg- 100kg, high >100kg). PK samples taken during the first dosing interval, days 4, 7, 9, 11, 14, were analyzed using noncompartmental analysis (NCA) methods to calculate the geometric mean. | Day 4, 7, 9, 11, 14: collected at approximately the same time of day as the administration of the Week 0 injection of tabalumab | 
| Number of Participants Reporting Incomplete Tabalumab Dose Administration | Participants reporting incomplete dose administration from the study drug administration log. | Week 0 through Week 12 | 
| Number of Participants Developing Anti-Tabalumab Antibodies | Participants with treatment-emergent anti-tabalumab antibodies were participants who had any samples from baseline up to and through Week 12 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 tabalumab. Percentage of participants with anti-tabalumab antibodies = (number of participants with treatment-emergent anti-tabalumab antibodies / number of participants assessed)*100. | Week 0 through Week 12 | 
| Subcutaneous Administration Assessment Questionnaire (SQAAQ) Score | The SQAAQ is a 12-item questionnaire using a 7-point Likert scale (from Strongly Disagree as 1 to Strongly Agree as 7) that provides assessment of ease of use and confidence with using a prefilled syringe or auto-injector to administer a subcutaneous injection of drug. The 12 items are: A-Easy for me to learn how to use, B-Easy for me to unlock, C- Easy to hold in my hand when I inject my dose, D- Easy to inject my dose, E- Easy to know that my dose is complete, F- Easy to store the device in my refrigerator, G- Easy to remove needle shield/cover, H- Easy to pick up, I- Overall, easy to use, J- The device is stable against my skin during the injection, K- I am confident in my ability to use the device, L- I am confident my dose is complete. | Week 0, Week 4 and Week 8 | 
| Pharmacokinetics (PK): Cmax of Tabalumab Based on Injection Site Stratifications | Maximum serum concentration of tabalumab in medium body weight group, after the loading dose via auto-injector, assessed over the 14-day dosing interval, stratified by injection site. PK samples taken during the first dosing interval, days 4, 7, 9, 11, 14, were analyzed using noncompartmental analysis (NCA) methods to calculate the geometric mean. | Day 4, 7, 9, 11, 14: collected at approximately the same time of day as the administration of the Week 0 injection of tabalumab | 
| Pharmacokinetics (PK): AUC 0-14 of Tabalumab Based on Injection Site Stratifications | Area under the concentration time curve in medium body weight group after the loading dose via auto-injector, assessed over the 14-day dosing interval, stratified by injection site. PK samples taken during the first dosing interval, days 4, 7, 9, 11, 14, were analyzed using noncompartmental analysis (NCA) methods to calculate the geometric mean. | Day 4, 7, 9, 11, 14: collected at approximately the same time of day as the administration of the Week 0 injection of tabalumab |