Phase 2 Study of Belimumab Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The purpose of this study is to test the safety and tolerability of repeated subcutaneous (SC) doses of belimumab in subjects with SLE.

Detailed Description
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This clinical trial will evaluate the safety, pharmacokinetics (PK), and effect on biomarkers of repeated subcutaneous (SC) administration of belimumab in subjects with SLE. As data permit, an exploratory pharmacodynamic analysis will be performed to evaluate the correlation between belimumab serum exposure, PGA, SELENA SELDAI, and biomarker effects.

Official Title
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A Phase 2, Multi-Center, Randomized, Open Label, Trial to Evaluate the Safety, Tolerability, and Biological Activity of 2 Dosing Schedules of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Belimumab 100 mg SC
* Drug: Belimumab 100 mg SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria Active SLE disease On stable SLE treatment regimen Exclusion Criteria: Pregnant or nursing Have received treatment with an B cell targeted therapy Have received treatment with a biologic investigational agent in the past year Have received intravenous (IV) cyclophosphamide within 180 days of Day 0 Have severe lupus kidney disease Have active central nervous system (CNS) lupus Have required management of acute or chronic infections with the past 60 days Have current drug or alcohol abuse or dependence or within the past year Have a historically positive test or test positive at screening for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C Have a history of an allergic or anaphylactic reaction to drugs, food, or insects requiring medical intervention

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: Belimumab Q2WKS<br>Every other week: 100 mg of belimumab (1 injection) subcutaneous (under the skin) on days 0, 7, and 14, then every other week until final evaluation at Week 24 with option to continue receiving belimumab at the same dose through 144 week continuation period. | Drug: Belimumab 100 mg SC<br>* Belimumab 100 mg SC for 1 injection on Days 0, 7, 14, and then every two weeks.<br>* Other names: LymphoStat-B™;|
| Experimental: Belimumab 3X/WK<br>Three times weekly: 200 mg of belimumab (2 injections of 100 mg each) subcutaneous (under the skin) on days 0, 2, and 4 then 100 mg three times a week until final evaluation at Week 24 with option to continue receiving belimumab at the same dose through 144 week continuation period. | Drug: Belimumab 100 mg SC<br>* Belimumab 100mg SC for 2 injections (of 100mg each) on Days 0, 2, and 4, then 100 mg (1 injection) three times per week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the Number of Participants Who Experienced Adverse Events (AEs) During the 24 Week Period. | SEE ALSO ADVERSE EVENTS RESULTS SECTION | Up to 24 weeks | 
| Absolute Change From Baseline in CD20+ (Total) B Cells at Week 24 |  | Baseline, 24 weeks | 
| Median Percent Change From Baseline in CD20+ (Total) B Cells at Week 24. |  | Baseline, 24 Weeks | 
| Absolute Change From Baseline in CD20+/CD27- (Naive) B Cells at Week 24 |  | Baseline, 24 weeks | 
| Median Percent Change From Baseline in CD20+/CD27-(Naive) B Cells at Week 24 |  | Baseline, 24 weeks | 
| Absolute Change From Baseline in CD20+/CD69+ (Activated) B Cells at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in CD20+/CD69+ (Activated) B Cells at Week 24 |  | Baseline, 24 Weeks | 
| Absolute Change From Baseline in CD20+/CD27+ (Memory) B Cells at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in CD20+/CD27+ (Memory) B Cells at Week 24 |  | Baseline, 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Serum Belimumab Concentration Levels (Pharmacokinetic [PK]) Over 24 Weeks. |  | Baseline, 24 weeks | 
| Absolute Change From Baseline in IgA at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in IgA at Week 24 |  | Baseline, 24 weeks | 
| Absolute Change From Baseline in IgG at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in IgG at Week 24 |  | Baseline, 24 Weeks | 
| Absolute Change From Baseline in IgM at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in IgM at Week 24 |  | Baseline, 24 weeks | 
| Absolute Change From Baseline in Physician's Global Assessment (PGA) Score at Week 24 | PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity. | Baseline, 24 Weeks | 
| Mean Percent Change From Baseline in PGA Score at Week 24. | The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity. | Baseline, 24 weeks | 
| Absolute Change From Baseline in the Safety of Estrogen in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24 | SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. | Baseline, 24 Weeks | 
| Mean Percent Change From Baseline in the SELENA SLEDAI Score at Week 24 |  | Baseline, 24 weeks | 
| Absolute Change From Baseline in Complement C3 at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in Compliment C3 at Week 24 |  | Baseline, 24 Weeks | 
| Absolute Change From Baseline in Complement C4 at Week 24 |  | Baseline, 24 weeks | 
| Median Percent Change From Baseline in Complement C4 at Week 24 |  | Baseline, 24 Weeks | 
| Absolute Change From Baseline in Anti-Double-Stranded DNA (Anti-dsDNA)at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in Anti-dsDNA at Week 24 |  | Baseline, 24 weeks | 
| Absolute Change From Baseline in High Density Lipoproteins (HDL) at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in HDL at Week 24 |  | Baseline, 24 week | 
| Absolute Change From Baseline in Total Cholesterol at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in Total Cholesterol at Week 24 |  | Baseline, 24 Weeks | 
| Median Percent Change From Baseline in Triglycerides at Week 24 |  | Baseline, 24 weeks | 
| Absolute Change From Baseline in Triglycerides at Week 24 |  | Baseline, 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Lupus, Systemic Lupus Erythematosus, Antibodies, Autoimmune Diseases, Belimumab