Phase 1 Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE)

Study Overview
=================
Brief Summary
-----------------
The purpose of thie study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of belimumab (LymphoStat-B™)in subjects with SLE.

Official Title
-----------------
A Phase 1, Multi-Center, Double-Blind, Single and Double Dose-Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of LymphoStat-B™ (Monoclonal Anti-BLyS Antibody) in Subjects With Systemic Lupus Erythematosus

Conditions
-----------------
Systemic Lupus Erythematosus

Intervention / Treatment
-----------------
* Biological: belimumab
* Biological: belimumab
* Biological: belimumab
* Biological: belimumab
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Clinical diagnosis of SLE by ACR criteria Stable SLE disease activity On stable SLE treatment regimen History of measurable autoantibodies Key Exclusion Criteria: Pregnant or nursing Received a non-FDA approved investigational agent within last 28 days Received cyclosporin, intravenous immunoglobulin (IVIG) or plasmapheresis within last 6 months Active lupus nephritis requiring hemodialysis, intravenous cyclophosphamide (Cytoxan™), or high-dose prednisone (> 100 mg/day) within last 6 months Active central nervous system (CNS) lupus requiring medical intervention within last 6 months History of renal transplant History of clinical evidence of an active significant acute or chronic diseases Have required management or hospitalization of any infection within last 4 weeks. History of hypogammaglobulinemia or IgA deficiency Have current drug or alcohol addiction History of or test positive at screening for HIV, Hepatitis B or Hepatitis C

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>IV infusion over 2 hours | Biological: Placebo<br>* IV (in the vein) on Day 0 (Cohorts 1-4). IV (in the vein) on Days 0 and 21 (Cohorts 5-8).<br>|
| Experimental: Belimumab 1 mg/kg<br>1 mg/kg IV infused over 2 hours | Biological: belimumab<br>* 1 mg/kg, IV (in the vein) once on Day 0, with a final evaluation at Day 84 (Cohort 1). 1 mg/kg, IV (in the vein) on Days 0 and 21, with a final evaluation at Day 105 (Cohort 5).<br>* Other names: BENLYSTA;|
| Experimental: Belimumab 4 mg/kg<br>4 mg/kg IV infused over 2 hours | Biological: belimumab<br>* 4 mg/kg, IV (in the vein) once on Day 0, with a final evaluation at Day 84 (Cohort 2). 4 mg/kg, IV (in the vein) on Days 0 and 21, with a final evaluation at Day 105 (Cohort 6).<br>* Other names: BENLYSTA;|
| Experimental: Beimumab 10 mg/kg<br>10 mg/kg IV infused over 2 hours | Biological: belimumab<br>* 10 mg/kg, IV (in the vein) once on Day 0, with a final evaluation at Day 84 (Cohort 3). 10 mg/kg, IV (in the vein) on Days 0 and 21, with a final evaluation at Day 105 (Cohort 7).<br>* Other names: BENLYSTA;|
| Experimental: Belimumab 20 mg/kg<br>20 mg/kg IV infused over 2 hours | Biological: belimumab<br>* 20 mg/kg, IV (in the vein) once on Day 0, with a final evaluation at Day 84 (Cohort 4). 20 mg/kg, IV (in the vein) on Days 0 and 21, with a final evaluation at Day 105 (Cohort 8).<br>* Other names: BENLYSTA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of belimumab in subjects with SLE. |  | Days 0-105 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of belimumab on clinical disease activity, total serum IgG (and IgM, IgA, IgE) and concentrations of peripheral mature B lymphocytes and plasmacytoid cells, and markers of SLE disease activity, including autoantibodies. |  | Days 0-105 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
lupus, SLE