A Continuation Trial for Subjects With Systemic Lupus Erythematosus That Have Completed Protocol LBSL02

Study Overview
=================
Brief Summary
-----------------
This is a continuation study to evaluate the long-term safety and efficacy of LymphoStat-B™ in subjects with SLE disease, that completed study LBSL02 and benefitted from treatment.

Detailed Description
-----------------
The purpose of this continuation study to evaluate the long-term safety and efficacy of LymphoStat-B™ in subjects with Systemic Lupus Erythematosus (SLE), that completed study LBSL02 and benefitted from treatment.

Official Title
-----------------
A Multi-Center, Open-Label, Continuation Trial LymphoStat-B™ Antibody (Monoclonal Anti-BLyS Antibody) in Subjects With Systemic Lupus Erythematosus (SLE) Who Completed the Phase 2 Protocol LBSL02

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

Intervention / Treatment
-----------------
* Biological: Belimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Primary Inclusion Criteria 1. Have completed the LBSL02 trial and achieved a satisfactory response. Primary Exclusion Criteria Required more than 2 courses of corticosteroids for treatment of severe SLE flares in the last 5 months of LBSL02. Had an SLE flare during the last 30 days of LBSL02 and through the 1st dose in LBSL99. Used any of the following prohibited medications during their participation in LBSL02: Other investigational agents. Biologic therapeutic agents: adalimumab (Humira™), etanercept (Enbrel™), infliximab (Remicade™), and rituximab (Rituxan™). Intravenous cyclophosphamide. Corticosteroids >100 mg/day prednisone equivalent for reasons other than severe SLE flare.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belimumab 10 mg/kg<br>Belimumab 10 mg/kg IV over one hour every 28 days. | Biological: Belimumab<br>* Belimumab 10mg/kg IV over one hour every 28 days<br>* Other names: BENLYSTA;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With the Indicated Type of Adverse Event (AEs) and Serious Adverse Event (SAEs) | An AE is defined as any unfavorable or unintended sign, symptom, or disease that is temporally associated with the use of a study agent but is not necessarily caused by the study agent. This includes worsening (example [eg], increase in frequency or severity) of pre-existing conditions. An SAE is defined as an AE resulting in any of the following outcomes: death, is life threatening (that is, an immediate threat to life), inpatient hospitalization, prolongation of an existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, and is medically important. | Approximately up to 13 years | 
| Adverse Event (AE) Rates by System Organ Class (SOC) During the Study | AE rates by SOC adjusting for participant-years on study drug anytime post Baseline are summarized, which included the follow up visits. Only treatmentemergent AEs are summarized. The Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. The event rate of an AE was calculated as the number of events per 100 participant years: Event Rate=100* number of events divided by participant years. Participant years were calculated as sum across all participants ([last visit of interval day minus first visit of interval day plus 1] divided by 365). | Approximately up to 13 years | 
| SAE Rates by System Organ Class (SOC) During the Study | SAE rates by SOC adjusting for participant-years on study drug anytime post Baseline are summarized, which included the follow up visits. Only treatmentemergent SAEs are summarized. The Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pretreatment value in the parent study for participants treated with belimumab in the parent study. The event rate of an SAE was calculated as the number of events per 100 participant years: Event Rate=100* number of events divided by participant years. Participant years were calculated as sum across all participants ([last visit of interval day minus first visit of interval day plus 1] divided by 365). | Approximately up to 13 years | 
| Change From Baseline in Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT) at the Indicated Time Points | Hematology parameters were assessed at Baseline, Week 8, 16, 24, 40, and 48 during Year 1 to 8; Week 8, 16, 24, and 40 during Year 9; Week 24 and 40 during Year 10; Week 48 during Year 11; Week 32 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in APTT and PT is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils Segmented and Platelets at the Indicated Time Points | Hematology parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils segmented and platelets is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Erythrocytes at the Indicated Time Points | Hematology parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in erythrocytes is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Hematocrit at the Indicated Time Points | Hematology parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in hematocrit is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Hemoglobin at the Indicated Time Points | Hematology parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in hemoglobin is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Albumin and Protein at the Indicated Time Points | Clinical chemistry parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in albumin and protein is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Blood Urea Nitrogen (BUN), Glucose, Calcium, Carbon Dioxide, Chloride, Magnesium, Phosphate, Potassium and Sodium at the Indicated Time Points | Clinical chemistry parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in BUN, glucose, calcium, carbon dioxide, chloride, magnesium, phosphate, potassium and sodium is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Creatinine, Urate and Bilirubin at the Indicated Time Points | Clinical chemistry parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in creatinine, urate, and bilirubin is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post- Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in BUN/Creatinine at the Indicated Time Points | Clinical chemistry parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in BUN/creatinine is summarized. The Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LD) at the Indicated Time Points | Clinical chemistry parameters were assessed at Baseline, Week 8, 16, 24, 32, 40 and 48 during Year 1 to 12; Week 8, 16, 24, 32, and 40 during Year 13; Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Change from Baseline in ALT, AP, AST, GGT and LD are summarized. Baseline is defined as the Extension Year 1 Day 0 values for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SLE Responder Index (SRI) Response at Indicated Time Points | SRI response was assessed at Week 16, 32, and 48 during Year 1 to 12 and Week 16 and 32 during Year 13. Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. SRI response is defined as:>=4 point reduction from the Baseline in safety of estrogen in lupus national assessment (SELENA) SLE disease activity index (SLEDAI) score and no worsening (increase of <0.30 points from the Baseline) in Physician's Global Assessment (PGA), and no new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with the Baseline at the time of assessment. | Approximately up to 13 years | 
| Observed Anti-double Stranded DNA Levels in Participants Positive at Baseline at Indicated Time Points | Anti-double stranded DNA levels in participants positive at Baseline were assessed at Baseline, Week 16, 32, and 48 during Year 1 to 11, Week 16 and 32 during Year 13, Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). The Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. For Year 1, Baseline included Extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with belimumab in the parent study. | Approximately up to 13 years | 
| Median Percent Change From Baseline in Anti-double Stranded DNA in Participants Positive at Baseline at Indicated Time Points | Anti-double stranded DNA levels for participants positive at Baseline were assessed at Baseline, Week 16, 32, and 48 during Year 1 to 11, Week 16 and 32 during Year 13, Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). The Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. For Year 1, Baseline included Extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with belimumab in the parent study. Percent change from Baseline is defined as the percentage of the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Observed Complement C3 and C4 Levels in Participants Low at Baseline at Indicated Time Points | Complement C3 and C4 levels were assessed in participants low at Baseline at Baseline, Week 16, 32, and 48 during Year 1 to 12, Week 16 and 32 during Year 13, and Exit visit. The Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. For Year 1, Baseline included Extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with belimumab in the parent study. | Approximately up to 13 years | 
| Median Percent Change From Baseline in Complement C3 and C4 Levels in Participants Low at Baseline at Indicated Time Points | Complement C3 and C4 levels were assessed in participants low at Baseline at Baseline, Week 16, 32, and 48 during Year 1 to 12, Week 16 and 32 during Year 13, and Exit visit. The Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. For Year 1, Baseline included Extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with belimumab in the parent study. Percent change from Baseline is defined as the percentage of the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 
| Percentage of Participants With Daily Prednisone Dose Reduction at Indicated Time Points | Daily prednisone dose reduction was assessed at Baseline, Week 8, 16, 24, 32, 40, and 48 during Year 1 to 12 and Week 8, 16, 24, 32, and 40 during Year 13. Percentage of participants with daily prednisone dose reduced to <=7.5 mg/day from >7.5 mg/kg at the Baseline are summarized. Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. | Approximately up to 13 years | 
| Absolute Serum Immunoglobulin G Values at Indicated Time Points | Serum immunoglobulin G values were assessed at Baseline, Week 8, 16, 24, 32, 40, and 48 during Year 1 to 12 and Week 8, 16, 24, 32, and 40 during Year 13, Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. For Year 1, Baseline included Extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with belimumab in the parent study. | Approximately up to 13 years | 
| Median Percent Change From Baseline in Immunoglobulin G at Indicated Time Points | Serum immunoglobulin G values were assessed at Baseline, Week 8, 16, 24, 32, 40, and 48 during Year 1 to 12 and Week 8, 16, 24, 32, and 40 during Year 13, Exit visit and at follow-up (up to 8 weeks and 24 weeks post last infusion). Baseline is defined as the last available value prior to belimumab start date, for participants treated with placebo in the parent study and last pre-treatment value in the parent study for participants treated with belimumab in the parent study. For Year 1, Baseline included Extension Year 1 Day 0 values for MITT participants treated with placebo in the parent study, and the last pre-treatment value in the parent study for MITT participants treated with belimumab in the parent study. Percent change from Baseline is defined as the percentage of the difference between the post-dose post-Baseline visit value and the Baseline value. | Baseline and approximately up to 13 years | 

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