Safety and Efficacy Study of LymphoStat-B (Belimumab) in Subjects With Systemic Lupus Erythematosus (SLE) - Full Text View

Purpose

The purpose of this study is to evaluate the safety and efficacy of 3 different doses of belimumab, administered in addition to standard therapy, in patients with active SLE disease.

Condition	Intervention	Phase
Lupus Erythematosus, Systemic	Drug: Placebo Drug: Belimumab 1 mg/kg Drug: Belimumab 4 mg/kg Drug: Belimumab 10 mg/kg	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Tolerability, and Efficacy of LymphoStat-B™ Antibody (Monoclonal Anti-BLyS Antibody) in Subjects With Systemic Lupus Erythematosus (SLE)

Resource links provided by NLM:

MedlinePlus related topics: Lupus

Drug Information available for: Belimumab

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare.
Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) [ Time Frame: 0 to 52 weeks ] [ Designated as safety issue: No ]
The SLE Flare Index categorized SLE flare as "mild or moderate" or "severe" based on 5 variables: 1) change in SELENA SLEDAI score from the most recent assessment to current, 2) change in signs or symptoms of disease activity, 3) change in prednisone dosage, 4) use of new medications for disease activity or hospitalization, and 5) change in Physician's Global Assessment score, a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe).

Secondary Outcome Measures:

Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare
Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 [ Time Frame: Baseline and every 4 to 8 weeks through Week 52 ] [ Designated as safety issue: No ]
SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. The normalized AUC was created as the ratio of the area under the SELENA SLEDAI score curve divided by baseline score.
Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.
Area Under the Curve (AUC) of BILAG Score at Week 52 [ Time Frame: Baseline and every 4 to 8 weeks through Week 52 ] [ Designated as safety issue: No ]
The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.The normalized AUC was created as the ratio of the area under the global BILAG score curve divided by baseline score.
Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks [ Time Frame: 0 to 52 weeks ] [ Designated as safety issue: No ]
SLE flare indicates an increase in SLE disease activity. An SLE flare was a type A or B SLE flare (as defined using BILAG) compared with the previous visit.
Percentage of Patients With a Reduction in Prednisone Dose [ Time Frame: Baseline, weeks 40 to 52 ] [ Designated as safety issue: No ]
Percentage of patients whose average prednisone dose has been reduced by ≥ 50% and/or has been reduced to ≤ 7.5 mg/day during Weeks 40 through 52 in patients receiving greater than 7.5 mg/day at baseline.

Other Outcome Measures:

Adverse Events (AE) Overview [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: Yes ]
Includes AEs reported in patients from the first dose of study agent throughout the study up to the Week 76/exit visit or 8 weeks following the last dose of study agent for patients who withdrew from this study or decided not to participate in the optional continuation protocol (LBSL99/NCT00583362).

Enrollment:	449
Study Start Date:	October 2003
Study Completion Date:	June 2006
Primary Completion Date:	August 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo plus SOC	Drug: Placebo Placebo IV plus standard therapy (SOC) for SLE; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, placebo patients who opted to participate received belimumab 10 mg/kg IV plus SOC every 28 days for an additional 24 weeks.
Experimental: Belimumab 1 mg/kg plus SOC	Drug: Belimumab 1 mg/kg Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate either continued on the same dose of belimumab or may have been switched to belimumab 10 mg/kg at the investigator's discretion for an additional 24 weeks. Other Names: LymphoStat-B® BENLYSTA®
Experimental: Belimumab 4 mg/kg plus SOC	Drug: Belimumab 4 mg/kg Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 4 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate either continued on the same dose of belimumab or may have been switched to belimumab 10 mg/kg at the investigator's discretion for an additional 24 weeks. Other Names: LymphoStat-B® BENLYSTA®
Experimental: Belimumab 10 mg/kg plus SOC	Drug: Belimumab 10 mg/kg Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate continued on belimumab 10 mg/kg for an additional 24 weeks. Other Names: LymphoStat-B® BENLYSTA®

Detailed Description:

The purpose of this study is to evaluate the safety and efficacy of three different doses of belimumab (1 mg/kg, 4 mg/kg, and 10 mg/kg), administered in addition to standard therapy, compared to placebo plus standard therapy in patients with active SLE disease. Patients were randomly assigned, following stratification by the screening SELENA SLEDAI score (4 to 7 versus ≥ 8), to 1 of the 4 study arms (3 active arms and 1 placebo arm plus standard therapy for SLE). All patients were to be dosed on Days 0, 14, and 28, then every 28 days for the remainder of 52 weeks. Patients completing the 52-week period could enter a 24-week open-label extension; belimumab patients received the same dose or were switched to 10 mg/kg at the investigator's discretion and former placebo patients received belimumab 10 mg/kg.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Primary Inclusion Criteria

Clinical diagnosis of SLE
"Active" SLE disease
On a stable SLE treatment regimen
History of measurable autoantibodies

Primary Exclusion Criteria

Received a non-FDA approved investigational agent within last 28 days
Cyclosporin, intravenous immunoglobulin (IVIG) or plasmapheresis within last 90 days
Active lupus nephritis requiring hemodialysis, cyclophosphamide (Cytoxan™), or high-dose prednisone (> 100 mg/day) within last 90 days
Active central nervous system (CNS) lupus requiring therapeutic intervention within last 60 days
History of renal transplant
History of chronic infection that has been active within last 6 months, herpes zoster within last 90 days or any infection requiring hospitalization or intravenous medication within last 60 days
History of hypogammaglobulinemia or immunoglobulin A (IgA) deficiency
Human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071487

Show 62 Study Locations

Sponsors and Collaborators

Human Genome Sciences Inc., a GSK Company

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

Publications:

Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, Petri MA, Ginzler EM, Chatham WW, McCune WJ, Fernandez V, Chevrier MR, Zhong ZJ, Freimuth WW. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum. 2009 Sep 15;61(9):1168-78.

Furie RA, Petri MA, Wallace DJ, Ginzler EM, Merrill JT, Stohl W, Chatham WW, Strand V, Weinstein A, Chevrier MR, Zhong ZJ, Freimuth WW. Novel evidence-based systemic lupus erythematosus responder index. Arthritis Rheum. 2009 Sep 15;61(9):1143-51.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wallace DJ, Navarra S, Petri MA, Gallacher A, Thomas M, Furie R, Levy RA, van Vollenhoven RF, Cooper S, Zhong ZJ, Freimuth W, Cervera R; BLISS-52 and -76, and LBSL02 Study Groups. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus. 2013;22(2):144-54. doi: 10.1177/0961203312469259. Epub 2012 Dec 4.

Merrill JT, Ginzler EM, Wallace DJ, McKay JD, Lisse JR, Aranow C, Wellborne FR, Burnette M, Condemi J, Zhong ZJ, Pineda L, Klein J, Freimuth WW; LBSL02/99 Study Group. Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Arthritis Rheum. 2012 Oct;64(10):3364-73. doi: 10.1002/art.34564.

Jacobi AM, Huang W, Wang T, Freimuth W, Sanz I, Furie R, Mackay M, Aranow C, Diamond B, Davidson A. Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2010 Jan;62(1):201-10.

Responsible Party:	GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )
ClinicalTrials.gov Identifier:	NCT00071487 History of Changes
Other Study ID Numbers:	LBSL02
Study First Received:	October 24, 2003
Results First Received:	February 27, 2012
Last Updated:	October 29, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

SLE

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013