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

Lupus Erythematosus, Systemic Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00071487
• Other study ID #: LBSL02
• Status: Completed
• Phase: Phase 2
• First received: October 24, 2003
• Last updated: August 1, 2013
• Start date: October 2003
• Est. completion date: June 2006

Study information

• Verified date: August 2013
• Source: Human Genome Sciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 449
• Est. completion date: June 2006
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Canada	McGill University Health Center	Montreal	Quebec
Canada	Toronto Western Hospital	Toronto	Ontario
United States	The Center for Rheumatology	Albany	New York
United States	The University of Michigan Health System	Ann Arbor	Michigan
United States	Arthritis Clinic of Northern Virginia, P.C.	Arlington	Virginia
United States	Emory University	Atlanta	Georgia
United States	Arthritis and Rheumatic Disease Specialties	Aventura	Florida
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Ochsner Clinic Foundation	Baton Rouge	Louisiana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Radiant Research Boise	Boise	Idaho
United States	Tufts--New England Medical Center	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	SUNY-Downstate Medical Center	Brooklyn	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Arthritis Clinic and Carolina Bone and Joint	Charlotte	North Carolina
United States	Northwestern University Medical School	Chicago	Illinois
United States	Rheumatology Associates	Chicago	Illinois
United States	Arthritis Associates & Osteoporosis Center Of Colorado Springs	Colorado Springs	Colorado
United States	Arthritis and Osteoporosis Center	Concord	New Hampshire
United States	The Osteoporosis and Arthritis Clinical Trial Center	Cumberland	Maryland
United States	Research Associates of North Texas	Dallas	Texas
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Stat Research Inc.	Dayton	Ohio
United States	Strafford Medical Associates, P.A.	Dover	New Hampshire
United States	Edmonds Rheumatology Associates	Edmonds	Washington
United States	Institute of Arthritis and Research	Idaho Falls	Idaho
United States	Gundersen Clinic, Ltd.	La Crosse	Wisconsin
United States	Scripps Clinic	LaJolla	California
United States	Arthritis Center of Nebraska	Lincoln	Nebraska
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Kentuckiana Center for Better Bone and Joint Health	Louisville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	The Medical College of Wisconsin , Inc	Milwaukee	Wisconsin
United States	Medical Specialists	Munster	Indiana
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Arthritis and Rheumatic Disease Clinic	Ogden	Utah
United States	Bone and Joint Hospital	Oklahoma City	Oklahoma
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Rheumatology Associates of Central Florida	Orlando	Florida
United States	Stanford University School of Medicine	Palo Alto	California
United States	Arizona Arthritis Research	Paradise Valley	Arizona
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh School of Medicine & ASPH	Pittsburgh	Pennsylvania
United States	Boling Clinical Trials	Rancho Cucamonga	California
United States	Aair Research	Rochester	New York
United States	UCDMC	Sacramento	California
United States	Arthritis Care Center, Inc.	San Jose	California
United States	Physicians Research Options, LC	Sandy	Utah
United States	Arthritis Northwest Rheumatology	Spokane	Washington
United States	Washington University in St. Louis	St. Louis	Missouri
United States	Texas Research Center	Sugar Land	Texas
United States	Tampa Medical Group, P.A.	Tampa	Florida
United States	University of Arizona	Tucson	Arizona
United States	Oklahoma Center For Arthritis Therapy & Research	Tulsa	Oklahoma
United States	Washington Hospital Center	Washington	District of Columbia
United States	Marshfield Medical Research Foundation	Wausau	Wisconsin
United States	Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Rheumatic Disease Associates	Willow Grove	Pennsylvania
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Human Genome Sciences Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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. doi: 10. — View Citation

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 patie — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events (AE) Overview	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).	Up to 84 weeks	Yes
Primary	Percentage Change From Baseline in Safety of Estrogens 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	No
Primary	Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index)	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).	0 to 52 weeks	No
Secondary	Percentage Change From Baseline in SELENA SLEDAI Score at Week 52	SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare	Baseline, 52 weeks	No
Secondary	Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52	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.	Baseline and every 4 to 8 weeks through Week 52	No
Secondary	Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52	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.	Baseline, 52 weeks	No
Secondary	Area Under the Curve (AUC) of BILAG Score at Week 52	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.	Baseline and every 4 to 8 weeks through Week 52	No
Secondary	Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks	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.	0 to 52 weeks	No
Secondary	Percentage of Patients With a Reduction in Prednisone Dose	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.	Baseline, weeks 40 to 52	No