Clinical trial NCT00071487: Safety and Efficacy Study of LymphoStat-B (Belimumab) in Subjects With Systemic Lupus Erythematosus (SLE)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Keywords: SLE
Lead sponsor: Human Genome Sciences Inc.
Sponsor class: INDUSTRY
First posted: 2003-10-28
Enrollment: 449
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24.
timeFrame: Baseline, 24 weeks
measure: Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index)
timeFrame: 0 to 52 weeks
Secondary outcomes:
measure: Percentage Change From Baseline in SELENA SLEDAI Score at Week 52
timeFrame: Baseline, 52 weeks
measure: Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52
timeFrame: Baseline and every 4 to 8 weeks through Week 52
measure: Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52
timeFrame: Baseline, 52 weeks
measure: Area Under the Curve (AUC) of BILAG Score at Week 52
timeFrame: Baseline and every 4 to 8 weeks through Week 52
measure: Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks
timeFrame: 0 to 52 weeks
measure: Percentage of Patients With a Reduction in Prednisone Dose
timeFrame: Baseline, weeks 40 to 52
Other outcomes:
measure: Adverse Events (AE) Overview
timeFrame: Up to 84 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Paradise Valley
country: United States
facility: Arizona Arthritis Research
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: LaJolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Rancho Cucamonga
country: United States
facility: Boling Clinical Trials
state: California
city: Sacramento
country: United States
facility: UCDMC
state: California
city: San Jose
country: United States
facility: Arthritis Care Center, Inc.
state: California
city: Colorado Springs
country: United States
facility: Arthritis Associates & Osteoporosis Center Of Colorado Springs
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Aventura
country: United States
facility: Arthritis and Rheumatic Disease Specialties
state: Florida
city: Orlando
country: United States
facility: Rheumatology Associates of Central Florida
state: Florida
city: Tampa
country: United States
facility: Tampa Medical Group, P.A.
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boise
country: United States
facility: Radiant Research Boise
state: Idaho
city: Idaho Falls
country: United States
facility: Institute of Arthritis and Research
state: Idaho
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Chicago
country: United States
facility: Rheumatology Associates
state: Illinois
city: Munster
country: United States
facility: Medical Specialists
state: Indiana
city: Louisville
country: United States
facility: Kentuckiana Center for Better Bone and Joint Health
state: Kentucky
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Cumberland
country: United States
facility: The Osteoporosis and Arthritis Clinical Trial Center
state: Maryland
city: Wheaton
country: United States
facility: Center for Rheumatology and Bone Research
state: Maryland
city: Boston
country: United States
facility: Tufts--New England Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: The University of Michigan Health System
state: Michigan
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Lincoln
country: United States
facility: Arthritis Center of Nebraska
state: Nebraska
city: Concord
country: United States
facility: Arthritis and Osteoporosis Center
state: New Hampshire
city: Dover
country: United States
facility: Strafford Medical Associates, P.A.
state: New Hampshire
city: Albany
country: United States
facility: The Center for Rheumatology
state: New York
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Brooklyn
country: United States
facility: SUNY-Downstate Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Rochester
country: United States
facility: Aair Research
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Arthritis Clinic and Carolina Bone and Joint
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Dayton
country: United States
facility: Stat Research Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Bone and Joint Hospital
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Center For Arthritis Therapy & Research
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine & ASPH
state: Pennsylvania
city: Willow Grove
country: United States
facility: Rheumatic Disease Associates
state: Pennsylvania
city: Dallas
country: United States
facility: Research Associates of North Texas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Sugar Land
country: United States
facility: Texas Research Center
state: Texas
city: Ogden
country: United States
facility: Arthritis and Rheumatic Disease Clinic
state: Utah
city: Sandy
country: United States
facility: Physicians Research Options, LC
state: Utah
city: Arlington
country: United States
facility: Arthritis Clinic of Northern Virginia, P.C.
state: Virginia
city: Edmonds
country: United States
facility: Edmonds Rheumatology Associates
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest Rheumatology
state: Washington
city: La Crosse
country: United States
facility: Gundersen Clinic, Ltd.
state: Wisconsin
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin , Inc
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Medical Research Foundation
state: Wisconsin
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
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 patients with active systemic lupus erythematosus. Arthritis Rheum. 2009 Sep 15;61(9):1168-78. doi: 10.1002/art.24699.
citation: 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: 10.1002/art.24698.
citation: Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6.
citation: Zhou X, Lee TI, Zhu M, Ma P. Prediction of Belimumab Pharmacokinetics in Chinese Pediatric Patients with Systemic Lupus Erythematosus. Drugs R D. 2021 Dec;21(4):407-417. doi: 10.1007/s40268-021-00363-2. Epub 2021 Oct 9.
citation: Brunner HI, Abud-Mendoza C, Mori M, Pilkington CA, Syed R, Takei S, Viola DO, Furie RA, Navarra S, Zhang F, Bass DL, Eriksson G, Hammer AE, Ji BN, Okily M, Roth DA, Quasny H, Ruperto N. Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open. 2021 Sep;7(3):e001747. doi: 10.1136/rmdopen-2021-001747.
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
citation: Ginzler EM, Wallace DJ, Merrill JT, Furie RA, Stohl W, Chatham WW, Weinstein A, McKay JD, McCune WJ, Zhong ZJ, Freimuth WW, Petri MA; LBSL02/99 Study Group. Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol. 2014 Feb;41(2):300-9. doi: 10.3899/jrheum.121368. Epub 2013 Nov 1.
citation: Struemper H, Chen C, Cai W. Population pharmacokinetics of belimumab following intravenous administration in patients with systemic lupus erythematosus. J Clin Pharmacol. 2013 Jul;53(7):711-20. doi: 10.1002/jcph.104. Epub 2013 May 16.
citation: 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 Feb;22(2):144-54. doi: 10.1177/0961203312469259. Epub 2012 Dec 4.
citation: 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.
citation: 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. doi: 10.1002/art.27189.