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

NCT00071487 | Completed Phase 2 Results DMC

• 1 other identifier: LBSL02
• Study Type: interventional
• Target: 449
• Locations: 2 countries
• Sites: 62

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.

Conditions

Lupus Erythematosus, Systemic

Keywords

SLE

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (6)

• Percentage Change From Baseline in SELENA SLEDAI Score at Week 52

  Baseline, 52 weeks

• Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52

  Baseline and every 4 to 8 weeks through Week 52

• Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52

  Baseline, 52 weeks

• Area Under the Curve (AUC) of BILAG Score at Week 52

  Baseline and every 4 to 8 weeks through Week 52

• Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks

  0 to 52 weeks

Other Outcomes (1)

• Adverse Events (AE) Overview

  Up to 84 weeks

Study Arms (4)

Placebo plus SOC

PLACEBO COMPARATOR

Drug: Placebo

Belimumab 1 mg/kg plus SOC

EXPERIMENTAL

Drug: Belimumab 1 mg/kg

Belimumab 4 mg/kg plus SOC

EXPERIMENTAL

Drug: Belimumab 4 mg/kg

Belimumab 10 mg/kg plus SOC

EXPERIMENTAL

Drug: Belimumab 10 mg/kg

Interventions

Placebo DRUG

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.

Placebo plus SOC

Belimumab 1 mg/kg DRUG

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.

Also known as: LymphoStat-B®, BENLYSTA®

Belimumab 1 mg/kg plus SOC

Belimumab 4 mg/kg DRUG

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.

Also known as: LymphoStat-B®, BENLYSTA®

Belimumab 4 mg/kg plus SOC

Belimumab 10 mg/kg DRUG

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.

Also known as: LymphoStat-B®, BENLYSTA®

Belimumab 10 mg/kg plus SOC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Human Genome Sciences Inc.: lead

Study Sites (62)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-0006, United States

Location

Arizona Arthritis Research

Paradise Valley, Arizona, 85253, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

Boling Clinical Trials

Rancho Cucamonga, California, 91730, United States

Location

UCDMC

Sacramento, California, 95817-1418, United States

Location

Arthritis Care Center, Inc.

San Jose, California, 95126-1650, United States

Location

Arthritis Associates & Osteoporosis Center Of Colorado Springs

Colorado Springs, Colorado, 80910, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Arthritis and Rheumatic Disease Specialties

Aventura, Florida, 33180, United States

Location

Rheumatology Associates of Central Florida

Orlando, Florida, 32806, United States

Location

Tampa Medical Group, P.A.

Tampa, Florida, 33614, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Radiant Research Boise

Boise, Idaho, 83704, United States

Location

Institute of Arthritis and Research

Idaho Falls, Idaho, 83404, United States

Location

Northwestern University Medical School

Chicago, Illinois, 60611, United States

Location

Rheumatology Associates

Chicago, Illinois, 60612, United States

Location

Medical Specialists

Munster, Indiana, 46321, United States

Location

Kentuckiana Center for Better Bone and Joint Health

Louisville, Kentucky, 40202, United States

Location

Ochsner Clinic Foundation

Baton Rouge, Louisiana, 70809, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

The Osteoporosis and Arthritis Clinical Trial Center

Cumberland, Maryland, 21502, United States

Location

Center for Rheumatology and Bone Research

Wheaton, Maryland, 20902, United States

Location

Tufts--New England Medical Center

Boston, Massachusetts, 02111, United States

Location

The University of Michigan Health System

Ann Arbor, Michigan, 48109-0358, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Arthritis Center of Nebraska

Lincoln, Nebraska, 68506, United States

Location

Arthritis and Osteoporosis Center

Concord, New Hampshire, 03301, United States

Location

Strafford Medical Associates, P.A.

Dover, New Hampshire, 03820, United States

Location

The Center for Rheumatology

Albany, New York, 12206, United States

Location

SUNY-Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Aair Research

Rochester, New York, 14618, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7280, United States

Location

Arthritis Clinic and Carolina Bone and Joint

Charlotte, North Carolina, 28210, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Stat Research Inc.

Dayton, Ohio, 45402, United States

Location

Bone and Joint Hospital

Oklahoma City, Oklahoma, 73103, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Center For Arthritis Therapy & Research

Tulsa, Oklahoma, 74114, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh School of Medicine & ASPH

Pittsburgh, Pennsylvania, 15261, United States

Location

Rheumatic Disease Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Research Associates of North Texas

Dallas, Texas, 75246, United States

Location

UT Southwestern Medical Center at Dallas

Dallas, Texas, 75390-8884, United States

Location

Texas Research Center

Sugar Land, Texas, 77479, United States

Location

Arthritis and Rheumatic Disease Clinic

Ogden, Utah, 84044, United States

Location

Physicians Research Options, LC

Sandy City, Utah, 84070, United States

Location

Arthritis Clinic of Northern Virginia, P.C.

Arlington, Virginia, 22205, United States

Location

Edmonds Rheumatology Associates

Edmonds, Washington, 98026-8047, United States

Location

Arthritis Northwest Rheumatology

Spokane, Washington, 99204, United States

Location

Gundersen Clinic, Ltd.

La Crosse, Wisconsin, 54610, United States

Location

The Medical College of Wisconsin , Inc

Milwaukee, Wisconsin, 53226, United States

Location

Marshfield Medical Research Foundation

Wausau, Wisconsin, 54401, United States

Location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

McGill University Health Center

Montreal, Quebec, H3G 1A4, Canada

Location

Related Publications (12)

• 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.

  PMID: 19714604 RESULT

• 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.

  PMID: 19714615 RESULT

• Arends EJ, Zlei M, Tipton CM, Cotic J, Osmani Z, de Bie FJ, Kamerling SWA, van Maurik A, Dimelow R, Gregan YI, Fox NL, Rabelink TJ, Roth DA, Sanz I, van Dongen JJM, van Kooten C, Teng YKO. Disruption of memory B-cell trafficking by belimumab in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2024 Sep 1;63(9):2387-2398. doi: 10.1093/rheumatology/keae286.

  PMID: 38775637 DERIVED

• 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.

  PMID: 34741731 DERIVED

• 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.

  PMID: 34628605 DERIVED

• 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.

  PMID: 34531304 DERIVED

• 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.

  PMID: 33687069 DERIVED

• 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.

  PMID: 24187095 DERIVED

• 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.

  PMID: 23681782 DERIVED

• 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.

  PMID: 23213069 DERIVED

• 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.

  PMID: 22674457 DERIVED

• 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.

  PMID: 20039404 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2003
• First Posted: October 28, 2003
• Study Start: October 1, 2003
• Primary Completion: August 1, 2005
• Study Completion: June 1, 2006
• Last Updated: August 7, 2013
• Results First Posted: August 28, 2012

Record last verified: 2013-08

Locations

CA (2); US (60)