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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Human Genome Sciences Inc.
ClinicalTrials.gov Identifier:
NCT00071487
First received: October 24, 2003
Last updated: August 1, 2013
Last verified: August 2013
  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:


Further study details as provided by Human Genome Sciences Inc.:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 62 Study Locations
Sponsors and Collaborators
Human Genome Sciences Inc.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

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

Responsible Party: Human Genome Sciences Inc.
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: August 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Human Genome Sciences Inc.:
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 July 22, 2014