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A Safety and Efficacy Study of LymphoStat-B™ (Monoclonal Anti-BLyS Antibody) in Subjects With Rheumatoid Arthritis (RA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )
ClinicalTrials.gov Identifier:
NCT00071812
First received: October 31, 2003
Last updated: October 29, 2012
Last verified: October 2012
History of Changes
  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 rheumatoid arthritis (RA).


Condition Intervention Phase
Arthritis, Rheumatoid
 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 Rheumatoid Arthritis (RA)

Resource links provided by NLM:

Drug Information available for: Belimumab
U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Percentage of Patients With ACR20 (American College of Rheumatology) Response at Week 24, Based on Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    An ACR20 response is defined as having at least a 20% improvement in tender and swollen joints as well as a 20% improvement in 3 of 5 other criteria (patient assessment, physician assessment, pain scale, disability/functional questionnaire, and acute phase reactant value based on erythrocyte sedimentation rate [ESR]).


Secondary Outcome Measures:
  • Percentage of Patients With an ACR50 Response at Week 24, Based on ESR [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    An ACR50 response is defined as having at least a 50% improvement in tender and swollen joints as well as a 50% improvement in 3 of 5 other criteria (patient assessment, physician assessment, pain scale, disability/functional questionnaire, and acute phase reactant value based on erythrocyte sedimentation rate [ESR]).

  • Percentage of Patients With an ACR70 Response at Week 24, Based on ESR [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    An ACR70 response is defined as having at least a 70% improvement in tender and swollen joints as well as a 70% improvement in 3 of 5 other criteria (patient assessment, physician assessment, pain scale, disability/functional questionnaire, and acute phase reactant value based on erythrocyte sedimentation rate [ESR]).

  • Time to First ACR20 Response, Based on ESR [ Time Frame: 0 to 24 weeks ] [ Designated as safety issue: No ]
    The time to first ACR20 response (based on ESR) is defined as the time from the first dose to the first visit at which a patient first exhibited an ACR20 response, which may or may not have been sustained through Week 24.

  • Time to First ACR50 Response, Based on ESR [ Time Frame: 0 to 24 weeks ] [ Designated as safety issue: No ]
    Measure not posted because time to ACR50 response was unable to be determined due to the small number of patients achieving an ACR50 response in the study.

  • Time to First ACR70 Response, Based on ESR [ Time Frame: 0 to 24 weeks ] [ Designated as safety issue: No ]
    Measure not posted because time to ACR70 response was unable to be determined due to the small number of patients achieving an ACR70 response in the study.

  • Mean Change in Disease Activity Score 28 (DAS28) at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    DAS is a composite index of a patient's level of RA disease activity. DAS28 is an abbreviated version of DAS, using a subset of 28 joints in the assessment, calculated based on 4 variables: 1) number of tender joints out of a total of 28 joints, 2) number of swollen joints out of a total of 28 joints, 3) ESR, 4) patient's global assessment of disease activity based on a 100-mm visual analog scale. The calculation provides a number on a scale from 0 to 10 (>5.1=active disease; <3.2=well controlled disease; <2.6=remission). Change from baseline >1.2 = good response and ≤0.6 = non-response.

  • Time to First DAS28 Response [ Time Frame: 0 to 24 weeks ] [ Designated as safety issue: No ]
    DAS28 response is defined as the time from the first dose to the first time at which a patient exhibited a "good" or a "moderate" improvement in RA disease activity, based on DAS28 improvements compared to baseline. Good response was defined as >1.2 change from baseline and DAS28 score ≤ 3.2. No response was defined as ≤ 0.6 change from baseline in DAS28 score or change between ≤ 1.2 and > 0.6 with a DAS28 score of > 5.1.

  • Mean Change in Modified Total Sharp Score at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    The modified total Sharp score method was used to evaluate radiographs of hands/wrists for erosions (ERO) and joint space narrowing (JSN). The total modified Sharp score ranges from 0 (no radiographic damage) to 200 (worst possible radiographic damage) and is the sum of the normalized ERO score (range 0-100) and the normalized JSN score (range 0-100). Higher scores indicated more damage.


Other Outcome Measures:
  • Adverse Events (AE) Overview [ Time Frame: Up to 56 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 48/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 (LBRA99/NCT00583557).


Enrollment: 283
Study Start Date: December 2003
Study Completion Date: December 2005
Primary Completion Date: January 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 RA; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 24 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 RA; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 24 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 RA; belimumab 4 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 24 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 RA; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 24 weeks in the double-blind period. In the open-label extension period, patients who opted to participate continued on the same dose of 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 RA. All patients were to be dosed on Days 0, 14, and 28, then every 28 days for the remainder of 24 weeks. Patients completing the 24-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:

  • Diagnosis of RA for at least 1 year
  • Failed at least 1 disease modifying anti-rheumatic drug (DMARD) due to toxicity or lack of efficacy. These drugs must include 1 or more of the following: methotrexate, parenteral gold, sulfasalazine, leflunomide, and tumor necrosis factor-alpha (TNFα) inhibitors (infliximab, etanercept or adalimumab)
  • Active RA disease of at least moderate disease activity
  • Be on a stable RA treatment regimen for at least the past 60 days (for DMARDS); if on non-steroidal anti-inflammatory drugs (NSAIDs) or steroids these must be at a stable dose for the last 30 days

Primary Exclusion Criteria:

  • Received a non-FDA approved investigational agent within the last 28 days
  • Currently receiving or received within the last 60 days the following: TNFα-inhibitors (infliximab, etanercept, adalimumab) or interleukin-1 receptor antagonist (anakinra)
  • Currently receiving or received within the last 6 months the following: anti-CD20 antibody (rituximab) or cyclophosphamide
  • Steroid injection into any joint within the last 30 days
  • History of hypogammaglobulinemia or immunoglobulin A (IgA) deficiency
  • History of chronic infection that has been active within last 6 months, or herpes zoster within last 90 days, or any infection requiring hospitalization or intravenous medication within last 60 days
  • Human immunodeficiency virus (HIV), Hepatitis-B, Hepatitis-C
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00071812

  Show 63 Study Locations
Sponsors and Collaborators
Human Genome Sciences Inc., a GSK Company
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

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

Responsible Party: GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )
ClinicalTrials.gov Identifier: NCT00071812     History of Changes
Other Study ID Numbers: LBRA01
Study First Received: October 31, 2003
Results First Received: February 27, 2012
Last Updated: October 29, 2012
Health Authority: United States: Food and Drug Administration
Poland: Ministry of Health

Keywords provided by GlaxoSmithKline:
RA

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
 Immune System Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013