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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00071812
Recruitment Status : Completed
First Posted : November 5, 2003
Results First Posted : June 25, 2012
Last Update Posted : August 14, 2013
Sponsor:
Information provided by (Responsible Party):
Human Genome Sciences Inc.

Tracking Information
First Submitted Date  ICMJE October 31, 2003
First Posted Date  ICMJE November 5, 2003
Results First Submitted Date  ICMJE February 27, 2012
Results First Posted Date  ICMJE June 25, 2012
Last Update Posted Date August 14, 2013
Study Start Date  ICMJE December 2003
Actual Primary Completion Date January 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2012)
Percentage of Patients With ACR20 (American College of Rheumatology) Response at Week 24, Based on Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, 24 weeks ]
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]).
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00071812 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2012)
  • Percentage of Patients With an ACR50 Response at Week 24, Based on ESR [ Time Frame: Baseline, 24 weeks ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: October 29, 2012)
Adverse Events (AE) Overview [ Time Frame: Up to 56 weeks ]
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).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of LymphoStat-B™ (Monoclonal Anti-BLyS Antibody) in Subjects With Rheumatoid Arthritis (RA)
Official Title  ICMJE 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)
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 rheumatoid arthritis (RA).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE
  • 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.
  • 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®
  • 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®
  • 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®
Study Arms  ICMJE
  • Placebo Comparator: Placebo plus SOC
    Intervention: Drug: Placebo
  • Experimental: Belimumab 1 mg/kg plus SOC
    Intervention: Drug: Belimumab 1 mg/kg
  • Experimental: Belimumab 4 mg/kg plus SOC
    Intervention: Drug: Belimumab 4 mg/kg
  • Experimental: Belimumab 10 mg/kg plus SOC
    Intervention: Drug: Belimumab 10 mg/kg
Publications * Stohl W, Merrill JT, McKay JD, Lisse JR, Zhong ZJ, Freimuth WW, Genovese MC. Efficacy and safety of belimumab in patients with rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled, dose-ranging Study. J Rheumatol. 2013 May;40(5):579-89. doi: 10.3899/jrheum.120886. Epub 2013 Apr 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 22, 2012)
283
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2005
Actual Primary Completion Date January 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00071812
Other Study ID Numbers  ICMJE LBRA01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Human Genome Sciences Inc.
Study Sponsor  ICMJE Human Genome Sciences Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account Human Genome Sciences Inc.
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP