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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.

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).

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Placebo Drug: Belimumab 1 mg/kg Drug: Belimumab 4 mg/kg Drug: Belimumab 10 mg/kg Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 283 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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)
Study Start Date : December 2003
Actual Primary Completion Date : January 2005
Actual Study Completion Date : December 2005

Resource links provided by the National Library of Medicine

Drug Information available for: Belimumab

Arm Intervention/treatment
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®




Primary Outcome Measures :
  1. 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]).


Secondary Outcome Measures :
  1. 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]).

  2. 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]).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.


Other Outcome Measures:
  1. 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).



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00071812


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Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-0006
United States, Arizona
Arizona Arthritis Research
Paradise Valley, Arizona, United States, 85253
University of Arizona
Tucson, Arizona, United States, 85724
United States, California
Scripps Clinic
LaJolla, California, United States, 92037
University of Southern California
Los Angeles, California, United States, 90033
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Wallace Rheumatic Disease Center
Los Angeles, California, United States, 90048
Stanford University School of Medicine
Palo Alto, California, United States, 94304
Boling Clinical Trials
Rancho Cucamonga, California, United States, 91730
UCDMC
Sacramento, California, United States, 95817-1418
Arthritis Care Center, Inc.
San Jose, California, United States, 95126-1650
United States, Colorado
Arthritis Associates & Osteoporosis Center Of Colorado Springs
Colorado Springs, Colorado, United States, 80910
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
Arthritis and Rheumatic Disease Specialties
Aventura, Florida, United States, 33180
Rheumatology Associates of Central Florida
Orlando, Florida, United States, 32806
Tampa Medical Group, P.A.
Tampa, Florida, United States, 33614
United States, Idaho
Radiant Research Boise
Boise, Idaho, United States, 83704
Institute of Arthritis and Research
Idaho Falls, Idaho, United States, 83404
United States, Illinois
Northwestern University Medical School
Chicago, Illinois, United States, 60611
Rheumatology Associates
Chicago, Illinois, United States, 60612
Rockford Clinic
Rockford, Illinois, United States, 61103
United States, Indiana
Medical Specialists
Munster, Indiana, United States, 46321
United States, Kentucky
Kentuckiana Center for Better Bone and Joint Health
Louisville, Kentucky, United States, 40202
United States, Louisiana
Ochsner Clinic Foundation
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
The Osteoporosis and Arthritis Clinical Trial Center
Cumberland, Maryland, United States, 21502
Center for Rhematology and Bone Research
Wheaton, Maryland, United States, 20902
United States, Massachusetts
Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
The University of Michigan Health System
Ann Arbor, Michigan, United States, 48109-0358
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University in St. Louis
St. Louis, Missouri, United States, 63110
United States, Nebraska
Arthritis Center of Nebraska
Lincoln, Nebraska, United States, 68506
United States, New Hampshire
Arthritis and Osteoporosis Center
Concord, New Hampshire, United States, 03301
Strafford Medical Associates, P.A.
Dover, New Hampshire, United States, 03820
United States, New York
The Center For Rheumatology
Albany, New York, United States, 12206
Jacobi Medical Center
Bronx, New York, United States, 10461
SUNY-Downstate Medical Center
Brooklyn, New York, United States, 11203
North Shore University Hospital
Manhasset, New York, United States, 11030
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7280
Arthritis Clinic and Carolina Bone and Joint
Charlotte, North Carolina, United States, 28210
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Stat Research, Inc.
Dayton, Ohio, United States, 45402
United States, Oklahoma
McBride Clinic
Oklahoma City, Oklahoma, United States, 73101
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
Oklahoma Center For Arthritis Therapy & Research
Tulsa, Oklahoma, United States, 74114
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh School of Medicine & ASPH
Pittsburgh, Pennsylvania, United States, 15261
Rheumatic Disease Associates
Willow Grove, Pennsylvania, United States, 19090
United States, Texas
Arthritis Centers of Texas
Dallas, Texas, United States, 75246
Research Associates of North Texas
Dallas, Texas, United States, 75246
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-8884
Houston Institute for Clinical Research
Houston, Texas, United States, 77074
Texas Research Center
Sugar Land, Texas, United States, 77479
United States, Utah
Arthritis and Rheumatic Diseases Clinic
Weber, Utah, United States, 84403
United States, Virginia
Arthritis Clinic of Northern Virginia, P.C.
Arlington, Virginia, United States, 22205
United States, Washington
Edmonds Rheumatology Associates
Edmonds, Washington, United States, 98026-8047
Evergreen Clinical Reserach
Edmonds, Washington, United States, 98026-8047
Arthritis Northwest Rheumatology
Spokane, Washington, United States, 99204
Rheumatology Northwest Clinical Trials
Yakima, Washington, United States, 98902
United States, Wisconsin
Rheumatic Disease Center
Glendale, Wisconsin, United States, 53217
Gundersen Clinic, Ltd.
La Crosse, Wisconsin, United States, 54610
The Medical College of Wisconsin , Inc
Milwaukee, Wisconsin, United States, 53226
Marshfield Medical Research Foundation
Wausau, Wisconsin, United States, 54401
Sponsors and Collaborators
Human Genome Sciences Inc.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Human Genome Sciences Inc.
ClinicalTrials.gov Identifier: NCT00071812     History of Changes
Other Study ID Numbers: LBRA01
First Posted: November 5, 2003    Key Record Dates
Results First Posted: June 25, 2012
Last Update Posted: August 14, 2013
Last Verified: August 2013
Keywords provided by Human Genome Sciences Inc.:
RA
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies
Belimumab
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents