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

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)

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).

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: Placebo; Drug: Belimumab 1 mg/kg; Drug: Belimumab 4 mg/kg; Drug: Belimumab 10 mg/kg

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: Interventional
• Enrollment (Actual): 283
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / 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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With ACR20 (American College of Rheumatology) Response at Week 24, Based on Erythrocyte Sedimentation Rate (ESR)	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]).	Baseline, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With an ACR50 Response at Week 24, Based on ESR	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]).	Baseline, 24 weeks
Percentage of Patients With an ACR70 Response at Week 24, Based on ESR	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]).	Baseline, 24 weeks
Time to First ACR20 Response, Based on ESR	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.	0 to 24 weeks
Time to First ACR50 Response, Based on ESR	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.	0 to 24 weeks
Time to First ACR70 Response, Based on ESR	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.	0 to 24 weeks
Mean Change in Disease Activity Score 28 (DAS28) at Week 24	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.	Baseline, 24 weeks
Time to First DAS28 Response	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.	0 to 24 weeks
Mean Change in Modified Total Sharp Score at Week 24	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.	Baseline, 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE) Overview	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).	Up to 56 weeks

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc.

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: October 31, 2003
• First Submitted That Met QC Criteria: November 4, 2003
• First Posted (Estimate): November 5, 2003

Study Record Updates

• Last Update Posted (Estimate): August 14, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: RA
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: LBRA01