Clinical trial NCT00071812: A Safety and Efficacy Study of LymphoStat-B™ (Monoclonal Anti-BLyS Antibody) in Subjects With Rheumatoid Arthritis (RA)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: RA
Lead sponsor: Human Genome Sciences Inc.
Sponsor class: INDUSTRY
First posted: 2003-11-05
Enrollment: 283
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Patients With ACR20 (American College of Rheumatology) Response at Week 24, Based on Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline, 24 weeks
Secondary outcomes:
measure: Percentage of Patients With an ACR50 Response at Week 24, Based on ESR
timeFrame: Baseline, 24 weeks
measure: Percentage of Patients With an ACR70 Response at Week 24, Based on ESR
timeFrame: Baseline, 24 weeks
measure: Time to First ACR20 Response, Based on ESR
timeFrame: 0 to 24 weeks
measure: Time to First ACR50 Response, Based on ESR
timeFrame: 0 to 24 weeks
measure: Time to First ACR70 Response, Based on ESR
timeFrame: 0 to 24 weeks
measure: Mean Change in Disease Activity Score 28 (DAS28) at Week 24
timeFrame: Baseline, 24 weeks
measure: Time to First DAS28 Response
timeFrame: 0 to 24 weeks
measure: Mean Change in Modified Total Sharp Score at Week 24
timeFrame: Baseline, 24 weeks
Other outcomes:
measure: Adverse Events (AE) Overview
timeFrame: Up to 56 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Paradise Valley
country: United States
facility: Arizona Arthritis Research
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: LaJolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Wallace Rheumatic Disease Center
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Rancho Cucamonga
country: United States
facility: Boling Clinical Trials
state: California
city: Sacramento
country: United States
facility: UCDMC
state: California
city: San Jose
country: United States
facility: Arthritis Care Center, Inc.
state: California
city: Colorado Springs
country: United States
facility: Arthritis Associates & Osteoporosis Center Of Colorado Springs
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Aventura
country: United States
facility: Arthritis and Rheumatic Disease Specialties
state: Florida
city: Orlando
country: United States
facility: Rheumatology Associates of Central Florida
state: Florida
city: Tampa
country: United States
facility: Tampa Medical Group, P.A.
state: Florida
city: Boise
country: United States
facility: Radiant Research Boise
state: Idaho
city: Idaho Falls
country: United States
facility: Institute of Arthritis and Research
state: Idaho
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Chicago
country: United States
facility: Rheumatology Associates
state: Illinois
city: Rockford
country: United States
facility: Rockford Clinic
state: Illinois
city: Munster
country: United States
facility: Medical Specialists
state: Indiana
city: Louisville
country: United States
facility: Kentuckiana Center for Better Bone and Joint Health
state: Kentucky
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Cumberland
country: United States
facility: The Osteoporosis and Arthritis Clinical Trial Center
state: Maryland
city: Wheaton
country: United States
facility: Center for Rhematology and Bone Research
state: Maryland
city: Boston
country: United States
facility: Tufts - New England Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: The University of Michigan Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Lincoln
country: United States
facility: Arthritis Center of Nebraska
state: Nebraska
city: Concord
country: United States
facility: Arthritis and Osteoporosis Center
state: New Hampshire
city: Dover
country: United States
facility: Strafford Medical Associates, P.A.
state: New Hampshire
city: Albany
country: United States
facility: The Center For Rheumatology
state: New York
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Brooklyn
country: United States
facility: SUNY-Downstate Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Arthritis Clinic and Carolina Bone and Joint
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Dayton
country: United States
facility: Stat Research, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: McBride Clinic
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Center For Arthritis Therapy & Research
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine & ASPH
state: Pennsylvania
city: Willow Grove
country: United States
facility: Rheumatic Disease Associates
state: Pennsylvania
city: Dallas
country: United States
facility: Arthritis Centers of Texas
state: Texas
city: Dallas
country: United States
facility: Research Associates of North Texas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Houston Institute for Clinical Research
state: Texas
city: Sugar Land
country: United States
facility: Texas Research Center
state: Texas
city: Weber
country: United States
facility: Arthritis and Rheumatic Diseases Clinic
state: Utah
city: Arlington
country: United States
facility: Arthritis Clinic of Northern Virginia, P.C.
state: Virginia
city: Edmonds
country: United States
facility: Edmonds Rheumatology Associates
state: Washington
city: Edmonds
country: United States
facility: Evergreen Clinical Reserach
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest Rheumatology
state: Washington
city: Yakima
country: United States
facility: Rheumatology Northwest Clinical Trials
state: Washington
city: Glendale
country: United States
facility: Rheumatic Disease Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Clinic, Ltd.
state: Wisconsin
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin , Inc
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Medical Research Foundation
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.