A Safety and Efficacy Study of LymphoStat-B™ (Monoclonal Anti-BLyS Antibody) in Subjects With Rheumatoid Arthritis (RA)
- Conditions
- Arthritis, Rheumatoid
- Interventions
- Registration Number
- NCT00071812
- Lead Sponsor
- 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 283
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Belimumab 1 mg/kg plus SOC Belimumab 1 mg/kg - Belimumab 4 mg/kg plus SOC Belimumab 4 mg/kg - Belimumab 10 mg/kg plus SOC Belimumab 10 mg/kg - Placebo plus SOC Placebo -
- Primary Outcome Measures
Name Time Method Percentage of Patients With ACR20 (American College of Rheumatology) Response at Week 24, Based on Erythrocyte Sedimentation Rate (ESR) 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
Name Time Method Percentage of Patients With an ACR50 Response at Week 24, Based on ESR 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 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 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 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 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 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 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 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.
Trial Locations
- Locations (63)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Arizona Arthritis Research
🇺🇸Paradise Valley, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Scripps Clinic
🇺🇸LaJolla, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Wallace Rheumatic Disease Center
🇺🇸Los Angeles, California, United States
Stanford University School of Medicine
🇺🇸Palo Alto, California, United States
Boling Clinical Trials
🇺🇸Rancho Cucamonga, California, United States
UCDMC
🇺🇸Sacramento, California, United States
Scroll for more (53 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States