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

Arthritis, Rheumatoid Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00071812
• Other study ID #: LBRA01
• Status: Completed
• Phase: Phase 2
• First received: October 31, 2003
• Last updated: August 1, 2013
• Start date: December 2003
• Est. completion date: December 2005

Study information

• Verified date: August 2013
• Source: Human Genome Sciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationPoland: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 283
• Est. completion date: December 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 (TNFa) 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:

TNFa-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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	The Center For Rheumatology	Albany	New York
United States	The University of Michigan Health System	Ann Arbor	Michigan
United States	Arthritis Clinic of Northern Virginia, P.C.	Arlington	Virginia
United States	Arthritis and Rheumatic Disease Specialties	Aventura	Florida
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Ochsner Clinic Foundation	Baton Rouge	Louisiana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Radiant Research Boise	Boise	Idaho
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	SUNY-Downstate Medical Center	Brooklyn	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Arthritis Clinic and Carolina Bone and Joint	Charlotte	North Carolina
United States	Northwestern University Medical School	Chicago	Illinois
United States	Rheumatology Associates	Chicago	Illinois
United States	Arthritis Associates & Osteoporosis Center Of Colorado Springs	Colorado Springs	Colorado
United States	Arthritis and Osteoporosis Center	Concord	New Hampshire
United States	The Osteoporosis and Arthritis Clinical Trial Center	Cumberland	Maryland
United States	Arthritis Centers of Texas	Dallas	Texas
United States	Research Associates of North Texas	Dallas	Texas
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Stat Research, Inc.	Dayton	Ohio
United States	Strafford Medical Associates, P.A.	Dover	New Hampshire
United States	Edmonds Rheumatology Associates	Edmonds	Washington
United States	Evergreen Clinical Reserach	Edmonds	Washington
United States	Rheumatic Disease Center	Glendale	Wisconsin
United States	Houston Institute for Clinical Research	Houston	Texas
United States	Institute of Arthritis and Research	Idaho Falls	Idaho
United States	Gundersen Clinic, Ltd.	La Crosse	Wisconsin
United States	Scripps Clinic	LaJolla	California
United States	Arthritis Center of Nebraska	Lincoln	Nebraska
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Wallace Rheumatic Disease Center	Los Angeles	California
United States	Kentuckiana Center for Better Bone and Joint Health	Louisville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	The Medical College of Wisconsin , Inc	Milwaukee	Wisconsin
United States	Medical Specialists	Munster	Indiana
United States	McBride Clinic	Oklahoma City	Oklahoma
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Rheumatology Associates of Central Florida	Orlando	Florida
United States	Stanford University School of Medicine	Palo Alto	California
United States	Arizona Arthritis Research	Paradise Valley	Arizona
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh School of Medicine & ASPH	Pittsburgh	Pennsylvania
United States	Boling Clinical Trials	Rancho Cucamonga	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Rockford Clinic	Rockford	Illinois
United States	UCDMC	Sacramento	California
United States	Arthritis Care Center, Inc.	San Jose	California
United States	Arthritis Northwest Rheumatology	Spokane	Washington
United States	Washington University in St. Louis	St. Louis	Missouri
United States	Texas Research Center	Sugar Land	Texas
United States	Tampa Medical Group, P.A.	Tampa	Florida
United States	University of Arizona	Tucson	Arizona
United States	Oklahoma Center For Arthritis Therapy & Research	Tulsa	Oklahoma
United States	Washington Hospital Center	Washington	District of Columbia
United States	Marshfield Medical Research Foundation	Wausau	Wisconsin
United States	Arthritis and Rheumatic Diseases Clinic	Weber	Utah
United States	Center for Rhematology and Bone Research	Wheaton	Maryland
United States	Rheumatic Disease Associates	Willow Grove	Pennsylvania
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina
United States	Rheumatology Northwest Clinical Trials	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Human Genome Sciences Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No