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

• Sponsor: Human Genome Sciences Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00071812
• Collaborator: (none)
• Enrollment: 283
• Locations: 63
• Arms: 4
• Duration (Months): 24
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Dec 1, 2003
• Actual Primary Completion Date: Jan 1, 2005
• Actual Study Completion Date: Dec 1, 2005

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]).

2. 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]).

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Other Outcome Measures

1. Adverse Events (AE) Overview [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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-0006
2	Arizona Arthritis Research	Paradise Valley	Arizona	United States	85253
3	University of Arizona	Tucson	Arizona	United States	85724
4	Scripps Clinic	LaJolla	California	United States	92037
5	University of Southern California	Los Angeles	California	United States	90033
6	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
7	Wallace Rheumatic Disease Center	Los Angeles	California	United States	90048
8	Stanford University School of Medicine	Palo Alto	California	United States	94304
9	Boling Clinical Trials	Rancho Cucamonga	California	United States	91730
10	UCDMC	Sacramento	California	United States	95817-1418
11	Arthritis Care Center, Inc.	San Jose	California	United States	95126-1650
12	Arthritis Associates & Osteoporosis Center Of Colorado Springs	Colorado Springs	Colorado	United States	80910
13	Washington Hospital Center	Washington	District of Columbia	United States	20010
14	Arthritis and Rheumatic Disease Specialties	Aventura	Florida	United States	33180
15	Rheumatology Associates of Central Florida	Orlando	Florida	United States	32806
16	Tampa Medical Group, P.A.	Tampa	Florida	United States	33614
17	Radiant Research Boise	Boise	Idaho	United States	83704
18	Institute of Arthritis and Research	Idaho Falls	Idaho	United States	83404
19	Northwestern University Medical School	Chicago	Illinois	United States	60611
20	Rheumatology Associates	Chicago	Illinois	United States	60612
21	Rockford Clinic	Rockford	Illinois	United States	61103
22	Medical Specialists	Munster	Indiana	United States	46321
23	Kentuckiana Center for Better Bone and Joint Health	Louisville	Kentucky	United States	40202
24	Ochsner Clinic Foundation	Baton Rouge	Louisiana	United States	70809
25	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
26	The Osteoporosis and Arthritis Clinical Trial Center	Cumberland	Maryland	United States	21502
27	Center for Rhematology and Bone Research	Wheaton	Maryland	United States	20902
28	Tufts - New England Medical Center	Boston	Massachusetts	United States	02111
29	The University of Michigan Health System	Ann Arbor	Michigan	United States	48109-0358
30	Mayo Clinic	Rochester	Minnesota	United States	55905
31	Washington University in St. Louis	St. Louis	Missouri	United States	63110
32	Arthritis Center of Nebraska	Lincoln	Nebraska	United States	68506
33	Arthritis and Osteoporosis Center	Concord	New Hampshire	United States	03301
34	Strafford Medical Associates, P.A.	Dover	New Hampshire	United States	03820
35	The Center For Rheumatology	Albany	New York	United States	12206
36	Jacobi Medical Center	Bronx	New York	United States	10461
37	SUNY-Downstate Medical Center	Brooklyn	New York	United States	11203
38	North Shore University Hospital	Manhasset	New York	United States	11030
39	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7280
40	Arthritis Clinic and Carolina Bone and Joint	Charlotte	North Carolina	United States	28210
41	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157
42	Stat Research, Inc.	Dayton	Ohio	United States	45402
43	McBride Clinic	Oklahoma City	Oklahoma	United States	73101
44	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
45	Oklahoma Center For Arthritis Therapy & Research	Tulsa	Oklahoma	United States	74114
46	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
47	University of Pittsburgh School of Medicine & ASPH	Pittsburgh	Pennsylvania	United States	15261
48	Rheumatic Disease Associates	Willow Grove	Pennsylvania	United States	19090
49	Arthritis Centers of Texas	Dallas	Texas	United States	75246
50	Research Associates of North Texas	Dallas	Texas	United States	75246
51	UT Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390-8884
52	Houston Institute for Clinical Research	Houston	Texas	United States	77074
53	Texas Research Center	Sugar Land	Texas	United States	77479
54	Arthritis and Rheumatic Diseases Clinic	Weber	Utah	United States	84403
55	Arthritis Clinic of Northern Virginia, P.C.	Arlington	Virginia	United States	22205
56	Edmonds Rheumatology Associates	Edmonds	Washington	United States	98026-8047
57	Evergreen Clinical Reserach	Edmonds	Washington	United States	98026-8047
58	Arthritis Northwest Rheumatology	Spokane	Washington	United States	99204
59	Rheumatology Northwest Clinical Trials	Yakima	Washington	United States	98902
60	Rheumatic Disease Center	Glendale	Wisconsin	United States	53217
61	Gundersen Clinic, Ltd.	La Crosse	Wisconsin	United States	54610
62	The Medical College of Wisconsin , Inc	Milwaukee	Wisconsin	United States	53226
63	Marshfield Medical Research Foundation	Wausau	Wisconsin	United States	54401

Sponsors and Collaborators

• Human Genome Sciences Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Human Genome Sciences Inc.
• ClinicalTrials.gov Identifier: NCT00071812
• Other Study ID Numbers: LBRA01
• First Posted: Nov 5, 2003
• Last Update Posted: Aug 14, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Human Genome Sciences Inc.: RA
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Belimumab

Study Results

Participant Flow

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study. The 24-week open-label extension period of the study included patients who completed the 24-week double-blind period and opted to continue to receive the same dose in the 24-week open-label extension period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study. The 24-week open-label extension period of the study included patients who completed the 24-week double-blind period and opted to continue to receive the same dose in the 24-week open-label extension period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study. The 24 week-open label extension period of the study included patients who completed the 24-week double-blind period and opted to continue in the 24-week open-label period of the study and included patients who were originally randomized to the belimumab 10 mg/kg group in the double-blind period, patients who switched to belimumab 10 mg/kg at the investigator's discretion, and former placebo patients.
Period Title: 24-Week Double-Blind Period
STARTED	69	72	71	71
COMPLETED	59	66	63	60
NOT COMPLETED	10	6	8	11
Period Title: 24-Week Double-Blind Period
STARTED	0	11	8	218
COMPLETED	0	11	7	178
NOT COMPLETED	0	0	1	40

Baseline Characteristics

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC	Total
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Total of all reporting groups
Overall Participants	69	72	71	71	283
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.7 (8.8)	50.6 (8.3)	50.7 (10.2)	49.5 (9.3)	50.4 (9.1)
Sex: Female, Male (Count of Participants)
Female	56 81.2%	56 77.8%	60 84.5%	54 76.1%	226 79.9%
Male	13 18.8%	16 22.2%	11 15.5%	17 23.9%	57 20.1%
Region of Enrollment (participants) [Number]
United States	55 79.7%	61 84.7%	59 83.1%	59 83.1%	234 82.7%
Poland	14 20.3%	11 15.3%	12 16.9%	12 16.9%	49 17.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on a modified intention-to-treat (MITT) population, defined as all patients who were randomized and received at least 1 dose of study agent.

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Measure Participants	69	72	71	71
Number [percentage of participants]	15.9 23%	34.7 48.2%	25.4 35.8%	28.2 39.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0097
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	18.8
	Confidence Interval	(2-Sided) 95%; 4.8 to 32.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1677
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	9.4
	Confidence Interval	(2-Sided) 95%; -3.9 to 22.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0796
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	12.2
	Confidence Interval	(2-Sided) 95%; -1.3 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Patients With an ACR50 Response at Week 24, Based on ESR
Description	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]).
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Measure Participants	69	72	71	71
Number [percentage of participants]	4.3 6.2%	9.7 13.5%	8.5 12%	14.1 19.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2074
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 95%; -3.0 to 13.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3177
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	4.1
	Confidence Interval	(2-Sided) 95%; -4.0 to 12.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0418
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	9.7
	Confidence Interval	(2-Sided) 95%; 0.3 to 19.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Patients With an ACR70 Response at Week 24, Based on ESR
Description	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 Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Measure Participants	69	72	71	71
Number [percentage of participants]	2.9 4.2%	5.6 7.8%	1.4 2%	2.8 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4299
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; -4.0 to 9.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5393
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -6.3 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9769
	Comments	P-value was not adjusted for multiple testing.
	Method	Likelihood ratio chi-squared
	Comments
Method of Estimation	Estimation Parameter	percent difference from placebo
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -5.6 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to First ACR20 Response, Based on ESR
Description	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 Frame	0 to 24 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Measure Participants	69	72	71	71
Median (Inter-Quartile Range) [days]	112	109	112	111

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have any ACR response were censored at the last visit or exit visit, whichever occurred first. Patients who did not have an ACR response and discontinued from the study prior to study completion were censored at the last date on study.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1752
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have any ACR response were censored at the last visit or exit visit, whichever occurred first. Patients who did not have an ACR response and discontinued from the study prior to study completion were censored at the last date on study.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3440
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have any ACR response were censored at the last visit or exit visit, whichever occurred first. Patients who did not have an ACR response and discontinued from the study prior to study completion were censored at the last date on study.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4308
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Time to First ACR50 Response, Based on ESR
Description	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 Frame	0 to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Time to First ACR70 Response, Based on ESR
Description	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.
Time Frame	0 to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Mean Change in Disease Activity Score 28 (DAS28) at Week 24
Description	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 Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent and who had both a baseline and a Week 24 DAS28 score.

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Measure Participants	69	72	71	70
Mean (Standard Error) [scores on a scale]	-0.9 (0.15)	-1.3 (0.18)	-0.9 (0.14)	-1.5 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Missing data was handled by using last observation carried forward (LOCF) imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0958
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Missing data was handled by using LOCF imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7864
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
	Comments	Missing data was handled by using LOCF imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0051
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Time to First DAS28 Response
Description	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.
Time Frame	0 to 24 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Measure Participants	69	72	71	71
Median (Full Range) [days]	111	82	84	57

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have good or moderate improvement in DAS28 were censored at the last visit or exit visit, whichever occurred first. Patients who did not have good or moderate improvement in DAS28 and discontinued from the study prior to study completion were censored at the last date on study.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0960
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have good or moderate improvement in DAS28 were censored at the last visit or exit visit, whichever occurred first. Patients who did not have good or moderate improvement in DAS28 and discontinued from the study prior to study completion were censored at the last date on study.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2859
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
	Comments	Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have good or moderate improvement in DAS28 were censored at the last visit or exit visit, whichever occurred first. Patients who did not have good or moderate improvement in DAS28 and discontinued from the study prior to study completion were censored at the last date on study.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0109
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

9. Secondary Outcome

Title	Mean Change in Modified Total Sharp Score at Week 24
Description	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.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent and who had both a modified total Sharp score at baseline and at Week 24.

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Measure Participants	67	70	66	68
Mean (Standard Error) [scores on a scale]	0.7 (0.2)	0.3 (0.2)	0.3 (0.2)	0.6 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Missing data was handled by using LOCF imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1940
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Missing data was handled by using LOCF imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2561
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
	Comments	Missing data was handled by using LOCF imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8707
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments

10. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Plus SOC	Belimumab 1 mg/kg Plus SOC	Belimumab 4 mg/kg Plus SOC	Belimumab 10 mg/kg Plus SOC	Open-label Extension Period: All Active
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study	Includes all patients who completed the 24-week double-blind period and opted to continue in a 24-week open-label extension period. 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. AE onset may be during the extension phase or continuing from the double-blind period.
Measure Participants	69	72	71	71	237
Percent of patients with at least 1 AE	89.9 130.3%	84.7 117.6%	90.1 126.9%	93.0 131%	91.6 32.4%
Percent of patients with at least 1 SAE	7.2 10.4%	6.9 9.6%	7.0 9.9%	8.5 12%	11.0 3.9%
Percent of patients with an AE resulting in death	1.5 2.2%	0 0%	0 0%	1.4 2%	0 0%

Adverse Events

Time Frame	Up to 56 weeks
Adverse Event Reporting Description	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).
Arm/Group Title	Placebo Plus SOC		Belimumab 1 mg/kg Plus SOC		Belimumab 4 mg/kg Plus SOC		Belimumab 10 mg/kg Plus SOC		Open-label Extension Period: All Active
Arm/Group Description	Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study		Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study		Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study		Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study		Includes all patients who completed the 24-week double blind period and opted to continue in the 24-week open-label extension period. Belimumab patients received the same dose or were switched to 10 mg/kg at investigator discretion and former placebo patients received belimumab 10 mg/kg. AE onset may be during the extension phase or continuing from the double-blind period.
All Cause Mortality
	Placebo Plus SOC		Belimumab 1 mg/kg Plus SOC		Belimumab 4 mg/kg Plus SOC		Belimumab 10 mg/kg Plus SOC		Open-label Extension Period: All Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Plus SOC		Belimumab 1 mg/kg Plus SOC		Belimumab 4 mg/kg Plus SOC		Belimumab 10 mg/kg Plus SOC		Open-label Extension Period: All Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/69 (7.2%)		5/72 (6.9%)		5/71 (7%)		6/71 (8.5%)		26/237 (11%)
Blood and lymphatic system disorders
Anaemia	0/69 (0%)		0/72 (0%)		0/71 (0%)		1/71 (1.4%)		1/237 (0.4%)
Cardiac disorders
Acute coronary syndrome	0/69 (0%)		0/72 (0%)		1/71 (1.4%)		0/71 (0%)		0/237 (0%)
Angina pectoris	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Cardiac arrest	1/69 (1.4%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Coronary artery disease	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Myocardial infarction	1/69 (1.4%)		0/72 (0%)		1/71 (1.4%)		0/71 (0%)		0/237 (0%)
Supraventricular tachycardia	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Congenital, familial and genetic disorders
Spondylolisthesis	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		2/237 (0.8%)
Gastrointestinal disorders
Gastric ulcer	0/69 (0%)		0/72 (0%)		1/71 (1.4%)		1/71 (1.4%)		0/237 (0%)
Pancreatitis acute	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Small intestinal obstruction	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
General disorders
Malaise	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Non-cardiac chest pain	1/69 (1.4%)		0/72 (0%)		1/71 (1.4%)		0/71 (0%)		0/237 (0%)
Pyrexia	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Hepatobiliary disorders
Cholecystitis	1/69 (1.4%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Cholelithiasis	1/69 (1.4%)		0/72 (0%)		0/71 (0%)		1/71 (1.4%)		0/237 (0%)
Infections and infestations
Cellulitis	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		2/237 (0.8%)
Clostridium colitis	0/69 (0%)		0/72 (0%)		0/71 (0%)		1/71 (1.4%)		0/237 (0%)
Groin abscess	0/69 (0%)		0/72 (0%)		1/71 (1.4%)		0/71 (0%)		0/237 (0%)
Pneumonia	0/69 (0%)		0/72 (0%)		1/71 (1.4%)		1/71 (1.4%)		1/237 (0.4%)
Pneumonia primary atypical	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Pyelonephritis	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Viral infection	1/69 (1.4%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Injury, poisoning and procedural complications
Femur fracture	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Medical device complication	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/69 (0%)		0/72 (0%)		1/71 (1.4%)		0/71 (0%)		3/237 (1.3%)
Arthropathy	1/69 (1.4%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Intervertebral disc protrusion	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Intervertebral disc space narrowing	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Localised osteoarthritis	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		2/237 (0.8%)
Osteoarthritis	0/69 (0%)		0/72 (0%)		0/71 (0%)		1/71 (1.4%)		1/237 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Breast cancer	0/69 (0%)		0/72 (0%)		0/71 (0%)		1/71 (1.4%)		0/237 (0%)
Lung squamous cell carcinoma stage unspecified	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Squamous cell carcinoma of skin	0/69 (0%)		0/72 (0%)		0/71 (0%)		1/71 (1.4%)		1/237 (0.4%)
Vulval cancer	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Nervous system disorders
Headache	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Psychiatric disorders
Major depression	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Obsessive-compulsive disorder	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Renal and urinary disorders
Cystocele	0/69 (0%)		0/72 (0%)		0/71 (0%)		1/71 (1.4%)		0/237 (0%)
Nephrolithiasis	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Renal colic	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Reproductive system and breast disorders
Endometrial hypertrophy	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Ovarian cyst	1/69 (1.4%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Respiratory, thoracic and mediastinal disorders
Pleurisy	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Pneumonia aspiration	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Vascular disorders
Hypertension	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Peripheral ischaemia	0/69 (0%)		0/72 (0%)		0/71 (0%)		0/71 (0%)		1/237 (0.4%)
Peripheral vascular disorder	0/69 (0%)		1/72 (1.4%)		0/71 (0%)		0/71 (0%)		0/237 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Plus SOC		Belimumab 1 mg/kg Plus SOC		Belimumab 4 mg/kg Plus SOC		Belimumab 10 mg/kg Plus SOC		Open-label Extension Period: All Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/69 (72.5%)		47/72 (65.3%)		48/71 (67.6%)		54/71 (76.1%)		165/237 (69.6%)
Gastrointestinal disorders
Diarrhoea	6/69 (8.7%)		6/72 (8.3%)		2/71 (2.8%)		8/71 (11.3%)		15/237 (6.3%)
Mouth ulceration	2/69 (2.9%)		1/72 (1.4%)		4/71 (5.6%)		0/71 (0%)		3/237 (1.3%)
Nausea	5/69 (7.2%)		1/72 (1.4%)		6/71 (8.5%)		3/71 (4.2%)		10/237 (4.2%)
General disorders
Fatigue	4/69 (5.8%)		5/72 (6.9%)		6/71 (8.5%)		7/71 (9.9%)		18/237 (7.6%)
Infusion site reaction	1/69 (1.4%)		4/72 (5.6%)		0/71 (0%)		2/71 (2.8%)		4/237 (1.7%)
Oedema peripheral	4/69 (5.8%)		3/72 (4.2%)		9/71 (12.7%)		3/71 (4.2%)		25/237 (10.5%)
Infections and infestations
Bronchitis	1/69 (1.4%)		4/72 (5.6%)		2/71 (2.8%)		2/71 (2.8%)		7/237 (3%)
Nasopharyngitis	1/69 (1.4%)		1/72 (1.4%)		4/71 (5.6%)		0/71 (0%)		9/237 (3.8%)
Sinusitis	2/69 (2.9%)		3/72 (4.2%)		7/71 (9.9%)		3/71 (4.2%)		13/237 (5.5%)
Upper respiratory tract infection	9/69 (13%)		6/72 (8.3%)		9/71 (12.7%)		10/71 (14.1%)		38/237 (16%)
Urinary tract infection	6/69 (8.7%)		8/72 (11.1%)		8/71 (11.3%)		4/71 (5.6%)		17/237 (7.2%)
Injury, poisoning and procedural complications
Contusion	0/69 (0%)		4/72 (5.6%)		3/71 (4.2%)		0/71 (0%)		2/237 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/69 (23.2%)		21/72 (29.2%)		15/71 (21.1%)		24/71 (33.8%)		75/237 (31.6%)
Back pain	2/69 (2.9%)		3/72 (4.2%)		2/71 (2.8%)		2/71 (2.8%)		18/237 (7.6%)
Joint swelling	3/69 (4.3%)		4/72 (5.6%)		6/71 (8.5%)		11/71 (15.5%)		21/237 (8.9%)
Pain in extremity	2/69 (2.9%)		6/72 (8.3%)		4/71 (5.6%)		4/71 (5.6%)		14/237 (5.9%)
Nervous system disorders
Dizziness	3/69 (4.3%)		2/72 (2.8%)		2/71 (2.8%)		4/71 (5.6%)		9/237 (3.8%)
Headache	4/69 (5.8%)		7/72 (9.7%)		5/71 (7%)		8/71 (11.3%)		12/237 (5.1%)
Renal and urinary disorders
Haematuria	4/69 (5.8%)		0/72 (0%)		1/71 (1.4%)		1/71 (1.4%)		4/237 (1.7%)
Respiratory, thoracic and mediastinal disorders
Cough	2/69 (2.9%)		1/72 (1.4%)		3/71 (4.2%)		8/71 (11.3%)		12/237 (5.1%)
Skin and subcutaneous tissue disorders
Pruritus	1/69 (1.4%)		7/72 (9.7%)		1/71 (1.4%)		2/71 (2.8%)		7/237 (3%)
Vascular disorders
Hypertension	2/69 (2.9%)		4/72 (5.6%)		2/71 (2.8%)		2/71 (2.8%)		10/237 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

For multi-center trials, no investigator will be authorized to publish study results from an individual center until the multi-center trial results are published. All manuscripts and abstracts must be submitted to the sponsor for review at least 30 days prior to submission for publication or for presentation at a scientific meeting. Proposed abstracts and publications will be reviewed promptly.