Safety and Efficacy Study of LymphoStat-B (Belimumab) in Subjects With Systemic Lupus Erythematosus (SLE)

• Sponsor: Human Genome Sciences Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00071487
• Collaborator: (none)
• Enrollment: 449
• Locations: 62
• Arms: 4
• Duration (Months): 32
• Patients Per Site: 7.2
• 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 active SLE disease.

Condition or Disease	Intervention/Treatment	Phase
Lupus Erythematosus, Systemic	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 active SLE disease. Patients were randomly assigned, following stratification by the screening SELENA SLEDAI score (4 to 7 versus ≥ 8), to 1 of the 4 study arms (3 active arms and 1 placebo arm plus standard therapy for SLE). All patients were to be dosed on Days 0, 14, and 28, then every 28 days for the remainder of 52 weeks. Patients completing the 52-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: 449 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 Systemic Lupus Erythematosus (SLE)
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Aug 1, 2005
• Actual Study Completion Date: Jun 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo plus SOC	Drug: Placebo; Placebo IV plus standard therapy (SOC) for SLE; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 52 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 SLE; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 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 SLE; belimumab 4 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 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 SLE; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate continued on belimumab 10 mg/kg for an additional 24 weeks.; Other Names: LymphoStat-B® BENLYSTA®

Outcome Measures

Primary Outcome Measures

1. Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. [Baseline, 24 weeks]

   SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare.

2. Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) [0 to 52 weeks]

   The SLE Flare Index categorized SLE flare as "mild or moderate" or "severe" based on 5 variables: 1) change in SELENA SLEDAI score from the most recent assessment to current, 2) change in signs or symptoms of disease activity, 3) change in prednisone dosage, 4) use of new medications for disease activity or hospitalization, and 5) change in Physician's Global Assessment score, a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe).

Secondary Outcome Measures

1. Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 [Baseline, 52 weeks]

   SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare

2. Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 [Baseline and every 4 to 8 weeks through Week 52]

   SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. The normalized AUC was created as the ratio of the area under the SELENA SLEDAI score curve divided by baseline score.

3. Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 [Baseline, 52 weeks]

   The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.

4. Area Under the Curve (AUC) of BILAG Score at Week 52 [Baseline and every 4 to 8 weeks through Week 52]

   The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.The normalized AUC was created as the ratio of the area under the global BILAG score curve divided by baseline score.

5. Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks [0 to 52 weeks]

   SLE flare indicates an increase in SLE disease activity. An SLE flare was a type A or B SLE flare (as defined using BILAG) compared with the previous visit.

6. Percentage of Patients With a Reduction in Prednisone Dose [Baseline, weeks 40 to 52]

   Percentage of patients whose average prednisone dose has been reduced by ≥ 50% and/or has been reduced to ≤ 7.5 mg/day during Weeks 40 through 52 in patients receiving greater than 7.5 mg/day at baseline.

Other Outcome Measures

1. Adverse Events (AE) Overview [Up to 84 weeks]

   Includes AEs reported in patients from the first dose of study agent throughout the study up to the Week 76/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 (LBSL99/NCT00583362).

Eligibility Criteria

Criteria

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

Primary Inclusion Criteria

• Clinical diagnosis of SLE

• "Active" SLE disease

• On a stable SLE treatment regimen

• History of measurable autoantibodies

Primary Exclusion Criteria

• Received a non-FDA approved investigational agent within last 28 days

• Cyclosporin, intravenous immunoglobulin (IVIG) or plasmapheresis within last 90 days

• Active lupus nephritis requiring hemodialysis, cyclophosphamide (Cytoxan™), or high-dose prednisone (> 100 mg/day) within last 90 days

• Active central nervous system (CNS) lupus requiring therapeutic intervention within last 60 days

• History of renal transplant

• History of chronic infection that has been active within last 6 months, herpes zoster within last 90 days or any infection requiring hospitalization or intravenous medication within last 60 days

• History of hypogammaglobulinemia or immunoglobulin A (IgA) deficiency

• 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	Stanford University School of Medicine	Palo Alto	California	United States	94304
8	Boling Clinical Trials	Rancho Cucamonga	California	United States	91730
9	UCDMC	Sacramento	California	United States	95817-1418
10	Arthritis Care Center, Inc.	San Jose	California	United States	95126-1650
11	Arthritis Associates & Osteoporosis Center Of Colorado Springs	Colorado Springs	Colorado	United States	80910
12	Washington Hospital Center	Washington	District of Columbia	United States	20010
13	Arthritis and Rheumatic Disease Specialties	Aventura	Florida	United States	33180
14	Rheumatology Associates of Central Florida	Orlando	Florida	United States	32806
15	Tampa Medical Group, P.A.	Tampa	Florida	United States	33614
16	Emory University	Atlanta	Georgia	United States	30303
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	Medical Specialists	Munster	Indiana	United States	46321
22	Kentuckiana Center for Better Bone and Joint Health	Louisville	Kentucky	United States	40202
23	Ochsner Clinic Foundation	Baton Rouge	Louisiana	United States	70809
24	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
25	University of Maryland	Baltimore	Maryland	United States	21201
26	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
27	The Osteoporosis and Arthritis Clinical Trial Center	Cumberland	Maryland	United States	21502
28	Center for Rheumatology and Bone Research	Wheaton	Maryland	United States	20902
29	Tufts--New England Medical Center	Boston	Massachusetts	United States	02111
30	The University of Michigan Health System	Ann Arbor	Michigan	United States	48109-0358
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	Aair Research	Rochester	New York	United States	14618
40	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7280
41	Arthritis Clinic and Carolina Bone and Joint	Charlotte	North Carolina	United States	28210
42	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157
43	Stat Research Inc.	Dayton	Ohio	United States	45402
44	Bone and Joint Hospital	Oklahoma City	Oklahoma	United States	73103
45	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
46	Oklahoma Center For Arthritis Therapy & Research	Tulsa	Oklahoma	United States	74114
47	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
48	University of Pittsburgh School of Medicine & ASPH	Pittsburgh	Pennsylvania	United States	15261
49	Rheumatic Disease Associates	Willow Grove	Pennsylvania	United States	19090
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	Texas Research Center	Sugar Land	Texas	United States	77479
53	Arthritis and Rheumatic Disease Clinic	Ogden	Utah	United States	84044
54	Physicians Research Options, LC	Sandy	Utah	United States	84070
55	Arthritis Clinic of Northern Virginia, P.C.	Arlington	Virginia	United States	22205
56	Edmonds Rheumatology Associates	Edmonds	Washington	United States	98026-8047
57	Arthritis Northwest Rheumatology	Spokane	Washington	United States	99204
58	Gundersen Clinic, Ltd.	La Crosse	Wisconsin	United States	54610
59	The Medical College of Wisconsin , Inc	Milwaukee	Wisconsin	United States	53226
60	Marshfield Medical Research Foundation	Wausau	Wisconsin	United States	54401
61	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
62	McGill University Health Center	Montreal	Quebec	Canada	H3G 1A4

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: NCT00071487
• Other Study ID Numbers: LBSL02
• First Posted: Oct 28, 2003
• Last Update Posted: Aug 7, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Human Genome Sciences Inc.: SLE
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; 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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study. The 24-week open-label extension period of the study included patients who completed the 52-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 SLE for 52-week double-blind period of the study. The 24-week open-label extension period of the study included patients who completed the 52-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 SLE for 52-week double-blind period of the study. The 24 week-open label extension period of the study included patients who completed the 52-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: 52-Week Double-Blind Period
STARTED	113	114	111	111
COMPLETED	93	87	94	90
NOT COMPLETED	20	27	17	21
Period Title: 52-Week Double-Blind Period
STARTED	0	19	24	302
COMPLETED	0	19	23	279
NOT COMPLETED	0	0	1	23

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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Total of all reporting groups
Overall Participants	113	114	111	111	449
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (10.9)	42.0 (11.7)	42.6 (10.7)	41.8 (11.7)	42.2 (11.2)
Sex: Female, Male (Count of Participants)
Female	102 90.3%	107 93.9%	105 94.6%	105 94.6%	419 93.3%
Male	11 9.7%	7 6.1%	6 5.4%	6 5.4%	30 6.7%
Region of Enrollment (participants) [Number]
United States	113 100%	113 99.1%	111 100%	109 98.2%	446 99.3%
Canada	0 0%	1 0.9%	0 0%	2 1.8%	3 0.7%

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24.
Description	SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare.
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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	113	114	111	111
Mean (Standard Error) [percent change]	-17.2 (5.1)	-23.3 (4.4)	-11.3 (5.4)	-23.7 (4.2)

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 a last observation carried forward (LOCF) imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3677
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -19.4 to 7.2
	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	Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4244
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95%; -8.7 to 20.6
	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	Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3296
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -19.6 to 6.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index)
Description	The SLE Flare Index categorized SLE flare as "mild or moderate" or "severe" based on 5 variables: 1) change in SELENA SLEDAI score from the most recent assessment to current, 2) change in signs or symptoms of disease activity, 3) change in prednisone dosage, 4) use of new medications for disease activity or hospitalization, and 5) change in Physician's Global Assessment score, a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe).
Time Frame	0 to 52 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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	113	114	111	111
Median (Inter-Quartile Range) [days]	83	68	61	70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Patients who required protocol-prohibited medications were considered to have a flare on the date the prohibited medication was started or date of the first flare, whichever came first. Patients who withdrew from the study for reasons other than SLE disease manifestations or hospitalization related to SLE or who missed 2 or more consecutive visits were censored at the time of the last assessment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6423
	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 protocol-prohibited medications were considered to have a flare on the date the prohibited medication was started or date of the first flare, whichever came first. Patients who withdrew from the study for reasons other than SLE disease manifestations or hospitalization related to SLE or who missed 2 or more consecutive visits were censored at the time of the last assessment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8536
	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 protocol-prohibited medications were considered to have a flare on the date the prohibited medication was started or date of the first flare, whichever came first. Patients who withdrew from the study for reasons other than SLE disease manifestations or hospitalization related to SLE or who missed 2 or more consecutive visits were censored at the time of the last assessment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9705
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Percentage Change From Baseline in SELENA SLEDAI Score at Week 52
Description	SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare
Time Frame	Baseline, 52 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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	113	114	111	111
Mean (Standard Error) [percent change]	-20.6 (5.2)	-29.7 (4.3)	-23.9 (7.3)	-27.9 (5.5)

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. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1763
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.1
	Confidence Interval	(2-Sided) 95%; -22.4 to 4.1
	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	Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7112
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.3
	Confidence Interval	(2-Sided) 95%; -20.9 to 14.3
	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	Missing data was handled by using LOCF imputation. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3320
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.4
	Confidence Interval	(2-Sided) 95%; -22.2 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52
Description	SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. The normalized AUC was created as the ratio of the area under the SELENA SLEDAI score curve divided by baseline score.
Time Frame	Baseline and every 4 to 8 weeks through Week 52

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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	113	114	111	111
Mean (Standard Error) [ratio score*days]	317.3 (14.0)	288.7 (12.5)	320.3 (14.0)	286.9 (13.0)

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. If patient required a protocol-prohibited medication, the SELENA SLEDAI score of the last visit prior to the use of the prohibited medication was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1287
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-28.6
	Confidence Interval	(2-Sided) 95%; -65.6 to 8.4
	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	Missing data was handled by using LOCF imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8807
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.98
	Confidence Interval	(2-Sided) 95%; -36.2 to 42.1
	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	Missing data was handled by using LOCF imputation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1131
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-30.41
	Confidence Interval	(2-Sided) 95%; -68.1 to 7.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52
Description	The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.
Time Frame	Baseline, 52 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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	113	114	111	111
Mean (Standard Error) [percent change]	-19.1 (4.3)	-20.8 (4.3)	-26.5 (3.4)	-22.0 (4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Missing data for BILAG were handled as described previously for SELENA SLEDAI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7823
	Comments	P-value was not adjusted for multiple testing
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -13.8 to 10.4
	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	Missing data for BILAG were handled as described previously for SELENA SLEDAI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1774
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.4
	Confidence Interval	(2-Sided) 95%; -18.2 to 3.4
	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	Missing data for BILAG were handled as described previously for SELENA SLEDAI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6406
	Comments
	Method	t-test, 2 sided
	Comments	P-value was not adjusted for multiple testing.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -14.8 to 9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Area Under the Curve (AUC) of BILAG Score at Week 52
Description	The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.The normalized AUC was created as the ratio of the area under the global BILAG score curve divided by baseline score.
Time Frame	Baseline and every 4 to 8 weeks through Week 52

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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	113	114	111	111
Mean (Standard Error) [ratio score*days]	315.4 (12.3)	310.6 (12.0)	300.4 (9.3)	302.7 (12.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Missing data for BILAG were handled as described previously for SELENA SLEDAI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7822
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -38.6 to 29.1
	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	Missing data for BILAG were handled as described previously for SELENA SLEDAI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3332
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-14.9
	Confidence Interval	(2-Sided) 95%; -45.3 to 15.4
	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	Missing data for BILAG were handled as described previously for SELENA SLEDAI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4660
	Comments	P-value was not adjusted for multiple testing.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.7
	Confidence Interval	(2-Sided) 95%; -46.9 to 21.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks
Description	SLE flare indicates an increase in SLE disease activity. An SLE flare was a type A or B SLE flare (as defined using BILAG) compared with the previous visit.
Time Frame	0 to 52 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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	113	114	111	111
Median (Inter-Quartile Range) [days]	78	63	84	62

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Missing data for BILAG were handled as described previously for SELENA SLEDAI (SLE Flare Index).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5615
	Comments	P-value was not adjusted for multiple comparisons.
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
	Comments	Missing data for BILAG were handled as described previously for SELENA SLEDAI (SLE Flare Index).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7593
	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	Missing data for BILAG were handled as described previously for SELENA SLEDAI (SLE Flare Index).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2273
	Comments	P-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments

8. Secondary Outcome

Title	Percentage of Patients With a Reduction in Prednisone Dose
Description	Percentage of patients whose average prednisone dose has been reduced by ≥ 50% and/or has been reduced to ≤ 7.5 mg/day during Weeks 40 through 52 in patients receiving greater than 7.5 mg/day at baseline.
Time Frame	Baseline, weeks 40 to 52

Outcome Measure Data

Analysis Population Description

Analysis was performed on a subgroup of the MITT population, which included only patients with baseline prednisone dose > 7.5 mg/day.

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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.
Measure Participants	48	40	35	38
Number [percentatge of particpants]	27.1	20.0	31.4	44.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
	Comments	Patients who dropped out or had missing data were considered failures.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4355
	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	-7.1
	Confidence Interval	(2-Sided) 95%; -24.7 to 10.6
	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 dropped out or had missing data were considered failures.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6669
	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	4.4
	Confidence Interval	(2-Sided) 95%; -15.5 to 24.2
	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 dropped out or had missing data were considered failures.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0882
	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	17.7
	Confidence Interval	(2-Sided) 95%; -2.5 to 37.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. 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 76/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 (LBSL99/NCT00583362).
Time Frame	Up to 84 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 SLE for 52-week double-blind period of the study.	Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study.	Includes all patients who completed the 52-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 belimumab 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	113	114	111	111	345
Percent of patients with at least 1 AE	97.3 86.1%	97.4 85.4%	96.4 86.8%	97.3 87.7%	96.2 21.4%
Percent of patients with at least 1 SAE	19.5 17.3%	18.4 16.1%	13.5 12.2%	16.2 14.6%	9.6 2.1%
Percent of patients with an AE resulting in death	0 0%	0.9 0.8%	0 0%	0.9 0.8%	0 0%

Adverse Events

Time Frame	Up to 84 weeks
Adverse Event Reporting Description	Includes AEs reported in patients from the first dose of study agent throughout the study up to the Week 76/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 (LBSL99/NCT00583362).
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 SLE for 52-week double-blind period of the study		Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study		Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study		Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE for 52-week double-blind period of the study		Includes all patients who completed the 52-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 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	22/113 (19.5%)		21/114 (18.4%)		15/111 (13.5%)		18/111 (16.2%)		33/345 (9.6%)
Blood and lymphatic system disorders
Aplastic anaemia	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Febrile neutropenia	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Haemolysis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Thrombocytopenia	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Cardiac disorders
Acute coronary syndrome	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Angina pectoris	1/113 (0.9%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Atrial fibrillation	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Coronary artery disease	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Myocardial infarction	1/113 (0.9%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Pericarditis lupus	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Pleuropericarditis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Endocrine disorders
Adrenal insufficiency	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Gastrointestinal disorders
Abdominal pain	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Appendicitis noninfective	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Gastroduodenitis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Gastroenteritis noninfectious	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Pancreatitis	0/113 (0%)		0/114 (0%)		2/111 (1.8%)		0/111 (0%)		0/345 (0%)
Rectal haemorrhage	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Rectocele	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Small intestinal obstruction	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
General disorders
Adhesion	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Non-cardiac chest pain	2/113 (1.8%)		1/114 (0.9%)		0/111 (0%)		1/111 (0.9%)		3/345 (0.9%)
Pyrexia	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Hepatobiliary disorders
Cholecystitis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Cholelithiasis	0/113 (0%)		1/114 (0.9%)		2/111 (1.8%)		0/111 (0%)		0/345 (0%)
Hepatotoxicity	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Infections and infestations
Anal infection	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Bronchitis acute	0/113 (0%)		1/114 (0.9%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Cellulitis	0/113 (0%)		2/114 (1.8%)		1/111 (0.9%)		0/111 (0%)		1/345 (0.3%)
Clostridium colitis	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Furuncle	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Gastroenteritis viral	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Herpes zoster	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Lobar pneumonia	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Pneumonia	1/113 (0.9%)		2/114 (1.8%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Pneumonia bacterial	0/113 (0%)		1/114 (0.9%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Pyelonephritis acute	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Sepsis	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Septic arthritis streptobacillus	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Streptococcal bacteraemia	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Urinary tract infection	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		1/345 (0.3%)
Viral infection	1/113 (0.9%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
West Nile viral infection	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Wound infection	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Injury, poisoning and procedural complications
Ankle fracture	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		1/345 (0.3%)
Patella fracture	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Post procedural haematoma	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Road traffic accident	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Seroma	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Therapeutic agent toxicity	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		1/345 (0.3%)
Investigations
Haematocrit decreased	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Haemoglobin decreased	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Pulmonary function test decreased	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Weight decreased	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Metabolism and nutrition disorders
Dehydration	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Hyperglycaemia	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Musculoskeletal and connective tissue disorders
Arthritis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Bursitis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Costochondritis	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Intervertebral disc degeneration	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Intervertebral disc protrusion	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Lumbar spinal stenosis	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Musculoskeletal chest pain	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Osteoarthritis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Osteonecrosis	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Spondylosis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Tenosynovitis	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Lung neoplasm malignant	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Metastases to bone	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Metastases to bone marrow	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Squamous cell carcinoma of skin	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Uterine leiomyoma	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Nervous system disorders
Cauda equina syndrome	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Convulsion	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Encephalopathy	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Grand mal convulsion	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Headache	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Neuralgia	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Paraesthesia	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Simple partial seizures	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Transient ischaemic attack	0/113 (0%)		2/114 (1.8%)		1/111 (0.9%)		1/111 (0.9%)		1/345 (0.3%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Pregnancy	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Psychiatric disorders
Completed suicide	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Depression	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Renal and urinary disorders
Calculus ureteric	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Cystocele	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Glomerulonephritis	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Lupus nephritis	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Proteinuria	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		2/111 (1.8%)		3/345 (0.9%)
Renal failure	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Reproductive system and breast disorders
Cervical dysplasia	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Menometrorrhagia	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Ovarian cyst	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Vulvar dysplasia	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Asthma	0/113 (0%)		1/114 (0.9%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Bronchospasm	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Chronic obstructive airways disease exacerbated	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Dyspnoea	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		2/345 (0.6%)
Dyspnoea exacerbated	0/113 (0%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		1/345 (0.3%)
Epistaxis	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Pleural effusion	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Pleurisy	2/113 (1.8%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Pneumonia aspiration	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Respiratory failure	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Skin and subcutaneous tissue disorders
Angioneurotic oedema	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Dermatitis allergic	0/113 (0%)		1/114 (0.9%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Systemic lupus erythematosus rash	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Surgical and medical procedures
Post procedural drainage	1/113 (0.9%)		0/114 (0%)		0/111 (0%)		0/111 (0%)		0/345 (0%)
Vascular disorders
Arteriosclerosis	0/113 (0%)		1/114 (0.9%)		1/111 (0.9%)		0/111 (0%)		0/345 (0%)
Deep vein thrombosis	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		1/345 (0.3%)
Hypertensive crisis	0/113 (0%)		0/114 (0%)		0/111 (0%)		1/111 (0.9%)		0/345 (0%)
Vasculitis	0/113 (0%)		0/114 (0%)		1/111 (0.9%)		0/111 (0%)		0/345 (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	103/113 (91.2%)		107/114 (93.9%)		100/111 (90.1%)		105/111 (94.6%)		312/345 (90.4%)
Blood and lymphatic system disorders
Anaemia	3/113 (2.7%)		5/114 (4.4%)		7/111 (6.3%)		2/111 (1.8%)		19/345 (5.5%)
Leukopenia	5/113 (4.4%)		4/114 (3.5%)		6/111 (5.4%)		9/111 (8.1%)		12/345 (3.5%)
Lymphadenopathy	5/113 (4.4%)		2/114 (1.8%)		5/111 (4.5%)		6/111 (5.4%)		5/345 (1.4%)
Gastrointestinal disorders
Abdominal pain	9/113 (8%)		6/114 (5.3%)		4/111 (3.6%)		4/111 (3.6%)		8/345 (2.3%)
Constipation	6/113 (5.3%)		3/114 (2.6%)		4/111 (3.6%)		4/111 (3.6%)		9/345 (2.6%)
Diarrhoea	19/113 (16.8%)		19/114 (16.7%)		23/111 (20.7%)		17/111 (15.3%)		34/345 (9.9%)
Dyspepsia	8/113 (7.1%)		3/114 (2.6%)		5/111 (4.5%)		7/111 (6.3%)		7/345 (2%)
Gastrooesophageal reflux disease	5/113 (4.4%)		11/114 (9.6%)		5/111 (4.5%)		7/111 (6.3%)		26/345 (7.5%)
Mouth ulceration	11/113 (9.7%)		9/114 (7.9%)		12/111 (10.8%)		17/111 (15.3%)		18/345 (5.2%)
Nausea	27/113 (23.9%)		31/114 (27.2%)		22/111 (19.8%)		33/111 (29.7%)		39/345 (11.3%)
Vomiting	13/113 (11.5%)		14/114 (12.3%)		15/111 (13.5%)		9/111 (8.1%)		15/345 (4.3%)
General disorders
Fatigue	34/113 (30.1%)		27/114 (23.7%)		33/111 (29.7%)		27/111 (24.3%)		72/345 (20.9%)
Infusion site reaction	6/113 (5.3%)		3/114 (2.6%)		12/111 (10.8%)		2/111 (1.8%)		2/345 (0.6%)
Non-cardiac chest pain	9/113 (8%)		6/114 (5.3%)		6/111 (5.4%)		6/111 (5.4%)		9/345 (2.6%)
Oedema peripheral	13/113 (11.5%)		15/114 (13.2%)		18/111 (16.2%)		15/111 (13.5%)		41/345 (11.9%)
Pain	3/113 (2.7%)		1/114 (0.9%)		6/111 (5.4%)		5/111 (4.5%)		12/345 (3.5%)
Pyrexia	14/113 (12.4%)		13/114 (11.4%)		17/111 (15.3%)		15/111 (13.5%)		18/345 (5.2%)
Infections and infestations
Bronchitis	7/113 (6.2%)		5/114 (4.4%)		11/111 (9.9%)		14/111 (12.6%)		23/345 (6.7%)
Gastroenteritis viral	4/113 (3.5%)		6/114 (5.3%)		5/111 (4.5%)		4/111 (3.6%)		6/345 (1.7%)
Influenza	8/113 (7.1%)		6/114 (5.3%)		11/111 (9.9%)		7/111 (6.3%)		7/345 (2%)
Sinusitis	21/113 (18.6%)		11/114 (9.6%)		15/111 (13.5%)		17/111 (15.3%)		34/345 (9.9%)
Upper respiratory tract infection	33/113 (29.2%)		36/114 (31.6%)		36/111 (32.4%)		29/111 (26.1%)		58/345 (16.8%)
Urinary tract infection	18/113 (15.9%)		16/114 (14%)		18/111 (16.2%)		20/111 (18%)		33/345 (9.6%)
Vaginal mycosis	8/113 (7.1%)		3/114 (2.6%)		8/111 (7.2%)		4/111 (3.6%)		10/345 (2.9%)
Viral infection	5/113 (4.4%)		3/114 (2.6%)		8/111 (7.2%)		0/111 (0%)		2/345 (0.6%)
Viral upper respiratory tract infection	5/113 (4.4%)		5/114 (4.4%)		6/111 (5.4%)		5/111 (4.5%)		10/345 (2.9%)
Injury, poisoning and procedural complications
Contusion	7/113 (6.2%)		10/114 (8.8%)		7/111 (6.3%)		6/111 (5.4%)		12/345 (3.5%)
Investigations
Creatinine renal clearance decreased	4/113 (3.5%)		5/114 (4.4%)		8/111 (7.2%)		5/111 (4.5%)		8/345 (2.3%)
Weight decreased	6/113 (5.3%)		6/114 (5.3%)		5/111 (4.5%)		5/111 (4.5%)		17/345 (4.9%)
Weight increased	8/113 (7.1%)		6/114 (5.3%)		8/111 (7.2%)		7/111 (6.3%)		28/345 (8.1%)
Metabolism and nutrition disorders
Decreased appetite	2/113 (1.8%)		6/114 (5.3%)		0/111 (0%)		0/111 (0%)		3/345 (0.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	42/113 (37.2%)		41/114 (36%)		37/111 (33.3%)		41/111 (36.9%)		102/345 (29.6%)
Arthritis	18/113 (15.9%)		16/114 (14%)		21/111 (18.9%)		18/111 (16.2%)		47/345 (13.6%)
Back pain	16/113 (14.2%)		15/114 (13.2%)		15/111 (13.5%)		16/111 (14.4%)		42/345 (12.2%)
Bursitis	2/113 (1.8%)		6/114 (5.3%)		6/111 (5.4%)		4/111 (3.6%)		7/345 (2%)
Fibromyalgia	4/113 (3.5%)		2/114 (1.8%)		5/111 (4.5%)		6/111 (5.4%)		12/345 (3.5%)
Joint swelling	10/113 (8.8%)		9/114 (7.9%)		11/111 (9.9%)		7/111 (6.3%)		14/345 (4.1%)
Myalgia	14/113 (12.4%)		15/114 (13.2%)		10/111 (9%)		15/111 (13.5%)		28/345 (8.1%)
Pain in extremity	8/113 (7.1%)		14/114 (12.3%)		13/111 (11.7%)		10/111 (9%)		34/345 (9.9%)
SLE arthritis	6/113 (5.3%)		5/114 (4.4%)		2/111 (1.8%)		9/111 (8.1%)		4/345 (1.2%)
Synovitis	4/113 (3.5%)		4/114 (3.5%)		6/111 (5.4%)		6/111 (5.4%)		8/345 (2.3%)
Tendonitis	3/113 (2.7%)		2/114 (1.8%)		4/111 (3.6%)		8/111 (7.2%)		8/345 (2.3%)
Nervous system disorders
Dizziness	8/113 (7.1%)		8/114 (7%)		12/111 (10.8%)		6/111 (5.4%)		10/345 (2.9%)
Headache	27/113 (23.9%)		29/114 (25.4%)		31/111 (27.9%)		35/111 (31.5%)		50/345 (14.5%)
Hypoaesthesia	3/113 (2.7%)		4/114 (3.5%)		5/111 (4.5%)		6/111 (5.4%)		13/345 (3.8%)
Migraine	11/113 (9.7%)		11/114 (9.6%)		6/111 (5.4%)		15/111 (13.5%)		19/345 (5.5%)
Paraesthesia	1/113 (0.9%)		7/114 (6.1%)		3/111 (2.7%)		1/111 (0.9%)		4/345 (1.2%)
Sinus headache	6/113 (5.3%)		1/114 (0.9%)		0/111 (0%)		2/111 (1.8%)		3/345 (0.9%)
Psychiatric disorders
Anxiety	6/113 (5.3%)		6/114 (5.3%)		8/111 (7.2%)		3/111 (2.7%)		19/345 (5.5%)
Depression	9/113 (8%)		16/114 (14%)		12/111 (10.8%)		10/111 (9%)		31/345 (9%)
Insomnia	10/113 (8.8%)		5/114 (4.4%)		5/111 (4.5%)		9/111 (8.1%)		35/345 (10.1%)
Renal and urinary disorders
Haematuria	3/113 (2.7%)		3/114 (2.6%)		4/111 (3.6%)		7/111 (6.3%)		5/345 (1.4%)
Proteinuria	6/113 (5.3%)		6/114 (5.3%)		7/111 (6.3%)		4/111 (3.6%)		17/345 (4.9%)
Pyuria	1/113 (0.9%)		6/114 (5.3%)		4/111 (3.6%)		3/111 (2.7%)		4/345 (1.2%)
Respiratory, thoracic and mediastinal disorders
Cough	12/113 (10.6%)		13/114 (11.4%)		8/111 (7.2%)		13/111 (11.7%)		25/345 (7.2%)
Dyspnoea	7/113 (6.2%)		3/114 (2.6%)		8/111 (7.2%)		9/111 (8.1%)		17/345 (4.9%)
Epistaxis	3/113 (2.7%)		3/114 (2.6%)		0/111 (0%)		7/111 (6.3%)		4/345 (1.2%)
Nasal congestion	9/113 (8%)		6/114 (5.3%)		3/111 (2.7%)		2/111 (1.8%)		7/345 (2%)
Nasal ulcer	2/113 (1.8%)		6/114 (5.3%)		2/111 (1.8%)		6/111 (5.4%)		5/345 (1.4%)
Pharyngolaryngeal pain	2/113 (1.8%)		7/114 (6.1%)		5/111 (4.5%)		2/111 (1.8%)		5/345 (1.4%)
Pleurisy	9/113 (8%)		5/114 (4.4%)		4/111 (3.6%)		2/111 (1.8%)		7/345 (2%)
Pleuritic pain	7/113 (6.2%)		6/114 (5.3%)		6/111 (5.4%)		5/111 (4.5%)		7/345 (2%)
Throat irritation	8/113 (7.1%)		4/114 (3.5%)		1/111 (0.9%)		3/111 (2.7%)		6/345 (1.7%)
Skin and subcutaneous tissue disorders
Alopecia	13/113 (11.5%)		10/114 (8.8%)		9/111 (8.1%)		11/111 (9.9%)		24/345 (7%)
Erythema	4/113 (3.5%)		6/114 (5.3%)		10/111 (9%)		3/111 (2.7%)		12/345 (3.5%)
Pruritus	8/113 (7.1%)		5/114 (4.4%)		5/111 (4.5%)		8/111 (7.2%)		13/345 (3.8%)
Rash	12/113 (10.6%)		16/114 (14%)		17/111 (15.3%)		8/111 (7.2%)		25/345 (7.2%)
Rash maculo-papular	9/113 (8%)		3/114 (2.6%)		7/111 (6.3%)		6/111 (5.4%)		13/345 (3.8%)
Systemic lupus erythematosus rash	5/113 (4.4%)		2/114 (1.8%)		4/111 (3.6%)		6/111 (5.4%)		12/345 (3.5%)
Urticaria	0/113 (0%)		5/114 (4.4%)		6/111 (5.4%)		3/111 (2.7%)		6/345 (1.7%)
Vascular disorders
Hypertension	5/113 (4.4%)		6/114 (5.3%)		5/111 (4.5%)		13/111 (11.7%)		25/345 (7.2%)
Raynaud's phenomenon	4/113 (3.5%)		6/114 (5.3%)		4/111 (3.6%)		4/111 (3.6%)		6/345 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.