BLISS-52: A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE)

• Sponsor: Human Genome Sciences Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00424476
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 865
• Locations: 92
• Arms: 3
• Duration (Months): 34
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, tolerability, and impact on quality of life of two different doses of belimumab administered in addition to standard therapy in subjects with active, autoantibody-positive systemic lupus erythematosus (SLE) disease.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Drug: Placebo; Drug: Belimumab 1 mg/kg; Drug: Belimumab 10 mg/kg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 865 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Wk Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects With Systemic Lupus Erythematosus (SLE)
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through Week 48.
Experimental: Belimumab 1 mg/kg Belimumab 1 mg/kg	Drug: Belimumab 1 mg/kg; Belimumab 1 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.; Other Names: BENLYSTA™ (formerly LymphoStat-B™)
Experimental: Belimumab 10 mg/kg Belimumab 10 mg/kg	Drug: Belimumab 10 mg/kg; Belimumab 10 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.; Other Names: BENLYSTA™ (formerly LymphoStat-B™)

Outcome Measures

Primary Outcome Measures

1. SLE Responder Index (SRI) Response Rate at Week 52 [Baseline, 52 weeks]

   Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of < 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline. SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E).

Secondary Outcome Measures

1. Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52. [Baseline, 52 weeks]

2. Mean Change in Physician's Global Assessment (PGA) at Wk 24. [Baseline, 24 weeks]

   The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity.

3. Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24. [Baseline, 24 weeks]

   The SF-36 is a generic health related quality of life (HRQOL) measurement. The survey includes 36 questions grouped to 8 domains and 2 summary measures (physical and mental health component, PCS and MCS, respectively) assessing HRQOL. Responses are scored according to the SF-36v2™ manual. A score is calculated for each SF-36 domain based on the patient's response to each question within it. This is then transformed to a scale ranging from 0 (worst) to 100 (best) points. The PCS is norm-based where the mean=50 and standard deviation (SD)=10. Higher scores represent better physical health.

4. Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52 [Baseline, Weeks 40 through 52]

Other Outcome Measures

1. Adverse Events (AE) Overview [Up to 56 Weeks]

   SEE ALSO ADVERSE EVENTS RESULTS SECTION

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Clinical diagnosis of SLE by ACR criteria.

• Active SLE disease.

• Autoantibody-positive.

• On stable SLE treatment regimen.

Key Exclusion Criteria:

• Pregnant or nursing

• Have received treatment with any B cell targeted therapy.

• Have received treatment with a biological investigational agent in the past year.

• Have received IV cyclophosphamide within 180 days of Day 0.

• Have severe lupus kidney disease.

• Have active central nervous system (CNS) lupus.

• Have required management of acute or chronic infections within the past 60 days.

• Have current drug or alcohol abuse or dependence.

• Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Britanico de Buenos Aires	Buenos Aires		Argentina	C1280AEB
2	Centro Privado de Medicina Familiar	Buenos Aires		Argentina	C1417EYG
3	Hospital Sirio Libanes	Buenos Aires		Argentina	C1419AHN
4	Atencion Integral en Reumatologia	Buenos Aires		Argentina	C1426AAL
5	Instituto de Investigaciones Medicas	Buenos Aires		Argentina	C1427ARO
6	OMI, Organización Médica de Investigación	Ciudad Autonoma de Buenos Aires		Argentina	C1015ABO
7	CIER, Centro de Investigaciones en Enfermedades Reumáticas	Ciudad Autonoma de Buenos Aires		Argentina	C1055AAF
8	Hospital General de Agudos Carlos G. Durand	Ciudad Autonoma de Buenos Aires		Argentina	C1405DCS
9	Hospital Interzonal General San Martín	La Plata		Argentina	B1904CFH
10	CAICI, Instituto Centralizado de Asistencia e Investigación Clínica Integral	Rosario		Argentina	S2000PBJ
11	Centro Medico Privado de Reumatologia	San Miguel de Tucuman		Argentina	T4000AXL
12	Repatriation Hospital	Daw Park		Australia	5041
13	Emeritus Research, Cabrini Hospital	Melbourne		Australia	3144
14	Monash Medical Centre	Melbourne		Australia	3168
15	Royal Perth Hospital	Shenton Park		Australia	6008
16	Hospital de Clínicas - UNICAMP	Campinas		Brazil	13083-888
17	Hospital das Clínicas - Universidade do Paraná	Curitiba		Brazil	80060-240
18	Hospital de Clínicas - Universidade Federal de Pernambuco	Fortaleza		Brazil	50670-901
19	Hospital Geral de Goiânia	Goiânia		Brazil	74110-120
20	Hospital Universitário - Universidade Federal de Juiz de Fora	Juiz de Fora		Brazil	36010-570
21	Hospital São Lucas da PUC-RS	Porto Alegre		Brazil	90610-000
22	Hospital Universitário Pedro Ernesto - UERJ	Rio de Janeiro		Brazil	20551-030
23	Hospital Unversitario Clementino Fraga Filho UFRJ	Rio de Janeiro		Brazil	21941-913
24	Hospital Santa Izabel	Salvador		Brazil	40050-410
25	Hospital Abreu Sodré	São Paulo		Brazil	04027-000
26	Hospital do Servidor Público Estadual de São Paulo - Francisco Morato de Oliveira	São Paulo		Brazil	04039-901
27	Hospital Heliópolis	São Paulo		Brazil	04266-010
28	Hospital Dr. Sotero del Rio	Santiago		Chile	8207257
29	Pontificia Universidad Católica de Chile	Santiago		Chile	8330033
30	Clínica Dávila	Santiago		Chile	8431657
31	Hospital Dr. Gustavo Fricke	Viña del Mar		Chile	2570017
32	Office of Dr. Guzman	Bogota	Cundinamarca	Colombia
33	Fundación Oftalmologica de Santander Clinica Carlos Ardila Lulle	Bucaramanga	Santander	Colombia
34	Centro de Reumatologia y Ortopedia	Barranquilla		Colombia
35	Fundación Instituto de Reumatología Fernando Chalem	Bogota		Colombia
36	Centrode de Investigaciones en Reumatologia Especialidades Medicas (CIREEH)	Bogotá		Colombia
37	Riesgo de Fracturas	Bogotá		Colombia
38	SERVIMED	Bucaramanga		Colombia
39	Corporación para Investigaciones Biológicas (CIB)	Medellín		Colombia
40	Office of Dr. Jose Molina	Medellín		Colombia
41	Pamela Youde Nethersole Eastern Hospital	Chai Wan		Hong Kong
42	Rheumatology Assessment and Treatment Center, Pok Oi Hospital	Shatin		Hong Kong
43	Tuen Mun Hospital	Tuen Mun		Hong Kong
44	St. John's Medical College Hospital	Bangalore		India	560 034
45	Krishna Institute of Medical Sciences	Hyderabaad		India	500 003
46	Nizam's Institute of Medical Sciences	Hyderabaad		India	500 082
47	Apollo Hospitals	Hyderabad		India	500 033
48	Chhatrapati Shahuji Maharaj Medical University	Lucknow		India	226018
49	King Edward Memorial (K.E.M.) Hospital	Mumbai		India	400 012
50	Kerala Institute of Medical Sciences	Trivandrum		India	695029
51	Kyungpook National Univesity Hospital	Daegu		Korea, Republic of	700-721
52	Eulji University Hospital	Daejeon		Korea, Republic of	302-799
53	Inha University Hospital	Inchon		Korea, Republic of	400-711
54	Dong-A University Hospital 3-1 (Dept. Rhuematology)	Pusan		Korea, Republic of	602-715
55	Pusan National University Hospital	Pusan		Korea, Republic of	602-739
56	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
57	The Hospital for Rheumatic Diseases, Hanyang University Hospital	Seoul		Korea, Republic of	133-792
58	Catholic Universtigy of Korea, Kangnam St. Mary's Hospital	Seoul		Korea, Republic of	137-701
59	Catholic University, Yoido St. Mary's Hospital	Seoul		Korea, Republic of	150-713
60	Ajou University Hospital	Suwon		Korea, Republic of	443-721
61	Hospital Nacional Alberto Sabogal Sologuren ESSALUD	Lima		Peru	Callao 2
62	Hospital Nacional Guillermo Almenara Irigoyen ESSALUD	Lima		Peru	L 13
63	Clinica Ricardo Palma Anexo 9 - Javier Prado Este	Lima		Peru	L 27
64	Instituto de Ginecología y Reproducción	Lima		Peru	L 33
65	Chong Hua Hospital	Cebu City		Philippines	6000
66	Davao Medical Center	Davao City		Philippines	8000
67	University of Perpetual Help -Rizal	Las Pinas City		Philippines	1740
68	Philippine General Hospital	Manila City		Philippines	1000
69	University of Santo Tomas Hospital	Manila City		Philippines	1008
70	St. Luke's Medical Center	Quezon City		Philippines	1102
71	Spitalul Clinic Sf Maria	Bucharest		Romania	011170
72	Spitalul Clinic Colentina	Bucharest		Romania	020125
73	Spitalul de Urgenta al Ministerului Administratiei si Internelor Prof. Dr. Dimitrie Gerota	Bucharest		Romania	020125
74	Spitalul Clinic Dr. Ion Cantacuzino	Bucharest		Romania	020475
75	Spitalul Clinic Judetean de Urgenta Cluj-Napoca	Cluj Napoca		Romania	40006
76	State Institution Scientific Research Institute of Rheumatology	Moscow		Russian Federation	115522
77	St. Petersburg City Hospital (Rheumatology Center)	St. Petersburg		Russian Federation	190068
78	Academy of Post-Graduated Education	St.-Petersburg		Russian Federation	191015
79	St.-Petersburg Region Clinical Hospital	St.-Petersburg		Russian Federation	194291
80	Soloviev's City Clinical Hospital,	Yaroslavl		Russian Federation	150003
81	City Healthcare Institution Municipal Hospital NPZ,	Yaroslavl		Russian Federation	190068
82	Buddhist Tzu Chi General Hospital, Dalin	Chia-Yi		Taiwan	622
83	Buddhist Tzu Chi General Hospital - Hualien	Haulien		Taiwan	970
84	Chung-Ho Memorial Hospital, Kaohsiung Medical University	Kaohsiung		Taiwan	807
85	Kaohsiung Veterans General Hospital	Kaohsiung		Taiwan	813
86	Chang Gung Memorial Hospital, Kaosiung	Kaosiung		Taiwan	833
87	Chang Gung Memorial Hospital-Keelung	Keelung		Taiwan	204
88	Chung Shan Medical University Hospital	Taichung		Taiwan	402
89	China Medical University Hospital	Taichung		Taiwan	404
90	Taichung Veterans General Hospital	Taichung		Taiwan	407
91	National Taiwan University Hospital	Taipei		Taiwan	100
92	Chang Gung Memorial Hospital, Linko	Tau-Yuan County		Taiwan	333

Sponsors and Collaborators

• Human Genome Sciences Inc.
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, Human Genome Sciences Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: Human Genome Sciences Inc.
• ClinicalTrials.gov Identifier: NCT00424476
• Other Study ID Numbers: HGS1006-C1057; BLISS-52; 110752
• First Posted: Jan 19, 2007
• Last Update Posted: Dec 12, 2016
• Last Verified: Oct 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Human Genome Sciences Inc.: Autoimmune Diseases; Lupus; SLE; Systemic Lupus Erythematosus; Belimumab; Antibodies
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; Belimumab

Study Results

Participant Flow

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
Period Title: Overall Study
STARTED	287	288	290
COMPLETED	226	240	241
NOT COMPLETED	61	48	49

Baseline Characteristics

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg	Total
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Total of all reporting groups
Overall Participants	287	288	290	865
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.2 (11.8)	35.0 (10.6)	35.4 (10.8)	35.5 (11.1)
Age, Customized (participants) [Number]
≤ 45 years	225 78.4%	236 81.9%	236 81.4%	697 80.6%
Between 45 and 65 years	57 19.9%	48 16.7%	52 17.9%	157 18.2%
≥ 65 years	5 1.7%	4 1.4%	2 0.7%	11 1.3%
Gender (Count of Participants)
Female	270 94.1%	271 94.1%	280 96.6%	821 94.9%
Male	17 5.9%	17 5.9%	10 3.4%	44 5.1%
Region of Enrollment (participants) [Number]
Europe	33 11.5%	34 11.8%	31 10.7%	98 11.3%
South America	145 50.5%	143 49.7%	140 48.3%	428 49.5%
Southeast Asia	103 35.9%	106 36.8%	115 39.7%	324 37.5%
Australia	6 2.1%	5 1.7%	4 1.4%	15 1.7%

Outcome Measures

1. Primary Outcome

Title	SLE Responder Index (SRI) Response Rate at Week 52
Description	Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of < 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline. SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E).
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on a modified intention-to-treat (MITT) population, defined as all subjects who were randomized and received at least 1 dose of study agent. Subjects who required rescue SLE medications were declared nonresponders, as were subjects who dropped out or were missing Week 52 data.

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
Measure Participants	287	288	290
Number [Percentage of participants]	43.6 15.2%	51.4 17.8%	57.6 19.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments	For the primary analysis of the primary efficacy endpoint, a step-down sequential testing procedure was used to control the type 1 error.
	Method	Regression, Logistic
	Comments	Adjusted for baseline stratification factors (SELENA SLEDAI Score: ≤9 vs ≥10; proteinuria: <2g vs ≥2g per 24hr; Race: African/indig-American vs Other)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.83
	Confidence Interval	() 95%; 1.30 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 1 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0129
	Comments	After superiority of 10 mg/kg vs placebo was established, the 1 mg/kg group was tested vs placebo (2-sided alpha=0.05).
	Method	Regression, Logistic
	Comments	Adjusted for baseline stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 1.10 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52.
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
Measure Participants	287	288	290
Number [Percentage of participants]	46.0 16%	53.1 18.4%	58.3 20.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments
	Method	Regression, Logistic
	Comments	Adjusted for baseline stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; 1.21 to 2.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 1 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0189
	Comments
	Method	Regression, Logistic
	Comments	Adjusted for baseline stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; 1.07 to 2.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change in Physician's Global Assessment (PGA) at Wk 24.
Description	The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
Measure Participants	287	288	290
Mean (Standard Error) [Scores on a 3-point scale]	-0.39 (0.03)	-0.44 (0.03)	-0.54 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline PGA score and baseline stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 1 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2712
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline PGA score and baseline stratification factors.

4. Secondary Outcome

Title	Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24.
Description	The SF-36 is a generic health related quality of life (HRQOL) measurement. The survey includes 36 questions grouped to 8 domains and 2 summary measures (physical and mental health component, PCS and MCS, respectively) assessing HRQOL. Responses are scored according to the SF-36v2™ manual. A score is calculated for each SF-36 domain based on the patient's response to each question within it. This is then transformed to a scale ranging from 0 (worst) to 100 (best) points. The PCS is norm-based where the mean=50 and standard deviation (SD)=10. Higher scores represent better physical health.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
Measure Participants	287	288	290
Mean (Standard Error) [Scores on a scale]	3.64 (0.42)	3.65 (0.43)	3.58 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8870
	Comments
	Method	ANCOVA
	Comments	Adjusted for the baseline PCS score and baseline stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 1 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8127
	Comments
	Method	ANCOVA
	Comments	Adjusted for the baseline PCS score and baseline stratification factors.

5. Secondary Outcome

Title	Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52
Time Frame	Baseline, Weeks 40 through 52

Outcome Measure Data

Analysis Population Description

Analysis was performed on a MITT population, defined as all subjects who were randomized and received at least 1 dose of study agent. Includes only subjects with baseline prednisone dose > 7.5 mg/day

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
Measure Participants	192	204	204
Number [Percentage of participants]	12.0 4.2%	20.6 7.2%	18.6 6.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0526
	Comments
	Method	Regression, Logistic
	Comments	Adjusted for baseline prednisone dose level and baseline stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.75
	Confidence Interval	(2-Sided) 95%; 0.99 to 3.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 1 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0252
	Comments
	Method	Regression, Logistic
	Comments	Adjusted for baseline prednisone dose level and baseline stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.89
	Confidence Interval	(2-Sided) 95%; 1.08 to 3.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Other Pre-specified Outcome

Title	Adverse Events (AE) Overview
Description	SEE ALSO ADVERSE EVENTS RESULTS SECTION
Time Frame	Up to 56 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Belimumab 1 mg/kg	Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.	Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
Measure Participants	287	288	290
Percent of patients with at least 1 AE	91.6 31.9%	91.7 31.8%	91.7 31.6%
Percent of patients with at least 1 Serious AE	12.5 4.4%	16.3 5.7%	14.1 4.9%
Percent of patients with an AE resulting in death	1.0 0.3%	0.7 0.2%	1.4 0.5%

Adverse Events

Time Frame	Up to 56 weeks.
Adverse Event Reporting Description	Includes AEs reported in subjects from first dose of study agent throughout the study up to the Week 52/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 (HGS 1006-C1074/NCT00712933).
Arm/Group Title	Placebo		Belimumab 1 mg/kg		Belimumab 10 mg/kg
Arm/Group Description	Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.		Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.		Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 48 weeks.
All Cause Mortality
	Placebo		Belimumab 1 mg/kg		Belimumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Belimumab 1 mg/kg		Belimumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/287 (12.5%)		47/288 (16.3%)		41/290 (14.1%)
Blood and lymphatic system disorders
Anaemia	0/287 (0%)		0/288 (0%)		2/290 (0.7%)
Anaemia haemolytic autoimmune	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Haemolytic anaemia	1/287 (0.3%)		0/288 (0%)		2/290 (0.7%)
Hypochromic anaemia	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Lymphopenia	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Thrombocytopenia	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Cardiac disorders
Cardiac arrest	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Cardiac failure congestive	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Myocardial infarction	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Myocardial ischaemia	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Pericardial effusion	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Pericarditis	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Pericarditis lupus	1/287 (0.3%)		0/288 (0%)		1/290 (0.3%)
Ear and labyrinth disorders
Vertigo positional	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Endocrine disorders
Hypothyroidism	0/287 (0%)		2/288 (0.7%)		0/290 (0%)
Eye disorders
Blindness unilateral	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Glaucoma	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Ocular vasculitis	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Retinal detachment	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Gastrointestinal disorders
Abdominal pain	1/287 (0.3%)		1/288 (0.3%)		0/290 (0%)
Diarrhoea	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Gastritis	0/287 (0%)		2/288 (0.7%)		0/290 (0%)
Haematemesis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Ileus paralytic	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Lupus enteritis	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Melaena	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Mesenteric vein thrombosis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Mouth ulceration	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Oesophagitis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Pancreatitis acute	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Peptic ulcer	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Peritonitis	1/287 (0.3%)		0/288 (0%)		1/290 (0.3%)
Vasculitis gastrointestinal	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
General disorders
Death	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Infusion related reaction	1/287 (0.3%)		1/288 (0.3%)		1/290 (0.3%)
Non-cardiac chest pain	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Pyrexia	1/287 (0.3%)		4/288 (1.4%)		4/290 (1.4%)
Hepatobiliary disorders
Biliary dilatation	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Cholangitis acute	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Cholecystitis chronic	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Cholelithiasis	1/287 (0.3%)		2/288 (0.7%)		1/290 (0.3%)
Portal vein thrombosis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Immune system disorders
Anaphylactic reaction	0/287 (0%)		2/288 (0.7%)		1/290 (0.3%)
Drug hypersensitivity	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Food allergy	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Infections and infestations
Acinetobacter bacteraemia	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Acute sinusitis	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Appendiceal abscess	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Appendicitis	0/287 (0%)		0/288 (0%)		2/290 (0.7%)
Appendicitis perforated	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Bacterial sepsis	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Bronchitis	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Cellulitis	1/287 (0.3%)		4/288 (1.4%)		1/290 (0.3%)
Conjunctivitis bacterial	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Cystitis	0/287 (0%)		1/288 (0.3%)		1/290 (0.3%)
Dengue fever	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Diarrhoea infectious	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Ecthyma	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Escherichia sepsis	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Gastroenteritis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Gastroenteritis bacterial	2/287 (0.7%)		0/288 (0%)		0/290 (0%)
Haematoma infection	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Hepatitis A	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Herpes zoster	2/287 (0.7%)		2/288 (0.7%)		1/290 (0.3%)
Herpes zoster multi-dermatomal	0/287 (0%)		2/288 (0.7%)		0/290 (0%)
Joint abscess	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Kidney infection	0/287 (0%)		0/288 (0%)		2/290 (0.7%)
Otitis media chronic	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Phlebitis infective	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Pneumonia	5/287 (1.7%)		1/288 (0.3%)		1/290 (0.3%)
Pneumonia bacterial	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Pyelonephritis	2/287 (0.7%)		1/288 (0.3%)		0/290 (0%)
Sepsis	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Septic shock	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Subcutaneous abscess	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Upper respiratory tract infection	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Urinary tract infection	2/287 (0.7%)		4/288 (1.4%)		2/290 (0.7%)
Viral upper respiratory tract infection	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/287 (0%)		1/288 (0.3%)		1/290 (0.3%)
Femoral neck fracture	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Fibula fracture	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Incisional hernia	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Investigations
Weight decreased	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Metabolism and nutrition disorders
Dehydration	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/287 (0.3%)		0/288 (0%)		1/290 (0.3%)
Intervertebral disc protrusion	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Myalgia	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Myositis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Osteochondrosis	1/287 (0.3%)		1/288 (0.3%)		0/290 (0%)
Osteonecrosis	0/287 (0%)		3/288 (1%)		1/290 (0.3%)
SLE arthritis	1/287 (0.3%)		0/288 (0%)		3/290 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Nervous system disorders
Cerebral haemorrhage	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Cerebral infarction	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Headache	1/287 (0.3%)		1/288 (0.3%)		1/290 (0.3%)
Ischaemic stroke	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Syncope	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Tension headache	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/287 (0.3%)		1/288 (0.3%)		3/290 (1%)
Abortion spontaneous incomplete	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Psychiatric disorders
Adjustment disorder	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Completed suicide	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Delirium	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Depression	1/287 (0.3%)		0/288 (0%)		1/290 (0.3%)
Intentional self-injury	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Mania	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Panic attack	1/287 (0.3%)		0/288 (0%)		1/290 (0.3%)
Personality disorder	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Renal and urinary disorders
Cystitis haemorrhagic	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Haematuria	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Lupus nephritis	0/287 (0%)		3/288 (1%)		3/290 (1%)
Nephrotic syndrome	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Renal failure acute	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Renal vein thrombosis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Reproductive system and breast disorders
Menorrhagia	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Uterine haemorrhage	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Uterine polyp	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Dyspnoea	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Pleural effusion	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Respiratory failure	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Skin and subcutaneous tissue disorders
Angioedema	0/287 (0%)		1/288 (0.3%)		1/290 (0.3%)
Cutaneous vasculitis	1/287 (0.3%)		0/288 (0%)		1/290 (0.3%)
Mucocutaneous rash	0/287 (0%)		0/288 (0%)		1/290 (0.3%)
Rash erythematous	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Rash maculo-papular	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Systemic lupus erythematosus rash	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Urticaria	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Vascular disorders
Aortic dissection	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Deep vein thrombosis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Hypertension	0/287 (0%)		1/288 (0.3%)		1/290 (0.3%)
Hypertensive crisis	0/287 (0%)		0/288 (0%)		2/290 (0.7%)
Hypotension	1/287 (0.3%)		1/288 (0.3%)		1/290 (0.3%)
Thrombophlebitis superficial	2/287 (0.7%)		0/288 (0%)		0/290 (0%)
Vasculitis	0/287 (0%)		1/288 (0.3%)		0/290 (0%)
Vena cava thrombosis	1/287 (0.3%)		0/288 (0%)		0/290 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Belimumab 1 mg/kg		Belimumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	222/287 (77.4%)		219/288 (76%)		223/290 (76.9%)
Blood and lymphatic system disorders
Anaemia	13/287 (4.5%)		13/288 (4.5%)		15/290 (5.2%)
Gastrointestinal disorders
Abdominal pain upper	18/287 (6.3%)		8/288 (2.8%)		13/290 (4.5%)
Diarrhoea	19/287 (6.6%)		28/288 (9.7%)		30/290 (10.3%)
Dyspepsia	15/287 (5.2%)		11/288 (3.8%)		11/290 (3.8%)
Gastritis	7/287 (2.4%)		10/288 (3.5%)		15/290 (5.2%)
Mouth ulceration	18/287 (6.3%)		5/288 (1.7%)		12/290 (4.1%)
Nausea	31/287 (10.8%)		16/288 (5.6%)		23/290 (7.9%)
Vomiting	13/287 (4.5%)		16/288 (5.6%)		14/290 (4.8%)
General disorders
Fatigue	12/287 (4.2%)		17/288 (5.9%)		18/290 (6.2%)
Oedema peripheral	21/287 (7.3%)		20/288 (6.9%)		17/290 (5.9%)
Pyrexia	17/287 (5.9%)		15/288 (5.2%)		16/290 (5.5%)
Infections and infestations
Bronchitis	7/287 (2.4%)		21/288 (7.3%)		16/290 (5.5%)
Cystitis	9/287 (3.1%)		12/288 (4.2%)		22/290 (7.6%)
Gastroenteritis	16/287 (5.6%)		20/288 (6.9%)		12/290 (4.1%)
Influenza	25/287 (8.7%)		22/288 (7.6%)		33/290 (11.4%)
Nasopharyngitis	23/287 (8%)		30/288 (10.4%)		20/290 (6.9%)
Pharyngitis	7/287 (2.4%)		16/288 (5.6%)		15/290 (5.2%)
Upper respiratory tract infection	47/287 (16.4%)		41/288 (14.2%)		36/290 (12.4%)
Urinary tract infection	24/287 (8.4%)		27/288 (9.4%)		26/290 (9%)
Musculoskeletal and connective tissue disorders
Arthralgia	33/287 (11.5%)		21/288 (7.3%)		32/290 (11%)
Arthritis	18/287 (6.3%)		13/288 (4.5%)		15/290 (5.2%)
Back pain	25/287 (8.7%)		25/288 (8.7%)		19/290 (6.6%)
Nervous system disorders
Dizziness	23/287 (8%)		16/288 (5.6%)		15/290 (5.2%)
Headache	75/287 (26.1%)		58/288 (20.1%)		66/290 (22.8%)
Psychiatric disorders
Insomnia	14/287 (4.9%)		9/288 (3.1%)		21/290 (7.2%)
Respiratory, thoracic and mediastinal disorders
Cough	25/287 (8.7%)		23/288 (8%)		16/290 (5.5%)
Dyspnoea	15/287 (5.2%)		6/288 (2.1%)		3/290 (1%)
Skin and subcutaneous tissue disorders
Pruritus	17/287 (5.9%)		10/288 (3.5%)		17/290 (5.9%)
Vascular disorders
Hypertension	30/287 (10.5%)		24/288 (8.3%)		17/290 (5.9%)

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 earlier of the multi-center trial results are published or 12 months after the end or termination of the multi-center trial at all sites. 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. The sponsor may delay publication for up to 3 months.