GSK1550188 A 52 Week Study of Belimumab Versus Placebo in the Treatment of Subjects With Systemic Lupus Erythematosus (SLE) Located in Northeast Asia

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01345253
• Collaborator: Human Genome Sciences Inc. (Industry)
• Enrollment: 709
• Locations: 47
• Arms: 2
• Actual Duration (Months): 88
• Patients Per Site: 15.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of belimumab in addition to standard therapy compared to placebo in subjects in Northeast Asia with systemic lupus erythematosus (SLE) over a 52 week period.

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

Detailed Description

The purpose of this study is to demonstrate the efficacy and safety of belimumab 10mg/kg administered intravenously (IV) every 4 weeks compared to placebo, in patients with SLE when added to standard of care therapy, as measured by the SLE Responder Index (SRI) at 52 weeks, defined by a composite endpoint using SELENA SLEDAI score, Physician's Global Assessment (PGA) and BILAG A and B organ domain scores.

Study Design

• Study Type: Interventional
• Actual Enrollment: 709 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: GSK1550188 A 52 Week Study of Belimumab Versus Placebo in the Treatment of Subjects With Systemic Lupus Erythematosus (SLE) Located in Northeast Asia
• Actual Study Start Date: May 23, 2011
• Actual Primary Completion Date: Sep 15, 2015
• Actual Study Completion Date: Sep 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Belimumab 10mg/kg	Drug: Belimumab; 10mg/kg administered intravenously. Dosing at Weeks 0, 2, and 4, then every 4 weeks through Week 48, with a final evaluation at Week 52. All study subjects will receive standard SLE therapies during the study.
Placebo Comparator: Placebo placebo	Drug: Placebo; Administered intravenously. Dosing at Weeks 0, 2, and 4, and then every 4 weeks through Week 48, with a final evaluation at Week 52. All study subjects will receive standard SLE therapies during the study.

Outcome Measures

Primary Outcome Measures

1. Percent of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response Rate at Week 52 for Double-blind Phase. [Week 52]

   SRI response is a composite index, defined as the percent of participants with >=4 point reduction from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score and no worsening (increase of < 0.30 points from Baseline) in physicians global assessment (PGA) and no new British isles lupus assessment group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period). A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range. The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).

Secondary Outcome Measures

1. Percent of Participants With >=4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52 for Double-blind Phase. [Baseline (Day 0) and Week 52]

   The SELENA SLEDAI score is a weighted index for assessing SLE disease activity in which signs and symptoms, laboratory tests and physician's assessment for each of 9 organ system were given a weighted score and summed if present at the time of the visit or in the preceding 10 days. A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. A decrease of 4 points or more equates to a clinically meaningful improvement. The Baseline value of a variable is defined as the value of the variable measured at Day 0 prior to dosing. In case of multiple results on Day 0 prior to dosing, the latest result was used. If a Day 0 value was not available, the last available value prior to Day 0 was used.

2. Percent of Participants With SRI7 Response at Week 52 for Double-blind Phase. [Baseline (Day 0) and Week 52]

   SRI7 response is defined as the percent of participants with >=7 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 at the time of assessment (at Week 52 of the blinded period). A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range. The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).

3. Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Reduced by 50 Percent From Baseline Over 52 Weeks for Double-blind Phase. [Week 52]

   Number of days of daily prednisone dose <=7.5 mg/day and/or reduced by 50 percent over time through each scheduled visit during the blinded period were compared between belimumab and placebo using Rank ANCOVA model which was used for comparing belimumab and placebo. The independent variables in the model included treatment group, Baseline prednisone dose level, country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4). This analysis was perfomed on the participants who used prednisone >7.5 mg/day at Baseline.

4. Time to First Severe SLE Flare Index (SFI) Flare Over 52 Weeks for Double-blind Phase. [52 weeks]

   Time to first severe SLE flare is defined as the number of days from first treatment until the participant had an event (event date-treatement start date +1). If a participant had a severe SFI flare and received protocol restricted medication then the event date was the earliest of the first severe SFI flare date, and the treatment failure date. Analysis of severe SFI flare was performed on the modified SELENA SLEDAI SLE flare index in which the modification excluded severe flares that were triggered only by an increase in SELENA SLEDAI score to >12. Analysis was from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).

5. Percent of Participants Achieving SLE SRI Response Rate for Open-label (OL) Phase [Weeks 24 and 48 for Years 2, 3, 4, 5 and 6]

   SRI response is a composite index, defined as the percent of participants with >=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 at time of assessment. Excludes participants with a SELENA SLEDAI score <4 at baseline. Participants randomized to belimumab in double-blinded (DB) phase, Baseline is last available value before first belimumab dose received in DB phase. Participants randomized to placebo in DB phase, Baseline is last available value before receiving first belimumab dose in OL phase. Observed case data are presented.Year 6 Week 48 is the Exit Visit obtained by slotting the Exit Visit to Week 48. A SELENA SLEDAI score of 0 (no lupus activity) and a score of 105 (maximum). PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 18 years and older.

• Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria.

• Have active SLE disease.

• Have positive anti-nuclear antibody (ANA) test results.

• Are on a stable SLE treatment regimen.

• Females of childbearing age are willing to use appropriate contraception

Exclusion Criteria:

• Have received treatment with any B cell targeted therapy at any time.

• Have received a biologic investigational agent in the past year.

• Have received 3 or more courses of systemic corticosteroids in the past year.

• Have received intravenous (IV) cyclophosphamide within 180 days prior to Day 0.

• Have severe lupus kidney disease.

• Have active central nervous system (CNS) lupus.

• Have had a major organ transplant.

• Have significant unstable or uncontrolled acute or chronic diseases or conditions not due to SLE.

• Have a planned surgical procedure.

• Cancer within the last 5 years, except for adequately treated skin cancer, or carcinoma in situ of the uterine cervix.

• Have required management of acute or chronic infections in 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.

• Have an IgA deficiency.

• Have severe laboratory Abnormalities.

• Have had anaphylactic reaction to X-ray contrast agents or biologic agents.

• Suicidal behavior or ideation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Hefei	Anhui	China	230001
2	GSK Investigational Site	Guangzhou	Guangdong	China	510080
3	GSK Investigational Site	Guangzhou	Guangdong	China	510260
4	GSK Investigational Site	Guangzhou	Guangdong	China	510630
5	GSK Investigational Site	Harbin	Heilongjiang	China	150001
6	GSK Investigational Site	Changsha	Hunan	China	410008
7	GSK Investigational Site	Changsha	Hunan	China	410011
8	GSK Investigational Site	Nanjing	Jiangsu	China	210029
9	GSK Investigational Site	Suzhou	Jiangsu	China	215006
10	GSK Investigational Site	Xian	Shaanxi	China	710032
11	GSK Investigational Site	Jinan	Shandong	China	250012
12	GSK Investigational Site	Chengdu	Sichuan	China	610041
13	GSK Investigational Site	Kunming	Yunnan	China	650101
14	GSK Investigational Site	Hangzhou	Zhejiang	China	310009
15	GSK Investigational Site	Beijing		China	100029
16	GSK Investigational Site	Beijing		China	100032
17	GSK Investigational Site	Beijing		China	100044
18	GSK Investigational Site	Chongqing		China	400038
19	GSK Investigational Site	Shanghai		China	200001
20	GSK Investigational Site	Shanghai		China	200003
21	GSK Investigational Site	Shanghai		China	200025
22	GSK Investigational Site	Shanghai		China	200433
23	GSK Investigational Site	Tianjin		China	300052
24	GSK Investigational Site	Chiba		Japan	275-8580
25	GSK Investigational Site	Ehime		Japan	791-0295
26	GSK Investigational Site	Fukuoka		Japan	807-8555
27	GSK Investigational Site	Fukuoka		Japan	810-8563
28	GSK Investigational Site	Hiroshima		Japan	730-8619
29	GSK Investigational Site	Hiroshima		Japan	739-0002
30	GSK Investigational Site	Hokkaido		Japan	060-8604
31	GSK Investigational Site	Hokkaido		Japan	060-8648
32	GSK Investigational Site	Hyogo		Japan	675-8545
33	GSK Investigational Site	Miyagi		Japan	980-8574
34	GSK Investigational Site	Nagasaki		Japan	852-8501
35	GSK Investigational Site	Nagasaki		Japan	857-1195
36	GSK Investigational Site	Okayama		Japan	710-0824
37	GSK Investigational Site	Okinawa		Japan	901-0243
38	GSK Investigational Site	Tochigi		Japan	321-0293
39	GSK Investigational Site	Tokyo		Japan	113-8431
40	GSK Investigational Site	Busan		Korea, Republic of
41	GSK Investigational Site	Daegu		Korea, Republic of	700-721
42	GSK Investigational Site	Incheon		Korea, Republic of	400-711
43	GSK Investigational Site	Seoul		Korea, Republic of	110-744
44	GSK Investigational Site	Seoul		Korea, Republic of	133-792
45	GSK Investigational Site	Seoul		Korea, Republic of	137-701
46	GSK Investigational Site	Seoul		Korea, Republic of
47	GSK Investigational Site	Suwon, Kyonggi-do		Korea, Republic of	443-721

Sponsors and Collaborators

• GlaxoSmithKline
• Human Genome Sciences Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• Zhang F, Bae SC, Bass D, Chu M, Egginton S, Gordon D, Roth DA, Zheng J, Tanaka Y. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018 Mar;77(3):355-363. doi: 10.1136/annrheumdis-2017-211631. Epub 2018 Jan 2.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01345253
• Other Study ID Numbers: 113750
• First Posted: May 2, 2011
• Last Update Posted: Oct 4, 2019
• Last Verified: Sep 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: SLEDAI; Asia; placebo; BLys; PGA; BILAG; systemic lupus erythematosus; SELENA; Lupus; SRI; efficacy; B cell; SLE Flare Index; belimumab; safety; phase III; B lymphocyte
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; Belimumab

Study Results

Participant Flow

Recruitment Details	This study consisted of a 52 week blinded treatment period in Northeast Asia (China, Japan, Korea) which was followed by an optional open-label (OL) extension period in China for evaluation of belimumab in participants (par.) with active systemic lupus erythematosus (SLE).
Pre-assignment Detail	A total of 707 par. were randomized, 705 received at least 1 dose of investigational product (Safety Population), 677 par. were included in the primary efficacy population (MITT Population) of which 663 were evaluable for the primary endpoint. The participant flow and baseline characteristics are presented for MITT Population (Pop).

Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 milligrams (mg)/kilogram (kg) up to Year 5 Week 28.	Participants received belimumab 10 mg/kg IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 mg/kg up to Year 5 Week 28.
Period Title: Double-blind (DB) Phase (52 Weeks)
STARTED	226	451
COMPLETED	170	372
NOT COMPLETED	56	79
Period Title: Double-blind (DB) Phase (52 Weeks)
STARTED	134	290
COMPLETED	69	146
NOT COMPLETED	65	144

Baseline Characteristics

Arm/Group Title	Placebo	Belimumab 10 mg/kg	Total
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 milligrams (mg)/kilogram (kg) up to Year 5 Week 28.	Participants received belimumab 10 mg/kg IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 mg/kg up to Year 5 Week 28.	Total of all reporting groups
Overall Participants	226	451	677
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.7 (9.18)	32.3 (9.65)	32.1 (9.50)
Sex: Female, Male (Count of Participants)
Female	210 92.9%	419 92.9%	629 92.9%
Male	16 7.1%	32 7.1%	48 7.1%
Race/Ethnicity, Customized (Count of Participants)
Asian - Central/South Asian Heritage	2 0.9%	4 0.9%	6 0.9%
Asian - East Asian Heritage	195 86.3%	403 89.4%	598 88.3%
Asian - Japanese Heritage	24 10.6%	40 8.9%	64 9.5%
Asian - South East Asian Heritage	4 1.8%	3 0.7%	7 1%
Asian - Mixed Race	1 0.4%	1 0.2%	2 0.3%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response Rate at Week 52 for Double-blind Phase.
Description	SRI response is a composite index, defined as the percent of participants with >=4 point reduction from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score and no worsening (increase of < 0.30 points from Baseline) in physicians global assessment (PGA) and no new British isles lupus assessment group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period). A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range. The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Modified Intention-to-Treat (MITT) Population: all participants who were randomized and treated with at least one dose of study treatment, with exclusion of participants from the site 086485.

Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 milligrams (mg)/kilogram (kg) up to Year 5 Week 28.	Participants received belimumab 10 mg/kg IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 mg/kg up to Year 5 Week 28.
Measure Participants	217	446
Number [Percentage of participants]	40.1 17.7%	53.8 11.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.99
	Confidence Interval	(2-Sided) 95%; 1.40 to 2.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (95% CI) and p-value were estimated by a logistic regression model with independent variables treatment group, country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement (C) levels (low C3 and/or C4 vs. no low C3 or C4).

2. Secondary Outcome

Title	Percent of Participants With >=4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52 for Double-blind Phase.
Description	The SELENA SLEDAI score is a weighted index for assessing SLE disease activity in which signs and symptoms, laboratory tests and physician's assessment for each of 9 organ system were given a weighted score and summed if present at the time of the visit or in the preceding 10 days. A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. A decrease of 4 points or more equates to a clinically meaningful improvement. The Baseline value of a variable is defined as the value of the variable measured at Day 0 prior to dosing. In case of multiple results on Day 0 prior to dosing, the latest result was used. If a Day 0 value was not available, the last available value prior to Day 0 was used.
Time Frame	Baseline (Day 0) and Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 milligrams (mg)/kilogram (kg) up to Year 5 Week 28.	Participants received belimumab 10 mg/kg IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 mg/kg up to Year 5 Week 28.
Measure Participants	218	447
Number [Percentage of participants]	42.2 18.7%	55.7 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 95%; 1.41 to 2.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (95% CI) and p-value were estimated by a logistic regression model with independent variables treatment group, country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).

3. Secondary Outcome

Title	Percent of Participants With SRI7 Response at Week 52 for Double-blind Phase.
Description	SRI7 response is defined as the percent of participants with >=7 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 at the time of assessment (at Week 52 of the blinded period). A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range. The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).
Time Frame	Baseline (Day 0) and Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 milligrams (mg)/kilogram (kg) up to Year 5 Week 28.	Participants received belimumab 10 mg/kg IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 mg/kg up to Year 5 Week 28.
Measure Participants	183	367
Number [Percentage of participants]	23.5 10.4%	32.4 7.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0116
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 1.13 to 2.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (95% CI) and p-value were estimated by a logistic regression model with independent variables treatment group, country, baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).

4. Secondary Outcome

Title	Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Reduced by 50 Percent From Baseline Over 52 Weeks for Double-blind Phase.
Description	Number of days of daily prednisone dose <=7.5 mg/day and/or reduced by 50 percent over time through each scheduled visit during the blinded period were compared between belimumab and placebo using Rank ANCOVA model which was used for comparing belimumab and placebo. The independent variables in the model included treatment group, Baseline prednisone dose level, country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4). This analysis was perfomed on the participants who used prednisone >7.5 mg/day at Baseline.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 milligrams (mg)/kilogram (kg) up to Year 5 Week 28.	Participants received belimumab 10 mg/kg IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 mg/kg up to Year 5 Week 28.
Measure Participants	184	352
Median (Inter-Quartile Range) [Days]	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0288
	Comments
	Method	Rank ANCOVA
	Comments

5. Secondary Outcome

Title	Time to First Severe SLE Flare Index (SFI) Flare Over 52 Weeks for Double-blind Phase.
Description	Time to first severe SLE flare is defined as the number of days from first treatment until the participant had an event (event date-treatement start date +1). If a participant had a severe SFI flare and received protocol restricted medication then the event date was the earliest of the first severe SFI flare date, and the treatment failure date. Analysis of severe SFI flare was performed on the modified SELENA SLEDAI SLE flare index in which the modification excluded severe flares that were triggered only by an increase in SELENA SLEDAI score to >12. Analysis was from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 milligrams (mg)/kilogram (kg) up to Year 5 Week 28.	Participants received belimumab 10 mg/kg IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the double-blind period. All China participants who completed double-blind period and eligible to enter open-label phase received belimumab 10 mg/kg up to Year 5 Week 28.
Measure Participants	226	451
Median (Inter-Quartile Range) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.34 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percent of Participants Achieving SLE SRI Response Rate for Open-label (OL) Phase
Description	SRI response is a composite index, defined as the percent of participants with >=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 at time of assessment. Excludes participants with a SELENA SLEDAI score <4 at baseline. Participants randomized to belimumab in double-blinded (DB) phase, Baseline is last available value before first belimumab dose received in DB phase. Participants randomized to placebo in DB phase, Baseline is last available value before receiving first belimumab dose in OL phase. Observed case data are presented.Year 6 Week 48 is the Exit Visit obtained by slotting the Exit Visit to Week 48. A SELENA SLEDAI score of 0 (no lupus activity) and a score of 105 (maximum). PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range.
Time Frame	Weeks 24 and 48 for Years 2, 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

Efficacy Population: all participants in China who received at least 1 dose of belimumab during open-label phase, exclusive of site 086485. Only those participants available at the specified time points were analyzed (represented by n=x).

Arm/Group Title	Belimumab 10mg/kg (Open-label Phase)
Arm/Group Description	All eligible China participants who had received placebo and belimumab in DB period and entered open-label phase to receive belimumab 10 mg/kg over 1 hour every 28 days from first belimumab date through end of open-label phase.
Measure Participants	399
Week 24, Year 2, n=326	66.0 29.2%
Week 48, Year 2, n=299	69.6 30.8%
Week 24, Year 3, n=271	72.3 32%
Week 48, Year 3, n=247	70.9 31.4%
Week 24, Year 4, n=233	71.7 31.7%
Week 48, Year 4, n=194	76.8 34%
Week 24, Year 5, n= 156	81.4 36%
Week 48, Year 5, n= 82	80.5 35.6%
Week 24, Year 6, n= 36	86.1 38.1%
Week 48, Year 6, n= 5	60.0 26.5%

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-SAEs were collected from study treatment start and until 16 weeks after the last infusion. The data presented for belimumab open-label group represents safety events period starting from the first belimumab date and up to Year 6 Week 44.
Adverse Event Reporting Description	SAEs and non-serious AEs were reported for the Safety Population consisted of all participants who received at least one dose of study drug. The first belimumab date was first dose received in DB phase for participants randomized to belimumab in DB phase; first dose received in OL phase for participants randomized to placebo in DB phase.
Arm/Group Title	Placebo (Double-blind Phase)		Belimumab 10 mg/kg (Double-blind Phase)		Belimumab 10 mg/kg (Open-label Phase)
Arm/Group Description	Participants received placebo intravenously (IV) on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the blinded period.		Participants received belimumab 10 miligrams (mg)/kilogram (kg) IV on Day 0, Day 14, Day 28 and then every 28 days until Week 48 of the blinded period.		All eligible China participants who had received placebo and belimumab in DB period and entered open-label phase to receive belimumab 10 mg/kg over 1 hour every 28 days from first belimumab date through end of open-label phase.
All Cause Mortality
	Placebo (Double-blind Phase)		Belimumab 10 mg/kg (Double-blind Phase)		Belimumab 10 mg/kg (Open-label Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/235 (0.4%)		0/470 (0%)		1/424 (0.2%)
Serious Adverse Events
	Placebo (Double-blind Phase)		Belimumab 10 mg/kg (Double-blind Phase)		Belimumab 10 mg/kg (Open-label Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/235 (18.3%)		58/470 (12.3%)		96/424 (22.6%)
Blood and lymphatic system disorders
Pancytopenia	1/235 (0.4%)		1/470 (0.2%)		0/424 (0%)
Histiocytosis haematophagic	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Leukopenia	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Anaemia	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Granulocytopenia	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Thrombocytopenia	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Haemolytic anaemia	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Cardiac disorders
Cardiomyopathy	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Cardiac failure	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Myocardial ischaemia	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Wolff-Parkinson-White syndrome	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Congenital, familial and genetic disorders
Dermoid cyst	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Ear and labyrinth disorders
Vertigo	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Vertigo positional	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Eye disorders
Cataract	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Glaucoma	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Retinal detachment	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Gastrointestinal disorders
Abdominal pain	0/235 (0%)		2/470 (0.4%)		1/424 (0.2%)
Allergic colitis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Haemorrhoidal haemorrhage	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Lupus pancreatitis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Oesophageal varices haemorrhage	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Pancreatitis chronic	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Ascites	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Chronic gastritis	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Gastric varices haemorrhage	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Haemorrhoids	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Intestinal obstruction	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Intestinal perforation	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Intestinal pseudo-obstruction	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Upper gastrointestinal haemorrhage	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
General disorders
Pyrexia	4/235 (1.7%)		2/470 (0.4%)		1/424 (0.2%)
Generalised oedema	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Polyserositis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Chest discomfort	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Granuloma	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Peripheral swelling	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Hepatobiliary disorders
Hepatic function abnormal	0/235 (0%)		2/470 (0.4%)		2/424 (0.5%)
Cholelithiasis	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Infections and infestations
Herpes zoster	2/235 (0.9%)		6/470 (1.3%)		6/424 (1.4%)
Pneumonia	1/235 (0.4%)		2/470 (0.4%)		4/424 (0.9%)
Appendicitis	0/235 (0%)		2/470 (0.4%)		2/424 (0.5%)
Lung infection	2/235 (0.9%)		0/470 (0%)		2/424 (0.5%)
Pyelonephritis acute	0/235 (0%)		2/470 (0.4%)		0/424 (0%)
Salmonella sepsis	2/235 (0.9%)		0/470 (0%)		0/424 (0%)
Skin infection	1/235 (0.4%)		1/470 (0.2%)		0/424 (0%)
Arthritis salmonella	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Bacterial pyelonephritis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Cellulitis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Cellulitis streptococcal	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Cystitis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Cytomegalovirus infection	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Disseminated tuberculosis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Enteritis infectious	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Escherichia urinary tract infection	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Gastroenteritis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Gastrointestinal fungal infection	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Infectious colitis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Lymph node tuberculosis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Meningitis tuberculous	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Otitis media acute	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Pneumonia bacterial	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Pneumonia mycoplasmal	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Pneumonia streptococcal	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Sepsis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Spleen tuberculosis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Tuberculosis liver	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Tuberculous pleurisy	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Upper respiratory tract infection bacterial	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Urinary tract infection enterococcal	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Viral upper respiratory tract infection	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Upper respiratory tract infection	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Soft tissue infection	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Pulmonary tuberculosis	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Pneumonia viral	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Periorbital infection	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Periodontitis	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Ludwig angina	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Gingivitis	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Cutaneous tuberculosis	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Breast abscess	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Bartholin's abscess	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Injury, poisoning and procedural complications
Contusion	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Femoral neck fracture	1/235 (0.4%)		0/470 (0%)		1/424 (0.2%)
Fractured sacrum	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Humerus fracture	0/235 (0%)		1/470 (0.2%)		1/424 (0.2%)
Jaw fracture	0/235 (0%)		1/470 (0.2%)		1/424 (0.2%)
Ligament rupture	0/235 (0%)		1/470 (0.2%)		1/424 (0.2%)
Patella fracture	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Road traffic accident	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Scapula fracture	0/235 (0%)		1/470 (0.2%)		1/424 (0.2%)
Fall	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Spinal compression fracture	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Concussion	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Lip injury	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Meniscus injury	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Multiple fractures	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Post procedural haemorrhage	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Thermal burn	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Thoracic vertebral fracture	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Investigations
Blood creatinine increased	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Platelet count decreased	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Protein urine present	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Metabolism and nutrition disorders
Hyperkalaemia	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Hypoproteinaemia	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Musculoskeletal and connective tissue disorders
SLE arthritis	2/235 (0.9%)		0/470 (0%)		0/424 (0%)
Intervertebral disc protrusion	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Synovial cyst	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Tenosynovitis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Loose body in joint	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Osteonecrosis	0/235 (0%)		0/470 (0%)		6/424 (1.4%)
Arthralgia	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Systemic lupus erythematosus	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/235 (0%)		2/470 (0.4%)		2/424 (0.5%)
Anogenital warts	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Benign breast neoplasm	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Cervix carcinoma	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Ovarian adenoma	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Thyroid adenoma	0/235 (0%)		1/470 (0.2%)		1/424 (0.2%)
Fibroadenoma of breast	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Benign ear neoplasm	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Benign renal neoplasm	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Haemangioma	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Haemangioma of liver	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Vaginal cancer	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Papillary thyroid cancer	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Nervous system disorders
Lupus encephalitis	1/235 (0.4%)		1/470 (0.2%)		1/424 (0.2%)
Brain stem infarction	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Cerebral infarction	0/235 (0%)		1/470 (0.2%)		1/424 (0.2%)
Dysarthria	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Epilepsy	1/235 (0.4%)		0/470 (0%)		1/424 (0.2%)
Syncope	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Cerebrovascular insufficiency	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Hypoaesthesia	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Neuropsychiatric lupus	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Noninfectious myelitis	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Abortion spontaneous	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Foetal growth restriction	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Psychiatric disorders
Acute psychosis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Suicidal ideation	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Suicide attempt	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Post-traumatic stress disorder	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Renal and urinary disorders
Lupus nephritis	5/235 (2.1%)		5/470 (1.1%)		12/424 (2.8%)
Proteinuria	2/235 (0.9%)		0/470 (0%)		0/424 (0%)
Renal failure	0/235 (0%)		2/470 (0.4%)		0/424 (0%)
Haematuria	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Hydronephrosis	1/235 (0.4%)		0/470 (0%)		1/424 (0.2%)
Lupus cystitis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Ureteric stenosis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Nephrolithiasis	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Ureterolithiasis	0/235 (0%)		0/470 (0%)		2/424 (0.5%)
Reproductive system and breast disorders
Metrorrhagia	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Bartholin's cyst	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Dysfunctional uterine bleeding	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Endometrial thickening	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Menstruation irregular	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Lupus pleurisy	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Lupus pneumonitis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Pulmonary hypertension	0/235 (0%)		1/470 (0.2%)		1/424 (0.2%)
Respiratory failure	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Erythema multiforme	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Systemic lupus erythematosus rash	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Drug eruption	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Erythema	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Vascular disorders
Arterial rupture	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Deep vein thrombosis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Lupus vasculitis	0/235 (0%)		1/470 (0.2%)		0/424 (0%)
Necrosis ischaemic	0/235 (0%)		1/470 (0.2%)		2/424 (0.5%)
Phlebitis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Varicose vein	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Vasculitis	1/235 (0.4%)		0/470 (0%)		0/424 (0%)
Thrombophlebitis superficial	0/235 (0%)		0/470 (0%)		1/424 (0.2%)
Other (Not Including Serious) Adverse Events
	Placebo (Double-blind Phase)		Belimumab 10 mg/kg (Double-blind Phase)		Belimumab 10 mg/kg (Open-label Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	108/235 (46%)		207/470 (44%)		263/424 (62%)
Gastrointestinal disorders
Diarrhoea	14/235 (6%)		28/470 (6%)		28/424 (6.6%)
General disorders
Pyrexia	17/235 (7.2%)		28/470 (6%)		36/424 (8.5%)
Infections and infestations
Upper respiratory tract infection	39/235 (16.6%)		65/470 (13.8%)		149/424 (35.1%)
Nasopharyngitis	26/235 (11.1%)		56/470 (11.9%)		24/424 (5.7%)
Viral upper respiratory tract infection	15/235 (6.4%)		33/470 (7%)		59/424 (13.9%)
Upper respiratory tract infection bacterial	12/235 (5.1%)		16/470 (3.4%)		37/424 (8.7%)
Urinary tract infection	11/235 (4.7%)		21/470 (4.5%)		41/424 (9.7%)
Herpes zoster	10/235 (4.3%)		23/470 (4.9%)		34/424 (8%)
Urinary tract infection bacterial	2/235 (0.9%)		20/470 (4.3%)		23/424 (5.4%)
Metabolism and nutrition disorders
Hypokalaemia	8/235 (3.4%)		11/470 (2.3%)		24/424 (5.7%)
Nervous system disorders
Headache	16/235 (6.8%)		23/470 (4.9%)		20/424 (4.7%)
Respiratory, thoracic and mediastinal disorders
Cough	16/235 (6.8%)		30/470 (6.4%)		30/424 (7.1%)

Limitations/Caveats

The primary objective for DB was efficacy and the participant flow is aligned with the MITT population. The primary objective for OL is safety and includes only China par. from DB + additional 25 China par. from the Safety Pop who were not in MITT.

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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.