Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis (BLISS-LN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01639339

Recruitment Status : Completed

First Posted : July 12, 2012

Results First Posted : July 7, 2020

Last Update Posted : March 19, 2021

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

GlaxoSmithKline

Information provided by (Responsible Party):

GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Lupus Nephritis
Interventions	Biological: Placebo plus standard therapy Biological: Belimumab 10 mg/kg plus standard therapy Drug: Standard therapy
Enrollment	448

Participant Flow

Recruitment Details	This study evaluated safety and efficacy of intravenous (IV) belimumab 10 mg/kg plus standard of care (SoC) compared to placebo plus SoC in adult participants with active lupus nephritis. This was a Phase 3, multi-center, multi-national study consisting of a randomized, double-blind, placebo-controlled period and an open-label extension period. The study was conducted in 21 countries.
Pre-assignment Details	A total of 797 participants were screened of which 349 participants failed screening and 448 participants were randomized in double-blind period. In open-label period, a total of 257 participants were enrolled of which 2 participants did not receive open-label study treatment and 255 participants received open-label belimumab.


Arm/Group Title	Placebo to Belimumab 10 mg/kg	Belimumab 10 mg/kg to Belimumab 10
Arm/Group Description	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description	Participants were randomized to receive matching placebo intravenous (IV) plus standard of care (SoC) on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race. After completing the double-blind period, eligible participants that were randomized to placebo IV plus SOC received Belimumab 10 milligram per kilogram (mg/kg) every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.	Participants were randomized to receive Belimumab 10 mg/kg IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race. After completing the double-blind period, eligible participants that were randomized to belimumab 10 mg/kg IV plus SOC continued to receive Belimumab 10 mg/kg every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.
Period Title: Double-blind Period (Up to Week 104)
Started	224	224
Completed	170	186
Not Completed	54	38
Reason Not Completed
Withdrawal by Subject	26	19
Physician Decision	11	5
Lost to Follow-up	5	4
Protocol Violation	0	2
Lack of Efficacy	2	1
Adverse Event	10	7
Period Title: Open-label Period (Up to Week 28)
Started	123 ^[1]	132
Completed	122	124
Not Completed	1	8
Reason Not Completed
Withdrawal by Subject	0	2
Lost to Follow-up	0	1
Protocol Violation	0	1
Adverse Event	1	4
[1] Of the 356 participants who completed the double-blind period, 279 were eligible for open-label treatment. As enrolling into the open-label period was optional, only 257 participants enrolled, of whom 255 started open-label treatment.

Baseline Characteristics

Arm/Group Title		Placebo to Belimumab 10 mg/kg	Belimumab 10 mg/kg to Belimumab 10	Total
Arm/Group Description		Participants were randomized to rec...	Participants were randomized to rec...	Total of all reporting groups
Arm/Group Description		Participants were randomized to receive matching placebo intravenous (IV) plus standard of care (SoC) on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race. After completing the double-blind period, eligible participants that were randomized to placebo IV plus SOC received Belimumab 10 milligram per kilogram (mg/kg) every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.	Participants were randomized to receive Belimumab 10 mg/kg IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race. After completing the double-blind period, eligible participants that were randomized to belimumab 10 mg/kg IV plus SOC continued to receive Belimumab 10 mg/kg every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.	Total of all reporting groups
Overall Number of Baseline Participants		224	224	448
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	224 participants	224 participants	448 participants
		33.0 (10.64)	33.7 (10.73)	33.4 (10.68)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	224 participants	224 participants	448 participants
	Female	196 87.5%	198 88.4%	394 87.9%
	Male	28 12.5%	26 11.6%	54 12.1%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	224 participants	224 participants	448 participants
American Indian (AI) or Alaska Native (AN)		6 2.7%	4 1.8%	10 2.2%
Asian-Central/South Asian Heritage (H)		2 0.9%	3 1.3%	5 1.1%
Asian-Japanese/East Asian/Southeast Asian H		107 47.8%	112 50.0%	219 48.9%
Mixed Asian		1 0.4%	0 0.0%	1 0.2%
Black or African American (AA)		31 13.8%	30 13.4%	61 13.6%
White/Caucasian/European H		71 31.7%	72 32.1%	143 31.9%
White/Caucasian/Arabic/North African H		4 1.8%	1 0.4%	5 1.1%
Multiple-AA/African H and AI or AN and White		1 0.4%	1 0.4%	2 0.4%
Multiple-Asian and White		1 0.4%	1 0.4%	2 0.4%

Outcome Measures

1.Primary Outcome


Title	Double-blind Period: Percentage of Participants With Primary Efficacy Renal Response (PERR) at Week 104
Description	PERR is defined as urinary protein creatinine ratio <=0.7, estimate...
Description	PERR is defined as urinary protein creatinine ratio <=0.7, estimated glomerular filtration rate (eGRF) was not more than 20 percent (%) below the pre-flare value or >=60 milliliters per minute per 1.73 square meter (mL/min/1.73m^2) and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates treatment group, induction regimen (CYC vs. MMF), race (Black vs. Non-Black), Baseline urine protein-creatinine ratio (uPCR), and Baseline eGFR. Modified Intent-to-treat (mITT) Population consisted of all randomized participants who received at least one dose of study treatment and were not excluded due to Good Clinical Practice (GCP) non-compliance. Percentage of participants with PERR at Week 104 has been presented.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

mITT Population.


Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.	Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.
Overall Number of Participants Analyzed	223	223
Measure Type: Number Unit of Measure: Percentage of participants
	32.3	43.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0311
	Comments	P-value was calculated using logistic regression model. Test 1 of 5 in a step-down sequential testing procedure.
	Method	Regression, Logistic
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95% 1.04 to 2.32
	Estimation Comments	Treatment comparison between Belimumab 10 mg/kg and placebo using odds ratio and its corresponding 95% confidence interval has been presented.

2.Primary Outcome


Title	Open-label Period: Number of Participants Reporting Adverse Events (AEs) and Serious AEs (SAEs)
Description	An AE is any untoward medical occurrence in a participant or clinical ...
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AEs and SAEs have been reported.
Time Frame	From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)

Outcome Measure Data

Analysis Population Description

Safety Open-Label Population comprised of all participants who received at least one dose of open-label treatment.


Arm/Group Title	Placebo to Belimumab 10 mg/kg	Belimumab 10 mg/kg to Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo intravenous (IV) plus standard of care (SoC) on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race. After completing the double-blind period, eligible participants that were randomized to placebo IV plus SOC received Belimumab 10 milligram per kilogram (mg/kg) every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.	Participants were randomized to receive Belimumab 10 mg/kg IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race. After completing the double-blind period, eligible participants that were randomized to belimumab 10 mg/kg IV plus SOC continued to receive Belimumab 10 mg/kg every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.
Overall Number of Participants Analyzed	123	132
Measure Type: Count of Participants Unit of Measure: Participants
Any AE	76 61.8%	92 69.7%
Any SAE	5 4.1%	10 7.6%

3.Primary Outcome


Title	Open-label Period: Number of Participants Reporting Adverse Events of Special Interest (AESI)
Description	An AESI is one of scientific and medical concern specific to the produ...
Description	An AESI is one of scientific and medical concern specific to the product, for which ongoing monitoring and rapid communication by investigator to sponsor can be appropriate. A summary of protocol defined AESIs include malignant neoplasms including and excluding non-melanoma skin cancer (NMSC), post-infusion systemic reactions (PISR), all infections of special interest (opportunistic infections [OI], Herpes Zoster [HZ], tuberculosis [TB], and sepsis), depression (including mood disorders and anxiety)/suicide/self-injury and deaths.
Time Frame	From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)

Outcome Measure Data

Analysis Population Description

Safety Open-Label Population.


Arm/Group Title	Placebo to Belimumab 10 mg/kg	Belimumab 10 mg/kg to Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo intravenous (IV) plus standard of care (SoC) on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race. After completing the double-blind period, eligible participants that were randomized to placebo IV plus SOC received Belimumab 10 milligram per kilogram (mg/kg) every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.	Participants were randomized to receive Belimumab 10 mg/kg IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race. After completing the double-blind period, eligible participants that were randomized to belimumab 10 mg/kg IV plus SOC continued to receive Belimumab 10 mg/kg every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.
Overall Number of Participants Analyzed	123	132
Measure Type: Count of Participants Unit of Measure: Participants
Malignancies excluding NMSC	0 0.0%	0 0.0%
Malignancies including NMSC	0 0.0%	0 0.0%
PISR	4 3.3%	5 3.8%
All infections of special interest	2 1.6%	6 4.5%
Depression/suicide/self-injury	2 1.6%	4 3.0%
Deaths	1 0.8%	0 0.0%

4.Secondary Outcome


Title	Double-blind Period: Percentage of Participants With Complete Renal Response (CRR) at Week 104
Description	CRR is defined as urinary protein creatinine ratio <0.5, eGRF was n...
Description	CRR is defined as urinary protein creatinine ratio <0.5, eGRF was not more than 10% below the pre-flare value or >=90 mL/min/1.73m^2 and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates of induction regimen (CYC vs. MMF), race (Black vs. Non-Black), Baseline uPCR and Baseline eGFR. Percentage of participants with CRR at Week 104 has been presented.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

mITT Population.


Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.	Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.
Overall Number of Participants Analyzed	223	223
Measure Type: Number Unit of Measure: Percentage of participants
	19.7	30.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0167
	Comments	P-value was calculated using logistic regression model. Test 2 of 5 in a step-down sequential testing procedure.
	Method	Regression, Logistic
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.74
	Confidence Interval	(2-Sided) 95% 1.11 to 2.74
	Estimation Comments	Treatment comparison between Belimumab 10 mg/kg and placebo using odds ratio and its corresponding 95% confidence interval has been presented.

5.Secondary Outcome


Title	Double-blind Period: Percentage of Participants With PERR at Week 52
Description	PERR is defined as urinary protein creatinine ratio <=0.7, eGRF was...
Description	PERR is defined as urinary protein creatinine ratio <=0.7, eGRF was not more than 20% below the pre-flare value or >=60 mL/min/1.73m^2 and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates of induction regimen (CYC vs. MMF), race (Black vs. Non-Black), uPCR, and Baseline eGFR. Percentage of participants with PERR at Week 52 has been presented.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

mITT Population.


Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.	Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.
Overall Number of Participants Analyzed	223	223
Measure Type: Number Unit of Measure: Percentage of participants
	35.4	46.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0245
	Comments	P-value was calculated using logistic regression model. Test 3 of 5 in a step-down sequential testing procedure.
	Method	Regression, Logistic
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95% 1.06 to 2.38
	Estimation Comments	Treatment comparison between Belimumab 10 mg/kg and placebo using odds ratio and its corresponding 95% confidence interval has been presented.

6.Secondary Outcome


Title	Double-blind Period: Number of Participants With Time to Death or Renal Related Event
Description	Events are defined as the first event experienced among the following:...
Description	Events are defined as the first event experienced among the following: death, progression to end stage renal disease, doubling of serum creatinine from Baseline, renal worsening or renal-related treatment failure. Participants who discontinued randomized treatment, withdrew from the study, were lost to follow-up, or had a non renal-related treatment failure were censored. Participants who completed the 104-week treatment period were censored at the Week 104 visit. Time to event is defined as event date minus treatment start date plus one. Analysis was performed using Cox proportional hazards model for the comparison between Belimumab and Placebo adjusting for induction regimen, race, Baseline uPCR and Baseline eGFR. Number of participants with time to death or renal related event up to Week 104 has been presented.
Time Frame	Up to Week 104

Outcome Measure Data

Analysis Population Description

mITT Population.


Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.	Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.
Overall Number of Participants Analyzed	223	223
Measure Type: Count of Participants Unit of Measure: Participants
	63 28.3%	35 15.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0014
	Comments	P-value was calculated using Cox proportional hazards model. Test 4 of 5 in a step-down sequential testing procedure.
	Method	Cox proportional hazards model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95% 0.34 to 0.77
	Estimation Comments	Treatment comparison between Belimumab 10 mg/kg and placebo using Cox proportional hazards ratio and its corresponding 95% confidence interval has been presented.

7.Secondary Outcome


Title	Double-blind Period: Percentage of Participants With Ordinal Renal Response (ORR) at Week 104
Description	ORR is defined with respect to reproducible responses that included CR...
Description	ORR is defined with respect to reproducible responses that included CRR, partial RR (PRR) and non responder. CRR is reported when uPCR was <0.5, eGFR was not more than 10% below pre-flare GFR or within normal range and not a treatment failure. PRR is >=50% decrease from Baseline in uPCR and one of the following: value <1 if Baseline <=3, or value <3 if the Baseline was >3, eGFR not more than 10% below Baseline GFR or within normal range and not a treatment failure and not a CRR. Non responder is reported when neither CRR nor PRR criteria was met. Percentage of participants reporting CRR, PRR and non responders at Week 104 has been presented.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

mITT Population.


Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.	Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.
Overall Number of Participants Analyzed	223	223
Measure Type: Number Unit of Measure: Percentage of participants
CRR	19.7	30.0
PRR	17.0	17.5
Non responder	63.2	52.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Belimumab 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0096
	Comments	P-value is rank analysis of covariance model comparing Belimumab and Placebo with covariates for treatment group, induction regimen(CYC vs MMF),race(Black vs Non-black), Baseline uPCR, and eGFR. Test 5 of 5 in step-down sequential testing procedure.
	Method	Rank ANCOVA
	Comments	[Not Specified]

8.Secondary Outcome


Title	Double-blind Period: Number of Participants Reporting On-treatment AEs and SAEs
Description	An AE is any untoward medical occurrence in a participant or clinical ...
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with on-treatment AEs and SAEs has been reported.
Time Frame	Up to Week 104

Outcome Measure Data

Analysis Population Description

Safety Population comprised of all randomized participants who received at least one dose of study treatment.


Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.	Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.
Overall Number of Participants Analyzed	224	224
Measure Type: Count of Participants Unit of Measure: Participants
Any AE	211 94.2%	214 95.5%
Any SAE	67 29.9%	58 25.9%

9.Secondary Outcome


Title	Double-blind Period: Number of Participants Reporting AESI
Description	An AESI is one of scientific and medical concern specific to the produ...
Description	An AESI is one of scientific and medical concern specific to the product, for which ongoing monitoring and rapid communication by investigator to sponsor can be appropriate. A summary of protocol defined AESIs include malignant neoplasms including and excluding non-melanoma skin cancer (NMSC), post-infusion systemic reactions (PISR), all infections of special interest (opportunistic infections [OI], Herpes Zoster [HZ], tuberculosis [TB], and sepsis), depression (including mood disorders and anxiety)/suicide/self-injury and deaths. On-treatment data is displayed.
Time Frame	Up to Week 104

Outcome Measure Data

Analysis Population Description

Safety Population.


Arm/Group Title	Placebo	Belimumab 10 mg/kg
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.	Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.
Overall Number of Participants Analyzed	224	224
Measure Type: Count of Participants Unit of Measure: Participants
Malignancies excluding NMSC	0 0.0%	2 0.9%
Malignancies including NMSC	0 0.0%	3 1.3%
PISR	29 12.9%	26 11.6%
All infections of special interest	34 15.2%	30 13.4%
Depression/suicide/self-injury	16 7.1%	11 4.9%
Deaths	3 1.3%	4 1.8%

Adverse Events

Time Frame	All-cause mortality, non-SAEs and SAEs were summarised from the start of the first treatment up to Week 104 in double-blind period and from the first open-label dose up to Week 32 (8 weeks after last dose) in open-label extension period.
Adverse Event Reporting Description	All-cause mortality, non-SAEs and SAEs were reported for safety population (double-blind period) and safety open-label population (open-label period). Non-serious adverse events not meeting 5% in the open label period were reported as 0% incidence but could have incidences between 0 and 5%.

Arm/Group Title	Placebo		Belimumab 10 mg/kg		Placebo to Belimumab 10 mg/kg		Belimumab 10 mg/kg to Belimumab 10 mg/kg
Arm/Group Description	Participants were randomized to rec...		Participants were randomized to rec...		Participants were randomized to rec...		Participants were randomized to rec...
Arm/Group Description	Participants were randomized to receive matching placebo IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race.		Participants were randomized to receive Belimumab 10 milligrams per kilogram (mg/kg) IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race.		Participants were randomized to receive matching placebo intravenous (IV) plus standard of care (SoC) on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (high dose cortiocsteroids [HDCS] plus Cyclophosphamide [CYC] versus [vs.] HDCS plus Mycophenolate Mofetil [MMF]) and race. After completing the double-blind period, eligible participants that were randomized to placebo IV plus SOC received Belimumab 10 milligram per kilogram (mg/kg) every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.		Participants were randomized to receive Belimumab 10 mg/kg IV plus SoC on Days 0 (Baseline), 14, 28 and then every 28 days thereafter through 100 Weeks with a final evaluation for the double-blind treatment period at Week 104. The randomization was stratified by their induction regimen (HDCS plus CYC vs. HDCS plus MMF) and race. After completing the double-blind period, eligible participants that were randomized to belimumab 10 mg/kg IV plus SOC continued to receive Belimumab 10 mg/kg every 28 days until Week 24 with a final evaluation at Week 28 (4 weeks after the last dose) in open-label extension period.
All-Cause Mortality
	Placebo		Belimumab 10 mg/kg		Placebo to Belimumab 10 mg/kg		Belimumab 10 mg/kg to Belimumab 10 mg/kg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	5/224 (2.23%)		6/224 (2.68%)		1/123 (0.81%)		0/132 (0.00%)
Serious Adverse Events Serious Adverse Events
	Placebo		Belimumab 10 mg/kg		Placebo to Belimumab 10 mg/kg		Belimumab 10 mg/kg to Belimumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/224 (34.82%)		65/224 (29.02%)		5/123 (4.07%)		10/132 (7.58%)
Blood and lymphatic system disorders
Anaemia ^† 1	6/224 (2.68%)	6	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Febrile neutropenia ^† 1	0/224 (0.00%)	0	3/224 (1.34%)	3	0/123 (0.00%)	0	0/132 (0.00%)	0
Leukopenia ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pancytopenia ^† 1	0/224 (0.00%)	0	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Bone marrow toxicity ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Hypoglobulinaemia ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Lymphadenopathy ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Cardiac disorders
Pericardial effusion ^† 1	3/224 (1.34%)	4	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Aortic valve incompetence ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Cardiac failure acute ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Cardiac failure congestive ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pericarditis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pericarditis uraemic ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Supraventricular tachycardia ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Acute myocardial infarction ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	0/123 (0.00%)	0	1/132 (0.76%)	1
Endocrine disorders
Hyperparathyroidism ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Gastrointestinal disorders
Vomiting ^† 1	2/224 (0.89%)	2	2/224 (0.89%)	2	1/123 (0.81%)	2	0/132 (0.00%)	0
Diarrhoea ^† 1	0/224 (0.00%)	0	3/224 (1.34%)	3	0/123 (0.00%)	0	0/132 (0.00%)	0
Gastritis ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Nausea ^† 1	0/224 (0.00%)	0	2/224 (0.89%)	2	1/123 (0.81%)	1	0/132 (0.00%)	0
Pancreatitis ^† 1	2/224 (0.89%)	2	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Abdominal pain ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Chronic gastritis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Enteritis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Epiploic appendagitis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Gastrointestinal inflammation ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Haemorrhoids ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Impaired gastric emptying ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Large intestine perforation ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Vasculitis gastrointestinal ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Cyclic vomiting syndrome ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	1/123 (0.81%)	1	0/132 (0.00%)	0
Abdominal pain lower ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	1/123 (0.81%)	1	0/132 (0.00%)	0
General disorders
Pyrexia ^† 1	3/224 (1.34%)	3	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Non-cardiac chest pain ^† 1	2/224 (0.89%)	2	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Asthenia ^† 1	2/224 (0.89%)	2	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Fatigue ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Generalised oedema ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Mucosal inflammation ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pain ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Serositis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Systemic inflammatory response syndrome ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Multiple organ dysfunction syndrome ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	1/123 (0.81%)	1	0/132 (0.00%)	0
Hepatobiliary disorders
Cholecystitis acute ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Immune system disorders
Hypersensitivity ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Immunosuppression ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Infections and infestations
Pneumonia ^† 1	10/224 (4.46%)	11	10/224 (4.46%)	11	2/123 (1.63%)	2	1/132 (0.76%)	1
Herpes zoster ^† 1	2/224 (0.89%)	2	4/224 (1.79%)	4	0/123 (0.00%)	0	1/132 (0.76%)	1
Lung infection ^† 1	4/224 (1.79%)	4	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Urinary tract infection ^† 1	2/224 (0.89%)	2	4/224 (1.79%)	4	0/123 (0.00%)	0	0/132 (0.00%)	0
Gastroenteritis ^† 1	5/224 (2.23%)	5	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Cellulitis ^† 1	3/224 (1.34%)	3	0/224 (0.00%)	0	0/123 (0.00%)	0	1/132 (0.76%)	1
Sepsis ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Subcutaneous abscess ^† 1	1/224 (0.45%)	1	2/224 (0.89%)	3	0/123 (0.00%)	0	0/132 (0.00%)	0
Bronchitis ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Cytomegalovirus colitis ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Endocarditis ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Influenza ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pulmonary tuberculosis ^† 1	0/224 (0.00%)	0	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Pyelonephritis ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	1/132 (0.76%)	1
Upper respiratory tract infection ^† 1	2/224 (0.89%)	2	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Abscess limb ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Acute sinusitis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	1/132 (0.76%)	1
Appendicitis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Arthritis bacterial ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Bacteraemia ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Bone abscess ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Bronchopulmonary aspergillosis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Clostridium difficile colitis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	1/132 (0.76%)	1
Cytomegalovirus infection ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Diverticulitis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Enteritis infectious ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Enterocolitis bacterial ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Enterocolitis viral ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Escherichia urinary tract infection ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Furuncle ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Herpes oesophagitis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Large intestine infection ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Periorbital cellulitis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Peritonitis bacterial ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Pneumocystis jirovecii pneumonia ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pneumonia bacterial ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Pneumonia cytomegaloviral ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pneumonia streptococcal ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Proteus infection ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Pulmonary nocardiosis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Respiratory syncytial virus bronchitis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Rhodococcus infection ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Septic shock ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Sinusitis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Staphylococcal abscess ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Staphylococcal infection ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Tuberculosis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Urosepsis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Varicella ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Varicella zoster viral infection ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Viral infection ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Wound infection ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Complicated appendicitis ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	1/123 (0.81%)	1	0/132 (0.00%)	0
Disseminated tuberculosis ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	0/123 (0.00%)	0	1/132 (0.76%)	1
Genital infection ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	1/123 (0.81%)	1	0/132 (0.00%)	0
Otitis media ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	0/123 (0.00%)	0	1/132 (0.76%)	1
Pyelonephritis acute ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	1/123 (0.81%)	1	0/132 (0.00%)	0
Injury, poisoning and procedural complications
Skin laceration ^† 1	0/224 (0.00%)	0	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Brain herniation ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Contusion ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Head injury ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Joint injury ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Ligament injury ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Post procedural haematoma ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Spinal compression fracture ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Tibia fracture ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Wrist fracture ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Investigations
Blood creatinine increased ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Blood immunoglobulin G decreased ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Foetal biophysical profile score equivocal ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Hepatic enzyme increased ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Weight decreased ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Metabolism and nutrition disorders
Hyperkalaemia ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Hypophagia ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Metabolic acidosis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus ^† 1	4/224 (1.79%)	4	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Arthralgia ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Back pain ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Flank pain ^† 1	2/224 (0.89%)	2	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Intervertebral disc protrusion ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Musculoskeletal chest pain ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Oligoarthritis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Osteonecrosis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Rhabdomyolysis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Spinal osteoarthritis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Tendonitis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Muscular weakness ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	1/123 (0.81%)	2	0/132 (0.00%)	0
Pain in extremity ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	0/123 (0.00%)	0	1/132 (0.76%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Thymoma ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Nervous system disorders
Cerebral infarction ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Cerebrovascular accident ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Central nervous system lupus ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Encephalopathy ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Epilepsy ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Generalized tonic-clonic seizure ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Haemorrhage intracranial ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Headache ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	1/123 (0.81%)	1	0/132 (0.00%)	0
Hypertensive encephalopathy ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Metabolic encephalopathy ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Polyneuropathy ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Posterior reversible encephalopathy syndrome ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Seizure ^† 1	1/224 (0.45%)	2	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Abortion missed ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Foetal death ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Prolonged labour ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Unintended pregnancy ^† 1	0/224 (0.00%)	0	0/224 (0.00%)	0	0/123 (0.00%)	0	1/132 (0.76%)	1
Psychiatric disorders
Mental status changes ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Suicide attempt ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	1/132 (0.76%)	1
Renal and urinary disorders
Lupus nephritis ^† 1	8/224 (3.57%)	10	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Acute kidney injury ^† 1	5/224 (2.23%)	5	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
End stage renal disease ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Nephrotic syndrome ^† 1	0/224 (0.00%)	0	2/224 (0.89%)	4	0/123 (0.00%)	0	0/132 (0.00%)	0
Renal impairment ^† 1	0/224 (0.00%)	0	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Azotaemia ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Nephrolithiasis ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Renal failure ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	1/123 (0.81%)	1	0/132 (0.00%)	0
Reproductive system and breast disorders
Cervical dysplasia ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Endometriosis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pleural effusion ^† 1	2/224 (0.89%)	2	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Acute pulmonary oedema ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Aspiration ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Dyspnoea ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Organizing pneumonia ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pneumomediastinum ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pneumothorax ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Pulmonary alveolar haemorrhage ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Pulmonary arterial hypertension ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Pulmonary embolism ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Respiratory failure ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Skin and subcutaneous tissue disorders
Angioedema ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Erythema annulare ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Systemic lupus erythematosus rash ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Vascular disorders
Hypertension ^† 1	1/224 (0.45%)	1	2/224 (0.89%)	2	0/123 (0.00%)	0	0/132 (0.00%)	0
Hypotension ^† 1	1/224 (0.45%)	1	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Deep vein thrombosis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
Hypertensive emergency ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Shock haemorrhagic ^† 1	1/224 (0.45%)	1	0/224 (0.00%)	0	0/123 (0.00%)	0	0/132 (0.00%)	0
Thrombosis ^† 1	0/224 (0.00%)	0	1/224 (0.45%)	1	0/123 (0.00%)	0	0/132 (0.00%)	0
1 Term from vocabulary, MedDRA 22.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Belimumab 10 mg/kg		Placebo to Belimumab 10 mg/kg		Belimumab 10 mg/kg to Belimumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	191/224 (85.27%)		186/224 (83.04%)		34/123 (27.64%)		39/132 (29.55%)
Blood and lymphatic system disorders
Anaemia ^† 1	23/224 (10.27%)	26	13/224 (5.80%)	16	0/123 (0.00%)	0	0/132 (0.00%)	0
Leukopenia ^† 1	19/224 (8.48%)	29	15/224 (6.70%)	28	0/123 (0.00%)	0	0/132 (0.00%)	0
Gastrointestinal disorders
Diarrhoea ^† 1	48/224 (21.43%)	56	45/224 (20.09%)	59	0/123 (0.00%)	0	0/132 (0.00%)	0
Nausea ^† 1	24/224 (10.71%)	33	21/224 (9.38%)	28	0/123 (0.00%)	0	0/132 (0.00%)	0
Vomiting ^† 1	16/224 (7.14%)	21	16/224 (7.14%)	25	0/123 (0.00%)	0	0/132 (0.00%)	0
Abdominal pain ^† 1	13/224 (5.80%)	13	12/224 (5.36%)	15	0/123 (0.00%)	0	0/132 (0.00%)	0
Dyspepsia ^† 1	15/224 (6.70%)	18	9/224 (4.02%)	10	0/123 (0.00%)	0	0/132 (0.00%)	0
Abdominal pain upper ^† 1	6/224 (2.68%)	7	16/224 (7.14%)	16	0/123 (0.00%)	0	0/132 (0.00%)	0
General disorders
Oedema peripheral ^† 1	13/224 (5.80%)	17	16/224 (7.14%)	23	0/123 (0.00%)	0	0/132 (0.00%)	0
Pyrexia ^† 1	17/224 (7.59%)	20	11/224 (4.91%)	14	0/123 (0.00%)	0	0/132 (0.00%)	0
Fatigue ^† 1	14/224 (6.25%)	15	12/224 (5.36%)	12	0/123 (0.00%)	0	0/132 (0.00%)	0
Oedema ^† 1	12/224 (5.36%)	15	9/224 (4.02%)	9	0/123 (0.00%)	0	0/132 (0.00%)	0
Infections and infestations
Upper respiratory tract infection ^† 1	74/224 (33.04%)	134	81/224 (36.16%)	159	14/123 (11.38%)	18	23/132 (17.42%)	24
Urinary tract infection ^† 1	37/224 (16.52%)	72	43/224 (19.20%)	73	10/123 (8.13%)	12	12/132 (9.09%)	14
Nasopharyngitis ^† 1	31/224 (13.84%)	50	35/224 (15.63%)	60	8/123 (6.50%)	9	3/132 (2.27%)	3
Gastroenteritis ^† 1	23/224 (10.27%)	28	21/224 (9.38%)	24	0/123 (0.00%)	0	0/132 (0.00%)	0
Bronchitis ^† 1	19/224 (8.48%)	26	18/224 (8.04%)	24	0/123 (0.00%)	0	0/132 (0.00%)	0
Herpes zoster ^† 1	19/224 (8.48%)	20	17/224 (7.59%)	17	0/123 (0.00%)	0	0/132 (0.00%)	0
Conjunctivitis ^† 1	5/224 (2.23%)	5	13/224 (5.80%)	13	0/123 (0.00%)	0	0/132 (0.00%)	0
Metabolism and nutrition disorders
Hypokalaemia ^† 1	20/224 (8.93%)	23	24/224 (10.71%)	36	0/123 (0.00%)	0	0/132 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	32/224 (14.29%)	52	26/224 (11.61%)	44	5/123 (4.07%)	5	7/132 (5.30%)	8
Back pain ^† 1	17/224 (7.59%)	17	17/224 (7.59%)	24	0/123 (0.00%)	0	0/132 (0.00%)	0
Muscle spasms ^† 1	15/224 (6.70%)	18	18/224 (8.04%)	25	0/123 (0.00%)	0	0/132 (0.00%)	0
Pain in extremity ^† 1	8/224 (3.57%)	9	12/224 (5.36%)	14	0/123 (0.00%)	0	0/132 (0.00%)	0
Nervous system disorders
Headache ^† 1	35/224 (15.63%)	57	34/224 (15.18%)	51	0/123 (0.00%)	0	0/132 (0.00%)	0
Dizziness ^† 1	19/224 (8.48%)	21	13/224 (5.80%)	18	0/123 (0.00%)	0	0/132 (0.00%)	0
Psychiatric disorders
Insomnia ^† 1	18/224 (8.04%)	19	10/224 (4.46%)	10	0/123 (0.00%)	0	0/132 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	21/224 (9.38%)	23	30/224 (13.39%)	38	0/123 (0.00%)	0	0/132 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash ^† 1	17/224 (7.59%)	18	23/224 (10.27%)	31	0/123 (0.00%)	0	0/132 (0.00%)	0
Acne ^† 1	9/224 (4.02%)	11	12/224 (5.36%)	13	0/123 (0.00%)	0	0/132 (0.00%)	0
Vascular disorders
Hypertension ^† 1	20/224 (8.93%)	23	12/224 (5.36%)	14	0/123 (0.00%)	0	0/132 (0.00%)	0
1 Term from vocabulary, MedDRA 22.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	GSK Response Center
Organization:	GlaxoSmithKline
Phone:	866-435-7343
EMail:	GSKClinicalSupportHD@gsk.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Furie R, Rovin BH, Houssiau F, Contreras G, Teng YKO, Curtis P, Green Y, Okily M, Madan A, Roth DA. Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study. Clin J Am Soc Nephrol. 2022 Nov;17(11):1620-1630. doi: 10.2215/CJN.02520322. Epub 2022 Oct 27.

Rovin BH, Furie R, Teng YKO, Contreras G, Malvar A, Yu X, Ji B, Green Y, Gonzalez-Rivera T, Bass D, Gilbride J, Tang CH, Roth DA. A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis. Kidney Int. 2022 Feb;101(2):403-413. doi: 10.1016/j.kint.2021.08.027. Epub 2021 Sep 22.

Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB, Saxena A, Green Y, Ji B, Kleoudis C, Burriss SW, Barnett C, Roth DA. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020 Sep 17;383(12):1117-1128. doi: 10.1056/NEJMoa2001180.

Layout table for additonal information

Responsible Party:	GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )
ClinicalTrials.gov Identifier:	NCT01639339
Other Study ID Numbers:	114054 2011-004570-28 ( EudraCT Number )
First Submitted:	July 10, 2012
First Posted:	July 12, 2012
Results First Submitted:	June 17, 2020
Results First Posted:	July 7, 2020
Last Update Posted:	March 19, 2021

To Top