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Clinical Trial Results:
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE)

Summary
EudraCT number	2016-003050-32
Trial protocol	DE NL ES
Global end of trial date	07 Jul 2021

Results information
Results version number	v1(current)
This version publication date	18 Apr 2022
First version publication date	18 Apr 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

205646

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Sep 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

07 Jul 2021

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of belimumab and a single cycle of rituximab administered in a combination regimen to adult participants with SLE.

Protection of trial subjects

Specific eligibility, monitoring and individual participant/study treatment stopping rules were implemented in the study protocol to mitigate potential risks. An independent data monitoring committee performed periodic review of unblinded safety data. The protocol was amended to ensure safety monitoring during the corona virus disease-19 (COVID-19) pandemic, including recommendations for a safety contact with subjects in the event they could not attend clinic visits and a local analysis of laboratory assessments if central lab results could not be obtained. Also, provisions were made to allow short term treatment with hydroxychloroquine for experimental treatment of COVID-19 and direct supply of Belimumab to participants if participant was unable to visit the site.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Mar 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 12

Country: Number of subjects enrolled

United States: 105

Country: Number of subjects enrolled

France: 19

Country: Number of subjects enrolled

Germany: 2

Country: Number of subjects enrolled

Netherlands: 18

Country: Number of subjects enrolled

Spain: 20

Country: Number of subjects enrolled

Argentina: 15

Country: Number of subjects enrolled

Brazil: 20

Country: Number of subjects enrolled

Korea, Republic of: 26

Country: Number of subjects enrolled

Mexico: 9

Country: Number of subjects enrolled

Russian Federation: 46

Worldwide total number of subjects

292

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

284

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was a multicenter study conducted at 71 centers in 11 countries. This was a randomized, placebo-controlled, parallel study where participants received treatment in any one of the treatment arms.

Screening details

A total of 396 participants were screened, of which 104 were screen failures. A total of 292 participants were enrolled in the study (Intent-to-Treat Population: It comprised of all randomized participants who received at least one dose of study treatment [Belimumab or Rituximab or Placebo]).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Belimumab + Placebo

Arm description

Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104.

Arm type

Placebo

Investigational medicinal product name

Belimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Belimumab 200 milligrams (mg) was administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52 (Belimumab + Placebo and Belimumab + Rituximab) and through Week 104 for Belimumab + Standard therapy.

Investigational medicinal product name

Rituximab-placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab-placebo was administered by intravenous (IV) infusions at Weeks 4 and 6.

Investigational medicinal product name

Standard therapy

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Standard therapy was administered.

Belimumab + Rituximab

Arm description

Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104.

Arm type

Experimental

Investigational medicinal product name

Belimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Investigational medicinal product name

Standard therapy

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Standard therapy was administered.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab 1000 mg was administered by IV infusions at Weeks 4 and 6.

Belimumab + Standard therapy

Arm description

Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.

Arm type

This was a part of exploratory analysis of study.

Investigational medicinal product name

Standard therapy

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Standard therapy was administered.

Investigational medicinal product name

Belimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 1	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Started	72	144	76
Completed	55	114	57
Not completed	17	30	19
Adverse event, serious fatal	1	2	-
Physician decision	3	4	2
Consent withdrawn by subject	9	14	10
Adverse event, non-fatal	-	4	1
Lost to follow-up	2	3	2
Protocol deviation	2	3	4

Baseline characteristics

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Reporting group title

Belimumab + Placebo

Reporting group description

Reporting group title

Belimumab + Rituximab

Reporting group description

Reporting group title

Belimumab + Standard therapy

Reporting group description

Reporting group values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy	Total
Number of subjects	72	144	76	292
Age categorical
Baseline characteristics were presented for Intent-to-Treat Population.
Units: Participants
All participants	72	144	76	292
Age Continuous
Baseline characteristics were presented for Intent-to-Treat Population.
Units: years
arithmetic mean (standard deviation)	40.6 ± 12.58	40.1 ± 11.45	41.0 ± 12.75	-
Sex: Female, Male
Baseline characteristics were presented for Intent-to-Treat Population.
Units: Participants
Female	66	129	73	268
Male	6	15	3	24
Race/Ethnicity, Customized
Baseline characteristics were presented for Intent-to-Treat Population.
Units: Subjects
White -Arabic/North African Heritage	0	1	1	2
White-White/Caucasian/European Heritage	39	100	47	186
Asian - Central/South Asian Heritage	0	1	1	2
Asian - East Asian Heritage	7	14	10	31
Asian - South East Asian Heritage	3	2	1	6
African American/African Heritage	21	22	13	56
American Indian or Alaskan Native	1	3	3	7
Native Hawaiian or Other Pacific Islander	1	1	0	2

End points

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Reporting group title

Belimumab + Placebo

Reporting group description

Reporting group title

Belimumab + Rituximab

Reporting group description

Reporting group title

Belimumab + Standard therapy

Reporting group description

Primary: Percentage of participants with a state of disease control at week 52

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End point title

Percentage of participants with a state of disease control at week 52

End point description

Percentage of participants with a state of disease control (Independent blinded assessor [IBA]) was defined as the percentage of participants with a Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K)score less than or equal to(<=)2 achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 52. SLEDAI-2K consisting 24 individual items within 9 organ systems. The SLEDAI-2K score was sum of all 24 individual items from the SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms) with higher scores representing increased disease activity .Modified Intent-to-Treat (MITT) Population comprised of all randomized participants who received at least one dose of study treatment (Belimumab or Rituximab or Placebo) and excluding participants from Arm 3 (Belimumab + Standard therapy) who were randomized prior to 07-Sep-2018.

End point type

Primary

End point timeframe

Week 52

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[1]	144 ^[2]	47 ^[3]
Units: Percentage of participants
number (confidence interval 95%)	16.7 (8.1 to 25.3)	19.4 (13.0 to 25.9)	25.5 (13.1 to 38.0)

Notes
[1] - Modified Intent-to-Treat (MITT) Population
[2] - Modified Intent-to-Treat (MITT) Population
[3] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 2

Statistical analysis description

Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, and Baseline prednisone equivalent dose. Belimumab + Placebo arm excluded from model.

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.54

Stastistical Analysis 1

Statistical analysis description

Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose. Belimumab + Standard therapy arm was excluded from model.

Comparison groups

Belimumab + Rituximab v Belimumab + Placebo

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5342

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

2.71

Secondary: Percentage of participants with a state of clinical remission at Week 64

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End point title

Percentage of participants with a state of clinical remission at Week 64

End point description

Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-double stranded deoxyribonucleic [dsDNA] and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day at Week 64. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician’s assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.

End point type

Secondary

End point timeframe

Week 64

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[4]	144 ^[5]	47 ^[6]
Units: Percentage of participants
number (confidence interval 95%)	5.6 (0.3 to 10.8)	6.3 (2.3 to 10.2)	10.6 (1.8 to 19.5)

Notes
[4] - Modified Intent-to-Treat (MITT) Population
[5] - Modified Intent-to-Treat (MITT) Population
[6] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 1

Statistical analysis description

Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8582

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

3.78

Stastistical Analysis 2

Statistical analysis description

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

1.7

Secondary: Percentage of participants with a state of disease control at Week 104

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End point title

Percentage of participants with a state of disease control at Week 104

End point description

Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 104. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician’s assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.

End point type

Secondary

End point timeframe

Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[7]	144 ^[8]	47 ^[9]
Units: Percentage of participants
number (confidence interval 95%)	6.9 (1.1 to 12.8)	11.1 (6.0 to 16.2)	21.3 (9.6 to 33.0)

Notes
[7] - Modified Intent-to-Treat (MITT) Population
[8] - Modified Intent-to-Treat (MITT) Population
[9] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 2

Statistical analysis description

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

1.09

Stastistical Analysis 1

Statistical analysis description

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3613

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

4.72

Secondary: Percentage of participants with a state of disease control by visits

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End point title

Percentage of participants with a state of disease control by visits

End point description

Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician’s assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.

End point type

Secondary

End point timeframe

Weeks 12, 26, 40, 52, 64, 80 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[10]	144 ^[11]	47 ^[12]
Units: Percentage of participants
number (confidence interval 95%)
Week 12	8.3 (1.9 to 14.7)	12.5 (7.1 to 17.9)	21.3 (9.6 to 33.0)
Week 26	16.7 (8.1 to 25.3)	21.5 (14.8 to 28.2)	25.5 (13.1 to 38.0)
Week 40	13.9 (5.9 to 21.9)	20.8 (14.2 to 27.5)	23.4 (11.3 to 35.5)
Week 52	16.7 (8.1 to 25.3)	19.4 (13.0 to 25.9)	25.5 (13.1 to 38.0)
Week 64	11.1 (3.9 to 18.4)	18.1 (11.8 to 24.3)	25.5 (13.1 to 38.0)
Week 80	6.9 (1.1 to 12.8)	13.2 (7.7 to 18.7)	27.7 (14.9 to 40.4)
Week 104	6.9 (1.1 to 12.8)	11.1 (6.0 to 16.2)	21.3 (9.6 to 33.0)

Notes
[10] - Modified Intent-to-Treat (MITT) Population
[11] - Modified Intent-to-Treat (MITT) Population
[12] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with a state of clinical remission by visits

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End point title

Percentage of participants with a state of clinical remission by visits

End point description

Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician’s assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity

End point type

Secondary

End point timeframe

Weeks 64, 80 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[13]	144 ^[14]	47 ^[15]
Units: Percentage of participants
number (confidence interval 95%)
Week 64	5.6 (0.3 to 10.8)	6.3 (2.3 to 10.2)	10.6 (1.8 to 19.5)
Week 80	4.2 (0 to 8.8)	4.2 (0.9 to 7.4)	12.8 (3.2 to 22.3)
Week 104	1.4 (0 to 4.1)	4.2 (0.9 to 7.4)	6.4 (0 to 13.4)

Notes
[13] - Modified Intent-to-Treat (MITT) Population
[14] - Modified Intent-to-Treat (MITT) Population
[15] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with a state of complete remission (CR) sustained for at least 24 weeks during Week 52 to Week 104

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End point title

Percentage of participants with a state of complete remission (CR) sustained for at least 24 weeks during Week 52 to Week 104

End point description

Percentage of participants with a state of CR (Principal Investigator [PI] assessed) was defined as percentage of participants with a SLEDAI-2K=0 achieved without immunosuppressants and with corticosteroids at prednisone equivalent dose of 0 mg/day,sustained for at least 24 weeks. Sustained CR was longest period a participant maintains CR without break calculated as last consecutive CR date minus first consecutive CR date plus 1. SLEDAI-2K consisted of 24 individual items within each 9 organ systems. Each item was given a weighted score (1 to 8,higher score indicates increased activity) and summed if present at time of visit or in preceding 10 days. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms),higher scores indicates increased disease activity. 99999 indicates that data was not available as confidence interval could not be calculated as there was no participant with a state of complete remission

End point type

Secondary

End point timeframe

Week 52 to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[16]	144 ^[17]	47 ^[18]
Units: Percentage of participants
number (confidence interval 95%)	2.8 (0 to 6.6)	0 (-99999 to 99999)	6.4 (0 to 13.4)

Notes
[16] - Modified Intent-to-Treat (MITT) Population
[17] - Modified Intent-to-Treat (MITT) Population
[18] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with a state of clinical remission (CLR) sustained for at least 24 weeks from Week 80 to Week 104

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End point title

Percentage of participants with a state of clinical remission (CLR) sustained for at least 24 weeks from Week 80 to Week 104

End point description

Percentage of participants with a state of CLR (PI assessed) at Week 104 was defined as percentage of participants with a clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores) achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day, sustained for at least 24 weeks(from Week 80 to Week 104). Sustained CLR is longest period a participant maintains CLR without a break, calculated as last consecutive CLR date minus first consecutive CLR date plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.

End point type

Secondary

End point timeframe

From Week 80 to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[19]	144 ^[20]	47 ^[21]
Units: Percentage of participants
number (confidence interval 95%)	2.8 (0 to 6.6)	2.1 (0 to 4.4)	4.3 (0 to 10.0)

Notes
[19] - Modified Intent-to-Treat (MITT) Population
[20] - Modified Intent-to-Treat (MITT) Population
[21] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with a state of complete remission by visits

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End point title

Percentage of participants with a state of complete remission by visits

End point description

Percentage of participants with a state of complete remission (PI assessed) was defined as the percentage of participants with a SLEDAI-2K score =0, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician’s assessment for each item within for each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. 99999 indicates that data was not available as confidence interval could not be calculated as there was no participant with a state of complete remission.

End point type

Secondary

End point timeframe

Weeks 60, 64, 72, 80, 88, 96 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[22]	144 ^[23]	47 ^[24]
Units: Percentage of participants
number (confidence interval 95%)
Week 60	5.6 (0.3 to 10.8)	0.7 (0 to 2.1)	6.4 (0 to 13.4)
Week 64	5.6 (0.3 to 10.8)	0.7 (0 to 2.1)	6.4 (0 to 13.4)
Week 72	4.2 (0 to 8.8)	0.7 (0 to 2.1)	6.4 (0 to 13.4)
Week 80	2.8 (0 to 6.6)	1.4 (0 to 3.3)	8.5 (0.5 to 16.5)
Week 88	2.8 (0 to 6.6)	0 (-99999 to 99999)	4.3 (0 to 10.0)
Week 96	1.4 (0 to 4.1)	0.7 (0 to 2.1)	6.4 (0 to 13.4)
Week 104	1.4 (0 to 4.1)	0.7 (0 to 2.1)	4.3 (0 to 10.0)

Notes
[22] - Modified Intent-to-Treat (MITT) Population
[23] - Modified Intent-to-Treat (MITT) Population
[24] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Time to first severe flare

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End point title

Time to first severe flare

End point description

Time to first severe SLE flare was the number of days from treatment start date until the participant met an event. Time to first severe flare was defined as event date minus treatment start date plus 1. Time to first severe flare was measured by Modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare. Analysis of first severe flare was performed on the modified SLE Flare index that excludes severe flares that were triggered only by an increase is SLEDAI-2K score to greater than 12. 99999 indicates that data was not available as only <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived

End point type

Secondary

End point timeframe

Up to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[25]	144 ^[26]	47 ^[27]
Units: Days
median (inter-quartile range (Q1-Q3))	372.0 (202.0 to 485.0)	379.0 (198.0 to 99999)	730.0 (210.0 to 99999)

Notes
[25] - Modified Intent-to-Treat (MITT) Population
[26] - Modified Intent-to-Treat (MITT) Population
[27] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 2

Statistical analysis description

Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm excluded from model.

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Hazard ratio (HR)

Point estimate

1.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

2.63

Stastistical Analysis 1

Statistical analysis description

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.215

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.13

Secondary: Time to first flare

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End point title

Time to first flare

End point description

Time to first SLE flare was the number of days from treatment start date until the participant met an event. Time to first flare was defined as event date minus treatment start date plus 1. Time to first flare was measured by modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare.

End point type

Secondary

End point timeframe

Up to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[28]	144 ^[29]	47 ^[30]
Units: Days
median (inter-quartile range (Q1-Q3))	168.0 (92.0 to 257.0)	170.0 (57.0 to 365.0)	168.0 (91.0 to 337.0)

Notes
[28] - Modified Intent-to-Treat (MITT) Population
[29] - Modified Intent-to-Treat (MITT) Population
[30] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 2

Statistical analysis description

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Hazard ratio (HR)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.49

Stastistical Analysis 1

Statistical analysis description

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3757

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.19

Secondary: Time to disease control sustained for at least 24 weeks and maintained through Week 104

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End point title

Time to disease control sustained for at least 24 weeks and maintained through Week 104

End point description

Disease control sustained for at least 24 weeks and maintained through Week 104 was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. Time to disease control (PI assessed) was defined as the first visit of sustained disease control until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained disease control was longest period a participant maintained disease control without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K , ranges from 0 (no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity. 99999 indicates that data was not available as only <25% of participants experienced the event within the treatment arm. Hence, median and inter-quartile range could not be derived.

End point type

Secondary

End point timeframe

Up to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[31]	144 ^[32]	47 ^[33]
Units: Days
median (inter-quartile range (Q1-Q3))	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[31] - Modified Intent-to-Treat (MITT) Population
[32] - Modified Intent-to-Treat (MITT) Population
[33] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 1

Statistical analysis description

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5127

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

1.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

5.78

Stastistical Analysis 2

Statistical analysis description

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

2.1

Secondary: Time to clinical remission sustained for at least 24 weeks and maintained through Week 104

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End point title

Time to clinical remission sustained for at least 24 weeks and maintained through Week 104

End point description

Clinical remission sustained for at least 24 weeks and maintained through Week 104 was defined as clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. Time to CLR (PI assessed) was defined as first visit of sustained CLR until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained CLR was longest period a participant maintained clinical remission without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity. 99999 indicates that data was not available as only <25% of participants experienced the event within the treatment arm.

End point type

Secondary

End point timeframe

Up to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[34]	144 ^[35]	47 ^[36]
Units: Days
median (inter-quartile range (Q1-Q3))	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[34] - Modified Intent-to-Treat (MITT) Population
[35] - Modified Intent-to-Treat (MITT) Population
[36] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 2

Statistical analysis description

Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm excluded from model.

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

3.14

Stastistical Analysis 1

Statistical analysis description

Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8436

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.14

upper limit

5.05

Secondary: Duration of disease control

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End point title

Duration of disease control

End point description

Duration of disease control was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. The duration of disease control (PI assessed) was the longest period between 2 visits that the participant was a disease control responder at all visits and calculated as the first visit of disease control minus last visit of disease control plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity. Only those participants with at least one assessment where disease control was met were analyzed.

End point type

Secondary

End point timeframe

Up to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	34 ^[37]	77 ^[38]	31 ^[39]
Units: Days
median (inter-quartile range (Q1-Q3))	49.5 (1.0 to 172.0)	116.0 (21.0 to 265.0)	116.0 (23.0 to 351.0)

Notes
[37] - Modified Intent-to-Treat (MITT) Population
[38] - Modified Intent-to-Treat (MITT) Population
[39] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Duration of clinical remission

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End point title

Duration of clinical remission

End point description

Clinical remission was defined as clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. The duration of clinical remission (PI assessed) was the longest period between 2 visits that the participant was a clinical remission responder at all visits and was calculated as the first visit of clinical remission minus last visit of clinical remission plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity. Only those participants with at least one assessment where clinical remission was met were analyzed.

End point type

Secondary

End point timeframe

Up to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	13 ^[40]	22 ^[41]	11 ^[42]
Units: Days
median (inter-quartile range (Q1-Q3))	31.0 (1.0 to 253.0)	73.0 (29.0 to 225.0)	176.0 (85.0 to 279.0)

Notes
[40] - Modified Intent-to-Treat (MITT) Population
[41] - Modified Intent-to-Treat (MITT) Population
[42] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Change from Baseline in systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score by visit (PI assessed)

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End point title

Change from Baseline in systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score by visit (PI assessed)

End point description

The SLEDAI-2K consisted of 24 individual items within 9 organ systems. Each item was given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in the preceding 10 days. Weighted scores for central nervous system (CNS) (7 items) was 8; for vascular (1 item) was 8; for Musculoskeletal (2 items) was 4; for Renal (4 items) was 4; for Mucocutaneous (3 items) was 2; for Cardiovascular and Respiratory (2 items) was 2; for Immunologic (2 items) was 2;for Constitutional (1 item) was 1 and for Hematologic (2 items) was 1. SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. Change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles)

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[43]	144 ^[44]	47 ^[45]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 4; n=69, 137, 43	-1.4 ± 2.75	-0.8 ± 3.39	-1.3 ± 3.15
Week 8; n=63, 132, 43	-3.2 ± 3.59	-2.9 ± 4.09	-2.9 ± 3.43
Week 12; n=63, 131, 43	-2.8 ± 3.50	-3.6 ± 4.32	-2.9 ± 3.68
Week 16; n=65, 129, 43	-3.4 ± 4.12	-4.4 ± 4.62	-4.1 ± 3.29
Week 20; n=63, 127, 44	-3.8 ± 4.06	-5.0 ± 4.44	-3.8 ± 3.98
Week 24; n=61, 128, 43	-4.0 ± 3.71	-5.0 ± 4.45	-5.0 ± 4.00
Week 26; n=61, 118, 40	-4.1 ± 3.61	-5.4 ± 4.79	-5.0 ± 3.18
Week 28; n=62, 125, 43	-3.7 ± 3.79	-5.1 ± 4.74	-5.2 ± 4.31
Week 32; n=61, 125, 43	-4.7 ± 3.87	-5.7 ± 5.03	-5.3 ± 3.90
Week 36; n=61, 125, 43	-5.0 ± 4.43	-5.6 ± 5.21	-5.0 ± 3.68
Week 40; n=62, 125, 43	-4.6 ± 4.14	-5.8 ± 4.83	-5.0 ± 3.78
Week 44; n=62, 122, 43	-4.7 ± 4.71	-6.1 ± 4.47	-5.2 ± 4.06
Week 48; n=59, 122, 40	-4.5 ± 4.16	-6.2 ± 4.59	-5.3 ± 4.08
Week 52; n=62, 119, 39	-5.3 ± 4.62	-6.1 ± 4.42	-5.6 ± 4.02
Week 60; n=57, 114, 37	-5.0 ± 4.15	-5.8 ± 5.17	-6.0 ± 3.94
Week 64; n=60, 117, 36	-5.1 ± 4.16	-6.2 ± 4.96	-5.5 ± 4.40
Week 72; n=49, 103, 30	-5.2 ± 4.32	-6.6 ± 4.50	-5.3 ± 4.63
Week 80; n=46, 102, 36	-5.4 ± 4.58	-6.5 ± 4.79	-6.0 ± 4.08
Week 88; n=49, 101, 34	-5.3 ± 4.61	-6.5 ± 4.29	-6.1 ± 3.80
Week 96; n=49, 100, 34	-5.6 ± 4.35	-7.0 ± 4.44	-6.1 ± 3.80
Week 104; n=50, 104, 34	-5.1 ± 3.69	-7.2 ± 4.22	-6.3 ± 3.76

Notes
[43] - Modified Intent-to-Treat (MITT) Population
[44] - Modified Intent-to-Treat (MITT) Population
[45] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with SLEDAI-2K organ improvement compared to Baseline by visits (PI assessed)

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End point title

Percentage of participants with SLEDAI-2K organ improvement compared to Baseline by visits (PI assessed)

End point description

SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. An improvement was defined as a decrease(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Data for following organ systems was reported: CNS total, Vascular total, Musculoskeletal total, Renal total, Mucocutaneous total, Cardiovascular (Cardio) and Respiratory (Resp) total, Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system. 99999 indicates data was not available. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). Only participants with organ system involvement at Baseline were included.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[46]	144 ^[47]	47 ^[48]
Units: Percentage of participants
number (not applicable)
CNS Total; Week 4; n= 2,3,2	0	33.3	0
CNS Total; Week 8; n= 2,3,2	50.0	66.7	0
CNS Total; Week 12; n= 2,3,2	50.0	66.7	50.0
CNS Total; Week 16; n= 2,3,2	50.0	66.7	0
CNS Total; Week 20; n= 2,3,2	100	66.7	0
CNS Total; Week 24; n= 2,3,2	100	66.7	100
CNS Total; Week 26; n= 2,3,2	50.0	66.7	0
CNS Total; Week 28; n= 2,3,2	100	66.7	100
CNS Total; Week 32; n= 2,3,2	100	66.7	100
CNS Total; Week 36; n= 2,3,2	100	66.7	50.0
CNS Total; Week 40; n= 2,3,2	100	66.7	100
CNS Total; Week 44; n= 2,3,2	100	66.7	100
CNS Total; Week 48; n= 2,3,2	100	66.7	50.0
CNS Total; Week 52; n= 2,3,2	100	66.7	100
CNS Total; Week 60; n= 2,3,2	100	66.7	100
CNS Total; Week 64; n= 2,3,2	100	66.7	100
CNS Total; Week 72; n= 2,3,2	100	33.3	50.0
CNS Total; Week 80; n= 2,3,2	100	33.3	50.0
CNS Total; Week 88; n= 2,3,2	100	33.3	100
CNS Total; Week 96; n= 2,3,2	100	33.3	100
CNS Total; Week 104; n=2,3,2	100	33.3	100
Vascular Total; Week 4; n= 6,11,0	50.0	9.1	99999
Vascular Total; Week 8; n= 6,11,0	33.3	36.4	99999
Vascular Total; Week 12; n= 6,11,0	50.0	54.5	99999
Vascular Total; Week 16; n= 6,11,0	50.0	54.5	99999
Vascular Total; Week 20; n=6,11,0	50.0	72.7	99999
Vascular Total; Week 24; n= 6,11,0	50.0	72.7	99999
Vascular Total; Week 26; n= 6, 11, 0	50.0	63.6	99999
Vascular Total; Week 28; n= 6, 11,0	33.3	72.7	99999
Vascular Total; Week 32; n= 6,11, 0	50.0	72.7	99999
Vascular Total; Week 36; n= 6, 11,0	50.0	63.6	99999
Vascular Total; Week 40; n= 6, 11,0	33.3	72.7	99999
Vascular Total; Week 44; n= 6, 11, 0	33.3	72.7	99999
Vascular Total; Week 48; n= 6, 11, 0	33.3	63.6	99999
Vascular Total; Week 52; n= 6, 11, 0	66.7	63.6	99999
Vascular Total; Week 60; n= 6, 11, 0	50.0	63.6	99999
Vascular Total; Week 64; n= 6, 11, 0	50.0	90.9	99999
Vascular Total; Week 72; n= 6, 11, 0	33.3	81.8	99999
Vascular Total; Week 80; n= 6, 11, 0	50.0	72.7	99999
Vascular Total; Week 88; n= 6, 11, 0	50.0	45.5	99999
Vascular Total; Week 96; n= 6, 11, 0	50.0	63.6	99999
Vascular Total; Week 104; n= 6, 11, 0	33.3	72.7	99999
Musculoskeletal Total; Week 4; n= 57, 110, 34	22.8	13.6	23.5
Musculoskeletal Total; Week 8; n=57,110, 34	40.4	40.0	50.0
Musculoskeletal Total; Week 12; n= 57,110,34	36.8	44.5	47.1
Musculoskeletal Total; Week 16; n= 57,110,34	42.1	56.4	67.6
Musculoskeletal Total; Week 20; n= 57,110,34	47.4	58.2	64.7
Musculoskeletal Total; Week 24; n= 57,110,34	42.1	54.5	70.6
Musculoskeletal Total; Week 26; n=57,110,34	43.9	46.4	73.5
Musculoskeletal Total; Week 28; n= 57,110,34	49.1	53.6	76.5
Musculoskeletal Total; Week 32; n= 57,110,34	54.4	63.6	76.5
Musculoskeletal Total; Week 36; n= 57,110,34	61.4	61.8	76.5
Musculoskeletal Total; Week 40; n= 57,110,34	54.4	58.2	73.5
Musculoskeletal Total; Week 44; n= 57,110,34	50.9	60.0	76.5
Musculoskeletal Total; Week 48; n= 57,110,34	57.9	60.9	73.5
Musculoskeletal Total; Week 52; n= 57,110,34	59.6	59.1	73.5
Musculoskeletal Total; Week 60; n= 57,110,34	54.4	54.5	67.6
Musculoskeletal Total; Week 64; n= 57,110,34	56.1	55.5	67.6
Musculoskeletal Total; Week 72; n= 57,110,34	47.4	58.2	58.8
Musculoskeletal Total; Week 80; n= 57,110,34	47.4	58.2	76.5
Musculoskeletal Total; Week 88; n= 57,110,34	57.9	59.1	67.6
Musculoskeletal Total; Week 96; n= 57,110,34	50.9	60.9	70.6
Musculoskeletal Total; Week 104; n= 57,110,34	47.4	64.5	67.6
Renal Total; Week 4; n= 14,23,8	21.4	30.4	12.5
Renal Total; Week 8; n= 14, 23, 8	50.0	43.5	12.5
Renal Total; Week 12; n= 14, 23, 8	28.6	52.2	12.5
Renal Total; Week 16; n= 14, 23, 8	35.7	52.2	12.5
Renal Total; Week 20; n= 14, 23, 8	57.1	60.9	12.5
Renal Total; Week 24; n= 14, 23, 8	35.7	60.9	12.5
Renal Total; Week 26; n= 14, 23, 8	28.6	65.2	25.0
Renal Total; Week 28; n= 14, 23, 8	21.4	56.5	37.5
Renal Total; Week 32; n= 14, 23, 8	35.7	65.2	25.0
Renal Total; Week 36; n= 14, 23, 8	42.9	65.2	50.0
Renal Total; Week 40; n=14, 23, 8	42.9	69.6	25.0
Renal Total; Week 44; n= 14, 23, 8	50.0	69.6	12.5
Renal Total; Week 48; n=14, 23, 8	42.9	69.6	50.0
Renal Total; Week 52; n= 14, 23, 8	64.3	69.6	25.0
Renal Total; Week 60; n= 14, 23, 8	50.0	65.2	25.0
Renal Total; Week 64; n= 14, 23, 8	50.0	69.6	12.5
Renal Total; Week 72; n= 14, 23, 8	50.0	65.2	12.5
Renal Total; Week 80; n= 14, 23, 8	42.9	65.2	50.0
Renal Total; Week 88; n= 14, 23, 8	50.0	73.9	25.0
Renal Total; Week 96; n= 14, 23, 8	35.7	78.3	37.5
Renal Total; Week 104; n= 14, 23, 8	35.7	69.6	50.0
Mucocutaneous Total; Week 4; n= 59, 126,43	30.5	28.6	32.6
Mucocutaneous Total; Week 8; n= 59,126,43	54.2	45.2	51.2
Mucocutaneous Total; Week 12; n= 59, 126, 43	55.9	57.1	55.8
Mucocutaneous Total; Week 16; n= 59, 126, 43	57.6	58.7	67.4
Mucocutaneous Total; Week 20; n= 59, 126, 43	50.8	62.7	69.8
Mucocutaneous Total; Week 24; n= 59, 126, 43	59.3	61.9	69.8
Mucocutaneous Total; Week 26; n=59, 126, 43	59.3	60.3	65.1
Mucocutaneous Total; Week 28; n= 59, 126, 43	62.7	62.7	69.8
Mucocutaneous Total; Week 32; n= 59, 126, 43	62.7	65.1	74.4
Mucocutaneous Total; Week 36; n= 59, 126, 43	66.1	65.9	69.8
Mucocutaneous Total; Week 40; n= 59, 126, 43	62.7	66.7	67.4
Mucocutaneous Total; Week 44; n= 59, 126, 43	61.0	61.1	69.8
Mucocutaneous Total; Week 48; n= 59, 126, 43	50.8	66.7	69.8
Mucocutaneous Total; Week 52; n=59, 126, 43	64.4	64.3	69.8
Mucocutaneous Total; Week 60; n=59, 126, 43	55.9	65.1	67.4
Mucocutaneous Total; Week 64; n=59, 126, 43	64.4	65.9	62.8
Mucocutaneous Total; Week 72; n=59, 126, 43	57.6	60.3	58.1
Mucocutaneous Total; Week 80; n= 59, 126, 43	62.7	61.9	62.8
Mucocutaneous Total; Week 88; n= 59, 126, 43	59.3	62.7	67.4
Mucocutaneous Total; Week 96; n= 59, 126, 43	52.5	62.7	62.7
Mucocutaneous Total; Week 104; n= 59, 126, 43	61.0	69.0	60.5
Cardio and Resp Total; Week 4; n= 3, 7, 0	0	42.9	99999
Cardio and Resp Total; Week 8; n= 3, 7, 0	0	71.4	99999
Cardio and Resp Total; Week 12; n= 3, 7, 0	0	71.4	99999
Cardio and Resp Total; Week 16; n= 3, 7, 0	0	85.7	99999
Cardio and Resp Total; Week 20; n= 3,7, 0	33.3	71.4	99999
Cardio and Resp Total; Week 24; n= 3, 7, 0	66.7	100	99999
Cardio and Resp Total; Week 26; n=3, 7, 0	0	85.7	99999
Cardio and Resp Total; Week 28; n= 3,7, 0	0	85.7	99999
Cardio and Resp Total; Week 32; n= 3, 7, 0	33.3	100	99999
Cardio and Resp Total; Week 36; n= 3, 7, 0	66.7	85.7	99999
Cardio and Resp Total; Week 40; n=3,7, 0	33.3	71.4	99999
Cardio and Resp Total; Week 44; n= 3,7, 0	66.7	57.1	99999
Cardio and Resp Total; Week 48; n= 3, 7, 0	33.3	85.7	99999
Cardio and Resp Total; Week 52; n= 3, 7, 0	66.7	85.7	99999
Cardio and Resp Total; Week 60; n= 3,7,0	100	71.4	99999
Cardio and Resp Total; Week 64; n=3,7,0	100	85.7	99999
Cardio and Resp Total; Week 72; n= 3,7,0	66.7	71.4	99999
Cardio and Resp Total; Week 80; n=3,7,0	66.7	85.7	99999
Cardio and Resp Total; Week 88; n= 3,7,0	66.7	71.4	99999
Cardio and Resp Total; Week 96; n= 3,7,0	66.7	71.4	99999
Cardio and Resp Total; Week 104; n= 3,7,0	66.7	71.4	99999
Immunologic Total; Week 4; n=48, 104, 34	12.5	10.6	17.6
Immunologic Total; Week 8; n= 48, 104, 34	16.7	17.3	17.6
Immunologic Total; Week 12; n= 48, 104, 34	22.9	24.0	17.6
Immunologic Total; Week 16; n= 48, 104, 34	20.8	30.8	11.8
Immunologic Total; Week 20; n= 48, 104, 34	20.8	36.5	23.5
Immunologic Total; Week 24; n= 48, 104, 34	22.9	34.6	20.6
Immunologic Total; Week 26; n= 48, 104, 34	18.8	39.4	11.8
Immunologic Total; Week 28; n= 48, 104, 34	18.8	34.6	20.6
Immunologic Total; Week 32; n= 48, 104, 34	25.0	40.4	23.5
Immunologic Total; Week 36; n= 48, 104, 34	20.8	41.3	17.6
Immunologic Total; Week 40; n= 48, 104, 34	14.6	44.2	23.5
Immunologic Total; Week 44; n= 48, 104, 34	25.0	39.4	38.2
Immunologic Total; Week 48; n= 48, 104, 34	20.8	41.3	29.4
Immunologic Total; Week 52; n= 48, 104, 34	20.8	37.5	26.5
Immunologic Total; Week 60; n= 48, 104, 34	25.0	45.2	20.6
Immunologic Total; Week 64; n= 48, 104, 34	20.8	43.3	26.5
Immunologic Total; Week 72; n=48, 104, 34	29.2	36.5	17.6
Immunologic Total; Week 80; n=48, 104, 34	22.9	31.7	23.5
Immunologic Total; Week 88; n=48, 104, 34	31.3	29.8	14.7
Immunologic Total; Week 96; n=48, 104, 34	20.8	33.7	20.6
Immunologic Total; Week 104; n=48, 104, 34	27.1	40.4	20.6
Hematologic Total; Week 4; n= 8, 19, 3	50.0	42.1	0
Hematologic Total; Week 8; n= 8, 19, 3	62.5	63.2	66.7
Hematologic Total; Week 12; n= 8, 19, 3	62.5	52.6	33.3
Hematologic Total; Week 16; n= 8, 19, 3	75.0	63.2	66.7
Hematologic Total; Week 20; n= 8, 19, 3	87.5	57.9	100
Hematologic Total; Week 24; n= 8, 19, 3	62.5	52.6	100
Hematologic Total; Week 26; n= 8, 19, 3	75.0	36.8	100
Hematologic Total; Week 28; n= 8, 19, 3	62.5	57.9	66.7
Hematologic Total; Week 32; n= 8, 19, 3	62.5	57.9	66.7
Hematologic Total; Week 36; n= 8, 19, 3	87.5	63.2	66.7
Hematologic Total; Week 40; n= 8, 19, 3	62.5	52.6	66.7
Hematologic Total; Week 44; n= 8, 19, 3	87.5	57.9	66.7
Hematologic Total; Week 48; n= 8, 19, 3	37.5	63.2	66.7
Hematologic Total; Week 52; n= 8, 19, 3	75.0	52.6	33.3
Hematologic Total; Week 60; n= 8, 19, 3	50.0	57.9	33.3
Hematologic Total; Week 64; n= 8, 19, 3	62.5	68.4	33.3
Hematologic Total; Week 72; n= 8, 19, 3	62.5	47.4	0
Hematologic Total; Week 80; n= 8, 19, 3	50.0	52.6	33.3
Hematologic Total; Week 88; n= 8, 19, 3	37.5	57.9	33.3
Hematologic Total; Week 96; n= 8, 19, 3	50.0	52.6	33.3
Hematologic Total; Week 104; n= 8, 19, 3	50.0	63.2	33.3

Notes
[46] - Modified Intent-to-Treat (MITT) Population
[47] - Modified Intent-to-Treat (MITT) Population
[48] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with SLEDAI-2K organ worsening compared to Baseline by visits (PI assessed)

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End point title

Percentage of participants with SLEDAI-2K organ worsening compared to Baseline by visits (PI assessed)

End point description

SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. A worsening was defined as an increase(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Percentage of participants with SLEDAI-2K organ worsening for following organ systems were reported;CNS total,Vascular total,Musculoskeletal total,Renal total,Mucocutaneous total,Cardio and Resp total,Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). Only participants with no organ system involvement at Baseline were included.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[49]	144 ^[50]	47 ^[51]
Units: Percentage of participants
number (not applicable)
CNS Total; Week 4; n= 69, 136, 43	0	0	0
CNS Total; Week 8; n= 64,132, 42	0	0	0
CNS Total; Week 12; n= 65, 134, 42	0	0	0
CNS Total; Week 16; n= 65, 130, 42	0	0.8	0
CNS Total; Week 20; n= 63, 128, 42	0	0	0
CNS Total; Week 24; n= 61, 127, 41	0	0.8	0
CNS Total; Week 26; n=61, 116, 38	0	0.9	0
CNS Total; Week 28; n=62, 124, 41	0	0	0
CNS Total; Week 32; n= 61, 124, 41	0	0.8	0
CNS Total; Week 36; n= 61, 124, 41	0	1.6	0
CNS Total; Week 40; n= 61, 123, 41	0	0	0
CNS Total; Week 44; n= 61, 121, 41	0	0	0
CNS Total; Week 48; n= 58, 120,39	0	0	0
CNS Total; Week 52; n= 62, 120, 38	0	0	0
CNS Total; Week 60; n=59, 117, 35	0	0	0
CNS Total; Week 64; n=60, 117, 34	0	0	0
CNS Total; Week 72; n= 56, 109, 31	0	0	0
CNS Total; Week 80; n=55, 111, 35	0	0	0
CNS Total; Week 88; n= 57, 107, 34	0	0	0
CNS Total; Week 96; n=52, 107, 33	0	0	0
CNS Total; Week 104; n= 53, 112, 34	0	0	0
Vascular Total;Week 4; n= 65, 128, 45	0	3.9	0
Vascular Total;Week 8; n= 61, 124, 44	0	2.4	0
Vascular Total; Week 12; n= 62, 126, 44	1.6	1.6	0
Vascular Total; Week 16; n=62, 122, 44	0	1.6	0
Vascular Total; Week 20; n=60, 120, 44	0	0.8	0
Vascular Total; Week 24; n= 59, 119, 43	0	0	0
Vascular Total; Week 26; n=58, 109, 40	0	0.9	0
Vascular Total;Week 28; n= 61, 116, 43	0	1.7	0
Vascular Total;Week 32; n=59, 116, 43	0	2.6	0
Vascular Total;Week 36; n= 59, 116, 43	0	1.7	0
Vascular Total;Week 40; n=59, 115, 43	0	1.7	0
Vascular Total;Week 44; n= 59, 113, 43	0	0	0
Vascular Total;Week 48; n= 57, 112, 40	0	0	0
Vascular Total;Week 52; n=60, 112, 40	0	0.9	0
Vascular Total;Week 60; n= 58, 109, 37	0	0	0
Vascular Total;Week 64; n=59, 109, 36	0	1.8	0
Vascular Total;Week 72; n=55, 101, 33	0	0	0
Vascular Total;Week 80; n= 54, 104, 37	0	1.0	0
Vascular Total;Week 88; n=56, 102, 36	0	0	0
Vascular Total;Week 96; n=51, 101, 35	0	0	0
Vascular Total;Week 104; n=53, 105, 36	0	0	0
Musculoskeletal Total; Week 4; n=15, 33, 12	0	12.1	0
Musculoskeletal Total; Week 8; n= 15, 33, 12	6.7	6.1	0
Musculoskeletal Total; Week 12; n= 15, 33, 12	13.3	6.1	0
Musculoskeletal Total; Week 16; n= 15, 32, 12	6.7	3.1	8.3
Musculoskeletal Total; Week 20; n= 15, 32, 12	6.7	6.3	0
Musculoskeletal Total; Week 24; n= 15, 31, 11	0	6.5	0
Musculoskeletal Total; Week 26; n= 15, 31, 11	0	3.2	0
Musculoskeletal Total; Week 28; n= 14, 31, 11	0	3.2	9.1
Musculoskeletal Total; Week 32; n= 15, 30, 11	0	6.7	9.1
Musculoskeletal Total; Week 36; n= 14, 30, 11	7.1	3.3	9.1
Musculoskeletal Total; Week 40; n=15, 30, 11	0	3.3	9.1
Musculoskeletal Total; Week 44; n=15, 29, 11	0	6.9	9.1
Musculoskeletal Total; Week 48; n= 14, 30, 10	7.1	3.3	10.0
Musculoskeletal Total; Week 52; n= 15, 30, 11	6.7	6.7	9.1
Musculoskeletal Total; Week 60; n= 14, 28, 11	0	0	9.1
Musculoskeletal Total; Week 64; n=14, 29, 10	0	3.4	10.0
Musculoskeletal Total; Week 72; n= 14, 27, 10	0	11.1	10.0
Musculoskeletal Total; Week 80; n= 13, 26, 9	0	0	11.1
Musculoskeletal Total; Week 88; n= 13, 25, 9	15.4	4.0	0
Musculoskeletal Total; Week 96; n= 12, 26, 9	0	3.8	0
Musculoskeletal Total; Week 104; n= 13, 27, 9	0	0	0
Renal Total; Week 4; n= 57, 117, 36	5.3	6.0	11.1
Renal Total; Week 8; n=51, 110, 36	2.0	3.6	5.6
Renal Total; Week 12; n=53, 115, 35	1.9	3.5	8.6
Renal Total; Week 16; n=53, 112, 35	7.5	4.5	2.9
Renal Total; Week 20; n= 49, 108, 36	8.2	3.7	8.3
Renal Total; Week 24; n= 49, 111, 35	10.2	3.6	2.9
Renal Total; Week 26; n= 49, 99, 33	6.1	0	0
Renal Total; Week 28; n= 50, 106, 36	10.0	1.9	2.8
Renal Total; Week 32; n= 50,107, 36	6.0	2.8	2.8
Renal Total; Week 36; n= 50, 107, 36	8.0	2.8	5.6
Renal Total; Week 40; n= 47, 106, 34	6.4	4.7	0
Renal Total; Week 44; n= 49, 103, 35	6.1	1.0	2.9
Renal Total; Week 48; n= 47, 101, 32	10.6	5.9	6.3
Renal Total; Week 52; n= 49, 103, 32	8.2	3.9	3.1
Renal Total; Week 60; n=47, 96, 30	6.4	4.2	0
Renal Total; Week 64; n= 50, 99, 29	2.0	2.0	0
Renal Total; Week 72; n= 40, 89, 26	5.0	4.5	0
Renal Total; Week 80; n= 41, 90, 29	14.6	3.3	6.9
Renal Total; Week 88; n= 44, 85, 29	13.6	1.2	0
Renal Total; Week 96; n= 43, 85, 29	4.7	1.2	0
Renal Total; Week 104; n= 44, 90, 30	6.8	2.2	0
Mucocutaneous Total; Week 4; n= 13, 18, 4	15.4	5.6	0
Mucocutaneous Total; Week 8; n= 12, 18, 4	8.3	11.1	0
Mucocutaneous Total; Week 12; n= 12, 18, 4	8.3	16.7	0
Mucocutaneous Total; Week 16; n= 12, 18, 4	0	5.6	0
Mucocutaneous Total; Week 20; n= 12, 18, 4	25.0	5.6	0
Mucocutaneous Total; Week 24; n= 11, 17, 4	18.2	5.9	0
Mucocutaneous Total; Week 26; n= 10, 17, 4	20.0	11.8	0
Mucocutaneous Total; Week 28; n= 10, 17, 4	0	11.8	0
Mucocutaneous Total; Week 32; n= 10, 17, 4	10.0	5.9	0
Mucocutaneous Total; Week 36; n= 10, 17, 4	0	5.9	0
Mucocutaneous Total; Week 40; n= 10, 17, 4	20.0	11.8	0
Mucocutaneous Total; Week 44; n= 10, 17, 4	10.0	0	0
Mucocutaneous Total; Week 48; n=10, 16, 3	0	6.3	0
Mucocutaneous Total; Week 52; n= 10, 17, 4	0	5.9	25.0
Mucocutaneous Total; Week 60; n= 9, 17, 4	11.1	11.8	0
Mucocutaneous Total; Week 64; n= 10, 16, 4	0	6.3	25.0
Mucocutaneous Total; Week 72; n=10, 16, 4	20	6.3	25.0
Mucocutaneous Total; Week 80; n= 9, 17, 4	0	0	25.0
Mucocutaneous Total; Week 88; n= 9, 16, 4	0	6.3	25.0
Mucocutaneous Total; Week 96; n= 9, 15, 4	11.1	0	25.0
Mucocutaneous Total; Week 104; n= 9, 17, 4	11.1	5.9	0
Cardio and Resp Total; Week 4; n= 68, 132, 45	2.9	0.8	0
Cardio and Resp Total; Week 8; n= 63, 128, 44	0	0.8	0
Cardio and Resp Total; Week 12; n= 64, 130, 44	0	0.8	0
Cardio and Resp Total; Week 16; n= 64, 126, 44	3.1	0	0
Cardio and Resp Total; Week 20; n= 63, 124, 44	1.6	0.8	0
Cardio and Resp Total; Week 24; n= 60, 123, 43	0	0	0
Cardio and Resp Total; Week 26; n=59, 112, 40	0	0	0
Cardio and Resp Total; Week 28; n= 61, 120, 43	3.3	0.8	0
Cardio and Resp Total; Week 32; n= 60, 120, 43	1.7	0	0
Cardio and Resp Total; Week 36; n= 60, 120, 43	1.7	0	0
Cardio and Resp Total; Week 40; n=60, 119, 43	0	0	0
Cardio and Resp Total; Week 44; n= 60, 117, 43	1.7	0	0
Cardio and Resp Total; Week 48; n= 57, 116, 40	0	0	2.5
Cardio and Resp Total; Week 52; n=61, 116, 40	0	0	0
Cardio and Resp Total; Week 60; n= 58, 114, 37	0	0	0
Cardio and Resp Total; Week 64; n= 59, 114, 36	0	0.9	0
Cardio and Resp Total; Week 72; n= 55, 106, 33	0	0	0
Cardio and Resp Total; Week 80; n= 54, 107, 37	1.9	0	0
Cardio and Resp Total; Week 88; n= 56, 104, 36	1.8	0	0
Cardio and Resp Total; Week 96; n=51, 104, 35	0	1.0	0
Cardio and Resp Total; Week 104; n= 52, 109, 36	0	0	0
Immunologic Total; Week 4; n=23, 37, 13	17.4	0	7.7
Immunologic Total; Week 8; n=20, 37, 12	20.0	10.8	0
Immunologic Total; Week 12; n=21, 37,12	23.8	8.1	16.7
Immunologic Total; Week 16; n= 21, 35, 12	9.5	11.4	0
Immunologic Total; Week 20; n= 19, 35, 12	15.8	11.4	0
Immunologic Total; Week 24; n= 18, 35, 12	5.6	5.7	0
Immunologic Total; Week 26; n= 18, 30, 12	5.6	6.7	8.3
Immunologic Total; Week 28; n= 19, 35, 12	15.8	8.6	16.7
Immunologic Total; Week 32; n= 19, 33, 12	10.5	12.1	8.3
Immunologic Total; Week 36; n= 19, 34, 12	15.8	8.8	16.7
Immunologic Total; Week 40; n= 19, 33, 12	21.1	6.1	8.3
Immunologic Total; Week 44; n= 18, 33, 12	22.2	0	0
Immunologic Total; Week 48; n= 18, 33, 11	22.2	3.0	27.3
Immunologic Total; Week 52; n= 19, 32, 12	21.1	3.1	8.3
Immunologic Total; Week 60; n= 18, 32, 10	16.7	6.3	0
Immunologic Total; Week 64; n= 19, 33, 10	21.1	6.1	20.0
Immunologic Total; Week 72; n= 17, 28, 9	23.5	7.1	11.1
Immunologic Total; Week 80; n= 18, 29, 11	5.6	6.9	18.2
Immunologic Total; Week 88; n= 19, 29, 11	10.5	6.9	18.2
Immunologic Total; Week 96; n= 16, 30, 11	12.5	13.3	18.2
Immunologic Total; Week 104; n= 17, 28, 12	11.8	17.9	16.7
Hematologic Total; Week 4; n= 59, 115, 40	5.1	3.5	5.0
Hematologic Total; Week 8; n= 52, 109, 38	3.8	5.5	0
Hematologic Total; Week 12; n= 55, 110, 38	1.8	4.5	10.5
Hematologic Total; Week 16; n=54, 107, 34	1.9	2.8	2.9
Hematologic Total; Week 20; n= 54, 108, 40	5.6	5.6	5.0
Hematologic Total; Week 24; n= 53, 111, 37	3.8	2.7	2.7
Hematologic Total; Week 26; n= 53, 101, 37	9.4	5.0	10.8
Hematologic Total; Week 28; n= 52, 106, 39	7.7	3.8	5.1
Hematologic Total; Week 32; n=52, 110, 38	0	4.5	7.9
Hematologic Total; Week 36; n= 53, 109, 40	5.7	6.4	2.5
Hematologic Total; Week 40; n= 51, 108, 37	0	10.2	5.4
Hematologic Total; Week 44; n=53, 107, 38	7.5	6.5	5.3
Hematologic Total; Week 48; n=51, 105, 35	5.9	4.8	0
Hematologic Total; Week 52; n= 53, 103, 37	3.8	3.9	2.7
Hematologic Total; Week 60; n=53, 101, 35	9.4	5.0	5.7
Hematologic Total; Week 64; n=54, 98, 32	11.1	5.1	6.3
Hematologic Total; Week 72; n= 47,96, 29	10.6	5.2	3.4
Hematologic Total; Week 80; n= 45, 94, 35	0	4.3	5.7
Hematologic Total; Week 88; n= 46, 88, 32	10.9	9.1	3.1
Hematologic Total; Week 96; n= 45, 90, 32	4.4	4.4	3.1
Hematologic Total; Week 104; n= 46, 94, 32	4.3	6.4	6.3

Notes
[49] - Modified Intent-to-Treat (MITT) Population
[50] - Modified Intent-to-Treat (MITT) Population
[51] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Change from Baseline in Physician Global Assessment (PGA) by visits

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End point title

Change from Baseline in Physician Global Assessment (PGA) by visits

End point description

The Physician's Global Assessment (PGA) was a physician-reported visual analogue scale that provides an overall measure of the participant's current disease activity. Physician's Global Assessment was collected on a 10 centimeter (cm) visual analogue scale (VAS) by placing a mark on the scale between 0 (no disease activity) to 10 (maximum disease activity). The PGA score was then rescaled for reporting by multiplying the collected score by 3 divided by 10. Hence, the PGA score ranges from 0 to 3 with higher scores indicating greater disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[52]	144 ^[53]	47 ^[54]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 4; n=72, 142, 45	-0.285 ± 0.4816	-0.247 ± 0.4640	-0.303 ± 0.5464
Week 8; n=66, 135, 44	-0.535 ± 0.5134	-0.520 ± 0.5243	-0.585 ± 0.5793
Week 12; n=66, 137, 44	-0.592 ± 0.5265	-0.660 ± 0.5776	-0.654 ± 0.5450
Week 16; n=68, 132, 44	-0.619 ± 0.5475	-0.717 ± 0.5802	-0.759 ± 0.6072
Week 20; n=66, 130, 44	-0.697 ± 0.6157	-0.787 ± 0.5445	-0.786 ± 0.6772
Week 24; n=62, 130, 43	-0.770 ± 0.5888	-0.766 ± 0.5059	-0.965 ± 0.6413
Week 26; n=62, 120, 40	-0.786 ± 0.5727	-0.811 ± 0.5445	-0.929 ± 0.6631
Week 28; n=63, 127, 43	-0.781 ± 0.5395	-0.817 ± 0.5360	-0.980 ± 0.6286
Week 32; n=62, 124, 43	-0.851 ± 0.5989	-0.864 ± 0.5519	-1.005 ± 0.6723
Week 36; n=64, 126, 43	-0.916 ± 0.6141	-0.927 ± 0.5400	-0.917 ± 0.5504
Week 40; n=63, 126, 43	-0.893 ± 0.6157	-0.925 ± 0.5621	-0.993 ± 0.6711
Week 44; n=63, 124, 43	-0.800 ± 0.6764	-0.905 ± 0.5289	-0.970 ± 0.6065
Week 48; n=59, 121, 40	-0.885 ± 0.6178	-0.928 ± 0.5627	-0.956 ± 0.5175
Week 52; n=64, 122, 41	-0.947 ± 0.6918	-0.938 ± 0.6125	-1.004 ± 0.5527
Week 60; n=61, 120, 37	-0.836 ± 0.6982	-0.848 ± 0.6085	-1.206 ± 0.5917
Week 64; n=62, 120, 36	-0.876 ± 0.6971	-0.943 ± 0.5711	-1.095 ± 0.6365
Week 72; n=58, 110, 33	-0.928 ± 0.6838	-0.944 ± 0.5708	-1.047 ± 0.6088
Week 80; n=57, 112, 37	-0.949 ± 0.6909	-0.954 ± 0.6221	-1.138 ± 0.5574
Week 88; n=59, 109, 36	-1.060 ± 0.6307	-0.993 ± 0.5733	-1.140 ± 0.5514
Week 96; n=54, 109, 35	-1.016 ± 0.6093	-0.994 ± 0.5669	-1.214 ± 0.5580
Week 104; n=55, 114, 36	-1.052 ± 0.5095	-1.074 ± 0.5166	-1.085 ± 0.5987

Notes
[52] - Modified Intent-to-Treat (MITT) Population
[53] - Modified Intent-to-Treat (MITT) Population
[54] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with Systemic Lupus International Collaborating Clinics (SLICC) -American College of Rheumatology (ACR) damage index worsening compared with Baseline at Week 52 and Week 104

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End point title

Percentage of participants with Systemic Lupus International Collaborating Clinics (SLICC) -American College of Rheumatology (ACR) damage index worsening compared with Baseline at Week 52 and Week 104

End point description

The SLICC-ACR Damage Index measures irreversible (not related to active inflammation) changes occurring since the diagnosis of SLE ascertained by clinical assessment and present for at least 6 months. The questionnaire contains 39 items covering 12 different organ systems which were scored on a numerical scale between 0 (no damage) to 7 (increasing disease damage). Individual ranges for organ systems were; ocular: 0-2, neuropsychiatric: 0-6, renal: 0-3, pulmonary: 0-5, cardiovascular:0-6, peripheral vascular: 0-5, gastrointestinal:0-5, musculoskeletal: 0-6, skin: 0-3, endocrine (diabetes): 0-1, gonadal:0-1 and malignancies: 0-2. The SLICC-ACR score was calculated by taking sum of the individual scores for 12 organ systems which ranges from 0 (no damage) to 45 (increasing disease damage) where higher score indicates increasing disease damage severity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 52 and Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[55]	144 ^[56]	47 ^[57]
Units: Percentage of participants
number (confidence interval 95%)
Week 52	1.4 (0 to 4.1)	2.1 (0 to 4.4)	2.1 (0 to 6.3)
Week 104	5.6 (0.3 to 10.8)	5.6 (1.8 to 9.3)	6.4 (0 to 13.4)

Notes
[55] - Modified Intent-to-Treat (MITT) Population
[56] - Modified Intent-to-Treat (MITT) Population
[57] - Modified Intent-to-Treat (MITT) Population

Stastistical Analysis 1

Statistical analysis description

Odds ratio at Week 52 was calculated using Logistic regression model with covariates:Baseline SLEDAI-2K,Baseline immunosuppressant,Baseline prednisone equivalent dose and treatment group. Belimumab+ Standard therapy arm was excluded from the model.

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7102 ^[58]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

15.7

Notes
[58] - Week 52

Stastistical Analysis 2

Statistical analysis description

Odds ratio at Week 52 was calculated using Logistic regression model with covariates:Baseline SLEDAI-2K,Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm was excluded from the model.

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

10.71

Stastistical Analysis 3

Statistical analysis description

Odds ratio at Week 104 was calculated using Logistic regression model with covariates:Baseline SLEDAI-2K,Baseline immunosuppressant,Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from the model.

Comparison groups

Belimumab + Placebo v Belimumab + Rituximab

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8641 ^[59]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

3.15

Notes
[59] - Week 104

Stastistical Analysis 4

Statistical analysis description

Comparison groups

Belimumab + Rituximab v Belimumab + Standard therapy

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

5.64

Secondary: Percentage of participants that met the Lupus Low Disease Activity State (LLDAS) response criteria by visits (PI assessed)

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End point title

Percentage of participants that met the Lupus Low Disease Activity State (LLDAS) response criteria by visits (PI assessed)

End point description

Lupus low disease activity state (LLDAS) was defined as a state which, if sustained, was associated with a low likelihood of adverse outcome, considering disease activity and medication safety. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; (2) no new features of lupus disease activity compared with the previous assessment; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs. Percentage of participants that met the LLDAS response criteria were reported. 99999 indicates that data was not available as there was no participant who met the LLDAS response criteria. Hence, 95% CI could not be calculated.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[60]	144 ^[61]	47 ^[62]
Units: Percentage of participants
number (confidence interval 95%)
Week 4	0 (-9999 to 9999)	2.1 (0 to 4.4)	2.1 (0 to 6.3)
Week 8	9.7 (2.9 to 16.6)	1.4 (0 to 3.3)	10.6 (1.8 to 19.5)
Week 12	8.3 (1.9 to 14.7)	9.7 (4.9 to 14.6)	6.4 (0 to 13.4)
Week 16	11.1 (3.9 to 18.4)	16.7 (10.6 to 22.8)	19.1 (7.9 to 30.4)
Week 20	11.1 (3.9 to 18.4)	25.7 (18.6 to 32.8)	19.1 (7.9 to 30.4)
Week 24	12.5 (4.9 to 20.1)	22.2 (15.4 to 29.0)	36.2 (22.4 to 49.9)
Week 26	22.2 (12.6 to 31.8)	25.7 (18.6 to 32.8)	34.0 (20.5 to 47.6)
Week 28	20.8 (11.5 to 30.2)	25.0 (17.9 to 32.1)	34.0 (20.5 to 47.6)
Week 32	29.2 (18.7 to 39.7)	31.9 (24.3 to 39.6)	36.2 (22.4 to 49.9)
Week 36	30.6 (19.9 to 41.2)	34.0 (26.3 to 41.8)	29.8 (16.7 to 42.9)
Week 40	22.2 (12.6 to 31.8)	33.3 (25.6 to 41.0)	38.3 (24.4 to 52.2)
Week 44	30.6 (19.9 to 41.2)	37.5 (29.6 to 45.4)	31.9 (18.6 to 45.2)
Week 48	26.4 (16.2 to 36.6)	37.5 (29.6 to 45.4)	31.9 (18.6 to 45.2)
Week 52	27.8 (17.4 to 38.1)	34.0 (26.3 to 41.8)	29.8 (16.7 to 42.9)
Week 60	26.4 (16.2 to 36.6)	23.6 (16.7 to 30.5)	36.2 (22.4 to 49.9)
Week 64	20.8 (11.5 to 30.2)	30.6 (23.0 to 38.1)	31.9 (18.6 to 45.2)
Week 72	22.2 (12.6 to 31.8)	31.3 (23.7 to 38.8)	31.9 (18.6 to 45.2)
Week 80	18.1 (9.2 to 26.9)	26.4 (19.2 to 33.6)	34.0 (20.5 to 47.6)
Week 88	23.6 (13.8 to 33.4)	24.3 (17.3 to 31.3)	29.8 (16.7 to 42.9)
Week 96	20.8 (11.5 to 30.2)	30.6 (23.0 to 38.1)	36.2 (22.4 to 49.9)
Week 104	20.8 (11.5 to 30.2)	32.6 (25.0 to 40.3)	38.3 (24.4 to 52.2)

Notes
[60] - Modified Intent-to-Treat (MITT) Population
[61] - Modified Intent-to-Treat (MITT) Population
[62] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K by visit

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End point title

Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K by visit

End point description

Percentage of participants with a state of disease control was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day, using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0 (no symptoms) to 105 (presence of all defined symptoms), higher scores representing increased disease activity. Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K were summarized.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[63]	144 ^[64]	47 ^[65]
Units: Percentage of participants
number (confidence interval 95%)
Week 4	2.8 (0 to 6.6)	3.5 (0.5 to 6.5)	8.5 (0.5 to 16.5)
Week 8	13.9 (5.9 to 21.9)	9.0 (4.3 to 13.7)	21.3 (9.6 to 33.0)
Week 12	11.1 (3.9 to 18.4)	12.5 (7.1 to 17.9)	19.1 (7.9 to 30.4)
Week 16	15.3 (7.0 to 23.6)	22.2 (15.4 to 29.0)	29.8 (16.7 to 42.9)
Week 20	13.9 (5.9 to 21.9)	24.3 (17.3 to 31.3)	31.9 (18.6 to 45.2)
Week 24	18.1 (9.2 to 26.9)	25.0 (17.9 to 32.1)	34.0 (20.5 to 47.6)
Week 26	15.3 (7.0 to 23.6)	25.7 (18.6 to 32.8)	25.5 (13.1 to 38.0)
Week 28	11.1 (3.9 to 18.4)	25.7 (18.6 to 32.8)	36.2 (22.4 to 49.9)
Week 32	15.3 (7.0 to 23.6)	28.5 (21.1 to 35.8)	31.9 (18.6 to 45.2)
Week 36	19.4 (10.3 to 28.6)	27.8 (20.5 to 35.1)	27.7 (14.9 to 40.4)
Week 40	16.7 (8.1 to 25.3)	24.3 (17.3 to 31.3)	23.4 (11.3 to 35.5)
Week 44	18.1 (9.2 to 26.9)	26.4 (19.2 to 33.6)	27.7 (14.9 to 40.4)
Week 48	18.1 (9.2 to 26.9)	26.4 (19.2 to 33.6)	27.7 (14.9 to 40.4)
Week 52	19.4 (10.3 to 28.6)	20.1 (13.6 to 26.7)	27.7 (14.9 to 40.4)
Week 60	18.1 (9.2 to 26.9)	20.8 (14.2 to 27.5)	23.4 (11.3 to 35.5)
Week 64	11.1 (3.9 to 18.4)	18.1 (11.8 to 24.3)	27.7 (14.9 to 40.4)
Week 72	9.7 (2.9 to 16.6)	12.5 (7.1 to 17.9)	23.4 (11.3 to 35.5)
Week 80	8.3 (1.9 to 14.7)	13.2 (7.7 to 18.7)	31.9 (18.6 to 45.2)
Week 88	11.1 (3.9 to 18.4)	9.7 (4.9 to 14.6)	21.3 (9.6 to 33.0)
Week 96	8.3 (1.9 to 14.7)	12.5 (7.1 to 17.9)	31.9 (18.6 to 45.2)
Week 104	8.3 (1.9 to 14.7)	11.8 (6.5 to 17.1)	23.4 (11.3 to 35.5)

Notes
[63] - Modified Intent-to-Treat (MITT) Population
[64] - Modified Intent-to-Treat (MITT) Population
[65] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K by visit

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End point title

Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K by visit

End point description

Percentage of participants with a state of clinical remission was defined as the percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants (which was allowed in Belimumab+ Standard therapy arm only) and with corticosteroids at a prednisone equivalent dose of 0 mg/day using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity. Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K were summarized.

End point type

Secondary

End point timeframe

Weeks 60, 64, 72, 80, 88, 96 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[66]	144 ^[67]	47 ^[68]
Units: Percentage of participants
number (confidence interval 95%)
Week 60	6.9 (1.1 to 12.8)	3.5 (0.5 to 6.5)	10.6 (1.8 to 19.5)
Week 64	6.9 (1.1 to 12.8)	5.6 (1.8 to 9.3)	10.6 (1.8 to 19.5)
Week 72	6.9 (1.1 to 12.8)	3.5 (0.5 to 6.5)	14.9 (4.7 to 25.1)
Week 80	6.9 (1.1 to 12.8)	4.2 (0.9 to 7.4)	14.9 (4.7 to 25.1)
Week 88	6.9 (1.1 to 12.8)	2.1 (0 to 4.4)	14.9 (4.7 to 25.1)
Week 96	4.2 (0 to 8.8)	4.2 (0.9 to 7.4)	12.8 (3.2 to 22.3)
Week 104	2.8 (0 to 6.6)	3.5 (0.5 to 6.5)	6.4 (0 to 13.4)

Notes
[66] - Modified Intent-to-Treat (MITT) Population
[67] - Modified Intent-to-Treat (MITT) Population
[68] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Number of participants with serious adverse events (SAE) and non-serious AE (non-SAE)

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End point title

Number of participants with serious adverse events (SAE) and non-serious AE (non-SAE)

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situations as per medical or scientific judgment. Data for number of participants with SAE and non-SAE (>=5 %) has been summarized. Intent-to-Treat Population comprised of all randomized participants who received at least one dose of study treatment (Belimumab or Rituximab or Placebo).

End point type

Secondary

End point timeframe

Up to Week 111 (including 8 weeks of safety follow-up)

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[69]	144 ^[70]	76 ^[71]
Units: Participants
SAE	10	32	15
non-SAE	48	109	53

Notes
[69] - Intent-to-Treat Population
[70] - Intent-to-Treat Population
[71] - Intent-to-Treat Population

No statistical analyses for this end point

Secondary: Number of participants with adverse events of special interest (AESIs)

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End point title

Number of participants with adverse events of special interest (AESIs)

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. AESIs were Malignant Neoplasms, Post-Injection 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. Data for number of participants with AESIs has been summarized.

End point type

Secondary

End point timeframe

Up to Week 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[72]	144 ^[73]	76 ^[74]
Units: Participants
Malignant Neoplasms	1	1	1
PISR	7	19	4
All Infections of Special Interest	5	12	5
Depression/suicide/self-injury	9	16	5
Deaths	1	2	0

Notes
[72] - InIntent-to-Treat Population
[73] - Intent-to-Treat Population
[74] - Intent-to-Treat Population

No statistical analyses for this end point

Secondary: Change from Baseline in Patient Global Assessment (PtGA) by visits

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End point title

Change from Baseline in Patient Global Assessment (PtGA) by visits

End point description

The Patient's Global Assessment (PtGA) of Disease Activity is a single-item, participant reported scale developed for the assessment of the participant’s overall rating of their disease activity due to SLE. The scale measures disease activity ranging from 0 (Very Well) to 10 (Very Poor) and the higher score indicates severe disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[75]	144 ^[76]	47 ^[77]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 8; n=66, 132, 44	-0.96 ± 2.751	-1.06 ± 2.141	-0.91 ± 2.848
Week 12; n=66, 133, 44	-0.69 ± 2.237	-1.07 ± 2.290	-1.57 ± 2.756
Week 26; n=61, 115, 40	-0.95 ± 2.765	-1.50 ± 2.596	-1.57 ± 2.450
Week 40; n=63, 123, 43	-1.77 ± 2.624	-1.60 ± 2.809	-1.67 ± 2.962
Week 52; n=64, 120, 41	-1.74 ± 2.752	-1.82 ± 2.631	-1.84 ± 3.228
Week 64; n=62, 117, 36	-1.41 ± 2.985	-1.96 ± 2.595	-1.96 ± 3.034
Week 72; n=59, 107, 33	-1.46 ± 3.209	-1.81 ± 2.609	-1.43 ± 3.487
Week 104; n=55, 111, 36	-1.61 ± 2.589	-2.00 ± 2.739	-1.98 ± 2.895

Notes
[75] - Modified Intent-to-Treat (MITT) Population
[76] - Modified Intent-to-Treat (MITT) Population
[77] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Change from Baseline in Lupus Quality of Life (LupusQoL) domain scores by visit

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End point title

Change from Baseline in Lupus Quality of Life (LupusQoL) domain scores by visit

End point description

LupusQoL is a SLE-specific health related qualify of life (HRQOL) instrument with 34 questions across 8 domains:Physical health(8 items),Pain(3 items),Planning(3 items),Intimate relationship(2 items),Burden to others(3 items),Emotional health(6 items),Body image(5 items),Fatigue(4 items)..A 5-point Likert response format was used, ranging from 0(all of the time) to 4(never) for each question. Individual domain scores were reported which were calculated by taking sum of responses to all items within each domain. Individual domain scores range:Physical health(0-32),Pain(0-12),Planning(0-12),Intimate relationship(0-8),Burden to others(0-12),Emotional health(0-24),Body image(0-20),Fatigue(0-16).Higher score indicates better HRQOL. Change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at specified time points were analyzed(represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[78]	144 ^[79]	47 ^[80]
Units: Scores on a scale
arithmetic mean (standard deviation)
Physical health; Week 8; n=66, 132, 44	3.0 ± 15.20	6.0 ± 15.08	6.3 ± 18.79
Physical health; Week 12; n=66, 133, 44	3.5 ± 16.60	5.8 ± 17.15	6.4 ± 20.06
Physical health; Week 26; n=61, 115, 40	3.3 ± 18.74	10.5 ± 17.27	11.6 ± 19.19
Physical health; Week 40; n=63, 122, 43	8.5 ± 19.53	9.5 ± 19.29	8.2 ± 19.46
Physical health; Week 52; n=64, 120, 41	8.1 ± 19.90	10.0 ± 20.16	11.6 ± 19.53
Physical health; Week 64; n=62, 117, 36	5.8 ± 18.66	10.2 ± 18.60	9.5 ± 21.74
Physical health; Week 72; n=59, 107, 33	7.0 ± 21.13	9.1 ± 18.84	8.5 ± 22.59
Physical health; Week 104; n=55, 111, 36	6.2 ± 20.19	10.6 ± 19.96	7.2 ± 23.33
Pain; Week 8; n=66, 132, 44	5.8 ± 19.67	11.4 ± 18.55	10.4 ± 21.87
Pain; Week 12; n=66, 133, 44	7.5 ± 19.78	13.0 ± 20.81	6.1 ± 28.44
Pain; Week 26; n=61, 115, 40	7.0 ± 22.42	17.2 ± 21.54	13.1 ± 22.79
Pain; Week 40; n=63, 122, 43	12.3 ± 23.18	18.0 ± 22.70	12.6 ± 29.17
Pain; Week 52; n=64, 120, 41	13.9 ± 24.26	17.6 ± 23.62	15.7 ± 27.34
Pain; Week 64; n=62, 117, 36	10.2 ± 21.89	17.4 ± 23.59	13.2 ± 26.90
Pain; Week 72; n=59, 107, 33	13.1 ± 24.91	17.0 ± 22.66	11.9 ± 29.02
Pain; Week 104; n=55, 111, 36	13.8 ± 25.82	19.0 ± 22.59	12.5 ± 27.92
Planning; Week 8; n=66, 132, 44	3.4 ± 19.77	8.0 ± 18.21	10.0 ± 27.88
Planning; Week 12; n=66, 133, 44	4.5 ± 23.03	7.6 ± 20.15	7.8 ± 27.81
Planning; Week 26; n=61, 115, 40	3.4 ± 25.20	9.9 ± 21.28	12.1 ± 27.86
Planning; Week 40; n=63, 122, 43	11.6 ± 29.08	12.2 ± 22.30	10.7 ± 26.62
Planning; Week 52; n=64, 120, 41	11.6 ± 28.66	12.6 ± 23.89	14.0 ± 28.35
Planning; Week 64; n=62, 117, 36	7.8 ± 24.42	14.5 ± 23.65	7.2 ± 30.55
Planning; Week 72; n=59, 107, 33	9.2 ± 30.78	11.4 ± 20.97	6.6 ± 31.02
Planning; Week 104; n=55, 111, 36	12.1 ± 30.76	14.2 ± 20.77	8.8 ± 34.96
Intimate relationship; Week 8; n=51, 110, 36	-1.2 ± 21.83	5.2 ± 20.63	7.6 ± 19.66
Intimate relationship; Week 12; n=52, 106, 36	-2.6 ± 25.16	4.6 ± 23.42	7.6 ± 27.10
Intimate relationship; Week 26; n=48, 86, 30	-1.3 ± 29.20	8.9 ± 24.32	14.2 ± 28.38
Intimate relationship; Week 40; n=50, 94, 30	4.3 ± 28.75	7.7 ± 25.01	15.8 ± 30.43
Intimate relationship; Week 52; n=51, 91, 30	4.7 ± 29.36	6.6 ± 22.54	15.8 ± 30.78
Intimate relationship; Week 64; n=47, 90, 25	-4.5 ± 28.00	11.0 ± 25.41	12.5 ± 29.76
Intimate relationship; Week 72; n=42, 83, 21	0.0 ± 31.60	8.6 ± 23.82	5.4 ± 39.44
Intimate relationship; Week 104; n=40, 85,27	-0.3 ± 23.93	11.2 ± 25.59	4.6 ± 35.21
Burden to others; Week 8; n=66, 132, 44	7.3 ± 22.95	6.8 ± 20.56	10.6 ± 23.46
Burden to others; Week 12; n=66, 133, 44	11.4 ± 27.91	8.4 ± 23.65	6.4 ± 29.90
Burden to others; Week 26; n=61, 115, 40	8.7 ± 26.68	10.5 ± 27.42	7.5 ± 27.66
Burden to others; Week 40; n=63, 122, 43	13.9 ± 27.23	12.6 ± 26.94	12.0 ± 27.66
Burden to others; Week 52; n=64, 120, 41	16.5 ± 29.15	14.9 ± 27.03	15.0 ± 33.40
Burden to others; Week 64; n=62, 117, 36	14.4 ± 28.83	17.0 ± 26.67	12.3 ± 28.21
Burden to others; Week 72; n=59, 107, 33	17.1 ± 28.68	14.4 ± 28.77	11.1 ± 27.85
Burden to others; Week 104; n=55, 111, 36	18.9 ± 25.93	15.0 ± 29.25	12.7 ± 33.42
Emotional health; Week 8; n=66, 132, 44	5.2 ± 18.33	6.4 ± 16.87	11.6 ± 20.55
Emotional health; Week 12; n=66, 133, 44	8.1 ± 17.32	4.5 ± 19.67	9.1 ± 23.87
Emotional health; Week 26; n=61,115, 40	7.7 ± 19.84	6.7 ± 17.35	10.1 ± 18.12
Emotional health; Week 40; n=63, 122, 43	9.7 ± 21.44	6.7 ± 20.85	9.4 ± 22.20
Emotional health; Week 52; n=64, 120, 41	10.2 ± 21.48	7.8 ± 20.63	11.4 ± 21.99
Emotional health; Week 64; n=62, 117, 36	8.1 ± 20.75	9.3 ± 20.73	8.1 ± 22.11
Emotional health; Week 72; n=59, 107, 33	8.8 ± 21.39	6.2 ± 19.05	6.6 ± 21.80
Emotional health; Week 104; n=55, 111, 36	6.8 ± 20.20	9.3 ± 19.67	10.5 ± 23.00
Body image; Week 8; n=60, 114, 37	5.7 ± 19.57	8.9 ± 19.26	5.7 ± 25.05
Body image; Week 12; n=58, 118, 39	1.9 ± 23.23	10.1 ± 20.73	5.9 ± 26.89
Body image; Week 26; n=56, 96, 33	5.8 ± 20.62	9.0 ± 25.03	5.7 ± 23.07
Body image; Week 40; n=54, 103, 35	8.9 ± 25.42	8.2 ± 24.82	5.1 ± 22.07
Body image; Week 52; n=55, 101, 33	7.9 ± 25.77	9.1 ± 24.07	10.3 ± 25.24
Body image; Week 64; n=52, 98, 27	6.0 ± 22.51	11.3 ± 23.08	7.7 ± 23.98
Body image; Week 72; n=44, 93, 25	7.8 ± 26.74	8.7 ± 24.91	2.5 ± 29.28
Body image; Week 104; n=48, 94, 28	4.4 ± 26.62	11.4 ± 25.65	3.5 ± 27.40
Fatigue; Week 8; n=66,132, 44	9.8 ± 17.02	9.2 ± 18.40	8.5 ± 24.30
Fatigue; Week 12; n=66, 133, 44	8.2 ± 18.48	7.0 ± 17.96	10.4 ± 28.11
Fatigue; Week 26; n=61, 115, 40	8.6 ± 20.23	11.4 ± 20.12	11.9 ± 20.21
Fatigue; Week 40; n=63, 122, 43	11.9 ± 22.33	10.3 ± 22.41	11.3 ± 24.75
Fatigue; Week 52; n=64, 120, 41	14.2 ± 21.17	12.0 ± 20.95	16.6 ± 25.30
Fatigue; Week 64; n=62, 117, 36	10.5 ± 21.94	14.0 ± 20.35	10.8 ± 25.21
Fatigue; Week 72; n=59, 107, 33	12.1 ± 22.74	13.1 ± 18.31	11.6 ± 25.87
Fatigue; Week 104; n=55, 111, 36	9.4 ± 20.41	14.3 ± 20.18	9.7 ± 24.25

Notes
[78] - Modified Intent-to-Treat (MITT) Population
[79] - Modified Intent-to-Treat (MITT) Population
[80] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score by visit

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End point title

Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score by visit

End point description

The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The higher score for the questions, the greater the fatigue. The total score was the sum of the responses from all questions (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[81]	144 ^[82]	47 ^[83]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 8; n=66, 132, 44	4.2 ± 9.84	4.6 ± 8.84	4.8 ± 8.25
Week 12; n=66, 133, 44	4.7 ± 9.50	4.0 ± 9.86	3.8 ± 10.94
Week 26; n=61, 115, 40	3.1 ± 10.08	5.4 ± 9.17	4.1 ± 8.54
Week 40; n=63, 122, 43	6.0 ± 10.18	5.2 ± 10.80	5.2 ± 10.14
Week 52; n=64, 120, 41	6.5 ± 10.12	6.1 ± 10.84	5.1 ± 10.51
Week 64;n=62, 117, 36	4.9 ± 10.61	6.2 ± 9.72	4.6 ± 10.32
Week 72; n=59, 107, 33	5.6 ± 10.21	5.2 ± 10.31	2.9 ± 12.75
Week 104; n=55, 111, 36	5.7 ± 9.07	7.1 ± 11.50	3.1 ± 10.30

Notes
[81] - Modified Intent-to-Treat (MITT) Population
[82] - Modified Intent-to-Treat (MITT) Population
[83] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Secondary: Percentage of participants with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, greater than or equal to [>=]4)

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End point title

Percentage of participants with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, greater than or equal to [>=]4)

End point description

The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions, the greater the fatigue. The total score was the sum of the responses (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. A participant was considered to had an improvement exceeding the minimal clinically important difference if they had >=4 points improvement in their FACIT-Fatigue Scale score from Baseline. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Weeks 8, 12, 26, 40, 52, 64, 72 and 104

End point values	Belimumab + Placebo	Belimumab + Rituximab	Belimumab + Standard therapy
Number of subjects analysed	72 ^[84]	144 ^[85]	47 ^[86]
Units: Percentage of participants
number (confidence interval 95%)
Week 8; n=66, 132, 44	47.0 (34.9 to 59.0)	51.5 (43.0 to 60.0)	59.1 (44.6 to 73.6)
Week 12; n=66, 133, 44	56.1 (44.1 to 68.0)	50.4 (41.9 to 58.9)	52.3 (37.5 to 67.0)
Week 26; n=61, 115, 40	47.5 (35.0 to 60.1)	56.5 (47.5 to 65.6)	45.0 (29.6 to 60.4)
Week 40; n=63, 122, 43	54.0 (41.7 to 66.3)	54.1 (45.3 to 62.9)	53.5 (38.6 to 68.4)
Week 52; n=64, 120, 41	60.9 (49.0 to 72.9)	58.3 (49.5 to 67.2)	56.1 (40.9 to 71.3)
Week 64; n=62, 117, 36	51.6 (39.2 to 64.1)	59.8 (50.9 to 68.7)	52.8 (36.5 to 69.1)
Week 72; n=59, 107, 33	57.6 (45.0 to 70.2)	57.0 (47.6 to 66.4)	42.4 (25.6 to 59.3)
Week 104; n=55, 111, 36	56.4 (43.3 to 69.5)	62.2 (53.1 to 71.2)	44.4 (28.2 to 60.7)

Notes
[84] - Modified Intent-to-Treat (MITT) Population
[85] - Modified Intent-to-Treat (MITT) Population
[86] - Modified Intent-to-Treat (MITT) Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All-cause mortality, serious adverse events (SAEs) and non-SAEs were collected up to Week 111 (including 8 weeks of safety follow-up).

Adverse event reporting additional description

Intent-To-Treat (ITT) Population was used to assess the all-cause mortality, SAEs and non-SAEs which comprised of all randomized participants who received at least one dose of study treatment (Belimumab or Rituximab or placebo) .

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Belimumab + Placebo

Reporting group description

Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<= 5) mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104.

Reporting group title

Belimumab + Standard therapy

Reporting group description

Reporting group title

Belimumab + Rituximab

Reporting group description

Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.Participants did not receive treatment after 52 weeks and were in observation until Week 104.

Serious adverse events	Belimumab + Placebo	Belimumab + Standard therapy	Belimumab + Rituximab
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 72 (13.89%)	15 / 76 (19.74%)	32 / 144 (22.22%)
number of deaths (all causes)	1	0	2
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Vascular disorders
Vasculitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	2 / 144 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Jugular vein thrombosis
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombophlebitis superficial
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vasculitis necrotising
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Abortion induced
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Immune system disorders
Allergy to vaccine
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anaphylactic reaction
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Uterine haemorrhage
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumonitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Shrinking lung syndrome
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal behaviour
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Adjustment disorder
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Poisoning deliberate
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post lumbar puncture syndrome
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleuropericarditis
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Hemiparesis
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neuropsychiatric lupus
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Agranulocytosis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperplasia of thymic epithelium
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombocytopenic purpura
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Ocular myasthenia
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain lower
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Volvulus
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Autoimmune hepatitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pemphigoid
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neurogenic bladder
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Systemic lupus erythematosus
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematoma muscle
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Urinary tract infection
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	2 / 144 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute sinusitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bartholinitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gangrene
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis viral
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis A
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Latent tuberculosis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orchitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 72 (0.00%)	1 / 76 (1.32%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	1 / 72 (1.39%)	0 / 76 (0.00%)	0 / 144 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal cord abscess
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 72 (0.00%)	0 / 76 (0.00%)	1 / 144 (0.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Belimumab + Placebo	Belimumab + Standard therapy	Belimumab + Rituximab
Total subjects affected by non serious adverse events
subjects affected / exposed	48 / 72 (66.67%)	53 / 76 (69.74%)	109 / 144 (75.69%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 72 (1.39%)	4 / 76 (5.26%)	7 / 144 (4.86%)
occurrences all number	1	5	8
Nervous system disorders
Headache
subjects affected / exposed	13 / 72 (18.06%)	8 / 76 (10.53%)	30 / 144 (20.83%)
occurrences all number	13	14	44
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 72 (1.39%)	3 / 76 (3.95%)	10 / 144 (6.94%)
occurrences all number	1	9	11
Chest pain
subjects affected / exposed	1 / 72 (1.39%)	4 / 76 (5.26%)	6 / 144 (4.17%)
occurrences all number	1	5	8
Fatigue
subjects affected / exposed	5 / 72 (6.94%)	1 / 76 (1.32%)	5 / 144 (3.47%)
occurrences all number	7	2	7
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	2 / 72 (2.78%)	4 / 76 (5.26%)	7 / 144 (4.86%)
occurrences all number	2	4	9
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 72 (2.78%)	2 / 76 (2.63%)	18 / 144 (12.50%)
occurrences all number	3	5	22
Diarrhoea
subjects affected / exposed	6 / 72 (8.33%)	5 / 76 (6.58%)	6 / 144 (4.17%)
occurrences all number	6	9	6
Vomiting
subjects affected / exposed	2 / 72 (2.78%)	2 / 76 (2.63%)	11 / 144 (7.64%)
occurrences all number	2	4	12
Abdominal pain upper
subjects affected / exposed	5 / 72 (6.94%)	1 / 76 (1.32%)	7 / 144 (4.86%)
occurrences all number	7	1	7
Abdominal pain
subjects affected / exposed	2 / 72 (2.78%)	1 / 76 (1.32%)	9 / 144 (6.25%)
occurrences all number	2	1	9
Dyspepsia
subjects affected / exposed	0 / 72 (0.00%)	4 / 76 (5.26%)	4 / 144 (2.78%)
occurrences all number	0	4	4
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 72 (5.56%)	4 / 76 (5.26%)	9 / 144 (6.25%)
occurrences all number	4	4	9
Psychiatric disorders
Depression
subjects affected / exposed	2 / 72 (2.78%)	4 / 76 (5.26%)	6 / 144 (4.17%)
occurrences all number	2	4	6
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 72 (6.94%)	10 / 76 (13.16%)	12 / 144 (8.33%)
occurrences all number	5	13	13
Back pain
subjects affected / exposed	4 / 72 (5.56%)	4 / 76 (5.26%)	8 / 144 (5.56%)
occurrences all number	5	7	8
Systemic lupus erythematosus
subjects affected / exposed	6 / 72 (8.33%)	2 / 76 (2.63%)	3 / 144 (2.08%)
occurrences all number	9	2	3
Musculoskeletal chest pain
subjects affected / exposed	1 / 72 (1.39%)	4 / 76 (5.26%)	2 / 144 (1.39%)
occurrences all number	1	4	3
Infections and infestations
Urinary tract infection
subjects affected / exposed	12 / 72 (16.67%)	10 / 76 (13.16%)	23 / 144 (15.97%)
occurrences all number	16	27	27
Nasopharyngitis
subjects affected / exposed	9 / 72 (12.50%)	11 / 76 (14.47%)	23 / 144 (15.97%)
occurrences all number	13	18	32
Upper respiratory tract infection
subjects affected / exposed	5 / 72 (6.94%)	9 / 76 (11.84%)	22 / 144 (15.28%)
occurrences all number	6	12	31
Bronchitis
subjects affected / exposed	6 / 72 (8.33%)	7 / 76 (9.21%)	10 / 144 (6.94%)
occurrences all number	6	7	10
Influenza
subjects affected / exposed	9 / 72 (12.50%)	4 / 76 (5.26%)	4 / 144 (2.78%)
occurrences all number	12	4	4
Oral herpes
subjects affected / exposed	3 / 72 (4.17%)	3 / 76 (3.95%)	9 / 144 (6.25%)
occurrences all number	6	7	13
Sinusitis
subjects affected / exposed	4 / 72 (5.56%)	2 / 76 (2.63%)	7 / 144 (4.86%)
occurrences all number	4	2	8
Pharyngitis
subjects affected / exposed	1 / 72 (1.39%)	4 / 76 (5.26%)	4 / 144 (2.78%)
occurrences all number	1	4	7

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Were there any global substantial amendments to the protocol? Yes

17 Apr 2017

Protocol Amendment 01: GlaxoSmithKline (GSK) received additional comments and feedback from European Medicines Agency (EMA) and Food and Drug Administration (FDA) and incorporated the recommendations in Amendment 1. In addition, further changes and updates were identified by the study team and incorporated in Amendment 1.

17 Nov 2018

Protocol Amendment 02: 1) To change the timing of the initial analysis from Study Week 64 to Study Week 52 to support an earlier submission to regulatory authorities, 2) Recruit additional 80 participants into the study to ensure adequate number of evaluable participants, and 3) provide clarification of changes and updates on wording related to study conduct.

15 Aug 2019

Protocol Amendment 03: 1) To define dosing interruptions based on neutrophil count, 2) Incorporate country-specific changes for South Korea, Germany and Argentina into Global Amendment 03 protocol, 3) define an modified Intent to Treat (MITT) Population for analysis, and 4) provide clarification of changes and updates on wording related to study conduct.

30 Apr 2020

Protocol Amendment 04: In response to the Coronavirus disease-2019 (COVID-19) pandemic, changes are being made in order to protect participant safety and data integrity. 1) Visit windows are being conditionally extended for all participant visits for the study. 2) Clarification that the independent blinded assessor can be called upon to perform the SLEDAI-2K (S2K) efficacy assessment at an unscheduled visit. 3) In the event that participants are unable to visit the site, it is acceptable for sites to supply investigational product (belimumab) to participants by shipment to the participant. 4) Clarification regarding acceptable use and dosage of antimalarial treatments (e.g. hydroxychloroquine). 5) Change to the language describing the timing of the primary analysis. 6) Recommendations for safety contact with participants in the event they cannot attend clinic visits. 7) Guidance for study treatment discontinuation if a participant has suspected or confirmed COVID-19 infection.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with a state of disease control at week 52

Primary: Percentage of participants with a state of disease control at week 52

Secondary: Percentage of participants with a state of clinical remission at Week 64

Secondary: Percentage of participants with a state of clinical remission at Week 64

Secondary: Percentage of participants with a state of disease control at Week 104

Secondary: Percentage of participants with a state of disease control at Week 104

Secondary: Percentage of participants with a state of disease control by visits

Secondary: Percentage of participants with a state of disease control by visits

Secondary: Percentage of participants with a state of clinical remission by visits

Secondary: Percentage of participants with a state of clinical remission by visits

Secondary: Percentage of participants with a state of complete remission (CR) sustained for at least 24 weeks during Week 52 to Week 104

Secondary: Percentage of participants with a state of complete remission (CR) sustained for at least 24 weeks during Week 52 to Week 104

Secondary: Percentage of participants with a state of clinical remission (CLR) sustained for at least 24 weeks from Week 80 to Week 104

Secondary: Percentage of participants with a state of clinical remission (CLR) sustained for at least 24 weeks from Week 80 to Week 104

Secondary: Percentage of participants with a state of complete remission by visits

Secondary: Percentage of participants with a state of complete remission by visits

Secondary: Time to first severe flare

Secondary: Time to first severe flare

Secondary: Time to first flare

Secondary: Time to first flare

Secondary: Time to disease control sustained for at least 24 weeks and maintained through Week 104

Secondary: Time to disease control sustained for at least 24 weeks and maintained through Week 104

Secondary: Time to clinical remission sustained for at least 24 weeks and maintained through Week 104

Secondary: Time to clinical remission sustained for at least 24 weeks and maintained through Week 104

Secondary: Duration of disease control

Secondary: Duration of disease control

Secondary: Duration of clinical remission

Secondary: Duration of clinical remission

Secondary: Change from Baseline in systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score by visit (PI assessed)

Secondary: Change from Baseline in systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score by visit (PI assessed)

Secondary: Percentage of participants with SLEDAI-2K organ improvement compared to Baseline by visits (PI assessed)

Secondary: Percentage of participants with SLEDAI-2K organ improvement compared to Baseline by visits (PI assessed)

Secondary: Percentage of participants with SLEDAI-2K organ worsening compared to Baseline by visits (PI assessed)

Secondary: Percentage of participants with SLEDAI-2K organ worsening compared to Baseline by visits (PI assessed)

Secondary: Change from Baseline in Physician Global Assessment (PGA) by visits

Secondary: Change from Baseline in Physician Global Assessment (PGA) by visits

Secondary: Percentage of participants with Systemic Lupus International Collaborating Clinics (SLICC) -American College of Rheumatology (ACR) damage index worsening compared with Baseline at Week 52 and Week 104

Secondary: Percentage of participants with Systemic Lupus International Collaborating Clinics (SLICC) -American College of Rheumatology (ACR) damage index worsening compared with Baseline at Week 52 and Week 104

Secondary: Percentage of participants that met the Lupus Low Disease Activity State (LLDAS) response criteria by visits (PI assessed)

Secondary: Percentage of participants that met the Lupus Low Disease Activity State (LLDAS) response criteria by visits (PI assessed)

Secondary: Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K by visit

Secondary: Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K by visit

Secondary: Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K by visit

Secondary: Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K by visit

Secondary: Number of participants with serious adverse events (SAE) and non-serious AE (non-SAE)

Secondary: Number of participants with serious adverse events (SAE) and non-serious AE (non-SAE)

Secondary: Number of participants with adverse events of special interest (AESIs)

Secondary: Number of participants with adverse events of special interest (AESIs)

Secondary: Change from Baseline in Patient Global Assessment (PtGA) by visits

Secondary: Change from Baseline in Patient Global Assessment (PtGA) by visits

Secondary: Change from Baseline in Lupus Quality of Life (LupusQoL) domain scores by visit

Secondary: Change from Baseline in Lupus Quality of Life (LupusQoL) domain scores by visit

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score by visit

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score by visit

Secondary: Percentage of participants with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, greater than or equal to [>=]4)

Secondary: Percentage of participants with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, greater than or equal to [>=]4)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE)