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Clinical Trial Results:
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 (Abatacept) or Placebo on a Background of Mycophenolate Mofetil (MMF) and Corticosteroids in Subjects with Active Class III or IV Lupus Nephritis

Summary
EudraCT number	2012-000714-11
Trial protocol	IT CZ ES RO Outside EU/EEA
Global end of trial date	30 May 2018

Results information
Results version number	v1(current)
This version publication date	22 Jun 2019
First version publication date	22 Jun 2019
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

IM101-291

ISRCTN number

US NCT number

NCT01714817

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussée de la Hulpe 185, Brussels, Belgium, 1170

Public contact

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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

30 May 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 May 2018

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to compare the proportion of subjects with Complete Renal Response (CRR) of lupus glomerulonephritis at Day 365 following 1 year treatment with abatacept or placebo administered on a background of MMF and corticosteroids

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Feb 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 50

Country: Number of subjects enrolled

Australia: 10

Country: Number of subjects enrolled

Brazil: 82

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Chile: 19

Country: Number of subjects enrolled

China: 90

Country: Number of subjects enrolled

Colombia: 66

Country: Number of subjects enrolled

Czech Republic: 6

Country: Number of subjects enrolled

Hong Kong: 6

Country: Number of subjects enrolled

Italy: 20

Country: Number of subjects enrolled

Japan: 56

Country: Number of subjects enrolled

Korea, Republic of: 16

Country: Number of subjects enrolled

Mexico: 87

Country: Number of subjects enrolled

Peru: 56

Country: Number of subjects enrolled

Romania: 10

Country: Number of subjects enrolled

Russian Federation: 12

Country: Number of subjects enrolled

Taiwan: 35

Country: Number of subjects enrolled

United States: 73

Worldwide total number of subjects

695

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)

689

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

695 participants were enrolled; 406 randomized; 405 received treatment (1 received ACE inhibition and was not treated). 289 participants were screen failures; 233 were due to no longer meeting study criteria; 19 withdrew consent; 4 due to Adverse Events; 1 due to death; 1 due to poor/non-compliance; 1 was lost to follow up; and 30 were other.

Period 1 title

Year 1 Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Abatacept IV

Arm description

Abatacept 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks

Arm type

Experimental

Investigational medicinal product name

Abatacept

Investigational medicinal product code

Other name

BMS-188667

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo IV

Arm description

Placebo matching with Abatacept injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Placebo matching with BMS-188667

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1 ^[1]	Abatacept IV	Placebo IV
Started	202	203
Completed	155	161
Not completed	47	42
Adverse event, serious fatal	1	1
Consent withdrawn by subject	6	7
Adverse event, non-fatal	20	17
Hypersensitivity to the medication	-	1
Pregnancy	2	-
Need of use of Prohibited Medications	1	-
Participant no longer meets criteria	6	2
Lost to follow-up	-	2
Poor / non-compliance	-	1
Change in Concomitant Medication	-	1
Lack of efficacy	11	9
Antiproteinuric changed/dose increased	-	1

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 695 participants enrolled, 406 were randomized to abatacept (203) and placebo arms (203). All but 1 randomized participant received at least 1 dose of double-blind study drug in the treatment period. A participant assigned to the abatacept group was not treated as the participant required initiation of ACE therapy.

Period 2 title

Year 2 Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Abatacept IV

Arm description

Arm type

Experimental

Investigational medicinal product name

Abatacept

Investigational medicinal product code

Other name

BMS-188667

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo IV

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Placebo matching with BMS-188667

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 2	Abatacept IV	Placebo IV
Started	155	161
Completed	129	123
Not completed	26	38
Participant request to stop treatment	4	4
Administrative reason by Sponsor	4	3
Participant withdrew consent	1	5
Adverse event, non-fatal	7	6
Participant went to US stopped treatment	-	1
Pregnancy	1	1
Given cyclophosphamide, corticosteroids	-	1
Participant no longer meets criteria	1	4
Lost to follow-up	2	-
Lack of efficacy	4	12
Completed Year 1, did not enter Year 2	2	1

Period 3 title

Long-Term Extension (LTE) Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Abatacept IV

Arm description

Arm type

Experimental

Investigational medicinal product name

Abatacept

Investigational medicinal product code

Other name

BMS-188667

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Placebo IV

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Placebo matching with BMS-188667

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 3	Abatacept IV	Placebo IV
Started	129	123
Completed	62	53
Not completed	67	70
Administrative reason by Sponsor	27	21
Disease progression	1	4
Participant request to stop treatment	1	1
Participant withdrew consent	1	1
Completed Year 2, did not enter LTE	33	38
Absence of renal response	-	1
Participant no longer meets criteria	1	-
Not effective	-	1
Adverse Event unrelated to study drug	1	-
Study drug toxicity	1	-
Pregnancy	1	-
Investigator decision, study termination	-	1
Lost to follow-up	-	1
Study was terminated	-	1

Baseline characteristics

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Reporting group title

Abatacept IV

Reporting group description

Reporting group title

Placebo IV

Reporting group description

Reporting group values	Abatacept IV	Placebo IV	Total
Number of subjects	202	203	405
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	1	0	1
Adults (18-64 years)	200	202	402
From 65-84 years	1	1	2
85 years and over	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	33.1 ( 10.75 )	33.2 ( 10.48 )	-
Gender, Male/Female
Units: Subjects
Female	182	178	360
Male	20	25	45
Race/Ethnicity, Customized
Units: Subjects
Asian	71	74	145
African American	15	15	30
Caucasian	85	71	156
Other	31	43	74

End points

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Reporting group title

Abatacept IV

Reporting group description

Reporting group title

Placebo IV

Reporting group description

Reporting group title

Abatacept IV

Reporting group description

Reporting group title

Placebo IV

Reporting group description

Reporting group title

Abatacept IV

Reporting group description

Reporting group title

Placebo IV

Reporting group description

Primary: Percentage of participants in Complete Renal Response (CR) of lupus glomerulonephritis at Day 365 of the double-blind period

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End point title

Percentage of participants in Complete Renal Response (CR) of lupus glomerulonephritis at Day 365 of the double-blind period

End point description

Number of participants achieving CR was divided by the total number of participants in that arm and expressed as a percentage. CR defined as: eGFR is normal or no <85% of the baseline; eGFR based on mean creatinine value from day 358 and 365. Proteinuria: UPCR<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no >10 mg prednisone or equiv. for at least 28 days prior to assessment. Participants with >10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as having achieved CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use (Yes/No), race (Asian/ Black/Caucasian/Other) and baseline UPCR as a continuous variable.

End point type

Primary

End point timeframe

Day 365

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202	203
Units: Percentage
number (not applicable)
Percentage of participants in CR	35.1	33.5

Percentage of participants in CR at Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

P-value

= 0.7264

Method

Stratified logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.7077

upper limit

1.6421

Secondary: Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 365 of the double-blind period

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End point title

Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 365 of the double-blind period

End point description

Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no <85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no >10 mg prednisone or equivalent for at least 28 days prior. Subjects with >10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.

End point type

Secondary

End point timeframe

Day 365

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	100	88
Units: Percentage
number (not applicable)
Percentage of nephrotic participants in CR	27	29.5

Percentage nephrotic participants in CR at Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Odds ratio (OR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.4148

upper limit

1.5956

Secondary: Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in nephrotic participants

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End point title

Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in nephrotic participants

End point description

Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in nephrotic participants

End point type

Secondary

End point timeframe

Baseline and Day 365

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	76	68
Units: UPCR (mg/mg)
arithmetic mean (standard error)
Adjusted Mean Change from Baseline in UPCR	-5.01 ( 0.33 )	-4.84 ( 0.35 )

Adjusted mean change UPCR at Day 365 (nephrotic)

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

P-value

= 0.571

Method

Mixed models analysis

Parameter type

Adjusted mean difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

0.42

Secondary: Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in overall population

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End point title

Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in overall population

End point description

Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population

End point type

Secondary

End point timeframe

Day 1 and Day 365

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	157	163
Units: UPCR (mg/mg)
arithmetic mean (standard error)
Adj. Mean Change from Baseline in UPCR	-2.99 ( 0.17 )	-2.90 ( 0.16 )

Adjusted mean change from baseline UPCR at Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

P-value

= 0.561

Method

Mixed models analysis

Parameter type

Adjusted mean difference

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

0.22

Secondary: Adjusted mean change from baseline in disease activity as measured by BILAG 2004 over time during Year 1 of the double-blind period

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End point title

Adjusted mean change from baseline in disease activity as measured by BILAG 2004 over time during Year 1 of the double-blind period

End point description

Adjusted mean change from baseline in British Isles Lupus Assessment Group (BILAG) score over time during Year 1 of the double-blind period based on a repeated measure mixed model and presented at each visit in the first 12-month of the double-blind period. BILAG index measures disease activity in different organs/systems separately. BILAG score is calculated for each of 9 systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. BILAG “A” represents the presence of serious features of lupus. BILAG “B” represents more moderate features of the disease. BILAG “C” includes only mild symptomatic features. BILAG “D” represents prior activity with no current symptoms due to active lupus. BILAG “E” represents an organ that has never been involved. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome.

End point type

Secondary

End point timeframe

at Day 365

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	157	161
Units: Number
arithmetic mean (confidence interval 95%)
Adj mean change from baseline in disease activity	-8.22 (-9.29 to -7.16)	-7.60 (-8.66 to -6.54)

No statistical analyses for this end point

Secondary: Number of participants with any Adverse Events (AEs) during Year 1 of the double-blind period

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End point title

Number of participants with any Adverse Events (AEs) during Year 1 of the double-blind period

End point description

All AEs were coded and grouped into preferred terms (PT) by system organ class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA, version 21.0). Investigators determined the intensity of each AE as mild, moderate, severe, or very severe and assessed the relationship to study drug.

End point type

Secondary

End point timeframe

From Day 1 up to 56 days post last dose in Year 1 of the double-blind period

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202	203
Units: Participants
Participants with Adverse Events	188	194
Participants with Serious Adverse Events	49	39
Participants with infection Adverse Events	150	147
Participants with malignancies	2	1
Participants with autoimmune events	10	9
Participants with peri-infusional Adverse Events	7	9
Participants with acute infusional Adverse Events	2	4

No statistical analyses for this end point

Secondary: Percentage of participants with ranked outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) during the double-blind period

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End point title

Percentage of participants with ranked outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) during the double-blind period

End point description

Complete Renal Response or Complete Response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; UPCR < 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment. Partial Renal Response or Partial Response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR < 0.5 OR 50% reduced from baseline and < 1 if baseline value was < 3, OR 50% reduced from baseline and < 3 if baseline value was greater than or equal to 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment. No Renal Response or No Response (NR): defined as not meeting criteria for CR or PR or withdrawn

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[1]	203 ^[2]
Units: Percentage
number (not applicable)
CR - Day 365	35.1	33.5
PR - Day 365	20.8	21.7
NR - Day 365	44.1	44.8
CR - Day 729	99999	99999
PR - Day 729	99999	99999
NR - Day 729	99999	99999

Notes
[1] - Study terminated, efficacy not met
[2] - Study terminated, efficacy not met

Percentage participants ranked outcome of CR PR NR

Statistical analysis description

CR - Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Estimate of Difference

Point estimate

1.651

Confidence interval

level

95%

sides

2-sided

lower limit

-7.595828

upper limit

10.897784

Percentage participants ranked outcome of CR PR NR

Statistical analysis description

PR - Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Estimate of Difference

Point estimate

-0.8828

Confidence interval

level

95%

sides

2-sided

lower limit

-8.848056

upper limit

7.082461

Percentage participants ranked outcome of CR PR NR

Statistical analysis description

NR - Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Estimate of Difference

Point estimate

-0.7682

Confidence interval

level

95%

sides

2-sided

lower limit

-10.446714

upper limit

8.910353

Secondary: Median time to Complete Renal Response during the double-blind period in all participants

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End point title

Median time to Complete Renal Response during the double-blind period in all participants

End point description

The estimate of median time to Complete Renal Response is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) < 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment.

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[3]	203 ^[4]
Units: Days
median (confidence interval 95%)
Day 365	280.0 (198.0 to 365.0)	309.0 (280.0 to 365.0)
Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[3] - Study terminated, efficacy not met
[4] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Median time to Complete Renal Response during the double-blind period in nephrotic participants

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End point title

Median time to Complete Renal Response during the double-blind period in nephrotic participants

End point description

The estimate of median time to Complete Renal Response in nephrotic participants is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) < 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment.

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[5]	203 ^[6]
Units: Days
median (confidence interval 95%)
Day 365	366.0 (337.0 to 99999)	368.0 (311.0 to 368.0)
Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[5] - Study terminated, efficacy not met
[6] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Median time to Partial Renal Response during the double-blind period in all participants

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End point title

Median time to Partial Renal Response during the double-blind period in all participants

End point description

The estimate of median time to Partial Response (PR) is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR < 0.5 OR 50% reduced from baseline and < 1 if baseline value was < 3, OR 50% reduced from baseline and < 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[7]	203 ^[8]
Units: Days
median (confidence interval 95%)
Day 365	226.0 (198.0 to 313.0)	253.0 (198.0 to 358.0)
Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[7] - Study terminated, efficacy not met
[8] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Median time to Partial Renal Response during the double-blind period in nephrotic participants

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End point title

Median time to Partial Renal Response during the double-blind period in nephrotic participants

End point description

The estimate of median time to Partial Response (PR) in nephrotic participants is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR < 0.5 OR 50% reduced from baseline and < 1 if baseline value was < 3, OR 50% reduced from baseline and < 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[9]	203 ^[10]
Units: Days
median (confidence interval 95%)
Day 365	225.0 (196.0 to 311.0)	196.0 (170.0 to 225.0)
Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[9] - Study terminated, efficacy not met
[10] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Adjusted mean change from baseline in UPCR over time

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End point title

Adjusted mean change from baseline in UPCR over time

End point description

A repeated measure mixed model that included the baseline UPCR value, randomization stratification factors, time, and time by treatment interaction as fixed effects and subject as a random effect was used.

End point type

Secondary

End point timeframe

Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	157	163
Units: UPCR (mg/mg)
arithmetic mean (standard error)
Day 365	-2.95 ( 0.17 )	-2.68 ( 0.17 )
Day 729	-3.13 ( 0.18 )	-2.72 ( 0.18 )

No statistical analyses for this end point

Secondary: Median Percent Change from Baseline in UPCR over Time

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End point title

Median Percent Change from Baseline in UPCR over Time

End point description

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[11]	203 ^[12]
Units: Percent
median (inter-quartile range (Q1-Q3))
Day 365	-83.77 (-92.42 to -64.18)	-84.12 (-94.03 to -59.98)
Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[11] - Study terminated, efficacy not met
[12] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Adjusted mean change from baseline in eGFR over time

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End point title

Adjusted mean change from baseline in eGFR over time

End point description

Estimated glomerular filtration rate(eGFR), will be calculated by the CKD-EPI formula shown below.50 eGFR is expressed as mL/min per 1.73m2. For the purpose of this study lower limit of normal eGFR is defined as 90mL/min per 1.73m2 eGFR = 141 X min (Scr/k, 1)α X max (Scr/k, 1)-1.209 X 0.993Age X (1.018 [if female]) X (1.159 [if black]) Where Scr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1, age in years.

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[13]	203 ^[14]
Units: mL/min per 1.73m2
arithmetic mean (confidence interval 95%)
Day 365	6.85 (3.47 to 10.23)	5.85 (2.51 to 9.20)
Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[13] - Study terminated, efficacy not met
[14] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Median Time to First Sustained Change to No Response During the Double-blind Period

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End point title

Median Time to First Sustained Change to No Response During the Double-blind Period

End point description

Sustained response defined as response present at 2 consecutive visits approximately 4 weeks apart. No renal response (NR): defined as not meeting criteria for CR or PR or withdrawn The estimate of median time is based on Kaplan-Meier analysis

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[15]	203 ^[16]
Units: Days
median (confidence interval 95%)
Day 365	99999 (392.0 to 99999)	99999 (99999 to 99999)
Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[15] - Study terminated, efficacy not met
[16] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with sustained change from higher level of response to no response during the double-blind period

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End point title

Number of participants with sustained change from higher level of response to no response during the double-blind period

End point description

Sustained change to no response is defined as going from CR (or PR) to NR and remaining in NR for at least 2 consecutive visits; visits should be approximately 4 weeks apart. This analysis will be based on time from response CR (or PR) to the first visit in which the no response (NR) was achieved and sustained to the next visit.

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[17]	203 ^[18]
Units: Participants
Day 365	5	3
Day 729	99999	99999

Notes
[17] - Study terminated, efficacy not met
[18] - Study terminated, efficacy not met

Sustained change from higher level response to NR

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.3251

upper limit

6.2849

Secondary: Adjusted mean change from baseline and from Day 365 in disease activity as measured by BILAG 2004 over time during the double-blind period

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End point title

Adjusted mean change from baseline and from Day 365 in disease activity as measured by BILAG 2004 over time during the double-blind period

End point description

BILAG index measures and reports disease activity in different organs/systems separately. The BILAG score is calculated for each of nine systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. A BILAG “A” represents the presence of one or more serious features of lupus. A BILAG “B” represents more moderate features of the disease. A BILAG “C” includes only mild symptomatic features. A BILAG “D” represents only prior activity with no current symptoms due to active lupus. A BILAG “E” represents an organ that has never been involved.

End point type

Secondary

End point timeframe

at Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[19]	203 ^[20]
Units: Number
arithmetic mean (standard error)
from baseline (Day 1)	99999 ( 99999 )	99999 ( 99999 )
from Day 365	99999 ( 99999 )	99999 ( 99999 )

Notes
[19] - Study terminated, efficacy not met
[20] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Cmin (ug/mL): Trough level serum concentration of abatacept prior to the administration of the IV infusion

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End point title

Cmin (ug/mL): Trough level serum concentration of abatacept prior to the administration of the IV infusion

End point description

Trough level serum concentration of abatacept prior to the administration of the IV infusion on Days 1 to 365

End point type

Secondary

End point timeframe

Days 1 to 365

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	189	0 ^[21]
Units: ug/mL
geometric mean (geometric coefficient of variation)
Day 15	69.97 ( 91.4 )	( )
Day 29	90.46 ( 56.8 )	( )
Day 57	36.43 ( 84.4 )	( )
Day 85	34.46 ( 55.4 )	( )
Day 113	16.42 ( 69.2 )	( )
Day 169	13.98 ( 64.5 )	( )
Day 281	14.44 ( 54.7 )	( )
Day 337	14.99 ( 73.6 )	( )
Day 365	13.62 ( 51.7 )	( )

Notes
[21] - Data reported for Abatacept only

No statistical analyses for this end point

Secondary: Cmax: Maximum observed serum concentration following participants receiving active abatacept IV

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End point title

Cmax: Maximum observed serum concentration following participants receiving active abatacept IV

End point description

Cmax: Maximum observed serum concentration following participants receiving active abatacept IV

End point type

Secondary

End point timeframe

at 1 hour post Day 1 dose and 30 minutes post Day 337 dose

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	185	0 ^[22]
Units: ug/mL
geometric mean (geometric coefficient of variation)
Day 1	527.43 ( 59.6 )	( )
Day 337	203.51 ( 30.6 )	( )

Notes
[22] - Data reported for Abatacept only

No statistical analyses for this end point

Secondary: AUC (TAU): Area under the serum concentration time curve over a dosing interval

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End point title

AUC (TAU): Area under the serum concentration time curve over a dosing interval

End point description

AUC (TAU): Area under the serum concentration time curve over a dosing interval between Days 337 to 365.

End point type

Secondary

End point timeframe

Days 337 to 365

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	106	0 ^[23]
Units: ug*h/mL
geometric mean (geometric coefficient of variation)
AUC (TAU)	36480.24 ( 29.2 )	( )

Notes
[23] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Summary statistics for systolic blood pressure

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End point title

Summary statistics for systolic blood pressure

End point description

Summary statistics for systolic blood pressure

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[24]	203 ^[25]
Units: mmHg
arithmetic mean (standard deviation)
Day 1, end of observation	122.0 ( 15.48 )	122.6 ( 15.31 )
Day 365, end of observation	112.3 ( 18.45 )	115.0 ( 7.07 )
Day 729	99999 ( 99999 )	99999 ( 99999 )

Notes
[24] - Study terminated, efficacy not met
[25] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Summary statistics for diastolic blood pressure

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End point title

Summary statistics for diastolic blood pressure

End point description

Summary statistics for diastolic blood pressure

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[26]	203 ^[27]
Units: mmHg
arithmetic mean (standard deviation)
Day 1, end of observation	76.5 ( 11.49 )	77.0 ( 11.19 )
Day 365, end of observation	73.5 ( 10.75 )	77.5 ( 10.61 )
Day 729	99999 ( 99999 )	99999 ( 99999 )

Notes
[26] - Study terminated, efficacy not met
[27] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Summary statistics for Heart Rate

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End point title

Summary statistics for Heart Rate

End point description

Summary statistics for Heart Rate

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[28]	203 ^[29]
Units: beats per minute
arithmetic mean (standard deviation)
Day 1, end of observation	80.6 ( 10.91 )	81.4 ( 10.64 )
Day 365, end of observation	78.5 ( 9.57 )	70.0 ( 14.14 )
Day 729	99999 ( 99999 )	99999 ( 99999 )

Notes
[28] - Study terminated, efficacy not met
[29] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Mean Change from Baseline in Laboratory Analytes During the Double-blind Period

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End point title

Mean Change from Baseline in Laboratory Analytes During the Double-blind Period

End point description

Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.

End point type

Secondary

End point timeframe

Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	153	160
Units: SI units
arithmetic mean (standard error)
ALANINE AMINOTRANSFERASE (ALT) (U/L)	-2.2 ( 1.318 )	-3.4 ( 1.521 )
ALBUMIN (G/L)	9.2 ( 0.580 )	8.1 ( 0.604 )
ALKALINE PHOSPHATASE (ALP) (U/L)	8.2 ( 1.884 )	11.7 ( 2.291 )
ASPARTATE AMINOTRANSFERASE (AST) (U/L)	0.3 ( 1.020 )	0.3 ( 0.826 )
BILIRUBIN, TOTAL (UMOL/L)	1.77 ( 0.3509 )	1.00 ( 0.2476 )
BLOOD UREA NITROGEN (MMOL/L)	-2.31 ( 0.3447 )	-2.25 ( 0.2950 )
CALCIUM, TOTAL (MMOL/L)	0.097 ( 0.01434 )	0.108 ( 0.01539 )
CHLORIDE, SERUM (MMOL/L)	-1.1 ( 0.307 )	-0.5 ( 0.362 )
CREATININE (UMOL/L)	-5.6 ( 1.869 )	-6.2 ( 2.314 )
EOSINOPHILS (ABSOLUTE) (X10*9 C/L)	0.034 ( 0.01119 )	0.010 ( 0.01403 )
G-GLUTAMYL TRANSFERASE (GGT) (U/L)	-5.3 ( 2.914 )	-4.1 ( 3.676 )
GLUCOSE, SERUM (MMOL/L)	-0.23 ( 0.1350 )	-0.58 ( 0.1946 )
HEMATOCRIT (VOL)	0.0328 ( 0.004494 )	0.0325 ( 0.005387 )
HEMOGLOBIN (G/L)	8.8 ( 1.414 )	9.0 ( 1.758 )
LYMPHOCYTES (ABSOLUTE) (X10*9 C/L)	0.141 ( 0.07806 )	-0.149 ( 0.07595 )
MONOCYTES (ABSOLUTE) (X10*9 C/L)	-0.018 ( 0.01735 )	-0.050 ( 0.02143 )
NEUTROPHILS (ABSOLUTE) (X10*9 C/L)	-2.259 ( 0.26617 )	-2.289 ( 0.33697 )
PHOSPHORUS, INORGANIC (MMOL/L)	-0.077 ( 0.02539 )	-0.037 ( 0.02261 )
PLATELET COUNT (X10*9 C/L)	-4.9 ( 6.092 )	-9.1 ( 7.581 )
POTASSIUM, SERUM (MMOL/L)	-0.02 ( 0.0403 )	-0.10 ( 0.0541 )
PROTEIN, TOTAL (G/L)	9.9 ( 0.871 )	10.1 ( 0.845 )
SODIUM, SERUM (MMOL/L)	-0.2 ( 0.263 )	-0.5 ( 0.287 )

No statistical analyses for this end point

Secondary: Number of participants with Marked Hematology laboratory abnormalities during Year 1 of the Double Blind period

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End point title

Number of participants with Marked Hematology laboratory abnormalities during Year 1 of the Double Blind period

End point description

LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value HEMOGLOBIN g/L 4.0 HB >3 G/DL DECREASE FROM PRE RX HEMATOCRIT vol 6.3 HCT <0.75X PRE RX ERYTHROCYTES x10*12 c/L 5.2 RBC <0.75X PRE RX PLATELET COUNT x10*9 c/L 5.0 PLAT <0.67X LLN OR >1.5X ULN, OR IF PRE RX<LLN THEN USE 0.5X PRE RX AND <100,000/MM3 LEUKOCYTES x10*9 c/L 6.2 WBC <0.75X LLN OR >1.25X ULN, OR IF PRE RX<LLN THEN USE <0.8X PRE RX OR >ULN, OR IF PRE RX>ULN THEN USE >1.2X PRE RX OR <LLN EOSINOPHILS (ABSOLUTE) x10*9 c/L 8.3 EOSA IF VALUE > .750 X10*3 c/uL BASOPHILS (ABSOLUTE) x10*9 c/L 8.3 BASOA IF VALUE > 400/MM3 MONOCYTES (ABSOLUTE) x10*9 c/L 8.3 MONOA IF VALUE > 2000/MM3 LYMPHOCYTES (ABSOLUTE) x10*9 c/L 8.3 LYMPA IF VALUE < .750 X10*3 c/uL OR IF VALUE > 7.50 X10*3 c/uL N = the number of participants with at least 1 on treatment lab result for each analyte

End point type

Secondary

End point timeframe

Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[30]	203 ^[31]
Units: participants
HEMOGLOBIN, low	6	10
HEMOGLOBIN, high	99999	99999
HEMATOCRIT, low	12	12
HEMATOCRIT, high	99999	99999
ERYTHROCYTES, low	7	10
ERYTHROCYTES, high	99999	99999
PLATELET COUNT, low	4	3
PLATELET COUNT, high	0	0
LEUKOCYTES, low	35	21
LEUKOCYTES, high	29	25
EOSINOPHILS (ABSOLUTE), low	99999	99999
EOSINOPHILS (ABSOLUTE), high	2	6
BASOPHILS (ABSOLUTE), low	99999	99999
BASOPHILS (ABSOLUTE), high	1	1
MONOCYTES (ABSOLUTE), low	99999	99999
MONOCYTES (ABSOLUTE), high	0	1
LYMPHOCYTES (ABSOLUTE), low	81	104
LYMPHOCYTES (ABSOLUTE), high	1	2

Notes
[30] - Study terminated, efficacy not met
[31] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with Marked Liver and Kidney Function Laboratory Abnormalities during Year 1 of the Double Blind period

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End point title

Number of participants with Marked Liver and Kidney Function Laboratory Abnormalities during Year 1 of the Double Blind period

End point description

LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value ALKALINE PHOSPHATASE (ALP) U/L 5.0 ALP >2X ULN, OR IF PRE RX>ULN THEN USE >3X PRE RX ASPARTATE AMINOTRANSFERASE (AST) U/L 5.0 AST >3X ULN, OR IF PRE RX>ULN THEN USE >4X PRE RX ALANINE AMINOTRANSFERASE (ALT) U/L 5.0 ALT >3X ULN, OR IF PRE RX>ULN THEN USE >4X PRE RX G-GLUTAMYL TRANSFERASE (GGT) U/L 5.0 GGT >2X ULN, OR IF PRE RX>ULN THEN USE >3X PRE RX BILIRUBIN, TOTAL umol/L 5.1 TBILI >2X ULN, OR IF PRE RX>ULN THEN USE >4X PRE RX BILIRUBIN, DIRECT umol/L 5.1 DBILI >1.5X ULN, OR IF PRE RX>ULN THEN USE >2X PRE RX BLOOD UREA NITROGEN mmol/L 5.1 BUN >2X PRE RX CREATININE umol/L 5.0 CREAT >1.5X PRE RX N = the number of participants with at least 1 on treatment lab result for each analyte

End point type

Secondary

End point timeframe

Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[32]	203 ^[33]
Units: participants
ALKALINE PHOSPHATASE (ALP), low	99999	99999
ALKALINE PHOSPHATASE (ALP), high	1	1
ASPARTATE AMINOTRANSFERASE (AST), low	99999	99999
ASPARTATE AMINOTRANSFERASE (AST), high	5	0
ALANINE AMINOTRANSFERASE (ALT), low	99999	99999
ALANINE AMINOTRANSFERASE (ALT), high	8	2
G-GLUTAMYL TRANSFERASE (GGT), low	99999	99999
G-GLUTAMYL TRANSFERASE (GGT), high	17	15
BILIRUBIN, TOTAL, low	99999	99999
BILIRUBIN, TOTAL, high	0	0
BILIRUBIN, DIRECT, low	99999	99999
BILIRUBIN, DIRECT, high	0	0
BLOOD UREA NITROGEN, low	99999	99999
BLOOD UREA NITROGEN, high	20	12
CREATININE, low	99999	99999
CREATININE, high	24	20

Notes
[32] - Study terminated, efficacy not met
[33] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with Marked Electrolyte Laboratory Abnormalities during Year 1 of the Double Blind period

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End point title

Number of participants with Marked Electrolyte Laboratory Abnormalities during Year 1 of the Double Blind period

End point description

LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value SODIUM, SERUM mmol/L 4.0 NA <0.95X LLN OR >1.05X ULN, OR IF PRE RX<LLN THEN USE <0.95X PRE RX OR >ULN, OR IF PRE RX>ULN THEN USE >1.05X PRE RX OR <LLN POTASSIUM, SERUM mmol/L 4.1 K <0.9X LLN OR >1.1X ULN, OR IF PRE RX<LLN THEN USE <0.9X PRE RX OR >ULN, OR IF PRE RX>ULN THEN USE >1.1X PRE RX OR <LLN CHLORIDE, SERUM mmol/L 5.0 CL <0.9X LLN OR >1.1X ULN, OR IF PRE RX<LLN THEN USE <0.9X PRE RX OR >ULN, OR IF PRE RX>ULN THEN USE >1.1X PRE RX OR <LLN N = the number of participants with at least 1 on treatment lab result for each analyte

End point type

Secondary

End point timeframe

Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202	203
Units: participants
SODIUM, SERUM, low	1	1
SODIUM, SERUM, high	2	2
POTASSIUM, SERUM, low	3	5
POTASSIUM, SERUM, high	7	7
CHLORIDE, SERUM, low	0	1
CHLORIDE, SERUM, high	0	0
CALCIUM, TOTAL, low	1	1
CALCIUM, TOTAL, high	2	0
PHOSPHORUS, INORGANIC, low	9	7
PHOSPHORUS, INORGANIC, high	13	13

No statistical analyses for this end point

Secondary: Number of participants with Marked Urinalysis Laboratory Abnormalities during Year 1 of the Double Blind period

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End point title

Number of participants with Marked Urinalysis Laboratory Abnormalities during Year 1 of the Double Blind period

End point description

LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value PROTEIN, URINE Unknown UPRO IF MISSING PRE THEN USE >=2, OR IF VALUE >=4, OR IF PRE RX =0 OR 0.5 THEN USE >=2, OR IF PRE RX =1 THEN USE >=3, OR IF PRE RX =2 OR 3 THEN USE >=4 GLUCOSE, URINE N/A UGLU IF MISSING PRE THEN USE >=2, OR IF VALUE >=4, OR IF PRE RX =0 OR 0.5 THEN USE >=2, OR IF PRE RX =1 THEN USE >=3, OR IF PRE RX =2 OR 3 THEN USE >=4 BLOOD, URINE N/A UBLD IF MISSING PRE THEN USE >=2, OR IF VALUE >=4, OR IF PRE RX =0 OR 0.5 THEN USE >=2, OR IF PRE RX =1 THEN USE >=3, OR IF PRE RX =2 OR 3 THEN USE >=4 RBC, URINE hpf 5.0 URBC IF MISSING PRE THEN USE >=2, OR IF VALUE >=4, OR IF PRE RX =0 OR 0.5 THEN USE >=2, OR IF PRE RX =1 THEN USE >=3, OR IF PRE RX =2 OR 3 THEN USE >=4 WBC, URINE hpf 5.0 UWBC IF MISSING PRE THEN USE >=2, OR IF VALUE >=4, OR IF PRE RX =0 OR 0.5 THEN USE >=2, OR IF PRE RX =1 THEN USE >=3, OR IF PRE RX =2 OR 3 THEN USE >=4

End point type

Secondary

End point timeframe

Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[34]	203 ^[35]
Units: participants
PROTEIN, URINE, low	99999	99999
PROTEIN, URINE, high	0	0
GLUCOSE, URINE, low	99999	99999
GLUCOSE, URINE, high	0	0
BLOOD, URINE, low	99999	99999
BLOOD, URINE, high	0	0
Red blood cells (RBC), URINE, low	99999	99999
Red blood cells (RBC), URINE, high	93	103
White blood cells (WBC), URINE, low	99999	99999
White blood cells (WBC), URINE, high	91	98

Notes
[34] - Study terminated, efficacy not met
[35] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with other Marked Chemistry Laboratory Abnormalities during Year 1 of the Double Blind period

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End point title

Number of participants with other Marked Chemistry Laboratory Abnormalities during Year 1 of the Double Blind period

End point description

LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value CALCIUM, TOTAL mmol/L 5.2 CA <0.8X LLN OR >1.2X ULN, OR IF PRE RX<LLN THEN USE <0.75X PRE RX OR >ULN, OR IF PRE RX>ULN THEN USE >1.25X PRE RX OR <LLN PHOSPHORUS, INORGANIC mmol/L 5.2 PHOS <0.75X LLN OR >1.25X ULN, OR IF PRE RX<LLN THEN USE <0.67X PRE RX OR >ULN GLUCOSE, SERUM mmol/L 4.1 GLUC <65 mg/dL, OR >220 mg/dL PROTEIN, TOTAL g/L 5.0 TPRO <0.9X LLN OR >1.1X ULN, OR IF PRE RX<LLN THEN USE 0.9X PRE RX OR >ULN, OR IF PRE RX>ULN THEN USE 1.1X PRE RX OR <LLN ALBUMIN g/L 3.0 ALB <0.9X LLN, OR IF PRE RX<LLN THEN USE <0.75X PRE RX CHOLESTEROL, TOTAL (TC) mmol/L 5.2 CHOL >2X PRE R N = the number of participants with at least 1 on treatment lab result for each analyte

End point type

Secondary

End point timeframe

Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[36]	203 ^[37]
Units: participants
GLUCOSE, SERUM, low	33	29
GLUCOSE, SERUM, high	10	5
PROTEIN, TOTAL, low	44	26
PROTEIN, TOTAL, high	0	1
ALBUMIN, low	10	11
ALBUMIN, high	99999	99999

Notes
[36] - Study terminated, efficacy not met
[37] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with any Adverse Events (AEs) during Year 2 of the double-blind period and long-term extension

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End point title

Number of participants with any Adverse Events (AEs) during Year 2 of the double-blind period and long-term extension

End point description

End point type

Secondary

End point timeframe

From the first dose in Year 2 of the double-blind period up to 56 days post last dose

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	153	160
Units: Participants
Participants with Adverse Events	127	137
Participants with Serious Adverse Events	15	25
Participants with infection Adverse Events	100	107
Participants with malignancies	0	1
Participants with autoimmune events	7	11

No statistical analyses for this end point

Secondary: Percentage of participants in treatment failure over time during the double-blind period

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End point title

Percentage of participants in treatment failure over time during the double-blind period

End point description

Lupus treatment failure is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor.

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[38]	203 ^[39]
Units: Percentage
number (confidence interval 95%)
Lupus treatment failure (LTF) - Day 365	3.5 (0.943 to 5.988)	4.4 (1.602 to 7.265)
Overall treatment failure (OTF) - Day 365	4.5 (1.610 to 7.301)	4.9 (1.949 to 7.903)
LTF - Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)
OTF - Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[38] - Study terminated, efficacy not met
[39] - Study terminated, efficacy not met

Percentage participants in treatment failure

Statistical analysis description

Lupus treatment failure - Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Estimate of Difference

Point estimate

-0.9682

Confidence interval

level

95%

sides

2-sided

lower limit

-4.760178

upper limit

2.823876

Percentage participants in treatment failure

Statistical analysis description

Overall treatment failure - Day 365

Comparison groups

Abatacept IV v Placebo IV

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Estimate of Difference

Point estimate

-0.4707

Confidence interval

level

95%

sides

2-sided

lower limit

-4.588691

upper limit

3.647365

Secondary: Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period

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End point title

Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period

End point description

First treatment failure (or Lupus treatment failure) is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor. The hazard ratio is estimated using the Cox proportional hazards model which includes treatment group, stratification variables (baseline ACEis/ARBs use, RACE) and baseline UPCR. The estimate of median time is based on Kaplan-Meier analysis

End point type

Secondary

End point timeframe

Day 365, Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[40]	203 ^[41]
Units: Days
median (confidence interval 95%)
First treatment failure (FTF) - Day 365	99999 (99999 to 99999)	99999 (99999 to 99999)
Overall treatment failure (OTF) - Day 365	99999 (99999 to 99999)	99999 (99999 to 99999)
FTF - Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)
OTF - Day 729	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[40] - Study terminated, efficacy not met
[41] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

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End point title

Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

End point description

End point type

Secondary

End point timeframe

Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[42]	203 ^[43]
Units: Percentage
number (not applicable)	99999	99999

Notes
[42] - Study terminated, efficacy not met
[43] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Percentage of participants in overall population in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

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End point title

Percentage of participants in overall population in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

End point description

End point type

Secondary

End point timeframe

Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[44]	203 ^[45]
Units: Percentage
number (not applicable)	99999	99999

Notes
[44] - Study terminated, efficacy not met
[45] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with Marked Hematology laboratory abnormalities throughout the Double Blind period

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End point title

Number of participants with Marked Hematology laboratory abnormalities throughout the Double Blind period

End point description

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[46]	203 ^[47]
Units: participants
HEMOGLOBIN, low	99999	99999
HEMOGLOBIN, high	99999	99999
HEMATOCRIT, low	99999	99999
HEMATOCRIT, high	99999	99999
ERYTHROCYTES, low	99999	99999
ERYTHROCYTES, high	99999	99999
PLATELET COUNT, low	99999	99999
PLATELET COUNT, high	99999	99999
LEUKOCYTES, low	99999	99999
LEUKOCYTES, high	99999	99999
EOSINOPHILS (ABSOLUTE), low	99999	99999
EOSINOPHILS (ABSOLUTE), high	99999	99999
BASOPHILS (ABSOLUTE), low	99999	99999
BASOPHILS (ABSOLUTE), high	99999	99999
MONOCYTES (ABSOLUTE), low	99999	99999
MONOCYTES (ABSOLUTE), high	99999	99999
LYMPHOCYTES (ABSOLUTE), low	99999	99999
LYMPHOCYTES (ABSOLUTE), high	99999	99999

Notes
[46] - Study terminated, efficacy not met
[47] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with Marked Liver and Kidney Function Laboratory Abnormalities throughout the Double Blind period

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End point title

Number of participants with Marked Liver and Kidney Function Laboratory Abnormalities throughout the Double Blind period

End point description

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[48]	203 ^[49]
Units: participants
ALKALINE PHOSPHATASE (ALP), low	99999	99999
ALKALINE PHOSPHATASE (ALP), high	99999	99999
ASPARTATE AMINOTRANSFERASE (AST), low	99999	99999
ASPARTATE AMINOTRANSFERASE (AST), high	99999	99999
ALANINE AMINOTRANSFERASE (ALT), low	99999	99999
ALANINE AMINOTRANSFERASE (ALT), high	99999	99999
G-GLUTAMYL TRANSFERASE (GGT), low	99999	99999
G-GLUTAMYL TRANSFERASE (GGT), high	99999	99999
BILIRUBIN, TOTAL, low	99999	99999
BILIRUBIN, TOTAL, high	99999	99999
BILIRUBIN, DIRECT, low	99999	99999
BILIRUBIN, DIRECT, high	99999	99999
BLOOD UREA NITROGEN, low	99999	99999
BLOOD UREA NITROGEN, high	99999	99999
CREATININE, low	99999	99999
CREATININE, high	99999	99999

Notes
[48] - Study terminated, efficacy not met
[49] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with Marked Electrolyte Laboratory Abnormalities throughout the Double Blind period

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End point title

Number of participants with Marked Electrolyte Laboratory Abnormalities throughout the Double Blind period

End point description

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[50]	203 ^[51]
Units: participants
SODIUM, SERUM, low	99999	99999
SODIUM, SERUM, high	99999	99999
POTASSIUM, SERUM, low	99999	99999
POTASSIUM, SERUM, high	99999	99999
CHLORIDE, SERUM, low	99999	99999
CHLORIDE, SERUM, high	99999	99999
CALCIUM, TOTAL, low	99999	99999
CALCIUM, TOTAL, high	99999	99999
PHOSPHORUS, INORGANIC, low	99999	99999
PHOSPHORUS, INORGANIC, high	99999	99999

Notes
[50] - Study terminated, efficacy not met
[51] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with Marked Urinalysis Laboratory Abnormalities throughout the Double Blind period

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End point title

Number of participants with Marked Urinalysis Laboratory Abnormalities throughout the Double Blind period

End point description

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[52]	203 ^[53]
Units: participants
PROTEIN, URINE, low	99999	99999
PROTEIN, URINE, high	99999	99999
GLUCOSE, URINE, low	99999	99999
GLUCOSE, URINE, high	99999	99999
BLOOD, URINE, low	99999	99999
BLOOD, URINE, high	99999	99999
Red blood cells (RBC), URINE, low	99999	99999
Red blood cells (RBC), URINE, high	99999	99999
White blood cells (WBC), URINE, low	99999	99999
White blood cells (WBC), URINE, high	99999	99999

Notes
[52] - Study terminated, efficacy not met
[53] - Study terminated, efficacy not met

No statistical analyses for this end point

Secondary: Number of participants with other Marked Chemistry Laboratory Abnormalities throughout the Double Blind period

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End point title

Number of participants with other Marked Chemistry Laboratory Abnormalities throughout the Double Blind period

End point description

End point type

Secondary

End point timeframe

Day 1 to Day 729

End point values	Abatacept IV	Placebo IV
Number of subjects analysed	202 ^[54]	203 ^[55]
Units: participants
GLUCOSE, SERUM, low	99999	99999
GLUCOSE, SERUM, high	99999	99999
PROTEIN, TOTAL, low	99999	99999
PROTEIN, TOTAL, high	99999	99999
ALBUMIN, low	99999	99999
ALBUMIN, high	99999	99999

Notes
[54] - Study terminated, efficacy not met
[55] - Study terminated, efficacy not met

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Day 1 up to 56 days post last dose (assessed up to May 2018, approximately 66 months)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Placebo IV

Reporting group description

Placebo IV

Reporting group title

Abatacept IV

Reporting group description

Abatacept IV

Serious adverse events	Placebo IV	Abatacept IV
Total subjects affected by serious adverse events
subjects affected / exposed	63 / 203 (31.03%)	64 / 202 (31.68%)
number of deaths (all causes)	7	7
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypergammaglobulinaemia benign monoclonal
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant neoplasm of conjunctiva
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myelofibrosis
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thyroid cancer
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hodgkin's disease
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Naevus lipomatosus cutaneous superficialis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Seborrhoeic keratosis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Vasculitis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed	0 / 203 (0.00%)	3 / 202 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Generalised oedema
subjects affected / exposed	3 / 203 (1.48%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Oedema peripheral
subjects affected / exposed	1 / 203 (0.49%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Serositis
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Immune system disorders
Hypogammaglobulinaemia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	2 / 203 (0.99%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Adenomyosis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Dyspnoea
subjects affected / exposed	1 / 203 (0.49%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	2 / 203 (0.99%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Pulmonary alveolar haemorrhage
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Respiratory failure
subjects affected / exposed	0 / 203 (0.00%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	2 / 2
Pleuritic pain
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychogenic seizure
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Substance-Induced psychotic disorder
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Liver function test abnormal
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Gamma-Glutamyltransferase increased
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Overdose
subjects affected / exposed	1 / 203 (0.49%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic fracture
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Lupus myocarditis
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebral infarction
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Embolic stroke
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 203 (0.00%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Idiopathic intracranial hypertension
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lupus encephalitis
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sensory loss
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 203 (1.48%)	3 / 202 (1.49%)
occurrences causally related to treatment / all	2 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Anaemia of chronic disease
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Histiocytosis haematophagic
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Thrombotic thrombocytopenic purpura
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Eye disorders
Cataract
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 203 (0.99%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic gastritis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Food poisoning
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	2 / 203 (0.99%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Intussusception
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin necrosis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dermal cyst
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	2 / 203 (0.99%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Azotaemia
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lupus nephritis
subjects affected / exposed	3 / 203 (1.48%)	4 / 202 (1.98%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0
Renal failure
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	2 / 203 (0.99%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Musculoskeletal and connective tissue disorders
Foot deformity
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myopathy
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	5 / 203 (2.46%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Systemic lupus erythematosus
subjects affected / exposed	2 / 203 (0.99%)	4 / 202 (1.98%)
occurrences causally related to treatment / all	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Candida infection
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 203 (0.49%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Disseminated tuberculosis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalitis
subjects affected / exposed	0 / 203 (0.00%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 203 (0.99%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	2 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Genital herpes
subjects affected / exposed	0 / 203 (0.00%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	5 / 203 (2.46%)	5 / 202 (2.48%)
occurrences causally related to treatment / all	3 / 5	3 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Lung infection
subjects affected / exposed	0 / 203 (0.00%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 203 (0.00%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	6 / 203 (2.96%)	17 / 202 (8.42%)
occurrences causally related to treatment / all	2 / 6	13 / 17
deaths causally related to treatment / all	0 / 1	3 / 3
Pyelonephritis
subjects affected / exposed	2 / 203 (0.99%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Salmonella bacteraemia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 203 (0.49%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Septic shock
subjects affected / exposed	1 / 203 (0.49%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	1 / 1	1 / 1
Sinusitis
subjects affected / exposed	1 / 203 (0.49%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Toxoplasmosis
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculous pleurisy
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 203 (0.49%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	2 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	4 / 203 (1.97%)	2 / 202 (0.99%)
occurrences causally related to treatment / all	1 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aspergillus infection
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Staphylococcal bacteraemia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Varicella zoster virus infection
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vulval abscess
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 203 (0.00%)	1 / 202 (0.50%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	1 / 203 (0.49%)	0 / 202 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Placebo IV	Abatacept IV
Total subjects affected by non serious adverse events
subjects affected / exposed	183 / 203 (90.15%)	167 / 202 (82.67%)
Vascular disorders
Hypertension
subjects affected / exposed	13 / 203 (6.40%)	7 / 202 (3.47%)
occurrences all number	14	7
Hypotension
subjects affected / exposed	13 / 203 (6.40%)	5 / 202 (2.48%)
occurrences all number	14	6
Nervous system disorders
Dizziness
subjects affected / exposed	6 / 203 (2.96%)	12 / 202 (5.94%)
occurrences all number	7	13
Headache
subjects affected / exposed	23 / 203 (11.33%)	26 / 202 (12.87%)
occurrences all number	61	35
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	25 / 203 (12.32%)	22 / 202 (10.89%)
occurrences all number	28	25
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	14 / 203 (6.90%)	17 / 202 (8.42%)
occurrences all number	17	19
Pyrexia
subjects affected / exposed	13 / 203 (6.40%)	9 / 202 (4.46%)
occurrences all number	15	10
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	15 / 203 (7.39%)	9 / 202 (4.46%)
occurrences all number	16	10
Diarrhoea
subjects affected / exposed	51 / 203 (25.12%)	49 / 202 (24.26%)
occurrences all number	64	85
Nausea
subjects affected / exposed	17 / 203 (8.37%)	16 / 202 (7.92%)
occurrences all number	25	21
Vomiting
subjects affected / exposed	7 / 203 (3.45%)	13 / 202 (6.44%)
occurrences all number	8	17
Dental caries
subjects affected / exposed	4 / 203 (1.97%)	11 / 202 (5.45%)
occurrences all number	7	13
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	27 / 203 (13.30%)	26 / 202 (12.87%)
occurrences all number	34	32
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	11 / 203 (5.42%)	13 / 202 (6.44%)
occurrences all number	14	17
Rash
subjects affected / exposed	20 / 203 (9.85%)	14 / 202 (6.93%)
occurrences all number	26	18
Psychiatric disorders
Insomnia
subjects affected / exposed	20 / 203 (9.85%)	15 / 202 (7.43%)
occurrences all number	20	16
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	20 / 203 (9.85%)	24 / 202 (11.88%)
occurrences all number	25	29
Back pain
subjects affected / exposed	19 / 203 (9.36%)	12 / 202 (5.94%)
occurrences all number	23	13
Osteonecrosis
subjects affected / exposed	11 / 203 (5.42%)	2 / 202 (0.99%)
occurrences all number	13	2
Infections and infestations
Bronchitis
subjects affected / exposed	27 / 203 (13.30%)	21 / 202 (10.40%)
occurrences all number	35	24
Conjunctivitis
subjects affected / exposed	16 / 203 (7.88%)	15 / 202 (7.43%)
occurrences all number	17	17
Gastroenteritis
subjects affected / exposed	17 / 203 (8.37%)	13 / 202 (6.44%)
occurrences all number	18	17
Herpes zoster
subjects affected / exposed	18 / 203 (8.87%)	21 / 202 (10.40%)
occurrences all number	19	22
Influenza
subjects affected / exposed	11 / 203 (5.42%)	14 / 202 (6.93%)
occurrences all number	15	17
Nasopharyngitis
subjects affected / exposed	46 / 203 (22.66%)	45 / 202 (22.28%)
occurrences all number	104	79
Pharyngitis
subjects affected / exposed	26 / 203 (12.81%)	21 / 202 (10.40%)
occurrences all number	35	30
Upper respiratory tract infection
subjects affected / exposed	44 / 203 (21.67%)	43 / 202 (21.29%)
occurrences all number	88	85
Urinary tract infection
subjects affected / exposed	42 / 203 (20.69%)	46 / 202 (22.77%)
occurrences all number	70	77

More information

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Were there any global substantial amendments to the protocol? Yes

10 Jun 2014

The primary purpose of this amendment is to revise and clarify the eligibility criteria and study assessments, clarify dosing of background medications, provide updated references and appendices and clarify protocol language to ensure consistency within the protocol.

27 Mar 2015

The primary purpose of this amendment is to identify key secondary objectives and to add a 52 week long-term extension to expand the observations of the effects of continued treatment with mycophenolic mofetil (MMF) with or without abatacept on the maintenance of renal response in subjects after 2 years of treatment of active Class III or Class IV lupus nephritis (LN). During this period, adjustment to treatment will be allowed including reduction of the MMF dose and switching from IV abatacept to subcutaneous (SC) abatacept.

06 Apr 2016

The main purpose of this amendment is to provide a mechanism for supply of study drug (MMF and abatacept/placebo) for study subjects who continue to derive benefit by extending the study past the Long-Term Extension (LTE).

19 Apr 2017

Provides clarification on the duration of Group C (MPE) and procedures to be performed during the MPE; updates Appendix 5 with the correct version of SF-36 used in the study; updates the Medical Monitor contact information.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
30 May 2018	This study was terminated prematurely by the sponsor after the primary analysis failed to show a statistical significant treatment difference in the primary endpoint, and analyses of secondary and other efficacy endpoints failed to demonstrate clinically meaningful differences between the abatacept and placebo groups.	-

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

Study terminated early after review of Year 1 data. At unblinding most participants had completed Year 2 and many entered LTE. Only Year 2/LTE data captured within blind was analyzed. Some post-Year 1 outcomes not calculated due to early termination.

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Clinical trials

Clinical Trial Results: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 (Abatacept) or Placebo on a Background of Mycophenolate Mofetil (MMF) and Corticosteroids in Subjects with Active Class III or IV Lupus Nephritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants in Complete Renal Response (CR) of lupus glomerulonephritis at Day 365 of the double-blind period

Primary: Percentage of participants in Complete Renal Response (CR) of lupus glomerulonephritis at Day 365 of the double-blind period

Secondary: Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 365 of the double-blind period

Secondary: Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 365 of the double-blind period

Secondary: Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in nephrotic participants

Secondary: Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in nephrotic participants

Secondary: Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in overall population

Secondary: Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in overall population

Secondary: Adjusted mean change from baseline in disease activity as measured by BILAG 2004 over time during Year 1 of the double-blind period

Secondary: Adjusted mean change from baseline in disease activity as measured by BILAG 2004 over time during Year 1 of the double-blind period

Secondary: Number of participants with any Adverse Events (AEs) during Year 1 of the double-blind period

Secondary: Number of participants with any Adverse Events (AEs) during Year 1 of the double-blind period

Secondary: Percentage of participants with ranked outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) during the double-blind period

Secondary: Percentage of participants with ranked outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) during the double-blind period

Secondary: Median time to Complete Renal Response during the double-blind period in all participants

Secondary: Median time to Complete Renal Response during the double-blind period in all participants

Secondary: Median time to Complete Renal Response during the double-blind period in nephrotic participants

Secondary: Median time to Complete Renal Response during the double-blind period in nephrotic participants

Secondary: Median time to Partial Renal Response during the double-blind period in all participants

Secondary: Median time to Partial Renal Response during the double-blind period in all participants

Secondary: Median time to Partial Renal Response during the double-blind period in nephrotic participants

Secondary: Median time to Partial Renal Response during the double-blind period in nephrotic participants

Secondary: Adjusted mean change from baseline in UPCR over time

Secondary: Adjusted mean change from baseline in UPCR over time

Secondary: Median Percent Change from Baseline in UPCR over Time

Secondary: Median Percent Change from Baseline in UPCR over Time

Secondary: Adjusted mean change from baseline in eGFR over time

Secondary: Adjusted mean change from baseline in eGFR over time

Secondary: Median Time to First Sustained Change to No Response During the Double-blind Period

Secondary: Median Time to First Sustained Change to No Response During the Double-blind Period

Secondary: Number of participants with sustained change from higher level of response to no response during the double-blind period

Secondary: Number of participants with sustained change from higher level of response to no response during the double-blind period

Secondary: Adjusted mean change from baseline and from Day 365 in disease activity as measured by BILAG 2004 over time during the double-blind period

Secondary: Adjusted mean change from baseline and from Day 365 in disease activity as measured by BILAG 2004 over time during the double-blind period

Secondary: Cmin (ug/mL): Trough level serum concentration of abatacept prior to the administration of the IV infusion

Secondary: Cmin (ug/mL): Trough level serum concentration of abatacept prior to the administration of the IV infusion

Secondary: Cmax: Maximum observed serum concentration following participants receiving active abatacept IV

Secondary: Cmax: Maximum observed serum concentration following participants receiving active abatacept IV

Secondary: AUC (TAU): Area under the serum concentration time curve over a dosing interval

Secondary: AUC (TAU): Area under the serum concentration time curve over a dosing interval

Secondary: Summary statistics for systolic blood pressure

Secondary: Summary statistics for systolic blood pressure

Secondary: Summary statistics for diastolic blood pressure

Secondary: Summary statistics for diastolic blood pressure

Secondary: Summary statistics for Heart Rate

Secondary: Summary statistics for Heart Rate

Secondary: Mean Change from Baseline in Laboratory Analytes During the Double-blind Period

Secondary: Mean Change from Baseline in Laboratory Analytes During the Double-blind Period

Secondary: Number of participants with Marked Hematology laboratory abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with Marked Hematology laboratory abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with Marked Liver and Kidney Function Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with Marked Liver and Kidney Function Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with Marked Electrolyte Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with Marked Electrolyte Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with Marked Urinalysis Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with Marked Urinalysis Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with other Marked Chemistry Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with other Marked Chemistry Laboratory Abnormalities during Year 1 of the Double Blind period

Secondary: Number of participants with any Adverse Events (AEs) during Year 2 of the double-blind period and long-term extension

Secondary: Number of participants with any Adverse Events (AEs) during Year 2 of the double-blind period and long-term extension

Secondary: Percentage of participants in treatment failure over time during the double-blind period

Secondary: Percentage of participants in treatment failure over time during the double-blind period

Secondary: Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period

Secondary: Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period

Secondary: Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

Secondary: Percentage of nephrotic participants in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

Secondary: Percentage of participants in overall population in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

Secondary: Percentage of participants in overall population in Complete Renal Response of lupus glomerulonephritis at Day 729 of the double-blind period

Secondary: Number of participants with Marked Hematology laboratory abnormalities throughout the Double Blind period

Secondary: Number of participants with Marked Hematology laboratory abnormalities throughout the Double Blind period

Clinical Trial Results:
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 (Abatacept) or Placebo on a Background of Mycophenolate Mofetil (MMF) and Corticosteroids in Subjects with Active Class III or IV Lupus Nephritis