Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

Lupus Nephritis Clinical Trial

Official title:

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 and Corticosteroids in the Treatment of Subjects With Active Class III or IV Lupus Nephritis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01714817
• Other study ID #: IM101-291
• Secondary ID: 2012-000714-11
• Status: Terminated
• Phase: Phase 3
• Start date: January 22, 2013
• Est. completion date: May 30, 2018

Study information

• Verified date: February 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate (Abatacept) for treatment of lupus nephritis when used on a background of Cellcept (mycophenolate) and prednisone (corticosteroids)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 695
• Est. completion date: May 30, 2018
• Est. primary completion date: November 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For additional information please contact the BMS Lupus Nephritis Clinical Trial Matching Service at 855-56-LUPUS. Please visit www.BMSStudyConnect.com for more information on clinical trial participation. Note: Subjects > 16 are eligible for enrollment at selected centers

Inclusion Criteria:

• Potential subjects must have active lupus nephritis
• Biopsy within 12 months prior to screening visit indicating active Class 3 or 4 proliferative lupus glomerulonephritis (lupus effecting your kidney)
• Urine protein creatinine ratio (UPCR) = 1 at Screening
• Serum creatinine = 3 mg/dL (ie, = 265 micromol/L)
• There must also be evidence of active disease within 3 months of Screening, based on

at least one of the following:

• Worsening of lupus nephritis OR
• UPCR = 3 at Screening OR
• Active urine sediment OR
• Biopsy within 3 months prior to screening visit indicating active Class 3 or Class 4 active proliferative lupus glomerulonephritis

Inclusion Criteria for the Long-Term Extension Period:

• Signed Written Informed Consent
• Subjects who achieve a complete or partial renal response after completing 2 years of double-blind treatment

Exclusion Criteria:

• Systemic Lupus Erythematosus (SLE) must be the primary/main autoimmune diagnosis
• Current symptoms of severe, progressive, or uncontrolled non-SLE related renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study
• Significant active Central nervous system (CNS) lupus with the exception of fatigue or mild stable cognitive
• Subjects who are diagnosed as end-stage renal disease or whose kidney damage is too significant and irreversible

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Biological:
• BMS-188667

Drug:
• Mycophenolate mofetil

• Prednisone

Biological:
• Placebo matching with BMS-188667

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Organizacion Medica De Investigacion S.A. (Omi)	Capital Federal	Buenos Aires
Argentina	Hospital Privado-Centro Medico De Cordoba S.A.	Cordoba
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Parkville	Victoria
Australia	Local Institution	Perth	Western Australia
Brazil	Local Institution	Belo Horizonte	Minas Gerais
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Juiz De Fora	Minas Gerais
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Savaldor	Bahia
Brazil	Local Institution	Uberlandia	Minas Gerais
Canada	Local Institution	Mississauga	Ontario
Canada	Local Institution	Toronto	Ontario
Chile	Local Institution	Independencia	Santiago
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago De Chile	Metropolitana
Chile	Local Institution	Vina Del Mar	Valparaiso
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing
China	Local Institution	Chengdu	Sichuan
China	Local Institution	Chong Qing
China	Local Institution	Guangzhou
China	Local Institution	Guangzhou	Guangdong
China	Local Institution	Haikou	Hainan
China	Local Institution	Hangzhou	Zhejiang
China	Local Institution	Harbin	Heilongjiang
China	Local Institution	Nanchang	Jiangxi
China	Local Institution	Nanchang
China	Local Institution	Nanning
China	Local Institution	Shanghai
China	Local Institution	Shanghai
China	Local Institution	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Wuhan	Hebei
China	Local Institution	Wuxi	Jiangsu
China	Local Institution	Xi'An
China	Local Institution	Xian	Shan1xi
China	Local Institution	Zhengzhou	Henan
Colombia	Circaribe S.A.S	Barranquilla
Colombia	Clinica De La Costa	Barranquilla
Colombia	Hospital Universitario San Ignacio	Bogota
Colombia	Riesgo De Fractura S.A. Cayre Ips	Bogota	Cundinamarca
Colombia	Servimed E.U	Bucaramanga	Santander
Colombia	Hospital Pablo Tobon Uribe	Medellin
Czechia	Local Institution	Praha 2
Hong Kong	Local Institution	Hong Kong
India	Local Institution	Ahmedabad	Gujrat
India	Local Institution	Gurgaon
India	Local Institution	Hyderabad
India	Local Institution	Lucknow-
India	Local Institution	New Delhi
India	Local Institution	Secunderabad	Andhra Pradesh
Israel	Local Institution	Haifa
Israel	Local Institution	Haifa
Israel	Local Institution	Ramat-gan
Israel	Local Institution	Tel Aviv
Italy	Local Institution	Brescia
Italy	Local Institution	Milano
Italy	Local Institution	Padova
Italy	Local Institution	Reggio Emilia
Italy	Local Institution	Torino
Japan	Local Institution	Bunkyo-ku	Tokyo
Japan	Local Institution	Bunkyo-ku	Tokyo
Japan	Local Institution	Chiba-shi	Chiba
Japan	Local Institution	Chuo-ku	Tokyo
Japan	Local Institution	Fuchu	Tokyo
Japan	Local Institution	Fukuoka-shi	Fukuoka
Japan	Local Institution	Iruma-gun	Saitama
Japan	Local Institution	Kanazawa-shi	Ishikawa
Japan	Local Institution	Kita-gun
Japan	Local Institution	Kitakyushu-shi	Fukuoka
Japan	Local Institution	Maebashi-shi	Gunma
Japan	Local Institution	Nagakute-shi	Aichi
Japan	Local Institution	Nagasaki-shi	Nagasaki
Japan	Local Institution	Nagoya-shi	Aichi
Japan	Local Institution	Niigata-shi	Niigata
Japan	Local Institution	Okayama-shi	Okayama
Japan	Local Institution	Osaka
Japan	Local Institution	Ota-ku	Tokyo
Japan	Local Institution	Sapporo-shi	Hokkaido
Japan	Local Institution	Sapporo-shi	Hokkaido
Japan	Local Institution	Sendai-shi	Miyagi
Japan	Local Institution	Shimotsuke-shi	Tochigi
Japan	Local Institution	Shinjuku-Ku	Tokyo
Japan	Local Institution	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Instituto Nacional De Ciencias Medicas Y Nutricion S.Z.	Distrito Federal
Mexico	Centro De Est D Inv. Basica Y Clinica	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara, Jalisco	Jalisco
Mexico	Centro Medico De Las Americas	Merida	Yucatan
Mexico	Hospital De Jesus	Mexico City	Distrito Federal
Mexico	Hospital General De Mexico O.D.	Mexico City	Distrito Federal
Mexico	Local Institution	Mexico City	Distrito Fededral
Mexico	Centro Potosino de Inv Clinica	San Luis Potosi
Mexico	Hosp Central I.Morones Prieto	San Luis Potosi
Peru	Hospital Nacional Cayetano Heredia	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen	Lima
Peru	Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac	Lima
Puerto Rico	Local Institution	San Juan
Romania	Local Institution	Bucharest
Romania	Local Institution	Bucuresti
Romania	Local Institution	Bucuresti
Romania	Local Institution	Cluj-napoca
Romania	Local Institution	Iasi
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	Ufa
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taoyuan
Turkey	Local Institution	Antalya
Turkey	Local Institution	Edirne
United States	Emory University.	Atlanta	Georgia
United States	Ochsner Clinic Foundation	Baton Rouge	Louisiana
United States	University Of Alabama At Birmingham (Uab)	Birmingham	Alabama
United States	Boston University Medical Center	Boston	Massachusetts
United States	Brigham & Women'S Hospital	Boston	Massachusetts
United States	Suny Downstate Medical Center	Brooklyn	New York
United States	Local Institution	Camden	New Jersey
United States	University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Local Institution	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University Of Connecticut Health Center	Farmington	Connecticut
United States	Northshore Lij Health System	Great Neck	New York
United States	Rheumatology Consultants Pllc	Knoxville	Tennessee
United States	Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.	Long Beach	California
United States	The Feinstein Institute For Medical Research	Manhasset	New York
United States	University Of Miami Miller School Of Medicine	Miami	Florida
United States	Paramount Medical Research & Consulting, Llc	Middleburg Heights	Ohio
United States	Tulane University School Of Medicine	New Orleans	Louisiana
United States	Hospital For Special Surgery	New York	New York
United States	Local Institution	New York	New York
United States	Integral Rheumatology & Immunology Specialists	Plantation	Florida
United States	Shanahan Rheum & Immunotherapy, PLLC	Raleigh	North Carolina
United States	University Of Utah Hospital	Salt Lake City	Utah
United States	East Bay Rheumatology Medical Group, Inc.	San Leandro	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  Hong Kong,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period	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.	Day 365
Secondary	Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period	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.	Day 365
Secondary	Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants	Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in nephrotic participants	Baseline and Day 365
Secondary	Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population	Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population	Day 1 and Day 365
Secondary	Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period	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.	Day 1 to Day 365
Secondary	Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period	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.	From Day 1 up to 56 days post last dose in 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	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	Day 365, Day 729
Secondary	Median Time to Complete Renal Response During the Double-blind Period in All Participants	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.	Day 365, Day 729
Secondary	Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants	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.	Day 365, Day 729
Secondary	Median Time to Partial Renal Response During the Double-blind Period in All Participants	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	Day 365, Day 729
Secondary	Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants	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	Day 365, Day 729
Secondary	Adjusted Mean Change From Baseline in UPCR Over Time	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.	Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended
Secondary	Median Percent Change From Baseline in UPCR Over Time	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.; % Change from Baseline = (post baseline - baseline value) / baseline value x 100	Day 365, Day 729
Secondary	Adjusted Mean Change From Baseline in eGFR Over Time	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)a 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, a 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.	Day 365, Day 729
Secondary	Median Time to First Sustained Change to No Response During the Double-blind Period	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	Day 365, Day 729
Secondary	Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period	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.	Day 365, Day 729
Secondary	Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period	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. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome.	Day 1 to Day 729; Day 365 to Day 729
Secondary	Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion	Trough level serum concentration of abatacept prior to the administration of the IV infusion on Days 1 to 365	Days 1 to 365
Secondary	Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV	Cmax: Maximum observed serum concentration following participants receiving active abatacept IV	at 1 hour post Day 1 dose and 30 minutes post Day 337 dose
Secondary	AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval	AUC (TAU): Area under the serum concentration time curve over a dosing interval between Days 337 to 365.	Days 337 to 365
Secondary	Summary Statistics for Systolic Blood Pressure	Summary statistics for systolic blood pressure	Day 1 to Day 729
Secondary	Summary Statistics for Diastolic Blood Pressure	Summary statistics for diastolic blood pressure	Day 1 to Day 729
Secondary	Summary Statistics for Heart Rate	Summary statistics for Heart Rate	Day 1 to Day 729
Secondary	Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L)	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.	Day 729
Secondary	Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L)	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.	Day 729
Secondary	Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood)	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.	Day 729
Secondary	Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L)	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.	Day 729
Secondary	Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L)	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.	Day 729
Secondary	Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L)	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.	Day 729
Secondary	Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period	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 RXN = the number of participants with at least 1 on treatment lab result for each analyte	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
Secondary	Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period	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	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
Secondary	Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period	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 RXN = the number of participants with at least 1 on treatment lab result for each analyte	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
Secondary	Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period	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	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
Secondary	Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period	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 RXN = the number of participants with at least 1 on treatment lab result for each analyte	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
Secondary	Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension	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.	From the first dose in Year 2 of the double-blind period up to 56 days post last dose
Secondary	Percentage of Participants in Treatment Failure Over Time During the Double-blind Period	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.	Day 365, Day 729
Secondary	Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period	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	Day 365, Day 729
Secondary	Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period	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.	Day 729
Secondary	Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period	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.	Day 729
Secondary	Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period	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 RXN = the number of participants with at least 1 on treatment lab result for each analyte	Day 1 to Day 729
Secondary	Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period	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	Day 1 to Day 729
Secondary	Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period	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 RXN = the number of participants with at least 1 on treatment lab result for each analyte	Day 1 to Day 729
Secondary	Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period	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	Day 1 to Day 729
Secondary	Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period	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 RXN = the number of participants with at least 1 on treatment lab result for each analyte	Day 1 to Day 729
Secondary	Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period	Participants who experienced a positive antibody response relative to baseline (ECL Assay)	Day 365, Day 729

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls