Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

Systemic Lupus Erythematosus Clinical Trial

Official title:

A Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects With Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00430677
• Other study ID #: IM101-075
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: February 1, 2007
• Last updated: March 3, 2015
• Start date: June 2007
• Est. completion date: August 2011

Study information

• Verified date: March 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical research study is to learn if addition of abatacept is safe and improves the effectiveness of treatment of patients with active lupus nephritis who are also taking mycophenolate mofetil (MMF) and corticosteroids.

Description:

Double Blind Period: Treatment, Parallel Assignment, Double Blind (Subject, Investigator), Randomized, Active Control, Safety/Efficacy Study

Open Label Period: Prevention, Single Group Assignment, Open Label, Uncontrolled, Safety/Efficacy Study

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 423
• Est. completion date: August 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Systemic Lupus Erythematosus (SLE) as defined by meeting at least 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus, either sequentially or coincident. The 4 criteria need not be present at study entry

• Renal biopsy within 12 months prior to screening visit indicating active proliferative lupus glomerulonephritis (met ISN/RPS Class III or IV classification criteria [2003], excluding Class III [C], IV-S [C] and IV-G [C], or the World Health Organization Class III or IV classification criteria [1982], excluding Class IIIc, IVd). If the renal biopsy was performed >3 months but =12 months prior to screening visit, at least 1 of the following 3 serologies (performed locally) must have been abnormal prior to screening visit: complement (C3 or C4) level below normal range OR anti-dsDNA >upper limit of normal range.

• A stable serum creatinine =3 mg/dL

Exclusion Criteria:

• Subjects with a rise in serum creatinine of =1 mg/dL within 1 month prior to the screening visit

• Subjects with drug-induced SLE, as opposed to idiopathic SLE

• Subjects with severe, unstable and/or progressive Central nervous system (CNS) lupus

• Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.; Rheumatoid arthritis (RA), Multiple Sclerosis [MS])

• Subjects who have received treatment with cyclophosphamide within 3 months of randomization (Day 1).

• Subjects who have received treatment with rituximab < 6 months prior to the screening visit

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily
• Abatacept
intravenous solution, injectable, 30 mg/kg, every 28 days
• Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days
• Mycophenolate mofetil (MMF)
tablets, oral, 1.5 to 2 g, daily
• Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days

Locations

Country	Name	City	State
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Ciudad Autonoma De Buenos Aire	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Tucuman
Australia	Local Institution	Clayton	Victoria
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution	Liverpool	New South Wales
Australia	Local Institution	Parkville	Victoria
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Leuven
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Winnipeg	Manitoba
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Guangzhou	Guangdong
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Xi'an	Shanxi
France	Local Institution	Creteil Cedex
France	Local Institution	Paris Cedex 13
France	Local Institution	Strasbourg Cedex
France	Local Institution	Toulouse Cedex 4
Hong Kong	Local Institution	Hong Kong
India	Local Institution	Ahmedabad	Gujarat
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Gujarat	Ahmedabad
India	Local Institution	Hyderabad
India	Local Institution	Kochi	Kerala
India	Local Institution	Mumbai	Maharajhsra
India	Local Institution	Nadiad	Gujarat
India	Local Institution	Secunderabad	Andhra Pradesh
India	Local Institution	Visakhapatnam
Korea, Republic of	Local Institution	Seoul	Sungdong-Gu
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Metepec	Estado De Mexico
Mexico	Local Institution	Mexico City	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	San Luis Potosi
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Gdansk
Poland	Local Institution	Wroclaw
Russian Federation	Local Institution	Ekaterinburg
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Yaroslaval
South Africa	Local Institution	Johannesburg	Gauteng
South Africa	Local Institution	Observatory	Western Cape
South Africa	Local Institution	Panorama	Western Cape
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taoyuan
Turkey	Local Institution	Gaziantep
United Kingdom	Local Institution	Cambridge	Cambridgeshire
United Kingdom	Local Institution	London	Greater London
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	Boston University School Of Medicine	Boston	Massachusetts
United States	Suny Downstate Medical Center	Brooklyn	New York
United States	University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	University Of Kansas Medical Center	Kansas City	Kansas
United States	Rheumatology Consultants Pllc	Knoxville	Tennessee
United States	Northshore Lij Health System	Lake Success	New York
United States	Wallace Rheumatic Study Center	Los Angeles	California
United States	The Feinstein Institute For Medical Research	Manhasset	New York
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Ok Medical Research Foundation	Oklahoma City	Oklahoma
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Suny Upstate Medical University	Syracuse	New York
United States	Arizona Arthritis Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Hong Kong,  India,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  South Africa,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Achieving Patient Response (PR) at Month 12 During the Short-term Period	PR is either CRR, Partial Renal Response(PRR),or no Response(NR).; CRR= Serum creatinine(SC)is normal, Inactive urinary sediment, No cellular casts, Urinary protein/creatinine (UPCR) ratio <56.5 mg/mmoL; PRR= SC is normal OR SC not >25% above BL, RBCs at reference range, UPCR <56.5 mg/mmoL OR =50% improvement in UPCR with one of the following: UPCR <113 or <339 mg/mmoL, based on the BL ratio; NR= Not achieving either a CRR or a PRR. Participants achieved response if criteria at both months 11 and 12 (Days 337 and 365) were met. Participants who Early discontinuations were categorized as NR.	Month 12	No
Primary	Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period	Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.	Day 1 (randomization) to 12 months.	No
Secondary	Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period	Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.	Day 1 to 12 months	No
Secondary	Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period	Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.	At Month 12 from Day 1	No
Secondary	Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology)	RI is defined as meeting all of the following criteria. Renal function: If MDRD is abnormal at screening, within 10% of the MDRD at screening; if MDRD is 60-89 at screening, greater than or equal to 50% improvement based on the screening value or 90% or greater of MDRD at screening; if MDRD is 15-59 at screening, if MDRD is normal at screening-within 10% of the MDRD at screening. Proteinuria: improvement greater than or equal to 50% from screening. Hematuria: red blood cell (RBC)count within normal limit of central laboratory. Pyuria: white blood cell (WBC) count within normal limit of central laboratory. Cylindruria: No RBC or WBC casts.	Day 1 (randomization) to 12 months.	No
Secondary	Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period	CRR defined as meeting all of 5 criteria. RF: (Glomerular filtration rate [GFR] calculated using MDRD equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.	At Month 12 from Day 1	No
Secondary	Number of Months CRR Was Maintained During Short-term Period	Durability of CRR, defined as the number of months (number of consecutive planned visits beyond Day 15) a participant met the definition of CRR during the double-blind treatment period. Refer to outcome 1 for description of CRR.	Day 1 (randomization) to 12 Months	No
Secondary	Baseline Renal Function Over Time During Short-term Period	Baseline (BL) renal function, as estimated by calculation of the MDRD (Modification of Diet in Renal Disease) equation, over time. Renal MDRD is an equation (calculation) used to estimate Glomerular Filtration Rate (GFR) in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine. A negative value indicates worsening.	Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365	No
Secondary	Change in Renal Function From Baseline Over Time During Short-term Period	Mean change from baseline in renal function, as estimated by calculation of the MDRD equation, over time. Renal MDRD is an equation (calculation) used to estimate Glomerular Filtration Rate (GFR) in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine. A positive value indicates improvement. Change from baseline=Post-baseline-baseline value.	Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365	No
Secondary	Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Short-term Period	SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as nonreversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as =1. The total maximum score is 48, and increasing score indicates increasing disease severity.	Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)	No
Secondary	Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period	RR is defined as meeting BOTH of the following criteria:RENAL FUNCTION: Less than or equal to 25% increase from baseline;PROTEINURIA: Greater than or equal to 50% improvement in the urine protein/creatinine ratio with one of the following - urine protein/creatinine ratio (UPCR) <113 mg/mmol,, if the baseline ratio was <=339 mg/mmol OR UPCR <339 mg/mmol,if the baseline ratio > 339 mg/mmol. A participant was considered as achieving RR if response criteria at both months 11 and 12 (Days 337 and 365, respectively) were met. For 95% CI within each group, normal approximation is used if n>=5.	Month 12	No
Secondary	Change in SLICC/ACR Damage Index From Baseline During Short-term Period	SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as non-reversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as =1. The total maximum score is 48, and increasing score indicates increasing disease severity. Change from baseline=Postbaseline - baseline value.	Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)	No
Secondary	Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period	The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period	The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Baseline Mental Component Summary of the Short SF-36 During Short-term Period	The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period	The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period	A visual analogue scale (VAS) is a psychometric response scale for measurement of subjective characteristics or attitudes that cannot be directly measured. The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period	A visual analogue scale is a psychometric response scale for measurement of subjective characteristics or attitudes that cannot be directly measured.; The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period	The reduction of fatigue assessed by Fatigue Severity Scale (FSS). The FSS questionnaire is comprised of 9 statements inquiring about the examinee's sleep habits over the preceding week. Participants are asked to rate their level of agreement (toward seven) or disagreement (toward zero) with the nine statements. A score of 36 and above (out of a maximum of 63) indicates the presence of significant fatigue.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period	The reduction of fatigue assessed by Fatigue Severity Scale (FSS). The FSS questionnaire is comprised of 9 statements inquiring about the examinee's sleep habits over the preceding week. Participants are asked to rate their level of agreement (toward seven) or disagreement (toward zero) with the nine statements. A score of 36 and above (out of a maximum of 63) indicates the presence of significant fatigue.	Baseline (Day 1), Days 85, 169, 253, and 365	No
Secondary	Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=possibly, probably, or certainly related to and of unknown relationship to study drug.	From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.	Yes
Secondary	Participants With AEs of Special Interest During the Short-term Period	AEs of special interest were prospectively identified to be those that may be associated with the use of immunomodulatory agents. They are a subset of all AEs and may be either serious or non-serious.	From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.	Yes
Secondary	Participants With Marked Hematology Abnormalities During the Short-term Period	LLN=lower limit of normal; ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age. Low(?)Hemoglobin:>3g/dL decrease from PTV; ?Hematocrit:<0.75xPTV;?Erythrocyte count:<0.75xPTV; high(?)Platelet count:>1.5xULN;?Platelet count:<0.67xLLN;?Leukocyte count:<0.75X LLN;?Leukocyte count:>1.25xULN;?Absolute(AB)Neutrophils+Bands:<1.00x10^3c/uL;?AB Lymphocyte count:>7.50x10^3 c/uL; ?AB lymphocyte count:<0.750x10^3 c/uL;?AB monocyte count:>2000/mm^3;?AB basophil count:>400/mm^3;?AB eosinophil count:>0.750x10^3 c/uL.	From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.	Yes
Secondary	Participants With Marked Laboratory Abnormalities During the Short-term Period	LLN=lower limit of normal; ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age. ?Serum Sodium:>1.05x ULN;?Serum Potassium:<0.9x LLN;?Serum Potassium:>1.1x ULN;?Total Calcium:<0.8X LLN;?Total Calcium:>1.2x ULN; ?Serum Glucose(SG):<65 mg/dL;?SG:>220 mg/dL;?Fasting SG:<0.8x LLN;?Fasting SG:>1.5x ULN;?Total Protein:<0.9x LLN;?Albumin:<0.9x LLN;?Total Cholesterol:>2x PTV;?Triglycerides:>=2.5x ULN;?Fasting Triglycerides:>=2x ULN	From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.	Yes
Secondary	Participants With Marked Liver and Kidney Function Abnormalities During the Short-term Period	ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age.; Alkaline Phosphatase:>2x ULN; ?Aspartate Aminotransferase: >3x ULN; ?Alanine Aminotransferase : >3x ULN; G-Glutamyl Transferase : >2x ULN; ?Total Bilirubin : >2x ULN or if PTV > ULN then > 4x PTV; ?Blood Urea Nitrogen >2x PTV; ?Creatinine >1.5x PTV.	From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.	Yes
Secondary	Participants With Marked Abnormalities Urinalysis During the Short-term Period	PTV=pretreatment value. Criteria for marked abnormality: Protein, glucose, blood, leukocyte esterase , if missing PTV then use >=2+ (or, if value >=4, or if PTV=0 or 0.5, >=2 or if PTV=1, >=3, or if PTV=2 or 3, >=4).	From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.	Yes
Secondary	Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP)		0 - 12 Months	Yes
Secondary	Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP)		0 - 12 Months	Yes
Secondary	Vital Signs Summary During the Short-term Period: Heart Rate		0 - 12 Months	Yes
Secondary	Vital Signs Summary During the Short-term Period: Temperature		0 - 12 Months	Yes
Secondary	Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period	A validated, sensitive electrochemiluminescence (ECL) immunoassay based on Meso-Scale Discovery instrumentation was used to evaluate immunogenicity. The ECL assay differentiated between two antibody specificities: (1) the 'Ig and/or Junction (Jn) Region' and (2) 'CLTA4 and possibly Ig'. A sample was considered positive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept with or without CTLA4-T.	Day 169, Day 365	Yes
Secondary	Baseline Quantitative Immunoglobulins During the Short-term Period	A quantitative immunoglobulins (Igs) test is used to detect abnormal levels of the three major classes of Igs (IgG, IgA, and IgM). Abnormal test results typically indicate that there is something affecting the immune system which requires further testing.	Baseline (Day 1)	Yes
Secondary	Change in Quantitative Immunoglobulin From Baseline During Short-term Period	A quantitative immunoglobulin (Ig) test is used to detect abnormal levels of the 3 major classes of Ig (IgG, IgA, and IgM). Abnormal test results typically indicate that something is affecting the immune system and further testing is required.; Please refer to Outcome 31 for the respective baseline values	Day 365	Yes
Secondary	Number of Participants Achieving Complete Response by ACCESS Definition	The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) defines complete response as a response meeting all of the following criteria: serum creatinine =upper limit of normal as defined by the central laboratory or =125% of the higher value at either screening or baseline; urine protein/creatinine ratio <50 mg/mmoL; and prednisone or prednisone-equivalent dose tapered to 10 mg per day.	End of short-term period (Day 365) to termination of the long-term extension period	No
Secondary	Number of Participants Achieving Patient Response of Complete or Partial Response, Based on the June 2010 Food and Drug Administration Guidance Document for Lupus Nephritis	Patient response=complete, partial, or no response. Complete response=serum creatinine (SCr) normal, inactive urinary sediment, no cellular casts, urinary protein/creatinine (UPCR) ratio<56.5 mg/mmol. Partial response=SCr normal or =25% above baseline value, RBCs at reference range, UPCR <56.5 mg/mmoL OR =50% improvement in UPCR with one of the following: UPCR <113 or <339 mg/mmoL, based on the baseline ratio. No response=Not achieving complete or partial response criteria.	At Day 365 (end of Short-term Period) and Day 645	No
Secondary	Mean Change From Baseline in SLICC/ACR Damage Index	SLICC=Systemic Lupus International Collaborating Clinics; ACR=American College of Rheumatology. The SLICC/ACR Damage Index measures organ damage (nonreversible change, unrelated to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months unless otherwise stated. The index assesses 47 items in 12 systems: Ocular, Neuropsychiatric, Renal, Pulmonary, Cardiovascular, Gastrointestinal, Peripheral Vascular, Musculoskeletal, Skin, Premature Gonadal Failure, Diabetes, Malignancy. Scores range from 0 to 2, and the same lesion cannot be scored twice. If damage is noted for a particular item, it is scored 1. No damage is scored 0. Some items may score 2 points if they occur more than once, so that the maximum possible score is 47. Scores can only increase with time, but scores rarely reach over 12. It is usually completed (or updated) yearly.	Day 365 to termination of the long-term extension phase	No
Secondary	Number of Participants With Death, Serious Adverse Events (SAE), Treatment-related Adverse Events SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs During Long-term Extension Period	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=possibly, probably, or certainly related to and of unknown relationship to study drug.	From start of study drug in long-term period (Day 365) to up to 56 days after the last dose of the long-term extension (LTE). Deaths in LTE reported to >56 days post last dose.	Yes
Secondary	Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period	Collected in at least 1 sample. Assessment includes immunogenicity (detection of serum antibodies which bind to CTLA4-Ig in the in vitro assays) and exposure to corticosteroids	Day 365 to end of long-term extension period	No
Secondary	Number of Participants Achieving Renal Response	Renal response=serum creatinine level =25% above baseline value and greater than or equal to 50% improvement in the urine protein/creatinine ratio with 1 of the following: urine protein/creatinine ratio (UPCR) <113 mg/mmol, if the baseline ratio was <= 339 mg/mmol OR UPCR <339 mg/mmol,if the baseline ratio >339 mg/mmol.	At Day 365 (end of short-term period) and Day 645	No
Secondary	Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period	preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Hemoglobin (g/dL): >3g/dL decrease from preRX value. Hematocrit(%): <0.75*preRX. Erythrocytes (*10^6 c/uL): <0.75*preRX. Platelet count (*10^9 c/L): <0.67*LLN, or >1.5*ULN, or if preRX	From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period	Yes
Secondary	Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)	LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Sodium, serum (mEq/L): <0.95*LLN or >1.05*ULN, or if preRX	From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period	Yes
Secondary	Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)	preRX=pretreatment. Protein, urine: If missing preRX, use >=2, or if value >=4, or if preRX =0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 OR 3 then use >=4. Glucose, urine: If missing preRX, use >=2, or if value >=4, or if preRX=0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4. Blood, urine: If missing preRX, use >=2, or if value >=4, or if preRX =0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4. Leukocyte esterase, urine: If missing preRX, use >=2, or if value >=4, or if preRX=0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4.	From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form