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Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Terminated
CT.gov ID
NCT01714817
Collaborator
(none)
695
Enrollment
149
Locations
2
Arms
64.2
Actual Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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)

Condition or Disease Intervention/Treatment Phase
  • Biological: BMS-188667
  • Drug: Mycophenolate mofetil
  • Drug: Prednisone
  • Biological: Placebo matching with BMS-188667
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
695 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 22, 2013
Actual Primary Completion Date :
Nov 21, 2016
Actual Study Completion Date :
May 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: BMS-188667 + Mycophenolate mofetil + Prednisone

BMS-188667 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

Biological: BMS-188667
Other Names:
  • Abatacept

    • Drug: Mycophenolate mofetil
    Other Names:
  • Cellcept

    • Drug: Prednisone
    Placebo Comparator: Placebo + Mycophenolate mofetil + Prednisone

    Placebo matching with BMS-188667 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

    Drug: Mycophenolate mofetil
    Other Names:
  • Cellcept

    • Drug: Prednisone

    Biological: Placebo matching with BMS-188667

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period [Day 365]

      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.

    Secondary Outcome Measures

    1. Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period [Day 365]

      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.

    2. Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants [Baseline and Day 365]

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

    3. Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population [Day 1 and Day 365]

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

    4. Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period [Day 1 to Day 365]

      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.

    5. Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period [From Day 1 up to 56 days post last dose in 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.

    6. Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period [Day 365, Day 729]

      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

    7. Median Time to Complete Renal Response During the Double-blind Period in All Participants [Day 365, Day 729]

      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.

    8. Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants [Day 365, Day 729]

      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.

    9. Median Time to Partial Renal Response During the Double-blind Period in All Participants [Day 365, Day 729]

      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

    10. Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants [Day 365, Day 729]

      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

    11. Adjusted Mean Change From Baseline in UPCR Over Time [Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended]

      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.

    12. Median Percent Change From Baseline in UPCR Over Time [Day 365, Day 729]

      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

    13. Adjusted Mean Change From Baseline in eGFR Over Time [Day 365, Day 729]

      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.

    14. Median Time to First Sustained Change to No Response During the Double-blind Period [Day 365, Day 729]

      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

    15. Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period [Day 365, Day 729]

      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.

    16. Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period [Day 1 to Day 729; Day 365 to Day 729]

      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.

    17. Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion [Days 1 to 365]

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

    18. 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]

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

    19. AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval [Days 337 to 365]

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

    20. Summary Statistics for Systolic Blood Pressure [Day 1 to Day 729]

      Summary statistics for systolic blood pressure

    21. Summary Statistics for Diastolic Blood Pressure [Day 1 to Day 729]

      Summary statistics for diastolic blood pressure

    22. Summary Statistics for Heart Rate [Day 1 to Day 729]

      Summary statistics for Heart Rate

    23. Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) [Day 729]

      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.

    24. Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) [Day 729]

      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.

    25. Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood) [Day 729]

      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.

    26. Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L) [Day 729]

      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.

    27. Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) [Day 729]

      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.

    28. Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) [Day 729]

      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.

    29. Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period [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]

      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

    30. Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period [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]

      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

    31. Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period [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]

      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

    32. Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period [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]

      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

    33. Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period [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]

      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

    34. Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension [From the first dose in Year 2 of the double-blind period up to 56 days post last dose]

      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.

    35. Percentage of Participants in Treatment Failure Over Time During the Double-blind Period [Day 365, Day 729]

      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.

    36. Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period [Day 365, Day 729]

      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

    37. Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period [Day 729]

      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.

    38. Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period [Day 729]

      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.

    39. Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period [Day 1 to Day 729]

      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

    40. Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period [Day 1 to Day 729]

      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

    41. Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period [Day 1 to Day 729]

      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

    42. Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period [Day 1 to Day 729]

      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

    43. Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period [Day 1 to Day 729]

      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

    44. Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period [Day 365, Day 729]

      Participants who experienced a positive antibody response relative to baseline (ECL Assay)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Of Alabama At Birmingham (Uab) Birmingham Alabama United States 35294
    2 Valerius Med Group & Res Ctr Of Greater Long Beach, Inc. Long Beach California United States 90806
    3 East Bay Rheumatology Medical Group, Inc. San Leandro California United States 94578
    4 University Of Connecticut Health Center Farmington Connecticut United States 06030
    5 University Of Miami Miller School Of Medicine Miami Florida United States 33136
    6 Integral Rheumatology & Immunology Specialists Plantation Florida United States 33324
    7 Emory University. Atlanta Georgia United States 30303
    8 Rush University Medical Center Chicago Illinois United States 60612
    9 Ochsner Clinic Foundation Baton Rouge Louisiana United States 70809
    10 Tulane University School Of Medicine New Orleans Louisiana United States 70112
    11 Brigham & Women'S Hospital Boston Massachusetts United States 02115
    12 Boston University Medical Center Boston Massachusetts United States 02118
    13 Local Institution Camden New Jersey United States 08103
    14 Suny Downstate Medical Center Brooklyn New York United States 11203-2056
    15 Northshore Lij Health System Great Neck New York United States 11021
    16 The Feinstein Institute For Medical Research Manhasset New York United States 11030
    17 Hospital For Special Surgery New York New York United States 10021-4892
    18 Local Institution New York New York United States 10032
    19 University Of North Carolina At Chapel Hill Chapel Hill North Carolina United States 27599
    20 Shanahan Rheum & Immunotherapy, PLLC Raleigh North Carolina United States 27617
    21 MetroHealth Medical Center Cleveland Ohio United States 44109
    22 Paramount Medical Research & Consulting, Llc Middleburg Heights Ohio United States 44130
    23 Rheumatology Consultants Pllc Knoxville Tennessee United States 37909-1907
    24 UT Southwestern Medical Center Dallas Texas United States 75390
    25 University Of Utah Hospital Salt Lake City Utah United States 84112
    26 Local Institution Charlottesville Virginia United States 22908
    27 Organizacion Medica De Investigacion S.A. (Omi) Capital Federal Buenos Aires Argentina 1015
    28 Local Institution Capital Federal Buenos Aires Argentina 1431
    29 Local Institution Buenos Aires Argentina 1181
    30 Hospital Privado-Centro Medico De Cordoba S.A. Cordoba Argentina 5016
    31 Local Institution Adelaide South Australia Australia 5000
    32 Local Institution Parkville Victoria Australia 3050
    33 Local Institution Perth Western Australia Australia 6009
    34 Local Institution Savaldor Bahia Brazil 40150-150
    35 Local Institution Goiania Goias Brazil 74110-120
    36 Local Institution Belo Horizonte Minas Gerais Brazil 30150-320
    37 Local Institution Juiz De Fora Minas Gerais Brazil 36010-570
    38 Local Institution Uberlandia Minas Gerais Brazil 38400-902
    39 Local Institution Porto Alegre Rio Grande Do Sul Brazil 91610000
    40 Local Institution Sao Paulo Brazil 01323-900
    41 Local Institution Mississauga Ontario Canada L5M 2V8
    42 Local Institution Toronto Ontario Canada M5T 2S8
    43 Local Institution Santiago De Chile Metropolitana Chile 8360156
    44 Local Institution Santiago Metropolitana Chile 8330024
    45 Local Institution Independencia Santiago Chile
    46 Local Institution Vina Del Mar Valparaiso Chile 2570017
    47 Local Institution Beijing Beijing China 100034
    48 Local Institution Beijing Beijing China 100044
    49 Local Institution Guangzhou Guangdong China 510080
    50 Local Institution Haikou Hainan China 570311
    51 Local Institution Wuhan Hebei China 430030
    52 Local Institution Harbin Heilongjiang China 150001
    53 Local Institution Zhengzhou Henan China 450004
    54 Local Institution Wuxi Jiangsu China 214023
    55 Local Institution Nanchang Jiangxi China
    56 Local Institution Xian Shan1xi China 710054
    57 Local Institution Shanghai Shanghai China 200032
    58 Local Institution Chengdu Sichuan China 610041
    59 Local Institution Hangzhou Zhejiang China 310003
    60 Local Institution Beijing China 100029
    61 Local Institution Chong Qing China 400010
    62 Local Institution Guangzhou China
    63 Local Institution Nanchang China 330006
    64 Local Institution Nanning China 530000
    65 Local Institution Shanghai China 200001
    66 Local Institution Shanghai China 200025
    67 Local Institution Shanghai China
    68 Local Institution Xi'An China
    69 Riesgo De Fractura S.A. Cayre Ips Bogota Cundinamarca Colombia
    70 Servimed E.U Bucaramanga Santander Colombia
    71 Clinica De La Costa Barranquilla Colombia XXXXXX
    72 Circaribe S.A.S Barranquilla Colombia
    73 Hospital Universitario San Ignacio Bogota Colombia
    74 Hospital Pablo Tobon Uribe Medellin Colombia MEDELLIN
    75 Local Institution Praha 2 Czechia 128 50
    76 Local Institution Hong Kong Hong Kong
    77 Local Institution Secunderabad Andhra Pradesh India 500003
    78 Local Institution Ahmedabad Gujrat India 380052
    79 Local Institution Gurgaon India 122001
    80 Local Institution Hyderabad India 500004
    81 Local Institution Lucknow- India 226018
    82 Local Institution New Delhi India 110029
    83 Local Institution Haifa Israel 31048
    84 Local Institution Haifa Israel 31096
    85 Local Institution Ramat-gan Israel
    86 Local Institution Tel Aviv Israel 64239
    87 Local Institution Brescia Italy 25123
    88 Local Institution Milano Italy 20122
    89 Local Institution Padova Italy 35128
    90 Local Institution Reggio Emilia Italy 42100
    91 Local Institution Torino Italy 10128
    92 Local Institution Nagakute-shi Aichi Japan 4801195
    93 Local Institution Nagoya-shi Aichi Japan 4668560
    94 Local Institution Chiba-shi Chiba Japan 2608677
    95 Local Institution Fukuoka-shi Fukuoka Japan 8108563
    96 Local Institution Kitakyushu-shi Fukuoka Japan 8078555
    97 Local Institution Maebashi-shi Gunma Japan 3718511
    98 Local Institution Sapporo-shi Hokkaido Japan 0608604
    99 Local Institution Sapporo-shi Hokkaido Japan
    100 Local Institution Kanazawa-shi Ishikawa Japan 9208641
    101 Local Institution Yokohama-shi Kanagawa Japan 2360004
    102 Local Institution Sendai-shi Miyagi Japan 9808574
    103 Local Institution Nagasaki-shi Nagasaki Japan 8528501
    104 Local Institution Niigata-shi Niigata Japan 9518520
    105 Local Institution Okayama-shi Okayama Japan 7008558
    106 Local Institution Iruma-gun Saitama Japan 3500495
    107 Local Institution Shimotsuke-shi Tochigi Japan 3290498
    108 Local Institution Bunkyo-ku Tokyo Japan 1138431
    109 Local Institution Bunkyo-ku Tokyo Japan 1138519
    110 Local Institution Chuo-ku Tokyo Japan 1048560
    111 Local Institution Fuchu Tokyo Japan 1838524
    112 Local Institution Ota-ku Tokyo Japan 1438541
    113 Local Institution Shinjuku-Ku Tokyo Japan 1608582
    114 Local Institution Kita-gun Japan 7610793
    115 Local Institution Osaka Japan 5308480
    116 Local Institution Daegu Korea, Republic of 41944
    117 Local Institution Seoul Korea, Republic of 06591
    118 Local Institution Seoul Korea, Republic of 07345
    119 Local Institution Mexico City Distrito Fededral Mexico 11850
    120 Hospital De Jesus Mexico City Distrito Federal Mexico 06090
    121 Hospital General De Mexico O.D. Mexico City Distrito Federal Mexico 06726
    122 Local Institution Guadalajara, Jalisco Jalisco Mexico 44160
    123 Centro De Est D Inv. Basica Y Clinica Guadalajara Jalisco Mexico 44690
    124 Centro Medico De Las Americas Merida Yucatan Mexico 97000
    125 Instituto Nacional De Ciencias Medicas Y Nutricion S.Z. Distrito Federal Mexico 14080
    126 Centro Potosino de Inv Clinica San Luis Potosi Mexico 78200
    127 Hosp Central I.Morones Prieto San Luis Potosi Mexico 78240
    128 Hospital Nacional Guillermo Almenara Irigoyen Lima Peru 13
    129 Hospital Nacional Cayetano Heredia Lima Peru LIMA 31
    130 Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac Lima Peru LIMA 33
    131 Local Institution San Juan Puerto Rico 00927
    132 Local Institution Bucharest Romania 011192
    133 Local Institution Bucuresti Romania 010976
    134 Local Institution Bucuresti Romania 020125
    135 Local Institution Cluj-napoca Romania 400006
    136 Local Institution Iasi Romania 700503
    137 Local Institution Moscow Russian Federation 115522
    138 Local Institution St. Petersburg Russian Federation 197341
    139 Local Institution Ufa Russian Federation 450005
    140 Local Institution Madrid Spain 28007
    141 Local Institution Madrid Spain 28041
    142 Local Institution Kaohsiung Taiwan 80756
    143 Local Institution Kaohsiung Taiwan 833
    144 Local Institution Taichung Taiwan 40447
    145 Local Institution Taichung Taiwan 40705
    146 Local Institution Taipei Taiwan 10051
    147 Local Institution Taoyuan Taiwan 333
    148 Local Institution Antalya Turkey 07070
    149 Local Institution Edirne Turkey 22030

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01714817
    Other Study ID Numbers:
    • IM101-291
    • 2012-000714-11
    First Posted:
    Oct 26, 2012
    Last Update Posted:
    Feb 26, 2021
    Last Verified:
    Feb 1, 2021
    Additional relevant MeSH terms:
    Nephritis
    Lupus Nephritis
    Mycophenolic Acid
    Prednisone
    Abatacept

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Overall, 695 participants were enrolled; 406 randomized; and 405 received treatment. 289 participants were screen failures and never treated with study medication; 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.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Period Title: Year 1 Period
    STARTED 203 203
    Treated 202 203
    COMPLETED 155 161
    NOT COMPLETED 48 42
    Period Title: Year 1 Period
    STARTED 155 161
    COMPLETED 129 123
    NOT COMPLETED 26 38
    Period Title: Year 1 Period
    STARTED 129 123
    COMPLETED 62 53
    NOT COMPLETED 67 70

    Baseline Characteristics

    Arm/Group Title Abatacept IV Placebo IV Total
    Arm/Group 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 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 Total of all reporting groups
    Overall Participants 202 203 405
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    33.1
    (10.75)
    33.2
    (10.48)
    33.1
    (10.60)
    Sex: Female, Male (Count of Participants)
    Female
    182
    90.1%
    178
    87.7%
    360
    88.9%
    Male
    20
    9.9%
    25
    12.3%
    45
    11.1%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    71
    35.1%
    74
    36.5%
    145
    35.8%
    African American
    15
    7.4%
    15
    7.4%
    30
    7.4%
    Caucasian
    85
    42.1%
    71
    35%
    156
    38.5%
    Other
    31
    15.3%
    43
    21.2%
    74
    18.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
    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.
    Time Frame Day 365

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Number [Percentage]
    35.1
    33.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7264
    Comments
    Method Stratified logistic regression
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.08
    Confidence Interval (2-Sided) 95%
    0.7077 to 1.6421
    Parameter Dispersion Type:
    Value:
    Estimation Comments Abatacept IV:Placebo IV 95%CI for Odds Ratio
    2. Secondary Outcome
    Title Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
    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.
    Time Frame Day 365

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated nephrotic participants. Nephrotic is defined as screening UPCR >= 3.0mg/mg (>=339mg/mmol)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 100 88
    Number [Percentage]
    27
    29.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.4148 to 1.5956
    Parameter Dispersion Type:
    Value:
    Estimation Comments Abatacept IV:Placebo IV
    3. Secondary Outcome
    Title Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants
    Description Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in nephrotic participants
    Time Frame Baseline and Day 365

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated nephrotic participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 76 68
    Mean (Standard Error) [UPCR (mg/mg)]
    -5.01
    (0.33)
    -4.84
    (0.35)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.571
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted mean difference
    Estimated Value -0.17
    Confidence Interval (2-Sided) 95%
    -0.76 to 0.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments Adjusted mean difference from placebo
    4. Secondary Outcome
    Title Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population
    Description Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population
    Time Frame Day 1 and Day 365

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 157 163
    Mean (Standard Error) [UPCR (mg/mg)]
    -2.99
    (0.17)
    -2.90
    (0.16)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.561
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted mean difference
    Estimated Value -0.09
    Confidence Interval (2-Sided) 95%
    -0.41 to 0.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments Adjusted mean difference from placebo
    5. Secondary Outcome
    Title Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period
    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.
    Time Frame Day 1 to Day 365

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 157 161
    Mean (95% Confidence Interval) [Scores on a Scale]
    -8.22
    -7.60
    6. Secondary Outcome
    Title Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period
    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.
    Time Frame From Day 1 up to 56 days post last dose in Year 1 of the double-blind period

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Participants with Adverse Events
    188
    93.1%
    194
    95.6%
    Participants with Serious Adverse Events
    49
    24.3%
    39
    19.2%
    Participants with infection Adverse Events
    150
    74.3%
    147
    72.4%
    Participants with malignancies
    2
    1%
    1
    0.5%
    Participants with autoimmune events
    10
    5%
    9
    4.4%
    Participants with peri-infusional Adverse Events
    7
    3.5%
    9
    4.4%
    Participants with acute infusional Adverse Events
    2
    1%
    4
    2%
    7. Secondary Outcome
    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
    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
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants. Year 1 data based on all elements of clinical response definition: UPCR, eGFR and cellular casts. Study terminated and Year 2 data based on only two clinical response definition elements: UPCR and eGFR. Data presented for the "as observed" population (those that completed Day 729).
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    CR - Day 365
    35.1
    33.5
    PR - Day 365
    20.8
    21.7
    NR - Day 365
    44.1
    44.8
    CR - Day 729
    60.7
    53.6
    PR - Day 729
    25.9
    22.7
    NR - Day 729
    13.4
    23.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments CR - Day 365
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference
    Estimated Value 1.6510
    Confidence Interval (2-Sided) 95%
    -7.595828 to 10.897784
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Abatacept IV
    Comments PR - Day 365
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference
    Estimated Value -0.8828
    Confidence Interval (2-Sided) 95%
    -8.848056 to 7.082461
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments NR - Day 365
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference
    Estimated Value -0.7682
    Confidence Interval (2-Sided) 95%
    -10.446714 to 8.910353
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Median Time to Complete Renal Response During the Double-blind Period in All Participants
    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.
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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. 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.
    Measure Participants 202 203
    Day 365
    280.0
    309.0
    Day 729
    170.0
    282.0
    9. Secondary Outcome
    Title Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants
    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.
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated nephrotic participants, as observed, calculated per modified criteria (UPCR and eGFR only); Nephrotic is defined as screening UPCR >= 3.0 mg/mg (>=339mg/mmol)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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.
    Measure Participants 100 88
    Day 365
    366.0
    368.0
    Day 729
    365.0
    368.0
    10. Secondary Outcome
    Title Median Time to Partial Renal Response During the Double-blind Period in All Participants
    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
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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. 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.
    Measure Participants 202 203
    Day 365
    226.0
    253.0
    Day 729
    59.0
    58.0
    11. Secondary Outcome
    Title Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants
    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
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated nephrotic participants, as observed, calculated per modified criteria (UPCR and eGFR only); Nephrotic is defined as screening UPCR >= 3.0 mg/mg (>=339mg/mmol)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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. 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.
    Measure Participants 100 88
    Day 365
    225.0
    196.0
    Day 729
    58.5
    56.0
    12. Secondary Outcome
    Title Adjusted Mean Change From Baseline in UPCR Over Time
    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.
    Time Frame Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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. 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
    Measure Participants 157 163
    Day 365
    -2.95
    (0.17)
    -2.68
    (0.17)
    Day 729
    -3.13
    (0.18)
    -2.72
    (0.18)
    13. Secondary Outcome
    Title Median Percent Change From Baseline in UPCR Over Time
    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. % Change from Baseline = (post baseline - baseline value) / baseline value x 100
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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. 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
    Measure Participants 202 203
    Day 365
    -83.77
    -84.12
    Day 729
    -89.83
    -87.28
    14. Secondary Outcome
    Title Adjusted Mean Change From Baseline in eGFR Over Time
    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.
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Day 365
    6.85
    5.85
    Day 729
    7.20
    7.91
    15. Secondary Outcome
    Title Median Time to First Sustained Change to No Response During the Double-blind Period
    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
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Day 365
    NA
    NA
    Day 729
    NA
    NA
    16. Secondary Outcome
    Title Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period
    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.
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Day 365
    5
    2.5%
    3
    1.5%
    Day 729
    52
    25.7%
    56
    27.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority
    Comments Day 365
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.43
    Confidence Interval (2-Sided) 95%
    0.3251 to 6.2849
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority
    Comments Day 729
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference vs Drug
    Estimated Value 3.4
    Confidence Interval (2-Sided) 95%
    -8.4 to 15.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period
    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. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome.
    Time Frame Day 1 to Day 729; Day 365 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Day 1 to Day 729
    -9.31
    (0.56)
    -8.53
    (0.56)
    Day 365 to Day 729
    -0.95
    (0.538)
    -0.40
    (0.530)
    18. Secondary Outcome
    Title Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion
    Description Trough level serum concentration of abatacept prior to the administration of the IV infusion on Days 1 to 365
    Time Frame Days 1 to 365

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during Year 1 of the double-blind period.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 189 0
    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)
    19. Secondary Outcome
    Title Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV
    Description Cmax: Maximum observed serum concentration following participants receiving active abatacept IV
    Time Frame at 1 hour post Day 1 dose and 30 minutes post Day 337 dose

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during Year 1 of the double-blind period
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 185 0
    Day 1
    527.43
    (59.6)
    Day 337
    203.51
    (30.6)
    20. Secondary Outcome
    Title AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval
    Description AUC (TAU): Area under the serum concentration time curve over a dosing interval between Days 337 to 365.
    Time Frame Days 337 to 365

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during Year 1 of the double-blind period
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 106 0
    Geometric Mean (Geometric Coefficient of Variation) [ug*h/mL]
    36480.24
    (29.2)
    21. Secondary Outcome
    Title Summary Statistics for Systolic Blood Pressure
    Description Summary statistics for systolic blood pressure
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    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, end of observation
    108.6
    (13.29)
    114.2
    (14.51)
    22. Secondary Outcome
    Title Summary Statistics for Diastolic Blood Pressure
    Description Summary statistics for diastolic blood pressure
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    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, end of observation
    67.5
    (9.60)
    72.7
    (9.45)
    23. Secondary Outcome
    Title Summary Statistics for Heart Rate
    Description Summary statistics for Heart Rate
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    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, end of observation
    76.2
    (11.69)
    76.7
    (10.36)
    24. Secondary Outcome
    Title Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L)
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    ALANINE AMINOTRANSFERASE (ALT) (U/L)
    -2.2
    -3.4
    ALKALINE PHOSPHATASE (ALP) (U/L)
    8.2
    11.7
    ASPARTATE AMINOTRANSFERASE (AST) (U/L)
    0.3
    0.3
    G-GLUTAMYL TRANSFERASE (GGT) (U/L)
    -5.3
    -4.1
    25. Secondary Outcome
    Title Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L)
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    ALBUMIN (g/L)
    9.2
    8.1
    HEMOGLOBIN (g/L)
    8.8
    9.0
    PROTEIN, TOTAL (g/L)
    9.9
    10.1
    26. Secondary Outcome
    Title Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood)
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    Mean (95% Confidence Interval) [Percentage]
    0.0328
    0.0325
    27. Secondary Outcome
    Title Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L)
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    BILIRUBIN, TOTAL (umol/L)
    1.77
    1.00
    CREATININE (umol/L)
    -5.6
    -6.2
    28. Secondary Outcome
    Title Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L)
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    BLOOD UREA NITROGEN (mmol/L)
    -2.31
    -2.25
    CALCIUM, TOTAL (mmol/L)
    0.097
    0.108
    CHLORIDE, SERUM (mmol/L)
    -1.1
    -0.5
    GLUCOSE, SERUM (mmol/L)
    -0.23
    -0.58
    PHOSPHORUS, INORGANIC (mmol/L)
    -0.077
    -0.037
    POTASSIUM, SERUM (mmol/L)
    -0.02
    -0.10
    SODIUM, SERUM (mmol/L)
    -0.2
    -0.5
    29. Secondary Outcome
    Title Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L)
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants with both post-baseline and baseline measurements
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    EOSINOPHILS (ABSOLUTE) (x10^9 cells/L)
    0.034
    0.010
    LYMPHOCYTES (ABSOLUTE) (x10^9 cells/L)
    0.141
    -0.149
    MONOCYTES (ABSOLUTE) (x10^9 cells/L)
    -0.018
    -0.050
    NEUTROPHILS (ABSOLUTE) (x10^9 cells/L)
    -2.259
    -2.289
    PLATELET COUNT (x10^9 cells/L)
    -4.9
    -9.1
    30. Secondary Outcome
    Title Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period
    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
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All treated participants NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    HEMOGLOBIN, low
    6
    3%
    10
    4.9%
    HEMOGLOBIN, high
    NA
    NaN
    NA
    NaN
    HEMATOCRIT, low
    12
    5.9%
    12
    5.9%
    HEMATOCRIT, high
    NA
    NaN
    NA
    NaN
    ERYTHROCYTES, low
    7
    3.5%
    10
    4.9%
    ERYTHROCYTES, high
    NA
    NaN
    NA
    NaN
    PLATELET COUNT, low
    4
    2%
    3
    1.5%
    PLATELET COUNT, high
    0
    0%
    0
    0%
    LEUKOCYTES, low
    35
    17.3%
    21
    10.3%
    LEUKOCYTES, high
    29
    14.4%
    25
    12.3%
    EOSINOPHILS (ABSOLUTE), low
    NA
    NaN
    NA
    NaN
    EOSINOPHILS (ABSOLUTE), high
    2
    1%
    6
    3%
    BASOPHILS (ABSOLUTE), low
    NA
    NaN
    NA
    NaN
    BASOPHILS (ABSOLUTE), high
    1
    0.5%
    1
    0.5%
    MONOCYTES (ABSOLUTE), low
    NA
    NaN
    NA
    NaN
    MONOCYTES (ABSOLUTE), high
    0
    0%
    1
    0.5%
    LYMPHOCYTES (ABSOLUTE), low
    81
    40.1%
    104
    51.2%
    LYMPHOCYTES (ABSOLUTE), high
    1
    0.5%
    2
    1%
    31. Secondary Outcome
    Title Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period
    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
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All treated participants NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    ALKALINE PHOSPHATASE (ALP), low
    NA
    NaN
    NA
    NaN
    ALKALINE PHOSPHATASE (ALP), high
    1
    0.5%
    1
    0.5%
    ASPARTATE AMINOTRANSFERASE (AST), low
    NA
    NaN
    NA
    NaN
    ASPARTATE AMINOTRANSFERASE (AST), high
    5
    2.5%
    0
    0%
    ALANINE AMINOTRANSFERASE (ALT), low
    NA
    NaN
    NA
    NaN
    ALANINE AMINOTRANSFERASE (ALT), high
    8
    4%
    2
    1%
    G-GLUTAMYL TRANSFERASE (GGT), low
    NA
    NaN
    NA
    NaN
    G-GLUTAMYL TRANSFERASE (GGT), high
    17
    8.4%
    15
    7.4%
    BILIRUBIN, TOTAL, low
    NA
    NaN
    NA
    NaN
    BILIRUBIN, TOTAL, high
    0
    0%
    0
    0%
    BILIRUBIN, DIRECT, low
    NA
    NaN
    NA
    NaN
    BILIRUBIN, DIRECT, high
    0
    0%
    0
    0%
    BLOOD UREA NITROGEN, low
    NA
    NaN
    NA
    NaN
    BLOOD UREA NITROGEN, high
    20
    9.9%
    12
    5.9%
    CREATININE, low
    NA
    NaN
    NA
    NaN
    CREATININE, high
    24
    11.9%
    20
    9.9%
    32. Secondary Outcome
    Title Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period
    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
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    SODIUM, SERUM, low
    1
    0.5%
    1
    0.5%
    SODIUM, SERUM, high
    2
    1%
    2
    1%
    POTASSIUM, SERUM, low
    3
    1.5%
    5
    2.5%
    POTASSIUM, SERUM, high
    7
    3.5%
    7
    3.4%
    CHLORIDE, SERUM, low
    0
    0%
    1
    0.5%
    CHLORIDE, SERUM, high
    0
    0%
    0
    0%
    CALCIUM, TOTAL, low
    1
    0.5%
    1
    0.5%
    CALCIUM, TOTAL, high
    2
    1%
    0
    0%
    PHOSPHORUS, INORGANIC, low
    9
    4.5%
    7
    3.4%
    PHOSPHORUS, INORGANIC, high
    13
    6.4%
    13
    6.4%
    33. Secondary Outcome
    Title Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period
    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
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All treated participants N = the number of participants with at least 1 on treatment lab result for each analyte NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    PROTEIN, URINE, low
    NA
    NaN
    NA
    NaN
    PROTEIN, URINE, high
    0
    0%
    0
    0%
    GLUCOSE, URINE, low
    NA
    NaN
    NA
    NaN
    GLUCOSE, URINE, high
    0
    0%
    0
    0%
    BLOOD, URINE, low
    NA
    NaN
    NA
    NaN
    BLOOD, URINE, high
    0
    0%
    0
    0%
    Red blood cells (RBC), URINE, low
    NA
    NaN
    NA
    NaN
    Red blood cells (RBC), URINE, high
    93
    46%
    103
    50.7%
    White blood cells (WBC), URINE, low
    NA
    NaN
    NA
    NaN
    White blood cells (WBC), URINE, high
    91
    45%
    98
    48.3%
    34. Secondary Outcome
    Title Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period
    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
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All treated participants NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    GLUCOSE, SERUM, low
    33
    16.3%
    29
    14.3%
    GLUCOSE, SERUM, high
    10
    5%
    5
    2.5%
    PROTEIN, TOTAL, low
    44
    21.8%
    26
    12.8%
    PROTEIN, TOTAL, high
    0
    0%
    1
    0.5%
    ALBUMIN, low
    10
    5%
    11
    5.4%
    ALBUMIN, high
    NA
    NaN
    NA
    NaN
    35. Secondary Outcome
    Title Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension
    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.
    Time Frame From the first dose in Year 2 of the double-blind period up to 56 days post last dose

    Outcome Measure Data

    Analysis Population Description
    All treated participants in Year 2
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    Participants with Adverse Events
    127
    62.9%
    137
    67.5%
    Participants with Serious Adverse Events
    15
    7.4%
    25
    12.3%
    Participants with infection Adverse Events
    100
    49.5%
    107
    52.7%
    Participants with malignancies
    0
    0%
    1
    0.5%
    Participants with autoimmune events
    7
    3.5%
    11
    5.4%
    36. Secondary Outcome
    Title Percentage of Participants in Treatment Failure Over Time During the Double-blind Period
    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.
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Lupus treatment failure (LTF) - Day 365
    3.5
    4.4
    Overall treatment failure (OTF) - Day 365
    4.5
    4.9
    LTF - Day 729
    4.5
    5.3
    OTF - Day 729
    5.2
    8.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments Lupus treatment failure - Day 365
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference
    Estimated Value -0.9682
    Confidence Interval (2-Sided) 95%
    -4.760178 to 2.823876
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Abatacept IV
    Comments Overall treatment failure - Day 365
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference
    Estimated Value -0.4707
    Confidence Interval (2-Sided) 95%
    -4.588691 to 3.647365
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority
    Comments Lupus treatment failure - Day 729
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference
    Estimated Value 0.8
    Confidence Interval (2-Sided) 95%
    -4.5 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
    Comments
    Type of Statistical Test Superiority
    Comments Overall treatment failure - Day 729
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Estimate of Difference
    Estimated Value 2.7
    Confidence Interval (2-Sided) 95%
    -3.3 to 8.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    37. Secondary Outcome
    Title Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period
    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
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    First treatment failure (FTF) - Day 365
    NA
    NA
    Overall treatment failure (OTF) - Day 365
    NA
    NA
    FTF - Day 729
    NA
    NA
    OTF - Day 729
    NA
    NA
    38. Secondary Outcome
    Title Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated nephrotic participants, as observed, calculated per modified criteria (UPCR and eGFR only). Nephrotic is defined as screening UPCR >= 3.0mg/mg (>=339mg/mmol)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 62 51
    Number [Percentage]
    50.0
    49.0
    39. Secondary Outcome
    Title Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period
    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.
    Time Frame Day 729

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 134 131
    Number [Percentage]
    61.9
    52.7
    40. Secondary Outcome
    Title Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period
    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
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    HEMOGLOBIN, low
    8
    4%
    9
    4.4%
    HEMOGLOBIN, high
    NA
    NaN
    NA
    NaN
    HEMATOCRIT, low
    6
    3%
    2
    1%
    HEMATOCRIT, high
    NA
    NaN
    NA
    NaN
    ERYTHROCYTES, low
    4
    2%
    2
    1%
    ERYTHROCYTES, high
    NA
    NaN
    NA
    NaN
    PLATELET COUNT, low
    2
    1%
    4
    2%
    PLATELET COUNT, high
    1
    0.5%
    0
    0%
    LEUKOCYTES, low
    19
    9.4%
    24
    11.8%
    LEUKOCYTES, high
    3
    1.5%
    5
    2.5%
    EOSINOPHILS (ABSOLUTE), low
    NA
    NaN
    NA
    NaN
    EOSINOPHILS (ABSOLUTE), high
    11
    5.4%
    6
    3%
    BASOPHILS (ABSOLUTE), low
    NA
    NaN
    NA
    NaN
    BASOPHILS (ABSOLUTE), high
    0
    0%
    0
    0%
    MONOCYTES (ABSOLUTE), low
    NA
    NaN
    NA
    NaN
    MONOCYTES (ABSOLUTE), high
    0
    0%
    0
    0%
    LYMPHOCYTES (ABSOLUTE), low
    43
    21.3%
    62
    30.5%
    LYMPHOCYTES (ABSOLUTE), high
    0
    0%
    0
    0%
    41. Secondary Outcome
    Title Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period
    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
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    ALKALINE PHOSPHATASE (ALP), low
    NA
    NaN
    NA
    NaN
    ALKALINE PHOSPHATASE (ALP), high
    4
    2%
    0
    0%
    ASPARTATE AMINOTRANSFERASE (AST), low
    NA
    NaN
    NA
    NaN
    ASPARTATE AMINOTRANSFERASE (AST), high
    2
    1%
    3
    1.5%
    ALANINE AMINOTRANSFERASE (ALT), low
    NA
    NaN
    NA
    NaN
    ALANINE AMINOTRANSFERASE (ALT), high
    4
    2%
    3
    1.5%
    G-GLUTAMYL TRANSFERASE (GGT), low
    NA
    NaN
    NA
    NaN
    G-GLUTAMYL TRANSFERASE (GGT), high
    17
    8.4%
    11
    5.4%
    BILIRUBIN, TOTAL, low
    NA
    NaN
    NA
    NaN
    BILIRUBIN, TOTAL, high
    0
    0%
    0
    0%
    BILIRUBIN, DIRECT, low
    NA
    NaN
    NA
    NaN
    BILIRUBIN, DIRECT, high
    1
    0.5%
    0
    0%
    BLOOD UREA NITROGEN, low
    NA
    NaN
    NA
    NaN
    BLOOD UREA NITROGEN, high
    10
    5%
    9
    4.4%
    CREATININE, low
    NA
    NaN
    NA
    NaN
    CREATININE, high
    17
    8.4%
    16
    7.9%
    42. Secondary Outcome
    Title Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period
    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
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    SODIUM, SERUM, low
    0
    0%
    0
    0%
    SODIUM, SERUM, high
    0
    0%
    1
    0.5%
    POTASSIUM, SERUM, low
    2
    1%
    2
    1%
    POTASSIUM, SERUM, high
    3
    1.5%
    2
    1%
    CHLORIDE, SERUM, low
    0
    0%
    1
    0.5%
    CHLORIDE, SERUM, high
    0
    0%
    0
    0%
    CALCIUM, TOTAL, low
    0
    0%
    0
    0%
    CALCIUM, TOTAL, high
    1
    0.5%
    0
    0%
    PHOSPHORUS, INORGANIC, low
    3
    1.5%
    4
    2%
    PHOSPHORUS, INORGANIC, high
    6
    3%
    3
    1.5%
    43. Secondary Outcome
    Title Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period
    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
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants N = the number of participants with at least 1 on treatment lab result for each analyte NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    PROTEIN, URINE, low
    NA
    NaN
    NA
    NaN
    PROTEIN, URINE, high
    0
    0%
    0
    0%
    GLUCOSE, URINE, low
    NA
    NaN
    NA
    NaN
    GLUCOSE, URINE, high
    0
    0%
    0
    0%
    BLOOD, URINE, low
    NA
    NaN
    NA
    NaN
    BLOOD, URINE, high
    0
    0%
    0
    0%
    Red blood cells (RBC), URINE, low
    NA
    NaN
    NA
    NaN
    Red blood cells (RBC), URINE, high
    58
    28.7%
    55
    27.1%
    White blood cells (WBC), URINE, low
    NA
    NaN
    NA
    NaN
    White blood cells (WBC), URINE, high
    46
    22.8%
    59
    29.1%
    44. Secondary Outcome
    Title Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period
    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
    Time Frame Day 1 to Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 153 160
    GLUCOSE, SERUM, low
    15
    7.4%
    24
    11.8%
    GLUCOSE, SERUM, high
    3
    1.5%
    2
    1%
    GLUCOSE, FASTING SERUM, low
    3
    1.5%
    1
    0.5%
    GLUCOSE, FASTING SERUM, high
    3
    1.5%
    1
    0.5%
    PROTEIN, TOTAL, low
    10
    5%
    7
    3.4%
    PROTEIN, TOTAL, high
    2
    1%
    3
    1.5%
    ALBUMIN, low
    4
    2%
    5
    2.5%
    ALBUMIN, high
    NA
    NaN
    NA
    NaN
    45. Secondary Outcome
    Title Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period
    Description Participants who experienced a positive antibody response relative to baseline (ECL Assay)
    Time Frame Day 365, Day 729

    Outcome Measure Data

    Analysis Population Description
    All treated participants in the immunogenicity analysis population for Year 1. Note: Study terminated, Year 2 data not collected
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    Measure Participants 202 203
    Day 365, overall
    7
    3.5%
    9
    4.4%

    Adverse Events

    Time Frame From Day 1 up to 56 days post last dose (assessed up to May 2018, approximately 66 months)
    Adverse Event Reporting Description
    Arm/Group Title Abatacept IV Placebo IV
    Arm/Group 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 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
    All Cause Mortality
    Abatacept IV Placebo IV
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/202 (3.5%) 6/203 (3%)
    Serious Adverse Events
    Abatacept IV Placebo IV
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 62/202 (30.7%) 58/203 (28.6%)
    Blood and lymphatic system disorders
    Anaemia 3/202 (1.5%) 2/203 (1%)
    Anaemia of chronic disease 0/202 (0%) 1/203 (0.5%)
    Febrile neutropenia 1/202 (0.5%) 0/203 (0%)
    Histiocytosis haematophagic 1/202 (0.5%) 0/203 (0%)
    Neutropenia 1/202 (0.5%) 0/203 (0%)
    Thrombocytopenia 1/202 (0.5%) 0/203 (0%)
    Thrombotic thrombocytopenic purpura 0/202 (0%) 1/203 (0.5%)
    Cardiac disorders
    Lupus myocarditis 1/202 (0.5%) 0/203 (0%)
    Tachycardia 0/202 (0%) 1/203 (0.5%)
    Eye disorders
    Cataract 0/202 (0%) 1/203 (0.5%)
    Gastrointestinal disorders
    Abdominal pain 0/202 (0%) 2/203 (1%)
    Abdominal pain upper 0/202 (0%) 1/203 (0.5%)
    Chronic gastritis 0/202 (0%) 1/203 (0.5%)
    Enteritis 0/202 (0%) 1/203 (0.5%)
    Food poisoning 1/202 (0.5%) 0/203 (0%)
    Gastritis 0/202 (0%) 1/203 (0.5%)
    Haematochezia 0/202 (0%) 1/203 (0.5%)
    Intestinal perforation 1/202 (0.5%) 0/203 (0%)
    Intussusception 0/202 (0%) 1/203 (0.5%)
    Upper gastrointestinal haemorrhage 0/202 (0%) 1/203 (0.5%)
    General disorders
    Chest pain 1/202 (0.5%) 0/203 (0%)
    Generalised oedema 0/202 (0%) 2/203 (1%)
    Multiple organ dysfunction syndrome 1/202 (0.5%) 0/203 (0%)
    Oedema peripheral 1/202 (0.5%) 1/203 (0.5%)
    Pyrexia 1/202 (0.5%) 0/203 (0%)
    Serositis 1/202 (0.5%) 0/203 (0%)
    Immune system disorders
    Hypogammaglobulinaemia 1/202 (0.5%) 0/203 (0%)
    Infections and infestations
    Anal abscess 1/202 (0.5%) 0/203 (0%)
    Bronchitis 0/202 (0%) 1/203 (0.5%)
    Candida infection 0/202 (0%) 1/203 (0.5%)
    Cellulitis 1/202 (0.5%) 1/203 (0.5%)
    Disseminated tuberculosis 0/202 (0%) 1/203 (0.5%)
    Encephalitis 2/202 (1%) 0/203 (0%)
    Gastroenteritis 2/202 (1%) 2/203 (1%)
    Genital herpes 2/202 (1%) 0/203 (0%)
    Herpes zoster 5/202 (2.5%) 4/203 (2%)
    Lower respiratory tract infection 1/202 (0.5%) 0/203 (0%)
    Lung infection 2/202 (1%) 0/203 (0%)
    Periorbital cellulitis 0/202 (0%) 1/203 (0.5%)
    Peritonitis 1/202 (0.5%) 0/203 (0%)
    Pneumocystis jirovecii pneumonia 2/202 (1%) 0/203 (0%)
    Pneumonia 15/202 (7.4%) 6/203 (3%)
    Pyelonephritis 0/202 (0%) 2/203 (1%)
    Respiratory syncytial virus bronchiolitis 0/202 (0%) 1/203 (0.5%)
    Salmonella bacteraemia 1/202 (0.5%) 0/203 (0%)
    Sepsis 1/202 (0.5%) 1/203 (0.5%)
    Septic shock 1/202 (0.5%) 1/203 (0.5%)
    Sinusitis 1/202 (0.5%) 1/203 (0.5%)
    Subcutaneous abscess 1/202 (0.5%) 0/203 (0%)
    Tooth abscess 0/202 (0%) 1/203 (0.5%)
    Toxoplasmosis 1/202 (0.5%) 0/203 (0%)
    Tuberculosis 1/202 (0.5%) 0/203 (0%)
    Tuberculous pleurisy 0/202 (0%) 1/203 (0.5%)
    Upper respiratory tract infection 2/202 (1%) 1/203 (0.5%)
    Urinary tract infection 1/202 (0.5%) 4/203 (2%)
    Urinary tract infection bacterial 1/202 (0.5%) 0/203 (0%)
    Viral infection 1/202 (0.5%) 0/203 (0%)
    Viral upper respiratory tract infection 0/202 (0%) 1/203 (0.5%)
    Injury, poisoning and procedural complications
    Contusion 0/202 (0%) 1/203 (0.5%)
    Overdose 1/202 (0.5%) 1/203 (0.5%)
    Radius fracture 0/202 (0%) 1/203 (0.5%)
    Tendon rupture 0/202 (0%) 1/203 (0.5%)
    Traumatic fracture 0/202 (0%) 1/203 (0.5%)
    Ulna fracture 0/202 (0%) 1/203 (0.5%)
    Investigations
    Gamma-glutamyltransferase increased 0/202 (0%) 1/203 (0.5%)
    Liver function test abnormal 0/202 (0%) 1/203 (0.5%)
    Metabolism and nutrition disorders
    Hyperkalaemia 0/202 (0%) 1/203 (0.5%)
    Hypokalaemia 1/202 (0.5%) 0/203 (0%)
    Metabolic acidosis 0/202 (0%) 1/203 (0.5%)
    Musculoskeletal and connective tissue disorders
    Foot deformity 0/202 (0%) 1/203 (0.5%)
    Myopathy 0/202 (0%) 1/203 (0.5%)
    Osteonecrosis 1/202 (0.5%) 5/203 (2.5%)
    Systemic lupus erythematosus 2/202 (1%) 2/203 (1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 0/202 (0%) 1/203 (0.5%)
    Basal cell carcinoma 0/202 (0%) 1/203 (0.5%)
    Hypergammaglobulinaemia benign monoclonal 1/202 (0.5%) 0/203 (0%)
    Malignant neoplasm of conjunctiva 1/202 (0.5%) 0/203 (0%)
    Myelofibrosis 1/202 (0.5%) 0/203 (0%)
    Thyroid cancer 1/202 (0.5%) 0/203 (0%)
    Nervous system disorders
    Cerebral infarction 0/202 (0%) 1/203 (0.5%)
    Embolic stroke 0/202 (0%) 1/203 (0.5%)
    Encephalopathy 0/202 (0%) 1/203 (0.5%)
    Headache 2/202 (1%) 0/203 (0%)
    Idiopathic intracranial hypertension 0/202 (0%) 1/203 (0.5%)
    Lupus encephalitis 1/202 (0.5%) 0/203 (0%)
    Presyncope 0/202 (0%) 1/203 (0.5%)
    Seizure 1/202 (0.5%) 0/203 (0%)
    Sensory loss 0/202 (0%) 1/203 (0.5%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 3/202 (1.5%) 0/203 (0%)
    Psychiatric disorders
    Depression 1/202 (0.5%) 0/203 (0%)
    Psychogenic seizure 0/202 (0%) 1/203 (0.5%)
    Substance-induced psychotic disorder 1/202 (0.5%) 0/203 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/202 (0.5%) 2/203 (1%)
    Azotaemia 0/202 (0%) 1/203 (0.5%)
    Chronic kidney disease 0/202 (0%) 1/203 (0.5%)
    Lupus nephritis 4/202 (2%) 2/203 (1%)
    Renal failure 1/202 (0.5%) 0/203 (0%)
    Renal impairment 2/202 (1%) 1/203 (0.5%)
    Reproductive system and breast disorders
    Cervical dysplasia 0/202 (0%) 2/203 (1%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 0/202 (0%) 1/203 (0.5%)
    Dyspnoea 1/202 (0.5%) 1/203 (0.5%)
    Interstitial lung disease 0/202 (0%) 2/203 (1%)
    Pleural effusion 1/202 (0.5%) 0/203 (0%)
    Pneumothorax 1/202 (0.5%) 0/203 (0%)
    Pulmonary alveolar haemorrhage 0/202 (0%) 1/203 (0.5%)
    Respiratory failure 2/202 (1%) 0/203 (0%)
    Skin and subcutaneous tissue disorders
    Skin necrosis 0/202 (0%) 1/203 (0.5%)
    Vascular disorders
    Deep vein thrombosis 0/202 (0%) 1/203 (0.5%)
    Hypertension 0/202 (0%) 1/203 (0.5%)
    Vasculitis 0/202 (0%) 1/203 (0.5%)
    Other (Not Including Serious) Adverse Events
    Abatacept IV Placebo IV
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 164/202 (81.2%) 179/203 (88.2%)
    Blood and lymphatic system disorders
    Anaemia 20/202 (9.9%) 23/203 (11.3%)
    Gastrointestinal disorders
    Abdominal pain upper 9/202 (4.5%) 14/203 (6.9%)
    Diarrhoea 47/202 (23.3%) 46/203 (22.7%)
    Nausea 13/202 (6.4%) 17/203 (8.4%)
    Vomiting 12/202 (5.9%) 7/203 (3.4%)
    General disorders
    Oedema peripheral 15/202 (7.4%) 13/203 (6.4%)
    Pyrexia 9/202 (4.5%) 13/203 (6.4%)
    Infections and infestations
    Bronchitis 18/202 (8.9%) 26/203 (12.8%)
    Conjunctivitis 14/202 (6.9%) 15/203 (7.4%)
    Gastroenteritis 12/202 (5.9%) 17/203 (8.4%)
    Herpes zoster 20/202 (9.9%) 18/203 (8.9%)
    Influenza 11/202 (5.4%) 9/203 (4.4%)
    Nasopharyngitis 40/202 (19.8%) 44/203 (21.7%)
    Pharyngitis 20/202 (9.9%) 24/203 (11.8%)
    Upper respiratory tract infection 43/202 (21.3%) 42/203 (20.7%)
    Urinary tract infection 45/202 (22.3%) 38/203 (18.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 21/202 (10.4%) 19/203 (9.4%)
    Back pain 9/202 (4.5%) 16/203 (7.9%)
    Nervous system disorders
    Dizziness 12/202 (5.9%) 5/203 (2.5%)
    Headache 24/202 (11.9%) 23/203 (11.3%)
    Psychiatric disorders
    Insomnia 13/202 (6.4%) 20/203 (9.9%)
    Respiratory, thoracic and mediastinal disorders
    Cough 25/202 (12.4%) 24/203 (11.8%)
    Skin and subcutaneous tissue disorders
    Alopecia 13/202 (6.4%) 10/203 (4.9%)
    Rash 11/202 (5.4%) 20/203 (9.9%)
    Vascular disorders
    Hypertension 7/202 (3.5%) 12/203 (5.9%)
    Hypotension 5/202 (2.5%) 13/203 (6.4%)

    Limitations/Caveats

    Study terminated early after review of Year 1 data. Only Year 2/LTE data captured within blind was analyzed. Outcomes related to renal responses were not calculated due to lack of data caused by the early termination.

    More Information

    Certain Agreements

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

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone Please email:
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01714817
    Other Study ID Numbers:
    • IM101-291
    • 2012-000714-11
    First Posted:
    Oct 26, 2012
    Last Update Posted:
    Feb 26, 2021
    Last Verified:
    Feb 1, 2021