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Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

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ClinicalTrials.gov Identifier: NCT01714817
Recruitment Status : Completed
First Posted : October 26, 2012
Results First Posted : December 21, 2017
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Lupus Nephritis
Interventions Biological: BMS-188667
Drug: Mycophenolate mofetil
Drug: Prednisone
Biological: Placebo matching with BMS-188667
Enrollment 695
Recruitment Details  
Pre-assignment Details 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
Hide 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: Overall Study
Started 203 203
Treated 202 203
Completed 155 [1] 161 [1]
Not Completed 48 42
Reason Not Completed
Lack of Efficacy             11             9
Adverse Event             20             17
Withdrawal by Subject             6             7
Death             1             1
Lost to Follow-up             0             2
Poor / non-compliance             0             1
Pregnancy             2             0
Participant no longer meets criteria             6             2
Not treated- received ACE inhibition             1             0
Change in Concomitant Medication             0             1
Need of use of Prohibited Medications             1             0
Antiproteinuric changed/dose increased             0             1
Hypersensitivity to the medication             0             1
[1]
Completed = continued study through Year 1
Arm/Group Title Abatacept IV Placebo IV Total
Hide 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 Number of Baseline Participants 202 203 405
Hide Baseline Analysis Population Description
All Randomized and Treated Subjects
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 202 participants 203 participants 405 participants
33.1  (10.75) 33.2  (10.48) 33.1  (10.60)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 202 participants 203 participants 405 participants
Female
182
  90.1%
178
  87.7%
360
  88.9%
Male
20
   9.9%
25
  12.3%
45
  11.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 202 participants 203 participants 405 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
  35.0%
156
  38.5%
Other
31
  15.3%
43
  21.2%
74
  18.3%
1.Primary Outcome
Title Percentage of Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
Hide Description Number of participants achieving CR was divided by the total number of participants in that arm and expressed as a percentage. Complete Response (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 365 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants
Arm/Group Title Abatacept IV Placebo IV
Hide 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
Overall Number of Participants Analyzed 202 203
Measure Type: Number
Unit of Measure: Percentage
35.1 33.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7264
Comments [Not Specified]
Method Stratified logistic regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.8967 to 1.5726
Estimation Comments Abatacept IV:Placebo IV 95%CI for Odds Ratio
2.Secondary Outcome
Title Percentage of Nephrotic Participants in CR of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
Hide Description Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. Nephrotic is defined as screening UPCR >=3.0 mg/mg (>=339mg/mmol). 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 365 days
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 100 88
Measure Type: Number
Unit of Measure: Percentage
27 29.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.5994 to 1.5554
Estimation Comments Abatacept IV:Placebo IV
3.Secondary Outcome
Title Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Nephrotic Participants
Hide Description Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in nephrotic participants
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized and Treated Nephrotic participants with both post-baseline and baseline measurements
Arm/Group Title Abatacept IV Placebo IV
Hide 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
Overall Number of Participants Analyzed 76 68
Mean (Standard Error)
Unit of Measure: UPCR (mg/mg)
-5.01  (0.33) -4.84  (0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.571
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.76 to 0.42
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized and Treated Participants with both post-baseline and baseline measurements
Arm/Group Title Abatacept IV Placebo IV
Hide 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
Overall Number of Participants Analyzed 157 163
Mean (Standard Error)
Unit of Measure: UPCR (mg/mg)
-2.99  (0.17) -2.90  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept IV, Placebo IV
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.561
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.41 to 0.22
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
Time Frame Day 1 to Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants
Arm/Group Title Abatacept IV Placebo IV
Hide 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
Overall Number of Participants Analyzed 157 161
Mean (95% Confidence Interval)
Unit of Measure: BILAG score
-8.22
(-9.29 to -7.16)
-7.60
(-8.66 to -6.54)
6.Secondary Outcome
Title Number of Participants With Any Adverse Events (AEs)
Hide 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 19.1). 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
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Abatacept IV Placebo IV
Hide 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
Overall Number of Participants Analyzed 202 203
Measure Type: Number
Unit of Measure: Participants
Participants with Adverse Events 188 194
Participants with Serious Adverse Events 49 39
Participants with infection Adverse Events 150 147
Participants with malignancies 2 1
Participants with autoimmune events 10 9
Participants with peri-infusional Adverse Events 7 9
Participants with acute infusional Adverse Events 2 4
7.Secondary Outcome
Title Number of Participants With Ranked Outcome of CR, PR, and No Response Throughout the Double-blind Period
Hide Description 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. Partial renal response (PR): defined as meeting ALL of the following criteria: Subject 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 (NR): defined as not meeting criteria for CR or PR or withdrawn
Time Frame Day 729
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Median Time to Complete Response (CR) During the Double-blind Period in All Participants
Hide Description The estimate of median time to Complete Response (CR) 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 729
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Median Time to Complete Response (CR) During the Double-blind Period in Nephrotic Participants
Hide Description The estimate of median time to Complete Response (CR) 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 729
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Median Time to Partial Response (PR) During the Double-blind Period in All Participants
Hide 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: Subject 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 729
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Median Time to Partial Response (PR) During the Double-blind Period in Nephrotic Participants
Hide 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: Subject 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 729
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Adjusted Mean Change From Baseline in UPCR Over Time
Hide 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 729
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Median Percent Change From Baseline in UPCR Over Time
Hide 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 729
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Adjusted Mean Change From Baseline in eGFR Over Time
Hide 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 729
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Time to First Sustained Change to No Response During the Double-blind Period
Hide 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
Time Frame Day 729
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period
Hide 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 729
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period
Hide 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.
Time Frame Day 1 to Day 729
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
As per the study protocol, this Outcome Measure was only planned to be analyzed upon the successful completion of the Primary Endpoint. Since the study failed to meet the primary endpoint, this Outcome was not analyzed.
Arm/Group Title All Treated
Hide Arm/Group Description:
all nephrotic and non-nephrotic participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during year 1 of the double-blind period
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
19.Secondary Outcome
Title Cmax: Maximum Observed Serum Concentration Following Subjects Receiving Active Abatacept IV
Hide Description Cmax: Maximum observed serum concentration following subjects receiving active abatacept IV
Time Frame at 1 hour post Day 1 dose and 30 minutes post Day 337 dose
Hide Outcome Measure Data
Hide Analysis Population Description
As per the study protocol, this Outcome Measure was only planned to be analyzed upon the successful completion of the Primary Endpoint. Since the study failed to meet the primary endpoint, this Outcome was not analyzed
Arm/Group Title All Treated
Hide Arm/Group Description:
all nephrotic and non-nephrotic participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during year 1 of the double-blind period
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
As per the study protocol, this Outcome Measure was only planned to be analyzed upon the successful completion of the Primary Endpoint. Since the study failed to meet the primary endpoint, this Outcome was not analyzed.
Arm/Group Title All Treated
Hide Arm/Group Description:
all nephrotic and non-nephrotic participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during year 1 of the double-blind period
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
21.Secondary Outcome
Title Summary Statistics for Systolic Blood Pressure
Hide Description Summary statistics for systolic blood pressure
Time Frame Day 1 to Day 729
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Summary Statistics for Diastolic Blood Pressure
Hide Description Summary statistics for diastolic blood pressure
Time Frame Day 1 to Day 729
Outcome Measure Data Not Reported
23.Secondary Outcome
Title Summary Statistics for Heart Rate
Hide Description Summary statistics for Heart Rate
Time Frame Day 1 to Day 729
Outcome Measure Data Not Reported
24.Secondary Outcome
Title Mean Change From Baseline in Laboratory Analytes During the Double-blind Period
Hide 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.
Time Frame Day 1 to Day 729
Outcome Measure Data Not Reported
25.Secondary Outcome
Title Number of Participants With Marked Hematology Laboratory Abnormalities During the Double Blind Period
Hide 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
Time Frame Day 729
Outcome Measure Data Not Reported
26.Secondary Outcome
Title Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During the Double Blind Period
Hide 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
Time Frame Day 729
Outcome Measure Data Not Reported
27.Secondary Outcome
Title Number of Participants With Marked Electrolyte Laboratory Abnormalities During the Double Blind Period
Hide 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
Time Frame Day 729
Outcome Measure Data Not Reported
28.Secondary Outcome
Title Number of Participants With Marked Urinalysis Laboratory Abnormalities During the Double Blind Period
Hide 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 729
Outcome Measure Data Not Reported
29.Secondary Outcome
Title Number of Participants With Other Marked Chemistry Laboratory Abnormalities During the Double Blind Period
Hide 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
Time Frame Day 729
Outcome Measure Data Not Reported
Time Frame From Day 1 up to 56 days post last dose in year 1 or first dose in year 2, whichever occurs first (assessed up to April 2017, approximately 51 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Abatacept IV Placebo IV
Hide 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 (%) Affected / at Risk (%)
Total   7/202 (3.47%)   5/203 (2.46%) 
Show Serious Adverse Events Hide Serious Adverse Events
Abatacept IV Placebo IV
Affected / at Risk (%) Affected / at Risk (%)
Total   49/202 (24.26%)   39/203 (19.21%) 
Blood and lymphatic system disorders     
Anaemia  1  2/202 (0.99%)  2/203 (0.99%) 
Anaemia of chronic disease  1  0/202 (0.00%)  1/203 (0.49%) 
Febrile neutropenia  1  1/202 (0.50%)  0/203 (0.00%) 
Histiocytosis haematophagic  1  1/202 (0.50%)  0/203 (0.00%) 
Neutropenia  1  1/202 (0.50%)  0/203 (0.00%) 
Thrombocytopenia  1  1/202 (0.50%)  0/203 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/202 (0.00%)  1/203 (0.49%) 
Abdominal pain upper  1  0/202 (0.00%)  1/203 (0.49%) 
Chronic gastritis  1  0/202 (0.00%)  1/203 (0.49%) 
Enteritis  1  0/202 (0.00%)  1/203 (0.49%) 
Food poisoning  1  1/202 (0.50%)  0/203 (0.00%) 
Gastritis  1  0/202 (0.00%)  1/203 (0.49%) 
Haematochezia  1  0/202 (0.00%)  1/203 (0.49%) 
Intestinal perforation  1  1/202 (0.50%)  0/203 (0.00%) 
Intussusception  1  0/202 (0.00%)  1/203 (0.49%) 
Upper gastrointestinal haemorrhage  1  0/202 (0.00%)  1/203 (0.49%) 
General disorders     
Chest pain  1  1/202 (0.50%)  0/203 (0.00%) 
Generalised oedema  1  0/202 (0.00%)  2/203 (0.99%) 
Multiple organ dysfunction syndrome  1  1/202 (0.50%)  0/203 (0.00%) 
Oedema peripheral  1  1/202 (0.50%)  1/203 (0.49%) 
Pyrexia  1  1/202 (0.50%)  0/203 (0.00%) 
Serositis  1  1/202 (0.50%)  0/203 (0.00%) 
Immune system disorders     
Hypogammaglobulinaemia  1  1/202 (0.50%)  0/203 (0.00%) 
Infections and infestations     
Anal abscess  1  1/202 (0.50%)  0/203 (0.00%) 
Bronchitis  1  0/202 (0.00%)  1/203 (0.49%) 
Candida infection  1  0/202 (0.00%)  1/203 (0.49%) 
Cellulitis  1  1/202 (0.50%)  1/203 (0.49%) 
Disseminated tuberculosis  1  0/202 (0.00%)  1/203 (0.49%) 
Encephalitis  1  2/202 (0.99%)  0/203 (0.00%) 
Gastroenteritis  1  2/202 (0.99%)  1/203 (0.49%) 
Genital herpes  1  1/202 (0.50%)  0/203 (0.00%) 
Herpes zoster  1  5/202 (2.48%)  3/203 (1.48%) 
Lower respiratory tract infection  1  1/202 (0.50%)  0/203 (0.00%) 
Lung infection  1  2/202 (0.99%)  0/203 (0.00%) 
Periorbital cellulitis  1  0/202 (0.00%)  1/203 (0.49%) 
Peritonitis  1  1/202 (0.50%)  0/203 (0.00%) 
Pneumocystis jirovecii pneumonia  1  2/202 (0.99%)  0/203 (0.00%) 
Pneumonia  1  11/202 (5.45%)  5/203 (2.46%) 
Pyelonephritis  1  0/202 (0.00%)  1/203 (0.49%) 
Salmonella bacteraemia  1  1/202 (0.50%)  0/203 (0.00%) 
Sepsis  1  1/202 (0.50%)  0/203 (0.00%) 
Septic shock  1  1/202 (0.50%)  1/203 (0.49%) 
Sinusitis  1  1/202 (0.50%)  1/203 (0.49%) 
Subcutaneous abscess  1  1/202 (0.50%)  0/203 (0.00%) 
Tooth abscess  1  0/202 (0.00%)  1/203 (0.49%) 
Toxoplasmosis  1  1/202 (0.50%)  0/203 (0.00%) 
Tuberculous pleurisy  1  0/202 (0.00%)  1/203 (0.49%) 
Upper respiratory tract infection  1  1/202 (0.50%)  1/203 (0.49%) 
Urinary tract infection  1  1/202 (0.50%)  1/203 (0.49%) 
Urinary tract infection bacterial  1  1/202 (0.50%)  0/203 (0.00%) 
Injury, poisoning and procedural complications     
Overdose  1  1/202 (0.50%)  1/203 (0.49%) 
Ulna fracture  1  0/202 (0.00%)  1/203 (0.49%) 
Investigations     
Gamma-glutamyltransferase increased  1  0/202 (0.00%)  1/203 (0.49%) 
Metabolism and nutrition disorders     
Hyperkalaemia  1  0/202 (0.00%)  1/203 (0.49%) 
Hypokalaemia  1  1/202 (0.50%)  0/203 (0.00%) 
Metabolic acidosis  1  0/202 (0.00%)  1/203 (0.49%) 
Musculoskeletal and connective tissue disorders     
Systemic lupus erythematosus  1  0/202 (0.00%)  2/203 (0.99%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  0/202 (0.00%)  1/203 (0.49%) 
Hypergammaglobulinaemia benign monoclonal  1  1/202 (0.50%)  0/203 (0.00%) 
Malignant neoplasm of conjunctiva  1  1/202 (0.50%)  0/203 (0.00%) 
Myelofibrosis  1  1/202 (0.50%)  0/203 (0.00%) 
Thyroid cancer  1  1/202 (0.50%)  0/203 (0.00%) 
Nervous system disorders     
Cerebral infarction  1  0/202 (0.00%)  1/203 (0.49%) 
Embolic stroke  1  0/202 (0.00%)  1/203 (0.49%) 
Encephalopathy  1  0/202 (0.00%)  1/203 (0.49%) 
Headache  1  1/202 (0.50%)  0/203 (0.00%) 
Lupus encephalitis  1  1/202 (0.50%)  0/203 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1  1/202 (0.50%)  0/203 (0.00%) 
Psychiatric disorders     
Depression  1  1/202 (0.50%)  0/203 (0.00%) 
Psychogenic seizure  1  0/202 (0.00%)  1/203 (0.49%) 
Substance-induced psychotic disorder  1  1/202 (0.50%)  0/203 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/202 (0.50%)  2/203 (0.99%) 
Azotaemia  1  0/202 (0.00%)  1/203 (0.49%) 
Chronic kidney disease  1  0/202 (0.00%)  1/203 (0.49%) 
Lupus nephritis  1  3/202 (1.49%)  1/203 (0.49%) 
Renal failure  1  1/202 (0.50%)  0/203 (0.00%) 
Renal impairment  1  2/202 (0.99%)  1/203 (0.49%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  0/202 (0.00%)  1/203 (0.49%) 
Dyspnoea  1  1/202 (0.50%)  1/203 (0.49%) 
Interstitial lung disease  1  0/202 (0.00%)  1/203 (0.49%) 
Pleural effusion  1  1/202 (0.50%)  0/203 (0.00%) 
Pneumonitis  1  1/202 (0.50%)  0/203 (0.00%) 
Pneumothorax  1  1/202 (0.50%)  0/203 (0.00%) 
Pulmonary alveolar haemorrhage  1  0/202 (0.00%)  1/203 (0.49%) 
Respiratory failure  1  2/202 (0.99%)  0/203 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin necrosis  1  0/202 (0.00%)  1/203 (0.49%) 
Vascular disorders     
Hypertension  1  0/202 (0.00%)  1/203 (0.49%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Abatacept IV Placebo IV
Affected / at Risk (%) Affected / at Risk (%)
Total   146/202 (72.28%)   154/203 (75.86%) 
Blood and lymphatic system disorders     
Anaemia  1  14/202 (6.93%)  11/203 (5.42%) 
Gastrointestinal disorders     
Diarrhoea  1  43/202 (21.29%)  35/203 (17.24%) 
Nausea  1  11/202 (5.45%)  13/203 (6.40%) 
General disorders     
Oedema peripheral  1  14/202 (6.93%)  12/203 (5.91%) 
Infections and infestations     
Bronchitis  1  13/202 (6.44%)  19/203 (9.36%) 
Conjunctivitis  1  9/202 (4.46%)  11/203 (5.42%) 
Herpes zoster  1  16/202 (7.92%)  14/203 (6.90%) 
Nasopharyngitis  1  24/202 (11.88%)  32/203 (15.76%) 
Pharyngitis  1  15/202 (7.43%)  11/203 (5.42%) 
Upper respiratory tract infection  1  31/202 (15.35%)  31/203 (15.27%) 
Urinary tract infection  1  30/202 (14.85%)  26/203 (12.81%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  16/202 (7.92%)  17/203 (8.37%) 
Back pain  1  4/202 (1.98%)  13/203 (6.40%) 
Nervous system disorders     
Headache  1  16/202 (7.92%)  12/203 (5.91%) 
Psychiatric disorders     
Insomnia  1  9/202 (4.46%)  14/203 (6.90%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  18/202 (8.91%)  17/203 (8.37%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  12/202 (5.94%)  7/203 (3.45%) 
Rash  1  8/202 (3.96%)  16/203 (7.88%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01714817     History of Changes
Other Study ID Numbers: IM101-291
2012-000714-11 ( EudraCT Number )
First Submitted: October 24, 2012
First Posted: October 26, 2012
Results First Submitted: November 20, 2017
Results First Posted: December 21, 2017
Last Update Posted: August 28, 2018