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Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT) (BENEFIT)

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ClinicalTrials.gov Identifier: NCT00256750
Recruitment Status : Completed
First Posted : November 22, 2005
Results First Posted : August 19, 2016
Last Update Posted : August 19, 2016
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Conditions Kidney Transplantation
Chronic Kidney Failure
Interventions Drug: Cyclosporine (CsA)
Drug: Belatacept LI (less intensive)
Drug: Belatacept MI (more intensive)
Enrollment 738
Recruitment Details  
Pre-assignment Details 738 participants enrolled, 686 randomized. Reasons for non-randomization include 5 participants withdrew consent, 1 lost to follow-up, 34 no longer met study criteria, and 12 for other non-listed reasons. 666 participants randomized, but not transplanted. 20 not transplanted; 10, 4, 6 in the CsA, Belatacept LI, Belatacept MI, respectively.
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT) Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Period Title: Transplanted Pre-Treatment
Started 221 226 219
Completed 215 226 219
Not Completed 6 0 0
Reason Not Completed
Withdrawal by Subject             3             0             0
Not Specified             2             0             0
Death             1             0             0
Period Title: Post-Transplant Treated (12 Months)
Started 215 226 219
Completed 174 183 173
Not Completed 41 43 46
Reason Not Completed
Adverse Event             20             12             8
Death             3             2             4
Lack of Efficacy             10             22             27
Lost to Follow-up             1             0             0
Not Specified             5             4             2
Withdrawal by Subject             0             3             5
Protocol Violation             2             0             0
Period Title: Post-Transplant Treated (24 Months)
Started 174 183 173
Completed 153 176 164
Not Completed 21 7 9
Reason Not Completed
Adverse Event             7             3             6
Withdrawal by Subject             5             1             0
Death             3             0             0
Lack of Efficacy             4             3             2
Not Specified             2             0             1
Period Title: Post-Transplant Treated (36 Months)
Started 153 176 164
Completed 143 170 158
Not Completed 10 6 6
Reason Not Completed
Adverse Event             5             1             2
Withdrawal by Subject             1             0             1
Death             0             2             1
Subject no longer meets study criteria             0             0             1
Lack of Efficacy             4             1             0
Protocol Violation             0             1             0
Not specified             0             1             1
Period Title: Long Term Extension (LTE; 84 Months)
Started 136 [1] 166 [2] 155 [3]
Completed 89 136 127
Not Completed 47 30 28
Reason Not Completed
Adverse Event             13             11             14
Withdrawal by Subject             5             4             1
Lost to Follow-up             4             1             1
Death             9             4             4
Lack of Efficacy             6             3             0
Poor/Non-compliance             4             1             1
Pregnancy             0             1             2
Administrative Reason By Sponsor             1             1             0
Not Specified             5             4             5
[1]
Participants on drug through month 36 eligible to enroll in LTE; 2 ineligible, 5 withdrew or refused
[2]
Participants on drug through month 36 were eligible to enroll in LTE; 4 withdrew or refused.
[3]
Participants on drug through month 36 were eligible to enroll in LTE; 3 withdrew or refused.
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI Total
Hide Arm/Group Description

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT) Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT) Total of all reporting groups
Overall Number of Baseline Participants 221 226 219 666
Hide Baseline Analysis Population Description
Baseline characteristics of transplant recipients: All randomized and transplanted participants, intent to treat (ITT) population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 221 participants 226 participants 219 participants 666 participants
43.5  (14.3) 42.6  (13.4) 43.6  (14.6) 43.2  (14.1)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 221 participants 226 participants 219 participants 666 participants
Between 18 and 45 years: 110 124 111 345
Between 46 and 65 years: 101 93 93 287
> 65 years: 10 9 15 34
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 221 participants 226 participants 219 participants 666 participants
Female
56
  25.3%
80
  35.4%
68
  31.1%
204
  30.6%
Male
165
  74.7%
146
  64.6%
151
  68.9%
462
  69.4%
Previous Number of Transplant  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 221 participants 226 participants 219 participants 666 participants
0 208 218 210 636
1 9 5 5 19
2 0 0 1 1
Missing 4 3 3 10
1.Primary Outcome
Title Percent of Participants Surviving With a Functioning Graft by Month 12
Hide Description Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss was defined as a sustained level of serum creatinine (SCr) ≥ 6.0 milligrams per deciliter (mg/dL) or 530 micromolar per liter (μmol/L) as determined by the central laboratory for ≥ 4 weeks or ≥ 56 consecutive days of dialysis or impairment of renal function to such a degree that the participant underwent retransplant.
Time Frame Day 1 to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
92.8
(89.3 to 96.2)
96.5
(94.1 to 98.9)
95.4
(92.7 to 98.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A non-inferiority margin of 10% for the co-primary endpoint of participant and graft survival was used. Determination of a margin for non-inferiority based on 'preservation of benefit' is not feasible, given the low rate of patient death and/or graft loss in the first year post-transplantation, and the absence of published, adequately sized, parallel-group trials with which to assess the effect of CsA on patient death and/or graft loss in the setting of MMF/steroids/basiliximab.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 3.7
Confidence Interval (2-Sided) 97.3%
-1.1 to 9.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A non-inferiority margin of 10% for the co-primary endpoint of participant and graft survival was used. Determination of a margin for non-inferiority based on ‘preservation of benefit’ is not feasible, given the low rate of patient death and/or graft loss in the first year post-transplantation, and the absence of published, adequately sized, parallel-group trials with which to assess the effect of CsA on patient death and/or graft loss in the setting of MMF/steroids/basiliximab.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 2.7
Confidence Interval (2-Sided) 97.3%
-2.5 to 8.1
Estimation Comments If the lower bound of the CI (belatacept-CsA) was > -10%, then the corresponding belatacept regimen was considered non-inferior to CsA.
2.Primary Outcome
Title Percent of Participants With a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or With a Decrease in mGFR Greater Than or Equal to 10 mL/Min/1.73m^2 From Month 3 to Month 12
Hide Description Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 mg/dL. A change in GFR of at least 10 mL/min/1.73 m^2 was used as the approximate change in SCr of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3.
Time Frame Month 12; Month 3 to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 213 214 209
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
77.9
(72.4 to 83.5)
54.2
(47.5 to 60.9)
55.0
(48.3 to 61.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Chi-squared, Corrected
Comments A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -23.7
Confidence Interval (2-Sided) 97.3%
-33.3 to -13.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Chi-squared, Corrected
Comments A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -22.9
Confidence Interval (2-Sided) 97.3%
-32.6 to -12.9
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12
Hide Description Acute rejection was defined as a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence was defined if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. AR was defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted.
Time Frame Day 1 to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.2
(3.8 to 10.7)
17.3
(12.3 to 22.2)
21.9
(16.4 to 27.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 10.0
Confidence Interval (2-Sided) 97.3%
3.3 to 17.1
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens. The 20% non-inferiority margin was not met in the belatacept MI group.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 14.7
Confidence Interval (2-Sided) 97.3%
7.5 to 22.2
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
4.Secondary Outcome
Title Mean Value of the Measured Glomerular Filtration Rate (mGFR)
Hide Description Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2.
Time Frame Months 3, 12, 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 201 215 209
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
Month 3 (n=201, 215, 209) 51.9  (21.09) 61.7  (25.43) 59.9  (28.47)
Month 12 (n=199, 206, 200) 50.4  (18.71) 63.4  (27.66) 65.0  (30.02)
Month 24 (n=185, 199, 192) 50.5  (20.52) 67.9  (29.90) 65.0  (27.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Time Frame = Day 1 to Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for missing measured GFR due to graft loss or death, an ANOVA model on the ranks of measured GFR (with imputed missing values) at Months 12 with factor for randomization group was applied. Measured GFR missing were assigned the worst rank.
Method Kruskal-Wallis
Comments Tests comparing a belatacept to CsA were based on the Kruskal-Wallis test (using a chi-square approximation of the distribution of the test statistic)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 13.0
Confidence Interval (2-Sided) 97.3%
7.3 to 18.7
Estimation Comments Test were conducted at a level of 0.027 (2-sided).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Time Frame = Day 1 to Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for missing measured GFR due to graft loss or death, an ANOVA model on the ranks of measured GFR (with imputed missing values) at Months 12 with factor for randomization group was applied. Measured GFR missing were assigned the worst rank.
Method Kruskal-Wallis
Comments Tests comparing a belatacept to CsA were based on the Kruskal-Wallis test (using a chi-square approximation of the distribution of the test statistic)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.6
Confidence Interval (2-Sided) 97.3%
8.9 to 20.4
Estimation Comments Test were conducted at a level of 0.027 (2-sided).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Time Frame = Day 1 to Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for missing measured GFR due to graft loss or death, an ANOVA model on the ranks of measured GFR (with imputed missing values) at Months 24 with factor for randomization group was applied. Measured GFR missing were assigned the worst rank.
Method Kruskal-Wallis
Comments Tests comparing a belatacept to CsA were based on the Kruskal-Wallis test (using a chi-square approximation of the distribution of the test statistic)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 17.4
Confidence Interval (2-Sided) 97.3%
11.5 to 23.4
Estimation Comments Test were conducted at a level of 0.027 (2-sided).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Time Frame = Day 1 to Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for missing measured GFR due to graft loss or death, an ANOVA model on the ranks of measured GFR (with imputed missing values) at Months 24 with factor for randomization group was applied. Measured GFR missing were assigned the worst rank.
Method Kruskal-Wallis
Comments Tests comparing a belatacept to CsA were based on the Kruskal-Wallis test (using a chi-square approximation of the distribution of the test statistic)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.5
Confidence Interval (2-Sided) 97.3%
8.5 to 20.5
Estimation Comments Test were conducted at a level of 0.027 (2-sided).
5.Secondary Outcome
Title Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12
Hide Description Prevalence of CAN = if participant met any of the following conditions: a: CAN observed in a biopsy either prior to 12 months (including baseline biopsy) or first post 12 months biopsy; b: participant had graft loss during the first year post transplant; c: no biopsy was available post 12 months and CAN not observed in biopsies prior to 12 months, but the measured GFR from Month 3 to Month 12 decreased at least 10 mL/min/1.73m^2; d: no biopsy available either prior to or post 12 months, and the measured GFR (incorporated missing data imputation) from Month 3 to Month 12 decreased at least 10 mL/min/1.73m^2. CAN = All allograft biopsies evaluated for presence and severity of CAN by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Onset of CAN determined by the biopsy date when it was observed.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component; Any participant not meeting CAN criteria and who has no biopsy either prior to or post 12 months and no GFR assessment (either measured or calculated) available were excluded from the analyses.
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 219 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
32.4
(26.2 to 38.6)
23.9
(18.3 to 29.5)
18.3
(13.1 to 23.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Test of superiority using DerSimonian-Laird statistic at 0.027 level of significance.
Statistical Test of Hypothesis P-Value 0.0581
Comments [Not Specified]
Method Chi-squared, Corrected
Comments A continuity corrected chi-square test at a significance level of 0.027 was performed.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -8.5
Confidence Interval (2-Sided) 97.3%
-17.9 to 0.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Test of superiority using DerSimonian-Laird statistic at 0.027 level of significance.
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Chi-squared, Corrected
Comments A continuity corrected chi-square test at a significance level of 0.027 was performed.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -14.2
Confidence Interval (2-Sided) 97.3%
-23.2 to -5.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84
Hide Description Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time Frame Randomization to Month 84
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants from the original intent-to-treat (ITT) population who continued on assigned therapy into the long-term extension phase (ITT-LTE)
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 136 166 155
Measure Type: Number
Unit of Measure: participants
Deaths 9 7 7
SAEs 107 113 117
Discontinued due to SAEs 5 8 6
Discontinued due to AEs 12 11 14
7.Secondary Outcome
Title Number of Participants With Adverse Events of Special Interest by Month 84
Hide Description Prospectively identified events of special interest which were a subset of all AEs, and were either SAEs or non-serious AEs, included the following categories: Serious Infections and Infestations, Thrombolic/embolic events, and Malignancy. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/ abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Time frame is from randomization to the event date, or to the last dose date+56, or to Month 84 (Day 2548), whichever is the earliest.
Time Frame Randomization to Month 84
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants from the original intent-to-treat (ITT) population who continued on assigned therapy into the long-term extension phase (ITT-LTE)
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 136 166 155
Measure Type: Number
Unit of Measure: participants
Malignancies 22 16 20
Cytomegalovirus (CMV) Infections 19 24 20
BK Polyoma Virus Infections 6 10 15
Herpes Virus Infections 29 37 37
Fungal Infections 42 47 55
Tuberculosis Infections 2 1 5
Central Nervous System (CNS) Infections 0 0 1
Pulmonary edema or Congestive Heart Failure 12 4 5
Auto-immune Events 8 8 6
8.Secondary Outcome
Title Mean Blood Pressure at Month 84
Hide Description Blood pressure was measured in millimeters of mercury (mmHg). Blood pressure was measured soon after the participant arrived and sat quietly at rest for 10 minutes. 3 consecutive seated blood pressure readings were made at least 1 minute apart.
Time Frame Month 84
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants from the original intent-to-treat (ITT) population who continued on assigned therapy into the long-term extension phase (ITT-LTE).
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 136 166 155
Mean (Standard Deviation)
Unit of Measure: mmHg
Diastolic Blood Pressure (n=82, 125, 112) 78.6  (11.03) 75.8  (10.56) 75.1  (10.15)
Systolic Blood Pressure (n=82, 125, 112) 129.0  (15.83) 126.7  (18.17) 126.0  (17.56)
9.Secondary Outcome
Title Number of Participants Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36
Hide Description

Upper limit of normal (ULN). Units per Liter (U/L). Cells per microliter (c/µL). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).Cells per Liter (c/L). Milliequivalents/Liter (mEq/L).

Hemoglobin (low): <8.0 g/dL; Platelet count: <50*10^9 c/L; Leukocytes: <2*10^3 c/µL; Alkaline phosphatase (ALP): >5.0*ULN U/L; Alanine aminotransferase (ALT): >5.0*ULN U/L; Asparate aminotransferase (AST): >5.0*ULN U/L; Bilirubin Total: >3.0*ULN mg/dL; Creatinine: >3.0*ULN mg/dL; Calcium Total: low if <7.0 mg/dL or high if >12.5 mg/dL; Bicarbonate: <11.0 mEq/L; Potassium serum: low if <3.0 mEq/L or high if >6.0 mEq/L; Magnesium serum: low is <0.8 mEq/L or high if >2.46 mEq/L; Sodium serum: low if <130.0 mEq/L or high if >155.0 mEq/L; Phosphorus inorganic: <2.0 mg/dL; Albumin: <2 g/dL; Uric acid: >10 mg/dL; Protein urine: >=3+

Time Frame Baseline to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants from the original intent-to-treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Unit of Measure: participants
Hemoglobin, low (n=213, 226, 219) 26 25 27
Platelet count, low (n=213, 226, 218) 0 1 0
Leukocytes, low (n=213, 226, 219) 10 5 5
Alkaline phosphatase, high (n=214, 226, 219) 1 4 0
Alanine aminotransferase, high (n=214, 226, 219) 6 6 4
Aspartate aminotransferase, high (n=214, 226, 219) 2 3 3
Bilirubin total, high (n=214, 226, 219) 1 0 0
Creatinine, high (n=213, 223, 219) 48 50 52
Calcium total, low (n=214, 226, 219) 7 8 4
Calcium total, high (n=214, 226, 219) 0 1 0
Bicarbonate, low (n=214, 226, 219) 1 0 0
Bicarbonate, high (n=214, 226, 219) 0 0 0
Potassium serum, low (n=213, 223, 219) 4 13 12
Potassium serum, high (n=213, 223, 219) 13 9 4
Magnessium serum, low (n=214, 225, 219) 1 2 1
Magnessium serum, high (n=214, 225, 219) 9 12 14
Sodium serum, low (n=214, 226, 219) 21 8 9
Sodium serum, high (n=214, 226, 219) 0 1 0
Phosphorus inorganic, low (n=213, 224, 219) 75 100 112
Albumin, low (n=214, 226, 219) 0 0 0
Uric acid, high (n=214, 226, 219) 42 7 11
Protein in urine, high (n=213, 224, 217) 33 30 36
10.Secondary Outcome
Title Percent of Participants With Development of Anti-Donor HLA Positive Antibodies by Month 84
Hide Description Only participants who had non-missing test result for Class I or Class II anti-donor HLA antibodies were included in analysis and only participants who had at least one non-NA test result or finding were counted. This was a cumulative summary (excluding baseline) and once a participant was positive, that participant remained positive for the later time point. Acute rejection (AR) defined: a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence defined: if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. AR defined as allograft biopsies of Banff 97 classification Grade IA or greater (higher scores indicate more severe rejection). Evaluated by blinded central independent pathologist.
Time Frame Randomization to Month 84
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 215 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
11.6
(7.34 to 15.91)
3.1
(0.84 to 5.36)
1.4
(0.28 to 3.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Percent treatment difference measured as Belatacept - LI minus Cyclosporine
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -8.5
Confidence Interval (2-Sided) 97.3%
-14.6 to -3.3
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Percent treatment difference measured as Belatacept - LI minus Cyclosporine
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -10.3
Confidence Interval (2-Sided) 97.3%
-16.1 to -5.1
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
11.Secondary Outcome
Title Mean Change of the Measured Glomerular Filtration Rate (mGFR) From Month 3 to Month 12 and From Month 3 to Month 24
Hide Description Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2.
Time Frame Month 3 to Month 12; Month 3 to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 195 206 200
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
Baseline (Month 3) to Month 12 (n=195, 206, 200) -1.7  (21.58) 1.2  (30.43) 4.4  (31.10)
Baseline (Month 3) to Month 24 (n=184, 199, 192) -2.0  (25.23) 5.3  (33.03) 4.2  (30.96)
12.Secondary Outcome
Title Percent of Participants With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/Min/1.73m^2 From Month 3 to Month 12
Hide Description Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A change in GFR of at least 10 mL/min/1.73 m^2 was used as the approximate change in serum creatinine (SCr) of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3. Month 3 = baseline
Time Frame Month 3 to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 213 214 209
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.2
(22.1 to 34.2)
23.4
(17.7 to 29.0)
23.0
(17.3 to 28.7)
13.Secondary Outcome
Title Percent of Participants With a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12
Hide Description Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 milligrams per deciliter (mg/dL).
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 213 214 209
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
67.6
(61.3 to 73.9)
43
(36.4 to 49.6)
43.5
(36.8 to 50.3)
14.Secondary Outcome
Title Mean Value of the Calculated Glomerular Filtration Rate (cGFR) With Imputation
Hide Description Calculated glomerular filtration rate (cGFR) was used to assess renal function (as measured by the estimated creatinine clearance) using the following modification of diet in renal disease (MDRD) formula: MDRD: GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if participant is female] x [1.180 if participant is black] x [BUN]^(-0.170) x [Alb]^(+0.318); Age in years; Alb = Albumin in g/dL; SCr = Serum creatinine in mg/dL; BUN = Blood urea nitrogen in mg/dL; cGFR = mL/min/1.73m2
Time Frame Months 6, 12, 24, 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 199 201 201
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73 m^2
Month 6 (n=189, 185, 170) 48.8  (19.22) 62.6  (20.41) 62.4  (20.94)
Month 12 (n=199, 200, 201) 50.1  (21.06) 65.4  (22.94) 65.2  (23.51)
Month 24 (n=182, 201, 191) 47.9  (23.00) 65.4  (25.22) 65.5  (24.87)
Month 36 (n=171, 190, 186) 44.4  (23.58) 65.8  (27.00) 65.2  (26.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 15.3
Confidence Interval (2-Sided) 97.3%
10.3 to 20.3
Estimation Comments ANOVA model: GFR = treatment
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 15.1
Confidence Interval (2-Sided) 97.3%
10.1 to 20.1
Estimation Comments ANOVA model: GFR = treatment
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 17.5
Confidence Interval (2-Sided) 97.3%
12.0 to 23.1
Estimation Comments ANOVA model: GFR = treatment
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 17.6
Confidence Interval (2-Sided) 97.3%
12.0 to 23.3
Estimation Comments ANOVA model: GFR = treatment
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 21.4
Confidence Interval (2-Sided) 97.3%
15.4 to 27.4
Estimation Comments ANOVA model: GFR = treatment
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 20.8
Confidence Interval (2-Sided) 97.3%
14.8 to 26.9
Estimation Comments ANOVA model: GFR = treatment
15.Secondary Outcome
Title Mean Change in Calculated Glomerular Filtration Rate (cGFR) From Month 6 to Month 12
Hide Description Calculated glomerular filtration rate (cGFR) was used to assess renal function (as measured by the estimated creatinine clearance) using the following modification of diet in renal disease (MDRD) formula: MDRD: GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if participant is female] x [1.180 if participant is black] x [BUN]^(-0.170) x [Alb]^(+0.318); Age in years; Alb = Albumin in g/dL; SCr = Serum creatinine in mg/dL; BUN = Blood urea nitrogen in mg/dL; cGFR = mL/min/1.73m^2
Time Frame Month 6 to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 166 169 160
Mean (Standard Deviation)
Unit of Measure: mL/Min/1.73 m^2
2.3  (10.09) 4.7  (11.52) 5.1  (11.37)
16.Secondary Outcome
Title Percent of Participants With Incidence of New Onset Diabetes Mellitus by Month 36
Hide Description The incidence of new onset diabetes mellitus defined as participants who developed diabetes mellitus after randomization and transplantation. Participants that did not have diabetes prior to randomization were determined to have new onset diabetes mellitus if (i) the participant received an anti-diabetic medication for a duration of at least 30 days or (ii) at least two fasting plasma glucose (FPG) tests indicate that FPG is >=126 mg/dL (7.0 mmol/L). New onset diabetes mellitus (NODM) = post-transplant diabetes mellitus (PTDM)
Time Frame Week 4 post-transplantation to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 162 168 156
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 12
9.9
(5.3 to 14.5)
4.2
(1.1 to 7.2)
7.1
(3.0 to 11.1)
Month 24
10.5
(5.8 to 15.2)
5.4
(2.0 to 8.8)
8.3
(4.0 to 12.7)
Month 36
11.1
(6.3 to 16.0)
6.5
(2.8 to 10.3)
10.3
(5.5 to 15.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0687
Comments Normal approximation is used if N>=5 in both arms. Otherwise, exact method is used.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -5.7
Confidence Interval (2-Sided) 97.3%
-12.6 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4825
Comments Normal approximation is used if N>=5 in both arms. Otherwise, exact method is used.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -2.8
Confidence Interval (2-Sided) 97.3%
-10.2 to 4.4
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1267
Comments Normal approximation is used if N>=5 in both arms. Otherwise, exact method is used.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -5.1
Confidence Interval (2-Sided) 97.3%
-12.3 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6405
Comments Normal approximation is used if N>=5 in both arms. Otherwise, exact method is used.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -2.2
Confidence Interval (2-Sided) 97.3%
-9.8 to 5.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2043
Comments [Not Specified]
Method Chi-squared
Comments Normal approximation is used if N>=5 in both arms. Otherwise, exact method is used.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -4.6
Confidence Interval (2-Sided) 97.3%
-12.0 to 2.5
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9481
Comments Normal approximation is used if N>=5 in both arms. Otherwise, exact method is used.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -0.9
Confidence Interval (2-Sided) 97.3%
-8.8 to 7.1
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Percent of Participants Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36
Hide Description This analysis was based on all participants who had been followed up at least 1092 days after transplantation. Hypertension was defined in according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for participants with chronic kidney disease. This definition was based upon SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg. In addition, all participants who had a SBP < 130 mm Hg and a DBP < 80 mm Hg who received an antihypertensive medication(s) for the indication of hypertension or with a medical history of hypertension were included in this definition. Systolic blood pressure = SBP; Diastolic blood pressure = DBP
Time Frame Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 182 199 192
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
92.9
(89.12 to 96.60)
81.9
(76.56 to 87.36)
83.9
(78.65 to 89.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.5
Confidence Interval (2-Sided) 97.3%
0.31 to 0.74
Estimation Comments Odds ratio is estimated by a cumulative logit model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0092
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.6
Confidence Interval (2-Sided) 97.3%
0.38 to 0.92
Estimation Comments Odds ratio is estimated by a cumulative logit model.
18.Secondary Outcome
Title Percent of Participants With Incidence of Hypertension Post-Transplantation at Month 12
Hide Description The incidence of hypertension was defined as the proportion of participants who developed hypertension after randomization and transplantation. Specifically, the incidence of hypertension was assessed only after the Week 4 visit. This period allowed for adequate stabilization and resolution of transient changes. If participants received antihypertensive medication for the indication of hypertension at this (or later) time point, they were considered to have developed hypertension. Hypertension was defined according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for subjects with chronic kidney disease. This definition was based upon SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg. Systolic blood pressure = SBP; Diastolic blood pressure = DBP
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 4 13 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
75.0
(19.4 to 99.4)
53.8
(26.7 to 80.9)
57.1
(18.4 to 90.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -21.2
Confidence Interval (2-Sided) 97.3%
-67.6 to 43.2
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -17.9
Confidence Interval (2-Sided) 97.3%
-72.3 to 52.2
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
19.Secondary Outcome
Title Percent of Participants With Prevalence of Hypertension Post-Transplantation at Month 12
Hide Description The prevalence of hypertension was defined as the proportion of participants at any given time who meet the definition of hypertension. Hypertension defined according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for participants with chronic kidney disease. This definition is based upon SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg. Systolic blood pressure = SBP; Diastolic blood pressure = DBP
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
91.0
(87.17 to 94.73)
89.8
(85.88 to 93.76)
88.6
(84.37 to 92.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -1.13
Confidence Interval (2-Sided) 97.3%
-7.51 to 5.23
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -2.37
Confidence Interval (2-Sided) 97.3%
-9.01 to 4.15
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
20.Secondary Outcome
Title Mean Systolic Blood Pressure and Diastolic Blood Pressure
Hide Description Blood pressure was measured in millimeters of mercury (mmHg). Blood pressure was measured soon after the participant arrived and sat quietly at rest for 10 minutes. 3 consecutive seated blood pressure readings were made at least 1 minute apart.
Time Frame Months 12, 24, 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 188 193 191
Mean (Standard Deviation)
Unit of Measure: mmHg
Systolic; Month 12 (n=188, 193, 191) 138.7  (19.98) 131.4  (16.54) 132.7  (16.21)
Diastolic; Month 12 (n=188, 193, 191) 81.9  (11.10) 78.7  (10.91) 79.3  (11.54)
Systolic; Month 24 (n=160, 185, 174) 135.4  (19.71) 130.5  (17.35) 129.8  (16.84)
Diastolic; Month 24 (n=160, 185, 174) 80.3  (10.20) 78.3  (10.51) 77.8  (10.31)
Systolic; Month 36 (n=145, 180, 166) 133.5  (17.93) 127.7  (16.48) 126.0  (16.14)
Diastolic; Month 36 (n=145, 180, 166) 79.5  (9.16) 76.6  (9.75) 76.1  (11.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Systolic, Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -7.3
Confidence Interval (2-Sided) 97.3%
-11.4 to -3.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Systolic, Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -6.0
Confidence Interval (2-Sided) 97.3%
-10.1 to -2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Diastolic, Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -3.2
Confidence Interval (2-Sided) 97.3%
-5.8 to -0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Diastolic, Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -2.6
Confidence Interval (2-Sided) 97.3%
-5.1 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Systolic, Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -4.9
Confidence Interval (2-Sided) 97.3%
-9.2 to -0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Systolic, Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -5.5
Confidence Interval (2-Sided) 97.3%
-9.9 to -1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Diastolic, Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -1.9
Confidence Interval (2-Sided) 97.3%
-4.4 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Diastolic, Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -2.4
Confidence Interval (2-Sided) 97.3%
-5.0 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Systolic, Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -5.8
Confidence Interval (2-Sided) 97.3%
-10.0 to -1.6
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Systolic, Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -7.5
Confidence Interval (2-Sided) 97.3%
-11.7 to -3.3
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Diastolic, Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -2.9
Confidence Interval (2-Sided) 97.3%
-5.4 to -0.4
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Diastolic, Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value -3.4
Confidence Interval (2-Sided) 97.3%
-6.0 to -0.9
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Percent of Participants at Baseline With Controlled Hypertension Post Transplantation by Month 12
Hide Description Controlled hypertension was defined as a SBP < 130 mm Hg and a DBP < 80 mm Hg while receiving an antihypertensive medication for the indication of hypertension or receiving an antihypertensive medication for another indication with a medical history of hypertension. Participants with a SBP < 130 mm Hg and a DBP < 80 mm Hg who were prescribed an antihypertensive medication(s) for an indication(s) other than hypertension (eg, beta blockers for migraine prophylaxis) with no medical history of hypertension were not considered to have either hypertension or controlled hypertension. Systolic blood pressure = SBP; Diastolic blood pressure = DBP
Time Frame Day 1 to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with baseline hypertension
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 182 182 183
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.4
(15.5 to 27.4)
28.6
(22.0 to 35.1)
24.6
(18.4 to 30.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments At Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 7.1
Confidence Interval (2-Sided) 97.3%
-2.9 to 17.1
Estimation Comments A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments At Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 3.2
Confidence Interval (2-Sided) 97.3%
-6.6 to 12.9
Estimation Comments A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine
22.Secondary Outcome
Title Percent of Participants With Prevalence of Controlled Hypertension at Month 12
Hide Description The prevalence of controlled hypertension was defined as the proportion of participants at any given time who met the definition of controlled hypertension. Controlled hypertension was defined as a SBP < 130 mm Hg and a DBP < 80 mm Hg while receiving an antihypertensive medication for the indication of hypertension or receiving an antihypertensive medication for another indication with a medical history of hypertension. Participants with a SBP < 130 mm Hg and a DBP < 80 mm Hg who were prescribed an antihypertensive medication(s) for an indication(s) other than hypertension (eg, beta blockers for migraine prophylaxis) with no medical history of hypertension were not considered to have either hypertension or controlled hypertension. Systolic blood pressure = SBP; Diastolic blood pressure = DBP
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 186 193 190
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.0
(15.12 to 26.82)
28.0
(21.65 to 34.31)
24.7
(18.60 to 30.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 7.01
Confidence Interval (2-Sided) 97.3%
-2.79 to 16.71
Estimation Comments A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 3.77
Confidence Interval (2-Sided) 97.3%
-5.86 to 13.35
Estimation Comments A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine
23.Secondary Outcome
Title Percent of Non-dyslipidemic Participants With Incidence of Dyslipidemia Post-Transplantation by Month 12
Hide Description Incidence of dyslipidemia was defined as the proportion of participants who developed dyslipidemia after randomization and transplantation. Dyslipidemia was defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia = hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). The TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used.
Time Frame Randomization to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 75 94 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
80.0
(70.9 to 89.1)
63.8
(54.1 to 73.5)
70.9
(60.9 to 80.9)
24.Secondary Outcome
Title Percent of Participants With Prevalence of Dyslipidemia at Month 12
Hide Description The prevalence of dyslipidemia was defined as the proportion of participants at any given time who met the definition of dyslipidemia. Dyslipidemia defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia defined as hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
52.9
(46.4 to 59.5)
44.7
(38.2 to 51.2)
46.1
(39.5 to 52.7)
25.Secondary Outcome
Title Percent of Participants With Controlled Dyslipidemia at Month 12
Hide Description Prevalence of controlled dyslipidemia = the proportion of participants at any given time who met the stated definition of dyslipidemia. Dyslipidemia defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia defined as hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). Controlled dyslipidemia defined as participants who received successful pharmacologic treatment for 1 of the above stated dyslipidemias, and their lipid values fell below the thresholds described. TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent-to-treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.1
(13.0 to 23.2)
15.5
(10.8 to 20.2)
15.5
(10.7 to 20.3)
26.Secondary Outcome
Title Number of Participants With Antihyperlipidemic Medication by Intensity Level
Hide Description An intensity level was associated with the dose level of the statin based anti-hyperlipidemic agent. Any other agent (i.e., non-statin therapy) used as an antihyperlipidemic were considered Level I treatment intensity. Multiple daily dose levels during a period were averaged to compute the daily dose during that period. Level I = 20 mg fluvastatin (flu), 10 mg lovastatin (lova), 10 mg pravastatin (prav), 5-10 mg simvastatin (sim); Level II = 10 mg atorvastatin (atorv), 40 mg flu, 20 mg lova, 20 mg prav, 5 mg rosuvastatin (rosu), 20 mg sim, 10/10 vytorin; Level III = 20 mg atorv, 80 mg flu, 40 mg lova, 40 mg prav, 10 mg rosu, 40 mg sim, 10/20 vytorin; Level IV = 40 mg atorv, 80 mg lova, 80 mg prav, 20 mg rosu, 80 mg sim, 10/40 vytorin; Level V = 80 mg atorv, 40 mg rosu, 10/80 vytorin. Concomitant use of a statin and an agent of another class elevated the intensity level of the statin therapy by 1 level; therefore, an intensity level of greater than V was possible.
Time Frame Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants that received at least one hyperlipidemic medication; Completer analysis is based on all participants who have been followed up at least 1092 days after transplantation.
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 103 92 92
Measure Type: Number
Unit of Measure: participants
Intensity Level I 17 15 17
Intensity Level II 46 27 39
Intensity Level III 27 32 23
Intensity Level IV 8 16 9
Intensity Level V 4 1 4
Intensity Level VI 1 1 0
27.Secondary Outcome
Title Percent of Participants Using At Least One Anti-Hyperlipidemic Medication
Hide Description This analysis is based on all participants who were followed up at least 1092 days after transplantation.
Time Frame Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent-to-treat (ITT) population; Completer analysis is based on all participants who have been followed up at least 1092 days after transplantation.
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 182 199 192
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
56.6
(49.4 to 63.8)
46.2
(39.3 to 53.2)
47.9
(40.9 to 55.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -10.4
Confidence Interval (2-Sided) 97.3%
-21.4 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -8.7
Confidence Interval (2-Sided) 97.3%
-19.9 to 2.7
Estimation Comments [Not Specified]
28.Secondary Outcome
Title Mean Value of Lipid Parameters
Hide Description Lipid parameters included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and triglycerides (TGs).
Time Frame Months 12, 24, 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent-to-treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 189 195 192
Mean (Standard Deviation)
Unit of Measure: mg/dL
non-HDL Cholesterol; Month 12 (n=189, 195, 192) 144.1  (47.31) 131.5  (38.18) 131.7  (36.76)
Total Cholesterol; Month 12 (n=189, 195, 192) 191.5  (49.29) 182.4  (39.78) 181.3  (39.92)
HDL Cholesterol; Month 12 (n=189, 195, 192) 47.4  (13.33) 50.8  (15.98) 49.7  (15.69)
LDL Cholesterol; Month 12 (n=187, 186, 183) 107.3  (39.60) 102.1  (33.40) 100.8  (29.48)
Triglyceride; Month 12 (n=187, 186, 183) 184.6  (106.42) 149.4  (87.25) 155.0  (85.08)
non-HDL Cholesterol; Month 24 (n=166, 190, 181) 145.1  (39.52) 126.7  (38.48) 127.0  (36.76)
Total Cholesterol; Month 24 (n=166, 190, 181) 193.5  (40.23) 175.3  (42.38) 175.4  (40.03)
HDL ; Month 24 (n=166, 190, 181) 48.4  (13.74) 48.6  (15.28) 48.5  (14.92)
LDL Cholesterol; Month 24 (n=164, 186, 168) 109.1  (35.92) 98.6  (33.71) 96.5  (30.52)
Triglyceride; Month 24 (n=164, 186, 168) 179.5  (97.51) 143.4  (88.97) 151.2  (95.88)
non-HDL Cholesterol; Month 36 (n=154, 184, 176) 142.2  (43.19) 122.4  (40.12) 122.1  (38.78)
Total Cholesterol; Month 36 (n=154, 184, 176) 190.7  (45.28) 171.3  (45.78) 170.7  (43.26)
HDL Cholesterol; Month 36 (n=154, 184, 176) 48.5  (14.27) 48.9  (15.37) 48.6  (16.86)
LDL Cholesterol; Month 36 (n=142, 170, 161) 107.6  (37.66) 96.7  (36.53) 92.5  (33.78)
Triglyceride; Month 36 (n=142, 170, 161) 179.1  (97.07) 132.7  (68.69) 144.0  (81.48)
29.Secondary Outcome
Title Percent of Participants With Prevalence of Acute Rejection (AR) by Month 36
Hide Description Prevalence of AR = participants with the stated definition of AR at any given time. AR defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted. Clinical evidence = if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification.
Time Frame Randomization to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 6 (n=221, 226, 219)
5.4
(2.4 to 8.4)
16.8
(11.9 to 21.7)
21.9
(16.4 to 27.4)
Month 24 (n=221, 226, 219)
9.0
(5.3 to 12.8)
17.3
(12.3 to 22.2)
24.2
(18.5 to 29.9)
Month 36 (n=221, 226, 219)
9.5
(5.6 to 13.4)
17.3
(12.3 to 22.2)
24.2
(18.5 to 29.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 6
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 11.4
Confidence Interval (2-Sided) 97.3%
5.0 to 18.2
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 6
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 16.5
Confidence Interval (2-Sided) 97.3%
9.6 to 23.8
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 24
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 8.2
Confidence Interval (2-Sided) 97.3%
1.2 to 15.4
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 24
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 15.2
Confidence Interval (2-Sided) 97.3%
7.5 to 23.0
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 36
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 7.8
Confidence Interval (2-Sided) 97.3%
0.6 to 15.0
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Month 36
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens.
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value 14.7
Confidence Interval (2-Sided) 97.3%
7.0 to 22.6
Estimation Comments For 97.3% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
30.Secondary Outcome
Title Number of Participants With Acute Rejection (AR) Post-transplant in Terms of Severity Using Banff Grades by Month 36
Hide Description Acute rejection was defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Clinical evidence defined: if either a or b was satisfied: a) an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b) an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Only the episode with the highest Banff grade for each participant was counted.
Time Frame Randomization to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Unit of Measure: participants
Mild Acute (IA); Month 6 1 4 7
Mild Acute (IB); Month 6 5 9 3
Moderate Acute (IIA); Month 6 5 14 16
Moderate Acute (IIB); Month 6 1 10 20
Severe Acute (III); Month 6 0 1 2
Mild Acute (IA); Month 12 3 4 7
Mild Acute (IB); Month 12 5 8 3
Moderate Acute (IIA); Month 12 6 16 17
Moderate Acute (IIB); Month 12 2 10 20
Severe Acute (III); Month 12 0 1 2
Mild Acute (IA); Month 24 4 4 7
Mild Acute (IB); Month 24 7 8 3
Moderate Acute (IIA); Month 24 6 16 18
Moderate Acute (IIB); Month 24 3 10 22
Severe Acute (III); Month 24 0 1 3
Mild Acute (IA); Month 36 5 4 7
Mild Acute (IB); Month 36 7 8 3
Moderate Acute (IIA); Month 36 6 16 18
Moderate Acute (IIB); Month 36 3 10 22
Severe Acute (III); Month 36 0 1 3
31.Secondary Outcome
Title Percent of Participants Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12
Hide Description A participant was considered to have delayed graft function (DGF), if treated with dialysis within the first week (Day 1 - 8) after transplantation. The use of polyclonal antilymphocyte preparations (LDT) was permitted only for participants randomized to cyclosporine (CsA) who experienced impaired renal allograft function and anticipated DGF following transplantation and were not permitted in belatacept-treated participants, except for the treatment of acute rejection. Participants treated with LDT began CsA at the discretion of the investigator by Day 7. LDT could also have been used in participants who met >= 1 of the following criteria, observed in the presence of a transplant artery and vein and no evidence of hydronephrosis by sonogram: Urine output < 250 mL/12 hours, no significant improvement (< 1 milligram per deciliter (mg/dL)) in serum creatinine from baseline value over the first 24 - 72 hours post-transplant, or dialysis treatment.
Time Frame Randomization to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.6
(1.2 to 6.1)
0.4
(0.0 to 2.4)
0.5
(0.0 to 2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-6.6 to -0.6
Estimation Comments For 95% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-6.6 to -0.6
Estimation Comments For 95% CI of difference, normal approximation is used if N>=5 in both arms. Otherwise exact method is used.
32.Secondary Outcome
Title Percent of Participants Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36
Hide Description The use of LDT (thymoglobulin or antithymocyte gamma globulin [ATGAM]) was permitted only for participants randomized to cyclosporine (CsA) who experienced impaired renal allograft function and anticipated delayed graft function following transplantation. Acute rejection (AR) defined as a clinico-pathological event requiring clinical evidence (an unexplained rise of serum creatinine ≥ 25% from baseline creatinine or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed) and biopsy confirmation. AR defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Only the episode with the highest Banff grade for each participant was counted.
Time Frame Randomization to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Unit of Measure: percentage of participants
Month 6 0.5 4.4 5.9
Month 12 0.9 4.4 5.9
Month 24 1.4 4.4 5.9
Month 36 1.8 4.4 5.9
33.Secondary Outcome
Title Percent of Participants With Corticosteroid Resistant Acute Rejection (AR) by Month 36
Hide Description Steroid-resistant acute rejection (AR) defined as the use of lymphocyte-depletion therapy following treatment with corticosteroids. AR defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Clinical evidence defined: either a or b was satisfied: a) an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b) an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 international standardized histopathological working classification of kidney transplant pathology. Only the episode with the highest Banff grade for each participant was counted.
Time Frame Randomization to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Unit of Measure: percentage of participants
Month 6 0.0 4.0 5.9
Month 12 0.0 5.3 6.4
Month 24 0.5 5.3 6.4
Month 36 0.5 5.3 6.8
34.Secondary Outcome
Title Number of Participants Who Recovered Completely From an Episode of Acute Rejection (AR) by Month 12
Hide Description Acute rejection (AR) = a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater. Clinical evidence = if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Complete recovery following AR defined as serum creatinine [SCr] levels returned to baseline. Recovery calculated using 2 algorithms: Algorithm 1 = last laboratory measurement prior to onset of AR (baseline and first laboratory measurement after 84 days since onset of AR = resolution); Algorithm 2 = lowest laboratory measurement on or after transplantation and prior to onset day of AR (baseline and lowest laboratory measurement after onset on first AR up to Month 12 = resolution)
Time Frame Randomization to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with at least one episode of AR up to Month 12
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 16 39 48
Measure Type: Number
Unit of Measure: participants
Algorithm 1 13 29 39
Algorithm 2 13 34 43
35.Secondary Outcome
Title Percent of Participants With Subclinical Rejection at Month 12
Hide Description Subclinical rejection defined as histological findings by the central pathologist consistent with acute rejection, but lacking its clinical correlate. Acute rejection defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted. Clinical evidence defined if either a or b was satisfied: a) an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b) an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized, transplanted, and treated participants; intent to treat (ITT) population with measurable component
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 155 170 164
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.2
(1.7 to 8.6)
4.7
(1.5 to 7.9)
4.3
(1.2 to 7.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -0.5
Confidence Interval (2-Sided) 97.3%
-6.5 to 5.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percent
Estimated Value -0.9
Confidence Interval (2-Sided) 97.3%
-6.9 to 4.8
Estimation Comments [Not Specified]
36.Secondary Outcome
Title Number of Participants Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36
Hide Description Allograft rejection includes any episode of rejection including: clinically suspected rejection, treated rejection, any central biopsy-proven acute rejection (BPAR), and acute rejection (AR: a subset of BPAR) defined as central biopsy-proven rejection that was either clinically suspected by protocol-defined reasons or by other reasons and was treated. Acute rejection (AR) defined as a clinico-pathological event requiring clinical evidence ( either an unexplained rise of serum creatinine ≥ 25% from baseline creatinine or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of AR) and renal biopsy confirmation biopsy demonstrating a Banff 97 working classification of kidney transplant pathology classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the highest Banff grade for each participant was counted.
Time Frame Randomization to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 221 226 219
Measure Type: Number
Unit of Measure: participants
Month 6 43 68 70
Month 12 56 72 75
Month 24 63 74 81
Month 36 69 76 82
37.Secondary Outcome
Title Mean Value of Physical and Mental Components Using SF-36 Questionnaire
Hide Description SF-36 was a Participant-Reported Quality of Life (QoL) Short Form (SF) questionnaire measuring health-related quality of life (HRQL) covering 2 scale measures: physical component summary (PCS) and mental component summary (MCS). PCS represented by 4 domains: physical function, role limitations due to physical problems, pain, and general health perception. MCS represented by 4 domains: vitality, social function, role limitations due to emotional problems, and mental health. Their scores were computed based on weighted combinations of the 8 domain scores, which were transformed to a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores reflect better health-related functional status. Scoring is standardized using the norm-based scoring method where data is scored in relation to the U.S. general population having a mean of 50 and a standard deviation of 10. Scores below 50 are below the U.S. general population norm and above 50 are above the U.S. general population norm.
Time Frame Months 6, 12, 24, 36
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and transplanted participants, intent to treat (ITT) population
Arm/Group Title Cyclosporine Belatacept LI Belatacept MI
Hide Arm/Group Description:

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Overall Number of Participants Analyzed 203 218 201
Mean (Standard Deviation)
Unit of Measure: units on a scale
Mental Component Score; Month 6 (n=191, 205, 189) 49.4  (11.08) 49.9  (10.55) 51.1  (10.53)
Physical Component Score; Month 6 (n=191,205,189) 47.3  (8.91) 48.9  (8.59) 49.2  (7.58)
Mental Component Score; Month 12 (n=198,210,194) 49.5  (10.78) 50.3  (10.08) 49.9  (10.54)
Physical Component Score; Month 12 (n=198,210,194) 47.5  (9.34) 49.6  (8.18) 50.3  (8.21)
Mental Component Score; Month 24 (n=200,214,198) 48.3  (11.14) 49.6  (10.77) 48.8  (11.03)
Physical Component Score; Month 24 (n=200,214,198) 47.3  (9.50) 49.0  (8.77) 49.9  (8.03)
Mental Component Score; Month 36 (n=203,218,201) 46.9  (11.60) 48.7  (11.26) 48.3  (11.50)
Physical Component Score; Month 36 (n=203,218,201) 47.1  (9.47) 49.2  (9.15) 48.7  (8.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Mental Component Score; Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6573
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.6 to 2.6
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Mental Component Score; Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1198
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-0.4 to 3.9
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Physical Component Score; Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0672
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-0.1 to 3.2
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Physical Component Score; Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0257
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
0.2 to 3.6
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Mental Component Score; Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4146
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-1.2 to 2.9
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Mental Component Score; Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7327
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.7 to 2.4
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Physical Component Score; Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0144
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
0.4 to 3.8
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Physical Component Score; Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
1.1 to 4.5
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Mental Component Score; Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2340
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-0.8 to 3.4
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Mental Component Score; Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6635
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.7 to 2.6
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Physical Component Score; Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0417
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
0.1 to 3.5
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept MI
Comments Physical Component Score; Month 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
0.9 to 4.4
Estimation Comments Statistical tests comparing each belatacept regimen to the CsA regimen were conducted at a significance level of 0.05. Subjects with only baseline observations were excluded from these summaries.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cyclosporine, Belatacept LI
Comments Mental Component Score; Month 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0953
Comments Baseline observations were not used for imputations at subsequent time points.
Method ANOVA
Comments ANOVA model: Component Score = treatment. Missing values were imputed using last observation carried forward (LOCF) method.
Method of Estimation Estimation Parameter Mean Difference (Final Value)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-0.3 to 4.1
Estimation Comments