Trial Outcomes & Findings for Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney (NCT NCT00035555)

Last Updated: 2014-01-13

Results Overview

No participant was to receive treatment for acute rejection without a biopsy to confirm the diagnosis. CSPAR=Clinically-suspected rejection, defined as an increase in serum creatinine ≥0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function, and biopsy-proven rejection, which includes all cases in which a biopsy was read by the central pathologist as demonstrating acute rejection regardless of the reason why the biopsy was performed.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

230 participants

Primary outcome timeframe

By Month 6 posttransplant (From Day 1 to Month 6)

Results posted on

2014-01-13

Participant Flow

A total of 230 participants who had undergone transplantation were enrolled

Participant milestones

Participant milestones
Measure	Belatacept: More Intensive (MI) Regimen The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen Cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Overall Study STARTED	74	71	73
Overall Study Number Who Had Undergone Transplantation	74	71	73
Overall Study Number Who Received Study Drug	74	71	71
Overall Study COMPLETED	58	55	51
Overall Study NOT COMPLETED	16	16	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Belatacept: More Intensive (MI) Regimen The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen Cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Overall Study Adverse Event	5	8	9
Overall Study Allograft loss	1	1	2
Overall Study Death	0	0	2
Overall Study Lost to Follow-up	0	0	1
Overall Study Noncompliance	0	1	1
Overall Study Prohibited medication	1	1	0
Overall Study Treatment failure/lack of efficacy	7	5	3
Overall Study Withdrawal by Subject	2	0	2
Overall Study Investigator deemed not a good candidate	0	0	1
Overall Study Received cyclosporin in error	0	0	1

Baseline Characteristics

Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants Cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Total n=218 Participants Total of all reporting groups
Age, Continuous	45.5 Years n=5 Participants	43.0 Years n=7 Participants	46.0 Years n=5 Participants	45.0 Years n=4 Participants
Age, Customized Between 18 and 45 years	37 Participants n=5 Participants	42 Participants n=7 Participants	36 Participants n=5 Participants	115 Participants n=4 Participants
Age, Customized Between 46 and 60 years	31 Participants n=5 Participants	26 Participants n=7 Participants	33 Participants n=5 Participants	90 Participants n=4 Participants
Age, Customized Older than 60 years	6 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	23 Participants n=7 Participants	24 Participants n=5 Participants	67 Participants n=4 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	48 Participants n=7 Participants	49 Participants n=5 Participants	151 Participants n=4 Participants
Race/Ethnicity, Customized White	64 Participants n=5 Participants	57 Participants n=7 Participants	59 Participants n=5 Participants	180 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Race/Ethnicity, Customized Asian/Pacific Islander	3 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: By Month 6 posttransplant (From Day 1 to Month 6)

Population: All randomized participants who underwent transplantation

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)	5 Participants Interval 1.0 to 12.5	4 Participants	6 Participants

SECONDARY outcome

Timeframe: Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)

Population: All randomized participants who underwent transplantation

BPAR includes all cases in which a biopsy read by the central pathologist demonstrates acute rejection, regardless of the reason that the biopsy was performed.

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12 Up to 12 months	18.9 Percentage of participants	29.6 Percentage of participants	17.8 Percentage of participants
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12 Up to 6 months	14.9 Percentage of participants	23.9 Percentage of participants	17.8 Percentage of participants

SECONDARY outcome

Timeframe: By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)

Population: All randomized participants who underwent transplantation

BPAR includes all cases in which a biopsy read by the central pathologist demonstrates acute rejection, regardless of the reason that the biopsy was performed. A participant was reported as having had an episode of treated acute rejection if he or she received antirejection therapy during an episode of rejection (clinically-suspected or biopsy-proven rejection).

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection By Month 3	21.6 Percentage of participants	29.6 Percentage of participants	17.8 Percentage of participants
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection By Month 12	28.4 Percentage of participants	38.0 Percentage of participants	27.4 Percentage of participants
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection By Month 6	23.0 Percentage of participants	32.4 Percentage of participants	24.7 Percentage of participants

SECONDARY outcome

Timeframe: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)

Population: All randomized participants who underwent transplantation

Throughout this study, acute rejection=clinically-suspected and biopsy-proven acute rejection (BPAR). Clinically-suspected rejection is defined as an increase in serum creatinine ≥0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function. BPAR includes all cases in which a biopsy was read by the central pathologist as demonstrating acute rejection regardless of the reason why the biopsy was performed. PAR is defined as an elevation in SCr ≥0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function that led the investigator to suspect that the participant had experienced acute rejection, and in whom either the biopsy did not confirm acute rejection and the participant received treatment for acute rejection or the participant received treatment for acute rejection without a biopsy to confirm the diagnosis.

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR) Month 6: Acute rejection or PAR	11 Percentage of participants	9 Percentage of participants	10 Percentage of participants
Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR) Month 6: PAR	5 Percentage of participants	3 Percentage of participants	1 Percentage of participants
Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR) Month 12: Acute rejection or PAR	11 Percentage of participants	10 Percentage of participants	11 Percentage of participants
Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR) Month 12: PAR	5 Percentage of participants	4 Percentage of participants	3 Percentage of participants

SECONDARY outcome

Timeframe: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)

Population: All randomized participants who underwent transplantation and who had at least 1 biopsy following Day 1; n=evaluable participants

Based on postbaseline biopsies

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Percentage of Participants Who Had Chronic Allograft Nephropathy Month 6 (n= 32, 33, 27)	18.8 Percentage of participants	9.1 Percentage of participants	33.3 Percentage of participants
Percentage of Participants Who Had Chronic Allograft Nephropathy Month 12 (n=52, 54, 45)	28.8 Percentage of participants	20.4 Percentage of participants	44.4 Percentage of participants

SECONDARY outcome

Timeframe: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)

Population: All randomized participants who underwent transplantation

Iohexol, a true glomerular filtration marker, is used to measure glomerular filtration rate.

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Mean Iohexol Clearance Month 1 (n=53, 51, 48)	59.7 mL/min per 1.73 m^2 Standard Deviation 17.3	60.2 mL/min per 1.73 m^2 Standard Deviation 14.4	54.0 mL/min per 1.73 m^2 Standard Deviation 19.3
Mean Iohexol Clearance Month 6 (n=41, 41, 31)	62.2 mL/min per 1.73 m^2 Standard Deviation 25.6	64.5 mL/min per 1.73 m^2 Standard Deviation 19.5	56.0 mL/min per 1.73 m^2 Standard Deviation 19.5
Mean Iohexol Clearance Month 12 (n=32, 37, 27)	66.3 mL/min per 1.73 m^2 Standard Deviation 20.7	62.1 mL/min per 1.73 m^2 Standard Deviation 15.9	53.5 mL/min per 1.73 m^2 Standard Deviation 16.4

SECONDARY outcome

Timeframe: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)

Population: All randomized participants who underwent transplantation

Hypertension is defined as diastolic blood pressure ≥90 mm Hg and/or systolic blood pressure ≥140 mm Hg

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Percentage of Participants Who Used Antihypertensive Medication Month 6: Requiring 6 medications	2.7 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Requiring 3 medications	23.2 Percentage of participants	9.0 Percentage of participants	22.0 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Requiring 4 medications	8.7 Percentage of participants	7.5 Percentage of participants	15.3 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 6: Total requiring at least 1 medication	87.7 Percentage of participants	78.6 Percentage of participants	88.4 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 6: Requiring 1 medication	24.7 Percentage of participants	27.1 Percentage of participants	21.7 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 6: Requiring 2 medications	23.3 Percentage of participants	28.6 Percentage of participants	31.9 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 6: Requiring 3 medications	23.3 Percentage of participants	14.3 Percentage of participants	21.7 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 6: Requiring 4 medications	11.0 Percentage of participants	7.1 Percentage of participants	11.6 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 6: Requiring 5 medications	2.7 Percentage of participants	1.4 Percentage of participants	1.4 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 6: Requiring >6 medications	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Total requiring at least 1 medication	79.7 Percentage of participants	71.6 Percentage of participants	86.4 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Requiring 1 medication	21.7 Percentage of participants	26.9 Percentage of participants	20.3 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Requiring 2 medications	23.2 Percentage of participants	9.0 Percentage of participants	22.0 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Requiring 5 medications	5.8 Percentage of participants	0.0 Percentage of participants	3.4 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Requiring 6 medications	1.4 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants Who Used Antihypertensive Medication Month 12: Requiring >6 medications	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)

Population: All randomized participants who underwent transplantation

Hypertension is defined as diastolic blood pressure ≥90 mm Hg and/or systolic blood pressure ≥140 mm Hg or, the use of any antihypertensive medication.

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Number of Participants With Hypertension At Month 6	16 Participants	15 Participants	18 Participants
Number of Participants With Hypertension At Month 12	14 Participants	12 Participants	11 Participants

SECONDARY outcome

Timeframe: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)

Population: All randomized participants who received a transplant; n=evaluable participants.

LDL=low-density lipoprotein; HDL=high-density lipoprotein. Total cholesterol=LDL + HDL + very low-density (VLDL) cholesterol. VLDL=triglycerides divided by 5. Non-HDL cholesterol=Total cholesterol minus HDL cholesterol.

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=73 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Non-HDL cholesterol: Month 6 (n=62, 64, 51)	150 mg/dL Standard Deviation 39.4	143 mg/dL Standard Deviation 42.1	165 mg/dL Standard Deviation 55.1
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Non-HDL cholesterol: Month 12 (n=59, 56, 48)	145 mg/dL Standard Deviation 36.7	144 mg/dL Standard Deviation 35.8	151 mg/dL Standard Deviation 43.4
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Total cholesterol: Month 6 (n=63, 65, 54)	204 mg/dL Standard Deviation 40.4	202 mg/dL Standard Deviation 47.7	224 mg/dL Standard Deviation 54.8
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Total cholesterol: Month 12 (n=60, 58, 50)	198 mg/dL Standard Deviation 41.4	201 mg/dL Standard Deviation 40.0	212 mg/dL Standard Deviation 44.2
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels LDL cholesterol: Month 1 (n=69, 69, 66)	129 mg/dL Standard Deviation 48.9	120 mg/dL Standard Deviation 33.2	137 mg/dL Standard Deviation 42.9
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels LDL cholesterol: Month 6 (n=63, 66, 55)	125 mg/dL Standard Deviation 33.9	121 mg/dL Standard Deviation 39.2	131 mg/dL Standard Deviation 41.4
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels LDL cholesterol: Month 12 (n=61, 60, 52)	120 mg/dL Standard Deviation 33.8	125 mg/dL Standard Deviation 32.0	125 mg/dL Standard Deviation 36.4
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels HDL cholesterol: Month 1 (n=68, 68, 64)	64 mg/dL Standard Deviation 19.4	68 mg/dL Standard Deviation 21.7	70 mg/dL Standard Deviation 21.6
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels HDL cholesterol: Month 6 (n=62, 65, 62)	54 mg/dL Standard Deviation 14.8	56 mg/dL Standard Deviation 19.0	62 mg/dL Standard Deviation 20.1
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels HDL cholesterol: Month 12 (n=60, 57, 48)	53 mg/dL Standard Deviation 15.7	56 mg/dL Standard Deviation 13.5	59 mg/dL Standard Deviation 18.5
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Total cholesterol: Month 1 (n=69, 69, 65)	222 mg/dL Standard Deviation 64.7	210 mg/dL Standard Deviation 45.6	239 mg/dL Standard Deviation 53.7
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Triglycerides: Month 1 (n=69, 69, 65)	168 mg/dL Standard Deviation 125.3	147 mg/dL Standard Deviation 65.3	185 mg/dL Standard Deviation 103.9
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Triglycerides: Month 6 (n=63, 65, 54)	177 mg/dL Standard Deviation 113.1	168 mg/dL Standard Deviation 87.4	198 mg/dL Standard Deviation 119.7
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Triglycerides: Month 12 (n=60, 58, 50)	176 mg/dL Standard Deviation 87.9	152 mg/dL Standard Deviation 63.5	186 mg/dL Standard Deviation 91.6
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels Non-HDL: Month 1 (n=68, 68, 64)	159 mg/dL Standard Deviation 62.7	142 mg/dL Standard Deviation 40.2	169 mg/dL Standard Deviation 51.5

SECONDARY outcome

Timeframe: By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )

Population: All randomized participants who received transplants and who were not known to be diabetic prior to transplant

Posttransplant diabetes mellitus is defined as the need for treatment of hyperglycemia with either an oral agent or insulin for a total of \>4 weeks or hemoglobin A1c (HbA1c) \>7% in a participant not known to be diabetic prior to transplantation

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=67 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=65 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=60 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 3: All events	5 Participants	1 Participants	3 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 3: Hypoglycemic medication	0 Participants	0 Participants	2 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 6: All events	6 Participants	3 Participants	4 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 6: Hyperglycemia medication	0 Participants	0 Participants	2 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 12: All events	8 Participants	4 Participants	7 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 12: Hyperglycemia medication	2 Participants	0 Participants	3 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 12: HbA1c >7%	7 Participants	4 Participants	4 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 1: All events	5 Participants	0 Participants	1 Participants
Number of Participants With Posttransplant Diabetes Mellitus Month 1: Hyperglycemia medication	0 Participants	0 Participants	1 Participants
Number of Participants With Posttransplant Diabetes Mellitus Month 1: HbA1c >7%	5 Participants	0 Participants	0 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 3: HbA1c >7%	5 Participants	1 Participants	1 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 6: HbA1c >7%	6 Participants	3 Participants	2 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 9: All events	8 Participants	3 Participants	5 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 9: Hyperglycemia medication	2 Participants	0 Participants	2 Participants
Number of Participants With Posttransplant Diabetes Mellitus Up to Month 9: HbA1c >7%	7 Participants	3 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 (posttransplant) continuously to 56 days following last dose of study medication

Population: All randomized participants who underwent transplantation and who received treatment

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. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=74 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=71 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=71 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs Deaths	0 Participants	0 Participants	2 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs SAEs	50 Participants	52 Participants	42 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs Treatment-related SAEs	21 Participants	23 Participants	21 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs Treatment-related AEs	43 Participants	40 Participants	50 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs Discontinuations due to SAEs	13 Participants	14 Participants	10 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs AEs	73 Participants	69 Participants	68 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs Discontinuations due to AEs	13 Participants	15 Participants	14 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)

Population: All randomized participants who underwent transplantation and who received treatment

Normal laboratory values: Hemoglobin (g/dL): Males (18-64 years) 13.8-17, (65 years and older) 11.8-16.8; Females (18-64 years) 12.0-15.6, F (65 years and older) 11.1-15.5. Platelets (per mm\^3) 130,000-400,000. Leukocytes (18 years and older) 3.8-10.8 1000/uL. ALT (u/L)(13 years and older) 0-48.

Outcome measures

Outcome measures
Measure	Belatacept: More Intensive (MI) Regimen n=72 Participants The MI regimen aimed to achieve projected serum trough concentrations of belatacept of 20 μg/mL through Day 99, and 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141 and 169). After Day 169, doses were reassigned to achieve projected trough serum concentrations of 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Belatacept: Less Intensive (LI) Regimen n=70 Participants The LI regimen was designed to achieve projected trough serum concentrations of belatacept of 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.	Cyclosporine Regimen n=69 Participants The cyclosporine regimen was designed to achieve a specified range of target serum concentrations consistent with current medical practice for the duration of the study. The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally or ≥1 doses intravenously (IV),depending on the investigators decision. The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. All participants also received induction therapy (2 doses) with basiliximab IV and daily corticosteroids.
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results Hemoglobin, low	13 Participants	7 Participants	9 Participants
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results Leukocytes, high	NA Participants Not evaluated	NA Participants Not evaluated	NA Participants Not evaluated
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results ALT, high	9 Participants	3 Participants	7 Participants
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results Hemoglobin, high	NA Participants Not evaluated	NA Participants Not evaluated	NA Participants Not evaluated
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results Platelet count, low	1 Participants	0 Participants	3 Participants
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results Platelet count, high	NA Participants Not evaluated	NA Participants Not evaluated	NA Participants Not evaluated
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results Leukocytes, low	1 Participants	4 Participants	5 Participants
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results Alanine aminotransferase (ALT), low	NA Participants Not evaluated	NA Participants Not evaluated	NA Participants Not evaluated

Adverse Events

Belatacept: Less-intensive (LI) Regimen

Serious events: 52 serious events

Other events: 66 other events

Deaths: 0 deaths

Belatacept: More-intensive (MI) Regimen

Serious events: 50 serious events

Other events: 68 other events

Deaths: 0 deaths

Cyclosporin Regimen

Serious events: 42 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER