Trial Outcomes & Findings for Belatacept Early Steroid Withdrawal Trial (NCT NCT01729494)

Results Overview

Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) \< 45 mL/min

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

316 participants

Primary outcome timeframe

12 months

Results posted on

2021-07-28

Participant Flow

Participant milestones

Participant milestones
Measure	Group A Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label.	Group C Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Overall Study STARTED	107	104	105
Overall Study COMPLETED	97	93	94
Overall Study NOT COMPLETED	10	11	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Belatacept Early Steroid Withdrawal Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).	Total n=316 Participants Total of all reporting groups
Age, Continuous	51.1 years STANDARD_DEVIATION 13.1 • n=5 Participants	51.6 years STANDARD_DEVIATION 11.7 • n=7 Participants	51.5 years STANDARD_DEVIATION 12.3 • n=5 Participants	51.4 years STANDARD_DEVIATION 12.1 • n=4 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	38 Participants n=7 Participants	36 Participants n=5 Participants	104 Participants n=4 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	66 Participants n=7 Participants	69 Participants n=5 Participants	212 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants	42 Participants n=4 Participants
Race (NIH/OMB) White	82 Participants n=5 Participants	88 Participants n=7 Participants	80 Participants n=5 Participants	250 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Region of Enrollment United States	107 participants n=5 Participants	104 participants n=7 Participants	105 participants n=5 Participants	316 participants n=4 Participants
# Patients with Pre-existing Donor Specific Antibody (DSA)	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
calculated panel reactive antibody (cPRA) %	4.9 percentage STANDARD_DEVIATION 12.7 • n=5 Participants	6.4 percentage STANDARD_DEVIATION 16.4 • n=7 Participants	5.9 percentage STANDARD_DEVIATION 15.7 • n=5 Participants	5.8 percentage STANDARD_DEVIATION 14.6 • n=4 Participants
Repeat Transplant	7 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants
Living related donor	25 Participants n=5 Participants	25 Participants n=7 Participants	33 Participants n=5 Participants	83 Participants n=4 Participants
Living unrelated donor	55 Participants n=5 Participants	53 Participants n=7 Participants	47 Participants n=5 Participants	155 Participants n=4 Participants
Deceased donor	27 Participants n=5 Participants	26 Participants n=7 Participants	25 Participants n=5 Participants	78 Participants n=4 Participants
Pre-emptive transplant	37 Participants n=5 Participants	27 Participants n=7 Participants	40 Participants n=5 Participants	104 Participants n=4 Participants
Cytomegalovirus (CMV) High Risk status (D+/R-)	18 Participants n=5 Participants	21 Participants n=7 Participants	25 Participants n=5 Participants	64 Participants n=4 Participants
Pre-existing diabetes mellitus	26 Participants n=5 Participants	33 Participants n=7 Participants	33 Participants n=5 Participants	92 Participants n=4 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Intent to treat analysis

Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) \< 45 mL/min

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
# Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min	9 Participants	15 Participants	14 Participants

SECONDARY outcome

Timeframe: 24 months

Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
# Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR \< 45 ml/min/1.73m2

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
# Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months	11 Participants	13 Participants	21 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to Treat

Patients with reduced Renal function measured by estimated GFR MDRD \< 45 ml/min at 24 months

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
eGFR (MRDRD) < 45 ml/Min/1.73m2	9 Participants	8 Participants	20 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Biopsy Proven Acute Rejection	20 Participants	26 Participants	7 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Biopsy proven acute cellular rejection (BPACR)

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Biopsy Proven Acute Cellular Rejection	14 Participants	22 Participants	2 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Biopsy Proven Acute Antibody Mediated Rejection	2 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Biopsy Proven Mixed Acute Rejection	4 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients (%) with development of denovo DSA after transplant

Outcome measures

Outcome measures
Measure	Group A n=89 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=85 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=84 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
# of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant	5 Participants	1 Participants	5 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint

Outcome measures

Outcome measures
Measure	Group A n=96 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=92 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=97 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Mean eGFR (MDRD) (ml/Min/1.73m2)	65.5 ml/min/1.73m2 Standard Deviation 18.9	65.3 ml/min/1.73m2 Standard Deviation 19.3	63.4 ml/min/1.73m2 Standard Deviation 19.8

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Number of Patients with a Urine protein/creatinine (UPC) ratio \> 0.8

Outcome measures

Outcome measures
Measure	Group A n=84 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=85 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=84 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Proteinuria UPC Ratio > 0.8	11 Participants	5 Participants	21 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Intent to treat

Number of Patients who experienced death, all causes

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Patient Death	2 Participants	4 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR)	8 Participants	15 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included

Outcome measures

Outcome measures
Measure	Group A n=80 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=71 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=72 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
New Onset Diabetes After Transplantation (NODAT)	11 Participants	5 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Mean Time to first episode of BPAR (days)

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Time to First BPAR	229 days Standard Deviation 147.7	131.6 days Standard Deviation 119.6	159.6 days Standard Deviation 219.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients with their First BPACR with a Banff grade \>= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3.

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
# Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade	5 Participants	12 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant.

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Delayed Graft Function	3 Participants	1 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients developing leukopenia defined as WBC \< 2000/mm3

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Leukopenia (WBC < 2000/mm3)	22 Participants	14 Participants	15 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients on treatment with corticosteroids at 2 years

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Steroid Therapy	16 Participants	14 Participants	9 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients who were discontinued from mycophenolate treatment at 2 years

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Discontinuation of Mycophenolate	11 Participants	9 Participants	13 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Intent to treat

Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years

Outcome measures

Outcome measures
Measure	Group A n=107 Participants Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 Participants Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 Participants Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Discontinuation of Study Treatment (Belatacept or Tacrolimus)	11 Participants	9 Participants	5 Participants

Adverse Events

Group A

Serious events: 58 serious events

Other events: 91 other events

Deaths: 2 deaths

Group B

Serious events: 66 serious events

Other events: 90 other events

Deaths: 4 deaths

Group C

Serious events: 62 serious events

Other events: 92 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Group A n=107 participants at risk Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 participants at risk Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 participants at risk Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Cardiac disorders Cardiovascular event	0.93% 1/107 • Number of events 1 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	8.7% 9/104 • Number of events 12 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	2.9% 3/105 • Number of events 5 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Infections and infestations Infection Requiring Hospitalization	22.4% 24/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	23.1% 24/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	21.9% 23/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Renal and urinary disorders Renal dysfunction resulting in hospitalization	28.0% 30/107 • Number of events 53 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	30.8% 32/104 • Number of events 50 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	26.7% 28/105 • Number of events 40 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Immune system disorders Malignancy	6.5% 7/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	5.8% 6/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	6.7% 7/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Blood and lymphatic system disorders PTLD	0.00% 0/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	0.96% 1/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	0.00% 0/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Gastrointestinal disorders Nausea/vomiting or GI requiring hospitalization	3.7% 4/107 • Number of events 6 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	6.7% 7/104 • Number of events 10 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	12.4% 13/105 • Number of events 16 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Nervous system disorders Mental status changes or neurological AE's	4.7% 5/107 • Number of events 8 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	0.00% 0/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	4.8% 5/105 • Number of events 9 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.

Other adverse events

Other adverse events
Measure	Group A n=107 participants at risk Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab. Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.	Group B n=104 participants at risk Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label	Group C n=105 participants at risk Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions. Tacrolimus: Tacrolimus will be administered orally twice daily (BID).
Blood and lymphatic system disorders Hematologic events	55.1% 59/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	52.9% 55/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	57.1% 60/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Blood and lymphatic system disorders Leukopenia WBC < 2000/mm3	20.6% 22/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	13.5% 14/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	14.3% 15/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Blood and lymphatic system disorders Anemia (Hg < 7gm/dL)	1.9% 2/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	2.9% 3/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	5.7% 6/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Blood and lymphatic system disorders Thrombocytopenia (PLT < 50,000/mm3)	4.7% 5/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	1.9% 2/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	0.95% 1/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Gastrointestinal disorders Gastrointestinal events	29.9% 32/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	32.7% 34/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	47.6% 50/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Renal and urinary disorders Nephrotoxicity events	20.6% 22/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	26.9% 28/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	35.2% 37/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Nervous system disorders Neurologic events	13.1% 14/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	13.5% 14/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	31.4% 33/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Metabolism and nutrition disorders Electrolyte/metabolic events	14.0% 15/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	20.2% 21/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	30.5% 32/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Skin and subcutaneous tissue disorders Wound healing	6.5% 7/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	9.6% 10/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	8.6% 9/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.
Musculoskeletal and connective tissue disorders Musculoskeletal/Bone events	1.9% 2/107 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	5.8% 6/104 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.	4.8% 5/105 • Adverse event data was collected in every patient over a 2 year time period. The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.

Additional Information

Rita R. Alloway, Pharm.D., Director of Clinical Trials

University of Cincinnati

Phone: 513-558-1568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place