Clinical trial NCT02137239
Conditions: Kidney Transplantation
Sponsor: Bristol-Myers Squibb
Start date: 2015-12-31; Completion date: 2019-05-02
Enrollment: 58 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Patients who undergo a kidney transplant require prolonged therapy with drugs that suppress the immune system (called immunosuppressive regimens) to stop the immune system from attacking the transplanted kidney in order to limit damage to or the possibility of rejecting the transplanted kidney. The purpose of this study is to evaluate benefits and risks of two immunosuppressive regimens (belatacept with everolimus or tacrolimus with mycophenolate mofetil) following thymoglobulin induction and rapid corticosteroid withdrawal.

Detailed description:
Calcineurin inhibitor (CNI)

Arms: arm 1: Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; belatacept (infusion) regimen of 10 mg/kg i.v. on Day 1, Weeks 1, 2, 4, 8 and 12 post transplant and then a maintenance dose of 5 mg/kg every 4 weeks after 12 weeks post transplant; everolimus (tablet) daily dosing at 3.0 mg/day, 2 divided doses, starting on Day 3 dosing adjusted based on blood sample tests; methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed) arm 2: Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; tacrolimus (tablet) daily dosing beginning at 0.1 mg/kg/day, then adjusted based on blood sample tests; MMF (tablet) daily dosing between 0.5 to 2.0 g/day divided in 2 doses (up to 3 g/day if African Americans/Blacks); methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed)
Interventions: intervention 1: Thymoglobulin intervention 2: Belatacept intervention 3: mycophenolate mofetil(MMF) intervention 4: Corticosteroids intervention 5: Everolimus(EVL) intervention 6: Tacrolimus(TAC)
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None

Protocol documents:
Prot_000.pdf: 


Clinical Protocol
IM103177
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belatacept
Revised Protocol No.: 06
Date: 14-Aug-2017
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who receives this document without due authorization from BMS is requested to return it 
to  BMS  or  promptly  destroy  it.  All  other  rights  reserved.  References  to  BMS  in  this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
Replace  all  previous  version(s)  of  
the  protocol  with  
this  
revised  protocol  and  please  provide  a 
copy  of  this  revised  protocol  to all  study  personnel  under  your  supervision,  and  archive  the 
previous versions.
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DOCUMENT HISTORY
Document 
Date of Issue
Summary of Change
Revised 
Protocol 06
14-Aug-2017
Incorporates Amendment 07
Amendment 07 
14-Aug-2017
Clarify timing of collection of belatacept and comparator blood levels for 
clinically suspected AR, PML or PTLD.  Update Procedural Outline 
Tables 5.1-2 and 5.1-3 to allow for collection of a blood sample for 
determination of the belatacept or comparator blood level at the time of 
any clinically suspected episode of acute rejection, PML or PTLD.
Provide guidance regarding the evaluation and acceptable range for oral 
immunosuppressive treatment compliance. The type of T-cell responses 
to be tested for in cases of clinically suspected PTLD or PML was 
clarified as being “anti-viral”, rather than specifically “anti-EBV” in 
nature.  Made modifications to secondary and exploratory endpoints to 
align the analyses of acute rejection with the statistical analysis plan, and 
corrected minor formatting and typographical errors throughout the 
protocol.
Revised 
Protocol 05
11-Nov-2016 
Incorporates Amendment 06
Amendment 06 
11-Nov-2016
Decrease number of sites and subjects.  Statistical Sample Size 
Considerations updated.  Clarification that all grades of acute rejection, 
will be included in analyses of the primary and relevant secondary 
endpoints. 
Revised 
Protocol 04
19-Jan-2016 
Incorporates Amendment 05
Amendment 05 
19-Jan-2016
Clarification of antiviral prophylaxis requirement. Updates treatment and 
rescreening of living donor patients with a positive IGRA at screening. 
Revise protocol with recent administrative changes.
Revised 
Protocol 03
25-Aug-2015
Incorporates Amendment 04
Amendment 04 
25-Aug-2015
Modification of the study design to remove an experimental treatment 
group: Thymoglobulin + belatacept + mycophenolate mofetil with rapid 
corticosteroid withdrawal, from the study design to eliminate a 
potentially higher risk of acute rejection. Updates to the randomization 
ratio, sample size per treatment group and sample size statistical 
determinations. Syntactical edits and clarifications to support the revised 
study design.
Revised 
Protocol 02
23-Dec-2014 
Incorporates Amendment 03 and Administrative Letter 01
Amendment 03 
23-Dec-2014
Modification of the study design, including the addition of an accepted 
standard of care active comparator treatment group and a change in the 
immunosuppressive medications paradigm. Updates to the research 
hypothesis and study objectives. Revisions to eligibility criteria. Addition 
of text for pregnancy precautions and U.S. reporting requirements from 
the CellCept Risk Evaluation and Mitigation Strategy. Clarification of 
the timing of randomization in relation to transplant surgery and initial 
dose of study drugs, and the temporal sequence of study drug dosing. 
Updates to the Time & Events Table including the addition of collection 
of safety and biomarker specimens; and clarifications to align the tables 
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Document 
Date of Issue
Summary of Change
with the protocol text and other studies within belatacept clinical study 
program. Update the requirements for evaluation of renal biopsy 
specimens to include assessments for acute antibody-mediated and as 
T-cell mediated rejection. Updates to the primary and secondary 
endpoints and statistical section to support the revised study design and 
to eliminate the allowance of crossover subjects. Minor edits and 
clarifications, including section numbering
Administrative 
Letter 01
12-Feb-2014
Clarify the everolimus trough sampling sequence during Year 1 of 
treatment.
Revised 
Protocol 01
21-Oct-2013 
Incorporates Amendment 01
Amendment 01 
21-Oct-2013
Modifications were made to the WOCBP definition, including FSH 
requirements and HRT washout period to align with BMS standards. 
Exclusion criteria were updated to remove annual mammogram, 
WOCBP criteria that do not apply. Updates to The Time & Events Table 
include removal of the Annual Mammogram to allow Investigators to use 
standard of care practices, the addition of a Neurological Exam and 
clarifications to align the table with the protocol text and with BMS 
belatacept program clinical studies. Protocol was updated with 
Neurological Exam requirements, modification of the clinical criteria and 
monitoring of PTLD. Modifications were made to the Events of Special 
Interest. Inclusion of Data Monitoring Committee. Minor edits and 
clarifications.
Original 
Protocol
28-Jun-2013 
Not applicable
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SYNOPSIS
Clinical Protocol IM103177
Protocol  Title: Evaluation  of  Acute  Rejection  Rates  in de novoRenal  Transplant  Recipients  Following 
Thymoglobulin Induction, CNI-free, Nulojix®(belatacept) -based Immunosuppression
Investigational Product(s) Dose and Mode of Administration, Duration of Treatment:
Belataceptwill be administered via intravenous (i.v.) infusion according to the following regimen:
Subjects randomized to the belatacept treatment group in the study  will receive a belatacept regimen consisting of 
10 mg/kg i.v. on Day 1 (started at least 12 but no more than 24 hours after completion of the initial induction dose of 
Thymoglobulin) and on Week 1 (Day 7), and then at weeks 2, 4, 8 and 12 post-transplant. After 3 months (Week 
12), subjects will receive belatacept at the maintenance dose of 5 mg/kg i.v. every 4 weeksuntil completion of the 
trial.
Thymoglobulinwill be administered via i.v. infusion according to the following regimen:
All subjects  will receive Thymoglobulin in a dose of up to 1.5 mg/kg i.v. on Day 1 (Day  of Transplant) and daily 
thereafter  (or  less  frequently,  as  tolerated)  to  reach  a  total cumulative  dose  between  3.0  and  5.5  mg/kg. 
Premedication  with  
i.v.  methylprednisolone is  
required; as  well  as  acetaminophen  and/or  antihistamine,  per  
local 
practice, are recommended to reduce the risk of infusion reactions.
Everolimus (EVL)will be administered orally according to the following regimen:
Subjects randomized to receive EVL will receive an initial dose  of 3.0 mg/day (1.5 mg bid) starting on Day 3. In 
subjects who experience delayed graft function (DGF), defined as the requirement for acute dialysis during the first 
post-transplant week, initiation of EVL may be delayed up to Day 7. In order to guide dose modifications, EVL pre 
dose trough levels should be obtained from the local laboratory per the protocol required schedule and 4 to 5 days 
after any change in dose. The dosing will be adjusted to keep pre-dose (C0) levels at 6 to 10 ng/mL for the initial 3 
months post transplantation and at 4 to 8 ng/mL after 3 months and for the remainder of the study.
Tacrolimus (TAC)will be administered orally according to the following regimen:
Subjects randomized to the tacrolimus treatment group will receive the recommended total initial dose of TAC is 0.1 
mg/kg/day orally in 2 divided doses and adjusted thereafter, on the basis of therapeutic drug monitoring, to target 
pre-dose (approximately 12-hour trough) blood concentrations of 4-11 ng/mL. Therapy with TAC may be initiated 
any time within the first 24 hours post-transplant, or delayed pending improvement in renal function, e.g., after the 
serum creatinine (SCr) concentration has decreased to ≤4 mg/dL (in the absence of dialysis). Initiation of dosing 
may be delayed up to Day 7, if, in the clinical judgment of the investigator, earlier initiation of TAC therapy is not in 
the best interest of the subject due to postoperative impairment of allograft function.
Non-Investigational Product Dose and Mode of Administration, Duration of Treatment:
Mycophenolate Mofetil (MMF) will be given orally according to the following regimen:
Subjects randomized to receive MMF will receive a daily dose of 0.5 to 2.0 g/day divided in 2 doses. The first dose 
of MMF should be administered preoperatively on the Day 1 (Day of Transplant). African Americans (Blacks) are 
eligible to be treated with higher doses, up to 3.0 g/day in divided doses. Doses can be given 4 times a day or can be 
reduced if intolerance occurs, per Investigator discretion. Subjects unable to tolerate the minimum allowable dose of 
0.5 g/day may  be  converted to mycophenolate sodium, at doses equivalent to those  
for MMF, at the investigator
's 
discretion.
Corticosteroids: will be administered throughout the study according to the following regimen:
This is a rapid corticosteroid withdrawal trial; corticosteroids are to be administered during the first week of study 
treatment  only.  All  subjects  will  
receive methylprednisolone  
(as  
the sodium  succinate,  as  premedication  prior  
to 
beginning  each  Thymoglobulin  infusion  to  reduce  the  risk  of  infusion  reactions),  to  be  administered  i.v.  over 
approximately 30 minutes, as follows:
1st Dose of Thymoglobulin:500 mg methylprednisolone i.v.
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2nd Dose of Thymoglobulin:250 mg methylprednisolone i.v.
3rd Dose of Thymoglobulin:100 to150 mg methylprednisolone i.v.
Any additional doses of Thymoglobulin:
4th Dose of Thymoglobulin: 60 mg methylprednisolone i.v.
5th  Dose  and  beyond  of  Thymoglobulin:  30  mg  methylprednisolone  
i.v.  prior  
to  each  Thymoglobulin 
infusion
Day 4 to Day 10:
• Subjects  completing  Thymoglobulin  induction  before  Day  7 may  receive  prednisone,  p.o.  (or  the 
equivalent) in lieu of the same dose of i.v. methylprednisolone:
o Day 4:60 mg prednisone p.o. (or equivalent)
o Days 5 through 7:30 mg prednisone p.o. daily (or the equivalent).
• Subjects continuing to receive Thymoglobulin induction during Days 4-10post-transplant should still 
be pre-treated with methylprednisolone i.v. as indicated above in lieu of p.o. prednisone.
• All  corticosteroids  are  to  be  discontinued  by  Day  7,  except  for  subjects  still  receiving  thymoglobulin 
induction  between  Days  8  - 10;  those  subjects  must  discontinue  corticosteroids  after  the  final  dose  of 
thymoglobulin induction has been completed.
Study Phase:IIb
Research Hypothesis: A belatacept-based maintenance immunosuppressive regimen incorporating Thymoglobulin 
induction, EVL  and  rapid  corticosteroid  withdrawal  will  result  in  acceptable  rates  of  AR  and  overall  safety
consistent with current standard of care in recipients of living and standard criteria deceased donor kidneys.
Objectives:
Primary Objective(s)
The  primary  objective  is  to  assess  the  incidence  of  clinically-suspected  and  biopsy  proven  acute  rejection 
(CSBPAR) at 6 months post-transplant in de novorenal allograft recipients treated with thymoglobulin induction, 
rapid  corticosteroid  withdrawal,  and  maintenance  belatacept  in combination  with  EVL,  or  maintenance  TAC  in 
combination with MMF.
Secondary Objectives
The effects  of each immunosuppressant regimen on the rates  of acute rejection, subject and allograft survival and 
allograft function will be evaluated as follows:
• The frequency and severity of acute rejection at 12 and 24 months post-transplant.
• Rates of subject and allograft survival at 6, 12 and 24 months post-transplant.
• Changes in renal function and severity of proteinuria at 3, 6, 12 and 24 months post-transplant.
• The  
frequency  and  
type  of  donor-specific  anti-HLA  antibodies  
(DSA)  detectable  prior  
to,  and  at  12  and 
24 months post-transplant.
• The  safety  and tolerability  of  each  
treatment regimen,  as  based  upon the results  of  vital  signs and  safety 
laboratory  assessments,  and  cumulative  rates  of  adverse events  reported  at  3,  6,  12,  and  24  months 
post-transplant.
• The  frequency  of  cardiovascular  and  metabolic  co-morbidities  reported  at  3,  6,  12,  and  24  months 
post-transplant.
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Key Exclusion Criteria:
• Subjects  who are seronegative for prior exposure to EBV or those whose EBV serologic status is unknown at 
randomization
• Genetically-identical donor recipient pairs (ie, identical twins)
• Subjects with a recent (within 3 months prior to transplant) PRA ≥20%
• Subjects with a past history of or a current need for desensitization therapy
• Subjects with a positive T-cell lymphocytotoxic cross match or any detectable donor specific antibodies prior to 
transplantation
• Recipients of an extended criteria donor (ECD) kidney
• Subjects  with prior or concurrent non-renal solid organ or cell (e.g., pancreas or kidney-pancreas, islet cell or 
stem-cell) transplants or deemed by the investigator as being likely to require a non-renal transplant in the next 
3 years 
• Subjects receiving paired (dual or en bloc) kidney transplants
• CMV negative subjects scheduled to receive a CMV positive donor kidney
• Subjects  with  
the any  of  
the  
following  underlying  conditions as  
the  primary  etiology  of  
their end-stage renal 
disease (ESRD):  Primary  focal  segmental  glomerulosclerosis;  Type  I  or  II  membranoproliferative 
glomerulonephritis; Hemolytic Uremic Syndrome (HUS) / Thrombotic Thrombocytopenic Purpura; 
• Subject with current evidence or past history of active or inadequately treated latent TB infection. Subjects must 
have documentation of negative screening for active and latent TB infection to be  eligible for randomization, 
specifically:
A chest x-ray (posterior-anterior and lateral views) that is negative for radiographic evidence of pulmonary 
TB within the last 6 months prior to transplant. 
A  negative  screening  
test  
for  
latent  TB  
infection  
(LTBI)  
[intradermal  PPD,  or  
interferon-gamma  
release 
assay (IGRA) such as QuantiFERON®TB Gold test or T-Spot-TB] that was performed at any timeprior to 
the current transplant. Those subjects who do not have a documented negative result, specifically from an 
IGRA test performed within the last 3 months prior to randomizationmust be screened for LTBI with an 
IGRA  test  performed  during  the  Screening  Visit.  Note:  Results  of  the  Screening  Visit  IGRA  are  not 
required for randomization when the results from a historical negative screening test (PPD or IGRA) are 
available.
−If the Screening IGRA test result is positive and there is no historical negative screening test (PPD or 
IGRA) result for LTBI available so that the patient is a screen failure, the patient may be re-screened 
following completion of what is considered, per local standard of care to be an adequate course of therapy 
for LTBI, so long as the only cause of the screen failure was the positive IGRA test result.  
• Subjects with a body mass index (BMI) at screening of > 35 kg/m2for nondiabetic subjects or > 30 kg/m2(due 
to higher risk of wound complications)
Study Assessments:
Study Endpoints
All primary and secondary endpoints listed below will be assessed and described for each treatment group.
Primary Endpoint(s)
The incidence of CSBPAR at 6 months post-transplant, in the individual treatment groups:
−Belatacept + EVL
−TAC + MMF
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Secondary Endpoint(s)
The two treatment groups will be compared for all secondary endpoints.
Acute Rejection
• Treatment differences in the incidence of CSBPAR at 6, 12 and 24 months post-transplant in the belatacept +
EVL versus TAC + MMF treatment groups
• Time to CSBPAR
• Treatment differences in the severity grades and therapeutic modalities used to treat all episodes of CSBPAR at 
6, 12, and 24 months post-transplant:
−Severity: To  be assessed  by the local pathologist, using the 2007 update to the Banff 97 classification of 
renal allograft pathology
−Treatment  regimen: Categorical  analysis  of  CSBPAR  episodes  by  treatment  received, including: 
a) corticosteroids;  b) T-cell  depleting  agent(s);  c)  
renal  
replacement  
therapy;  d)  plasmapheresis;  e)  
IVIg; 
f) rituximab.
Subject and graft survival
• Proportion of all subjects who survive with a functioning graft at 6, 12 and 24 months post-transplant;
• Proportion of all subjects who experience death by 6, 12 and 24 months post-transplant;
• Proportion of all subjects who experience graft loss by 6, 12 and 24 months post-transplant;
• Time to event analysis of death and graft loss.
Renal Function
• Absolute (mean and median) cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from  the 4 
variable Modification of Diet in Renal Disease (MDRD) formula;
• The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant;
• Slope of the change in cGFR from Month 3 to Months 6, 12 and 24post-transplant;
• Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.
Donor Specific Anti-HLA Antibodies (DSA)
• Percentage of subjects with, and titers of , pre-existing (pre-transplant) and de novo (post transplant) DSA on 
Day 1 (pre-transplant, pre-dose), and at Months 12 and 24 post-transplant;
• Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of 
complement fixing properties.
Safety and tolerability of each treatment regimen
• Incidence of all AEs and SAEs at 6, 12, and 24 months post-transplant;
• Incidence of Events of Special Interest (ESI) at 6, 12 and 24 months post-transplant;
• Description and incidence of clinically significant changes in vital signs;
• Description and incidence of laboratory test abnormalities.
Cardiovascular and metabolic co-morbidities
• Incidence of NODAT at 6, 12, and 24 months post-transplant;
• Absolute (mean and median) values  for SBP and DBP at 3, 6, 12 and 24 months post-transplant;
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• Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant;
• Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant, and mean change from baseline 
levels at Months 12 and 24 for the following fasting lipid levels:
−Serum total serum cholesterol
−Serum high density lipoprotein (HDL) cholesterol
−Serum low density lipoprotein (LDL) cholesterol
−Serum triglycerides (TG)
• Mean  fasting  blood  glucose  
levels  and mean  changes  from  baseline values  at Months  6,  12  and  24 months 
post-transplant;
• Mean  whole  blood  HbA1C  concentrations  and  mean  changes  from  baseline values  at Months  6,  12  and 
24 months post-transplant.
Statistical Considerations:
Sample Size:
This study is descriptive in nature and is not powered to show statistically significant treatment differences for any 
outcome  measure.  A  sample  approximately  70 subjects  
randomized  
in a  1:1 ratio  
to  belatacept  + EVL  or  TAC  + 
MMF groups is planned.
If the true probability  of CSBPAR in the belatacept + EVL treatment group is 3.8%, a sample size of 35 subjects 
allows  
the  estimation  of  
the  population  proportion  (πp)  with  a 95%  CI of  0.2  %  
to  16.4%  around  
the  observed 
proportion of CSBPAR. If the rate is 3%, in the TAC +MMF treatment group, then the 95% CIǂaround the estimate 
would be 0.1 % to 15.1 %, for lower and upper limits, respectively
Analyses:
Demographic  and  baseline  characteristics  of  recipients  and  donors will  be  summarized  descriptively  for  each 
treatment  group,  by  means  and  standard  deviation  for  continuous  variables,  and  by  frequency  distribution  for 
categorical variables.
Rate of acute rejection will be summarized by treatment group at Months 6, 12 and 24 using point estimates of the 
proportion  of  subjects  who  have  experienced  at  
least  one  episode  of  CSBPAR  along  with  and  
the  corresponding 
95%  CIs.  Two-sided  95%  CIs  will  be  generated  for  the  differences between  treatment  groups.  Descriptive 
summaries will be provided for the percentages of subjects with CSBPAR in each treatment group, including those 
for severity grade and treatment received. All grades of acute rejection, excluding those assessed by the pathologist 
as "borderline  changes"  (biopsy  findings  “suspicious”  for  acute cellular  
rejection  per  
the  Banff  criteria),  will  be 
included  
in  
the  analyses of  
the primary  and relevant  secondary  endpoints  
for  acute  
rejection. Sensitivity  analyses 
will  be  performed  
including  acute  
rejections  assessed  by  
the pathologist  as  "borderline  changes"  
(biopsy  
findings 
“suspicious”  
for  acute  cellular rejection  per the  Banff  criteria).  
In  addition,  Kaplan-Meier  
(KM)  cumulative  event 
rates will also be performed by treatment groups.
The endpoint of subject and graft survival at 6, 12 and 24 months post-transplantation will be summarized within 
each treatment group using point estimates of the proportion of subjects surviving with a functioning graft, and the 
corresponding 95% CIs. The proportion of subjects who die, proportion of subjects who have a graft loss, and the 
proportion of subjects  who experience the following outcomes will each be summarized using point estimates and
95% CI within each treatment group.
• Overall graft loss rates at 6, 12 and 24 months
• Rates of death with a functioning graft at 6, 12 and 24 months
• Rates of pure death (death censored) graft loss at 6, 12 and 24 months
Calculated GFR at Months 3, 6, 12, and 24 and change in cGFR from Month 3 to Months 6, 12 and 24, respectively 
will be descriptively summarized. For a subject who has one or more missing values for cGFR due to a graft loss or 
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death, the missing cGFR will be imputed as “zero”. A linear mixed effects model will be used to analyze changes 
from Month 3 cGFR. Details of the analyses will be available in the Statistical Analysis Plan.
Safety analysis will be based on all randomized, transplanted, and treated subjects. All AEs will be summarized and
listed by treatment groups. SAEs and AEs that result in discontinuation of the study drug will also be tabulated in 
detail.  Laboratory  marked  abnormalities,  defined  as  those  identified  as  “critically”  out  of  range  per  the  central 
laboratory manual, will be summarized descriptively. There will be no statistical testing of group differences with 
respect to  
frequencies of adverse  events or laboratory marked abnormalities or changes in clinical laboratory tests 
from baseline (last measurement prior to randomization).
All safety summaries except those for reports of death, graft loss, PTLD, malignancies, and serious infections, will 
be  based  only  on  data  at the  scheduled  analysis  
time  point  applying  
‘last dose  date  +  56’  cut  counting rules.  For 
events of death, graft loss, PTLD, malignancies, and serious infections, two different summaries will be prepared. 
The first summary will be based only on data at the scheduled analysis time point applying ‘last dose date + 56’ cut 
counting  
rules.  The  secondary  summary  will  be  based  on  all  available  data  at  
the  scheduled  analysis  
time  point 
without  applying  
‘last  dose  date  +  56’  cut  counting  
rules.  The frequencies  and  
incidence  
rates  using  person-year 
method with exposure will be summarized by treatment groups.
All other endpoints will be descriptively summarized and presented by treatment group.
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3.5 Discontinuation of Subjects from Treatment 
.................................................... 
3.6 Post Treatment Study Follow up....................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up 
.................................................................................... 
4 TREATMENT 
........................................................................................................... 
4.1 Study Treatments 
.............................................................................................. 
4.1.1 Investigational Product 
............................................................................ 
4.1.2 Non-investigational Product 
.................................................................... 
4.1.3 Handling and Dispensing ........................................................................ 
4.1.3.1 Belatacept for Injection................................................................... 
4.1.3.2 Thymoglobulin for Injection ........................................................... 
4.1.3.3 Everolimus Tablets.......................................................................... 
4.1.3.4 Tacrolimus Tablets.......................................................................... 
4.2 Method of Assigning Subject Identification 
..................................................... 
4.3 Selection and Timing of Dose for Each Subject 
............................................... 
4.3.1 Belatacept ................................................................................................ 
4.3.2 Thymoglobulin 
......................................................................................... 
4.3.3 Everolimus 
............................................................................................... 
4.3.4 Mycophenolate Mofetil ............................................................................ 
4.3.5 Tacrolimus 
............................................................................................... 
4.3.6 Corticosteroids 
......................................................................................... 
4.3.7 Prophylaxis After Transplantation .......................................................... 
4.3.7.1 Antiviral 
.......................................................................................... 
4.3.7.2 Pneumocystis jiroveci pneumonia (PJP) 
........................................ 
4.3.7.3 Oral Moniliasis/Candidiasis 
........................................................... 
4.3.8 Dose Modifications 
.................................................................................. 
4.4 Blinding/Unblinding 
......................................................................................... 
4.5 Treatment Compliance 
...................................................................................... 
4.6 Destruction and Return of Study Drug 
............................................................. 
4.6.1 Destruction of Study Drug 
....................................................................... 
4.6.2 Return of Study Drug 
............................................................................... 
5 STUDY ASSESSMENTS AND PROCEDURES 
..................................................... 
5.1 Flow Chart/Time and Events Schedule 
............................................................. 
5.2 Study Materials 
................................................................................................. 
5.3 Safety Assessments 
........................................................................................... 
5.3.1 Imaging Assessment for the Study............................................................ 
5.3.2 Visit Windows........................................................................................... 
5.3.3 Vital Signs 
................................................................................................ 
5.3.4 Physical Measurements ........................................................................... 
5.3.5 Physical Examination 
.............................................................................. 
5.3.6 Laboratory Assessments........................................................................... 
5.3.6.1 Central Laboratory 
......................................................................... 
5.3.6.2 Local Laboratory 
............................................................................ 
5.3.6.3 Collection, Shipping and Transport 
................................................ 
5.3.7 Assessment of Clinical Suspicion of Acute Rejection .............................. 
5.3.8 Renal Biopsy Procedure .......................................................................... 
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1.3 
Objectives(s)
1.3.1 
Primary Objective
The primary objective is to assess the incidence of clinically-suspected and biopsy proven acute 
rejection (CSBPAR) at 6 months post-transplant in de novorenal allograft recipients treated with 
thymoglobulin  induction,  rapid  corticosteroid  withdrawal,  and  maintenance  belatacept,  in 
combination with EVL, or maintenance TAC in combination with MMF.
1.3.2 
Secondary Objectives
The  effects  of  each  immunosuppressant  regimen  on  the  rates  of  acute  rejection,  subject and 
allograft survival and allograft function will be evaluated as follows (endpoints to measure these
objectives are described with further specified details in Section 8.3):
• The frequency and severity of acute rejection at 12 and 24 months post-transplant.
• Rates of subject and allograft survival at 6, 12 and 24 months post-transplant.
• Changes  in  renal  function  and  severity  of  proteinuria  at  3,  6, 12  and  24  months  post-
transplant.
• The frequency and type of donor-specific anti-HLA antibodies (DSA) detectable prior to, and 
at 12 and 24 months post-transplant.
• The safety and tolerability of each treatment regimen, as based upon the results of vital signs 
and  safety  
laboratory  assessments,  and  cumulative  
rates  of  adverse events  
reported  at  3,  6, 
12, and 24 months post-transplant.
• The  frequency  of  cardiovascular  and  metabolic  co-morbidities  reported  at  3,  6,  12,  and 
24 months post-transplant.
 
 
 
 
 
 
  
  
 
 
 
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1.4 
Product Development Background
A detailed description of the preclinical and clinical studies conducted to-date is available in the 
current version of the Investigator Brochure.
Belatacept  has  been  studied  in  a  comprehensive  clinical  development  program  totaling
2366 subjects across all indications as of June/July 2010. Assessment of the efficacy and safety 
of belatacept is based on results from three similarly designed studies in de novorenal transplant 
recipients, collectively referred to as the core studies, these include: one Phase 2 (IM103100)45
and  two  Phase  3  (IM103008  and  IM103027)  studies46,47.  These  trials  evaluated  two  dosing 
regimens  of  belatacept  
in  blinded  fashion,  a  more  
intensive  
(MI)  
regimen  and  a  
less  
intensive 
(LI) regimen, each compared to a cyclosporine (CsA) active comparator treatment regimen. All 
treatment  groups  also  received  basiliximab  induction,  mycophenolate  mofetil  (MMF),  and 
corticosteroids.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2 ETHICAL CONSIDERATIONS
2.1 
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying  European  Union  Directive  2001/20/EC  and  the  United  States  Code  of  Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and  the  subject  informed  consent  will  receive  Institutional  Review  Board/Independent  Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS and/or designee immediately. A serious 
breach  
is a  breach of the conditions and principles of GCP  
in connection with the study or the 
protocol,  which  is  likely  to  affect,  to  a  significant  degree,  the  safety  or  physical  or  mental 
integrity of the subjects of the study or the scientific value of the study.
Personnel  involved  in  conducting  this  study  will  be  qualified  by  education,  training,  and 
experience to perform their respective tasks.
This  study  will  not  use  
the  services  of  study  personnel  where  sanctions  have  been  
invoked  or 
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
2.2 
Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from  the  IRB/IEC  for  the  protocol,  consent  form,  subject  recruitment  materials 
(eg, advertisements),  and  any  other  written  information  to  be  provided  to  subjects.  The 
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investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure 
or product labeling information to be provided to subjects and any updates.
The  investigator  or  BMS  should  provide  the  IRB/IEC  with  reports,  updates  and  other 
information (eg, expedited safety reports, amendments, and administrative  
letters) according to 
regulatory requirements or institution procedures.
2.3 
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate.
In situations where consent cannot be given to subjects, their legally acceptable representatives 
are  clearly  and  fully  informed about  the  purpose,  potential  risks,  and  other  critical  issues 
regarding clinical studies in which the subject volunteers to participate.
BMS  and/or  designee  will  provide  the  investigator  with  an  appropriate  (ie,  Global  or  Local) 
sample  informed  consent  form  which  will  include  all  elements  required  by  ICH,  GCP  and 
applicable regulatory requirements. The sample informed consent form will adhere to the ethical 
principles that have their origin in the Declaration of Helsinki.
Investigators must:
1. Provide a copy of the consent form and written information about the study in the language 
in  which  the  subject  is  most  proficient  prior  to  clinical  study  participation.  The  language 
must be non-technical and easily understood.
2. Allow  time  necessary  for  subject  or  subject
's  legally  acceptable  representative  to  inquire 
about the details of the study.
3. Obtain  an  informed  consent  signed  and  personally  dated  by  the  subject  or  the  subject
's 
legally  acceptable  representative  and  by  the  person  who  conducted  the  informed  consent 
discussion.
4. Obtain  the  IRB/IEC’s  written  approval/favorable  opinion  of  the  written  informed  consent 
form and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
5. If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently  becomes  capable of  making and communicating  his 
or  her  informed  consent  during  
the  study,  consent  must  additionally  be obtained from  
the 
subject.
6. Revise the informed consent whenever important new information becomes available that is 
relevant to the subject
's consent. The investigator, or a person designated by the investigator, 
should  fully  inform  the  subject  or  the  subject
's  legally  acceptable  representative  or  legal 
guardian, of all pertinent aspects of the study and of any new information  relevant  
to  
the 
subject
's  willingness  
to  continue  participation  
in  
the  study.  This  communication  should  be 
documented.
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The  confidentiality  of  records  that  could  identify  subjects  must  be  protected,  respecting  the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects
' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The  consent  form  must  also  include  a  statement  that  BMS  and/or designee  and  regulatory 
authorities have direct access to subject records.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3 INVESTIGATIONAL PLAN
3.1 
Study Design and Duration
This  is  a  randomized,  open-label,  multicenter, parallel-group  study to  be  conducted  at 
approximately 20 sites in North and South America and the European Union. Approximately70
subjects (n = 35 per group), scheduled to receive ade novokidney transplant,will be randomized 
(stratified by study site/center) in a 1:1 ratio, to 1 of the following 2 treatment arms:
a) Thymoglobulin + Belatacept + Everolimus
b) Thymoglobulin + Tacrolimus + MMF
For  administrative  reasons  related  to  the  availability  of  study  drug,  BMS  will  prematurely 
terminate enrollment in this clinical trial according to the following schedule:
• 
As of 18 October 2016 at all sites without previously randomized subjects;
• 
As of 31 December 2016 at all remaining sites. 
All subjects randomized on or prior to 31 December 2016 will remain in the study on assigned 
therapy to complete the protocol-specified period of study participation.
This  
is a rapid corticosteroid withdrawal trial; corticosteroids are to be administered during the 
first week of study treatment only, and discontinued by Day 7, except for subjects still receiving 
Thymoglobulin induction between Days 8-10, who will continue to require methylprednisolone 
i.v. prior to beginning their Thymoglobulin infusions on those days. The duration of the study is 
24 months, with a subsequent 8-week post last dose safety  
follow-up  period  
for  all  
subjects.  
In 
addition, belatacept-treated subjects who discontinue treatment or complete the study and do not 
continue  
treatment  with  commercially  available  Nulojix® thereafter, will  be  seen  at  12  and  24 
weeks post last dose for the collection of PK and/or immunogenicity samples.
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Eligibility criteria for this study have been carefully considered to ensure the safety of the 
study subjects and that the results of the study can be used. It is imperative that subjects 
fully meet all eligibility criteria.
3.3.1 
Inclusion Criteria
For entry into the study, the following criteria MUST be met.
1. Signed Written Informed Consent
a) The subject or legal representative is willing to provide signed written informed consent
2. Target Population
a) Adults  with  end-stage  renal  disease (ESRD) scheduled  
to  undergo  
transplantation  of  a
non-HLA identical, living or standard criteria deceased (SCD) donor kidney
b) Subject Re-enrollment: This study does not permit the re-enrollment of a subject who has 
discontinued the study as a pre-treatment failure.
c) Subjects with serologic evidence of prior exposure to EBV. Evidence of prior exposure is 
to be determined locally by positive testing for IgG antibodies directed against EBV viral 
capsid  antigen  
(VCA)  and  Epstein-Barr  nuclear  antigen  
(EBNA).  Historical  
results  are 
acceptable.
3. Age and Reproductive Status
a) Men and women, ages 18 to 75 years at Screening, inclusive
b) Women of childbearing potential (WOCBP)  must use  method(s) of contraception  based 
on  the  tables  in Appendix  1.  Since  there  is  insufficient  information  to  assess 
teratogenicity  
(preclinical studies  have  not  been  done),  a  highly  effective  method(s)  of 
contraception (failure rate of less than 1% per year) is required. The individual methods 
of contraception and duration should be determined in consultation with the investigator. 
WOCBP must follow instructions for birth control for a period of 8 weeks after the last 
dose of study drug.
NOTE:  According  to  the  US  product  information  for  mycophenolate  mofetil 
(CellCept
®), two reliable forms of contraception must be used simultaneously unless 
abstinence is the chosen method.
c) WOCBP must  have  a  negative  serum  or  urine  pregnancy  test  (minimum  sensitivity 
25 IU/L  or  equivalent  units  of  beta-human  chorionic  gonadotrophin  [β-HCG])  within 
24 hours prior to the start of investigational product.
d) Women must not be breastfeeding
e) Men  who  are  sexually  active  with  WOCBP  must  use  any  contraceptive  method  with  a 
failure rate of less than 1% per year. The investigator shall review contraception methods 
and  
the  
time  period  
that  contraception  must  be  followed.  Men  
that  are  sexually  active 
with WOCBP must follow instructions for birth control for a period of 8 weeks after the 
last dose of study drug.
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f) Women  who  are  not  of  childbearing  potential  (i.e.,  
those  who are  postmenopausal  or 
surgically sterile; see Section 3.3.3for the definition of WOCBP) and azoospermic men 
do not require contraception.
3.3.2 
Exclusion Criteria
Subjects meeting the following criteria are prohibited from entry into the study.
1. Target Disease Exceptions
a) Subjects who are seronegative for prior exposure to EBV or those whose EBV serologic 
status is unknown at randomization.
b) Genetically-identical donor recipient pairs (ie, identical twins)
c) Subjects with a recent (within 3 months prior to transplant) PRA ≥20%
d) Subjects with a past history of, or current need for desensitization therapy
e) Subjects with previous graft loss due to acute rejection
f) Subjects  with  a  positive  T-cell  lymphocytotoxic  cross  match  or  any  detectable  donor 
specific antibodies prior to transplantation
g) Recipients of kidneys from donors < 10 years old
h) Recipients of an extended criteria donor (ECD) kidney, defined as:
i) Donors ≥60 years old, or
ii) Donors aged 50 – 59 years with any 2 of the following:
• death from cerebrovascular accident;
• hypertension;
• serum creatinine > 1.5 mg/dL; or
iii) Not applicable per Protocol Amendment 03
iv) Recipients of kidneys donated after cardiac death
i) Subjects with prior or concurrent, non-renal  solid organ or cell (e.g., pancreas, kidney-
pancreas, or islet cell orstem-cell) transplants, and those deemed  by the Investigator as 
being likely to require a non-renal transplant in the next 3 years 
j) Subjects receiving paired (dual or en bloc) kidney transplants
k) CMV-negative subjects scheduled to receive a kidney from a CMV-positive donor
2. Medical History and Concurrent Diseases
a) Subjects with ESRD due to any of the following underlying chronic renal diseases:
• Primary focal segmental glomerulosclerosis (FSGS)
• Type I or II membranoproliferative glomerulonephritis (MPGN)
• Hemolytic uremic syndrome (HUS) / Thrombotic Thrombocytopenic Purpura 
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If  a  subject  has  ESRD  of  unknown  etiology  and/or  has  no  histologically-confirmed 
underlying diagnosis, the subject may be enrolled into the study if, in the opinion of the 
Investigator,  the  patient
's  prior  clinical,  laboratory,  and/or radiographic  findings  are 
unlikely to be consistent with any of the above diagnoses.
b) Hepatitis C virus (HCV): Subjects or donors known to be positive for anti-HCV antibody,
or for HCV RNA detectable by polymerase chain reaction (PCR)
c) Hepatitis B virus (HBV): subjects or donors known to be positive for hepatitis B surface 
antigen or for HBV DNA detectable by PCR
d) Human immunodeficiency virus (HIV): subjects or donors known to be HIV positive
e) Subjects with current evidence or past history of active or inadequately* treated latent TB 
infection
52. Subjects must have documentation of negative screening for active and latent 
TB infection to be eligible for randomization*, specifically:
i) A  chest  x-ray  
(posterior-anterior  and  
lateral  views)  
that  
is negative  
for  
radiographic 
evidence of pulmonary TB within the last 6 months prior to transplant. 
ii) A  negative  screening  test  for  latent  TB  infection  (LTBI)  [intradermal  PPD,  or 
interferon-gamma  release  assay  (IGRA)  such  as  QuantiFERON® TB  Gold  test  or 
T-Spot-TB] that was performed at any timeprior to the current transplant. 
(1) Those subjects who do not have a documented negative result, specifically  
from 
an IGRA test performed within the last 3 months prior to randomization,must be 
screened for LTBI with an IGRA test performed during the Screening Visit.
*Notes: 
♦For this  protocol,  "adequately  
treated"  LTBI  
is  defined  as  completion  of  a  standard 
course of antimicrobial therapy per a local standard of care, e.g., for the U.S., recent 
CDC guidelines52.
♦Results  of  the  Screening  Visit  IGRA  are  not  required  for  randomization when  the 
results from a historical negative screening test (PPD or IGRA) are available [see (2) 
(e) (ii) above].
♦If the Screening IGRA test result is positive and there is no historical negative 
screening test (PPD or IGRA) result for LTBI available so that the patient is a screen 
failure, the patient may be re-screened following completion of what is considered, 
per local standard of care to be an adequate course of therapy for LTBI, so long as the 
only cause of the screen failure was the positive IGRA test result.  
♦IGRA  testing  is  to  be  done  by  the  central  laboratory.  However, if  equipment  for 
sample preparation prior to shipment to the central  
laboratory is  not available at the 
site, a local laboratory IGRA test is acceptable.
♦If a  historical  negative  screening test (PPD or IGRA) result  
for LTBI was available 
and  the  patient  was  randomized  on  that  basis,  but  the  Screening  Visit  IGRA  is 
subsequently  
reported (post-transplant)  
to  be  positive,  
treatment  
for  
latent  TB must
be initiated upon receipt of the test result by the Investigator. Treatment may consist 
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of isoniazid (INH, isonicotinic acid hydrazide), 300 mg p.o. once daily for 9 months
52
or an alternative that is consistent with the local standard of care.
f) History of biopsy-confirmed malignancy (other than nonmelanoma skin cancer cured by 
resection) within the previous 5 years prior to the current transplant.
g) Subjects with a body mass index (BMI) at screening of > 35 kg/m
2 for  nondiabetic 
subjects or > 30 kg/m
2for diabetic subjects (due to higher risk of wound complications)
h) Subjects whose life expectancy is severely limited (< 6 months).
i) Subjects  with  a  current  or  past  history  of  substance  abuse  
(drug  or alcohol)  within  
the 
past  5  years,  or  psychotic  disorders  that  are  not  compatible  with  adequate  study 
adherence and follow-up.
j) Subjects with active peptic ulcer disease, chronic diarrhea, or gastrointestinal 
malabsorption
k) Subjects with any active infection or other contraindication that would normally preclude 
transplantation
3. Physical and Laboratory Test Findings
a) Female subjects who had a breast cancer screening that is suspicious for malignancy, and in 
whom  the  possibility  of  malignancy  cannot  be  reasonably  excluded  following  additional 
clinical, laboratory or other diagnostic evaluations.
b) Subjects  with  
laboratory  values  
that  meet  any  of  
the  following  criteria  are  
to  be  excluded 
from the study:
Hematology:
• Hemoglobin < 7 g/dL
• Platelets < 80,000/mm
3
• White blood cell (WBC) count < 3000/mm3(3 x 109/L)
Chemistry:
• Bilirubin > 1.5 x upper limit of normal range (ULN); exception: subjects who have a 
clinical or genetic diagnosis of Gilbert’s Syndrome and have a normal direct bilirubin 
are eligible.
• Aspartate aminotransferase (AST) ≥2 x ULN
• Alanine aminotransferase (ALT) ≥2 x ULN
4. Allergies and Adverse Drug Reaction
a) History of drug or other allergy which in the opinion of the principal investigator makes 
the subject unsuitable for participation in the study
5. Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for 
the entire study period and for up to 8 weeks after the last infusion.
b) Not applicable per Protocol Amendment 03
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c) Not applicable per Protocol Amendment 03
6. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects  who  are  compulsorily  detained  
for  
treatment  of  either  a  psychiatric  or  physical 
(eg, infectious disease) illness
c) Subjects  currently  receiving  immunosuppressive  agent(s)  (eg, methotrexate,  infliximab, 
etanercept,  etc.)  for  other  indications,  such  as  an  autoimmune disease,  or  subjects  with 
comorbidities that treatment with such agents are likely during the trial
d) Subjects who have used any investigational drug within 30 days prior to Day 1 visit
Eligibility criteria for this study have been carefully considered to ensure the safety of the 
study subjects and that the results of the study can be used. It is imperative that subjects 
fully meet all eligibility criteria.
3.3.3 
Women of Childbearing Potential
A  woman  of  childbearing  potential  (WOCBP)  is  defined  as  any  female  who  has  experienced 
menarche  and  who  has  not  undergone  surgical  sterilization  (hysterectomy  or  bilateral 
oophorectomy) or is not postmenopausal. Menopause is defined as 6 months of amenorrhea in a 
woman  over  age  45  in  the  absence  of  other  biological  or  physiological  causes.  In  addition, 
women  under  the  age  of  55  must  have  a  serum  follicle  stimulating hormone  (FSH)  level 
> 40mIU/mL to confirm menopause*.
*Women  treated  with  hormone  replacement  therapy,  (HRT)  are  likely  to  have  artificially 
suppressed  FSH  
levels and  may require a washout period  
in order to obtain a physiologic  FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the  washout  period  below  are  suggested  guidelines  and  the  investigators  should  use  their 
judgment  
in  checking  serum  FSH  
levels.  
If  
the  serum  FSH  
level  
is  >  40  mIU/mL  at  any  
time 
during the washout period, the woman can be considered postmenopausal:
• 1 week minimum for vaginal hormonal products, (rings, creams, gels)
• 4 week minimum for transdermal products
• 8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
If an FSH level is not available at enrollment and if it is deemed medically important to maintain 
HRT, these women will be considered as WOCBP.
WOCBP  must  be  made  aware  of  the  increased  risk  of  first  trimester  pregnancy  loss  and 
congenital malformations with mycophenolic acid (MPA) products (both mycophenolate mofetil 
and mycophenolate  sodium) and  must  be  counseled  regarding  pregnancy  prevention  and 
planning.
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As required by BMS Standard Operating Procedure, participation in this study requires the use of 
two  forms  of  contraception  for  both  WOCBP  and  female  partners  of  male  subjects  who  are 
WOCBP. Male subjects must inform their female partners who are WOCBP of the contraceptive 
requirements of the protocol and are expected to adhere to using 2 forms of contraception with 
their partner.
Acceptable birth control methods for WOCBP are listed in Appendix I to this protocol.
For WOCBP assigned to receive TAC in combination with MMF (and those who, subsequently, 
may be switched to mycophenolate sodium for intolerance to MMF) and who become pregnant 
while using either mycophenolate preparation, or within 6 weeks of discontinuing therapy:
• They should be apprised of the potential hazard to the fetus. In certain situations, the subject 
and her healthcare practitioner may decide that the maternal benefits outweigh the risks to the 
fetus.
• (U.S.  sites  only):  The  principal  investigator  should  report  the  pregnancy  to  the 
Mycophenolate  
Pregnancy  
Registry  
(1-800-617-8191 
or 
https://www.mycophenolatepregnancyregistry.com  (as  of  November 13,  2014))  and  should 
strongly encourage the patient to enroll in the pregnancy registry.)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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If  study treatment  
is discontinued prior to the subject’s  completion of the study, the reason for 
the  discontinuation  must  be  documented  in  the  subject’s  medical  records  and  entered  on  the 
appropriate case report form (CRF) pages.
3.6 
Post Treatment Study Follow up
Withdrawal  of  a  subject  from  study  medication  does  not  
imply  
that  
the  subject  is  withdrawn 
from  the  study.  Early  Termination  (ET)  and  Follow-Up  Safety  visit procedures  must  be 
completed  per Table  5.1-3for  all  subjects  who  discontinue  study  drug. Information  on  subject 
and allograft survival will  be collected for all  
subjects through 24 months post-transplant (at 6, 
12 and 24 months).
3.6.1 
Withdrawal of Consent
Subjects who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision  to  withdraw  consent  from  future  follow-up in  writing,  whenever  possible.  The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to  whether  
the  withdrawal  is  from  further  
treatment  with  study drug  only  or  also  from  study 
procedures  and/or  post  
treatment study  follow-up, and  entered  on  the  appropriate  CRF  page. 
Since  vital  status  (whether  
the  subject  is  alive  or  dead)  is  being  measured,  publicly  available 
information should be used to determine vital status only as appropriately directed in accordance 
with local law.
3.6.2 
Lost to Follow-Up
All  reasonable  efforts  must  be  made  
to  
locate  subjects  
to  determine  and  report  
their  ongoing 
status.  This  
includes  
follow-up  with  persons  authorized  by  
the subject  as  noted  above.  Lost  
to 
follow-up  
is defined  by the  
inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If  
investigator’s use of third-party representative  
to assist  
in the  
follow-up portion of the study 
has  been  included  in  the  subject’s  informed  consent,  then  the  investigator  may  use  a 
Sponsor-retained  third-party  representative  to  assist  site  staff  with  obtaining subject’s  contact 
information or other public  vital status data necessary to complete the  
follow-up portion of the 
study. The  site  staff  and  
representative  will  consult  publicly  available  sources,  such  as  public 
health  registries  and  databases,  in  order  to  obtain  updated  contact  information.  If  after  all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
4 TREATMENT
Study  drugs  include  both  Investigational  Medicinal  Products  (IMP)  and  Non-investigational 
(NIMP) and can consist of the following:
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• All products, active or placebo, being tested or used as a comparator in a clinical trial.
• Study required premedication, and
• Other  drugs  administered  as  part  of  the  study  that  are  critical  to  claims  of efficacy 
(eg, background therapy, rescue medications)
• Diagnostic  agents:  (such  as  glucose  for  glucose  challenge)  given  as  part  of  the  protocol 
requirements must also be included in the dosing data collection.
4.1 
Study Treatments 
Table 4.1-1: 
Product Description 
Product 
Description and 
Dosage Form
Potency
Primary 
Packaging
(Volume)/ 
Label Type
Secondary 
Packaging
(Qty) /Label 
Type
Appearance
Storage Conditions
(per label)
Belatacept 
Infusion
250 mg
Glass vial/one 
panel open
White 
cardboard 
container/one 
panel open label
White to off-
white, whole or 
fragmented 
cake in a vial.
Store Refrigerated;
2-8 Degrees C 
36-46 Degrees F; 
Protect From Light 
Thymoglobulin 
Infusion
25 mg
Dispensed in 
original market 
product vial
Card board 
dispensing box 
(if applicable)
Lyophilized 
powder in a vial
Store Refrigerated at 
2- 8 Degrees C
Everolimus tablet
0.25 mg 
and 0.75 
mg tablets
Dispensed in 
original market 
product 
package/over 
label
Card board 
dispensing box 
(if applicable)
Tablet-Market 
product image
Store as per market 
product label
Tacrolimus tablet
0.5 mg 
and 1.0 
mg tablets
Dispensed in 
original market 
product 
package/over 
label
Card board 
dispensing box 
(if applicable)
Tablet-Market 
product image
Store as per market 
product label
4.1.1 
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined  as  a  pharmaceutical  form  of  an  active  substance  or  placebo  being  
tested  or  used  as  a 
reference in a clinical study, including products already with a marketing authorization but used 
or  assembled  (formulated  or  packaged)  differently  than  the  authorized  form,  or  used  for  an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the  
responsibility  of  
the  
investigator to  ensure  
that  
investigational  product  
is  only  dispensed  
to 
study  subjects and only used as described  
in this  protocol. The  
investigational product must be 
dispensed only from official study sites by authorized personnel according to local regulations.
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In  this  protocol,  investigational  product(s)  is/are:  belatacept,  Thymoglobulin  everolimus  and 
tacrolimus.
4.1.2 
Non-investigational Product
Other  medications  used  as  support  or  escape medication  for  preventative,  diagnostic,  or 
therapeutic  reasons,  as  components  of  the  standard  of  care  for a  given  diagnosis,  may  be 
considered as non-investigational products.
In  this  protocol,  non-investigational  product(s)  is/are:  mycophenolate  mofetil  (MMF), 
mycophenolate sodium and corticosteroids, or their equivalents.
4.1.3 
Handling and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding  the  quality  or  appearance  of  the  study  drug  arise,  the  study  drug  should  not  be 
dispensed and contact BMS immediately.
Investigational product documentation must be maintained that includes all processes required to 
ensure  drug  is accurately  administered.  This  includes  documentation  of  drug  storage, 
administration  and,  as  applicable,  storage  temperatures,  reconstitution,  and  use  of  required 
processes (eg, required diluents, administration sets).
For non-investigational product, if marketed product is utilized, it should be stored in accordance 
with the package insert, summary of product characteristics (SmPC), or similar.
4.1.3.1 
Belatacept for Injection
Description of the Dosage Form
Belatacept for Injection, 250  mg/Vial,  
is a sterile non pyrogenic  
lyophilized powder. Each  vial 
contains  275  mg  of  belatacept,  550  mg  of  sucrose,  38.0  mg  of  sodium  phosphate  monobasic 
monohydrate,  6.4  mg  of  sodium  chloride,  and  1  N  sodium  hydroxide/1  N  hydrochloric  acid 
solution sufficient to adjust pH to 7.5. A 10% overfill is included in each vial to account for vial 
needle syringe (VNS) holdup.
Drug Product Preparation
Constitution  and  dilution  of belatacept  for  Injection  250  mg/Vial  must  be  performed  using 
silicone-free  disposable  syringes.  Suitable  
fluids  
for  constitution  of  
the  
lyophile  
include  sterile 
water  for  injection  (SWFI),  0.9%  sodium  chloride  injection  (NS)  or  5%  dextrose  injection 
(D5W).  Prior  to  IV  administration,  the  constituted  solution  is further  diluted  to  a  sufficient 
infusion  volume  (eg,  100 mL)  with  NS  or  D5W  to  final  belatacept concentrations  between 
2 mg/mL  and  10  mg/mL.  The  
infusion  
is  
to  be  administered  
through  a  sterile,  non-pyrogenic, 
low  protein  binding  
in-line  filter.  The  syringe  and  
in  
line  filter  set  will  be  provided  by  BMS. 
Additionally,  care  must  be  taken  to  ensure  the  sterility  of  the  prepared  solution,  as  the drug 
product does not contain antimicrobial preservatives or bacteriostatic agents.
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Constitution of the Lyophile
Each  250  mg  vial of  belatacept  
for  
Injection  should  be  constituted  with  10.5  mL  of  a  suitable 
constitution  
fluid (SWFI, NS or D5W) to provide a solution with a  belatacept concentration of 
approximately 25 mg/mL. Belatacept for Injection, 250 mg/Vial, is not stoppered under vacuum. 
To avoid excessive  
foam  
formation in the  vial,  slowly  
inject the constitution  
fluid  
into the vial 
with the stream directed toward the vial wall  and  not into the lyophilized cake. The vial should 
be gently swirled and inverted until the lyophile dissolves. Although some foam may remain on 
the surface of the constituted solution, a sufficient excess of belatacept is included in each vial to 
account  for  withdrawal  losses,  thus,  10.0  mL  of  a  25  mg/mL  belatacept  solution  can  be 
withdrawn  from  each  vial.  Constituted  solutions  of  belatacept  may  foam,  therefore,  shaking 
should be avoided.
Preparation of the Infusion
Prior  to  IV  administration,  the  constituted  belatacept  solution  (25  mg/mL)  should  be  further 
diluted  with  either  NS  or  D5W to  final  belatacept concentrations  ranging  from  2 mg/mL  to 
10 mg/mL.  Lyophiles  constituted  with  SWFI  may  be  further  diluted with either NS or D5W. 
Lyophiles constituted with NS should be further diluted with NS and lyophiles constituted with 
D5W should be further diluted with D5W.
The entire  belatacept infusion should  be administered over a period of 30 minutes and  must be 
administered with an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (with a 
pore size of 0.2 - 1.2 μm).
Recommended Storage Conditions
Belatacept  for  injection  lyophilized  powder  is  stored  and  refrigerated  at  2°C  
to  8°C  (36°F to 
46°F). Belatacept for injection should be protected from light by storing in the original package 
until time of use. The reconstituted solution  should  be transferred  
from the  vial to the  
infusion 
bag  or  bottle  immediately.  The  belatacept  for injection  infusion  must  be  completed  within 
24 hours  of  constitution  of the  belatacept  for  injection  lyophilized  powder.  If  not  used 
immediately,  the  infusion  solution  may  be  stored  under  refrigeration  conditions:  2°C  to  8°C 
(36°C to 46°F) for up to 24 hours (a maximum of 4 hours of the total 24 hours can be at room 
temperature: 20°C to 25°C [68°F to 77°F] and room light).
Regardless  of  storage  condition,  
the  belatacept  
infusion  must  be  completed  within  24  hours  of 
constitution of the lyophile.
4.1.3.2 
Thymoglobulin for Injection
Thymoglobulin  for  injection  should  be  stored  and  prepared  in  accordance  with  the  package 
insert, SmPC, or similar document for the region.
Thymoglobulin should be administered using a 0.22-micron filter through a peripheral or central 
vein  only.  Each  
reconstituted  Thymoglobulin  vial  
(25  mg  or  5  mg/mL)  should  be  diluted  
to  a 
recommended volume of 50 mL with NSS or D5W. Premedication with methylprednisolone (as 
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per Section 4.3.5)  as  well  as  with  acetaminophen  and/or  antihistamine  
is  
recommended,  as  per 
local practice to reduce the incidence of infusion reactions.
For preparation and full prescribing information, see the package insert, SmPC, or similar.
4.1.3.3 
Everolimus Tablets
Everolimus  
tablets  should  be  stored  
in  accordance  with  
the  package  insert,  SmPC,  or  similar 
document for the region.
For full prescribing information, see the package insert, SmPC, or similar.
4.1.3.4 
Tacrolimus Tablets
Tacrolimus  tablets  should  be  stored  in  accordance  with  the  package  insert,  SmPC,  or  similar 
document for the region.
For full prescribing information, see the package insert, SmPC, or similar.
4.2 
Method of Assigning Subject Identification
Approximately  70 subjects  (n  = 35 per  group) receiving de novokidney  transplants  will  be 
randomized  (stratified  by  study  site/center)  in  a  1:1  ratio  to  1  of  the  2 treatment  groups.  A 
randomization schedule will be generated and kept by BMS.
At  
the  
time  of  enrollment,  
immediately  after  written  
informed  consent  is  obtained  and  before 
performing any study-specific procedures, the physician/coordinator must contact IVRS to enroll 
each  subject  into  
the centralized  database.  Each  subject will  be  assigned  a  unique  sequential 
5 digit subject number beginning with 80001, 80002, 80003, etc. by the IVRS for identification 
throughout  
the  study.  This  subject  number  must  not  be  
reused  
for  any  other  participant  
in  
the 
study.  SAE  reporting  will  begin  at  the  time  of  enrollment  for  all  subjects,  immediately  after 
written  informed  consent  is  obtained,  see Section  6,  Adverse  Events,  for  detailed  (S)AE 
reporting requirements.
The subject may be randomized once all entry criteria (inclusion and exclusion) have been met. 
The  physician/coordinator  must  contact  IVRS prior  totransplant  surgery  to  randomize  each 
eligible  subject  into  the  centralized  database.  The  collection of  nonserious  AE  information 
should begin at initiation of study drug. The IVRS must also be contacted at each visit to obtain 
belatacept  vial  assignments  and  each  
time  additional  supplies  of  other  
investigational  products 
are dispensed.
4.3 
Selection and Timing of Dose for Each Subject
4.3.1 
Belatacept
Subjects  randomized  to  a belatacept  treatment  group  in the  study  will  receive  a  belatacept 
regimen consisting of 10 mg/kg i.v. for the first 3 months post transplant. (Refer to Table 5.1-4) 
After 3  months (week 12), subjects will receive  belatacept at the maintenance dose of 5  mg/kg 
i.v.  every  4  weeks  until  completion  of  the  trial. (Refer  to Table  5.1-5) The  entire  belatacept 
infusion should be administered over a period of 30 minutes.
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The  
initial  
infusion of  belatacept should  be  started at least 12 but no  more than 24  hours after
completion of the initial induction dose of Thymoglobulin. If the Week 1 dose of belatacept will 
be  infused  on  the  same  day  as  a  dose  of  Thymoglobulin,  the  belatacept  infusion  must  be 
completed: a) at least 12 hours prior tothe  
initiation of the  methylprednisolone premedication 
dose  for  the  Thymoglobulin  infusion;  or  b)  at  least  12  hours aftercompletion  of  the 
Thymoglobulin infusion. To facilitate scheduling, infusion windows are permitted for belatacept 
infusion (Table 5.3.2-1). 
Based upon Pharmacodynamic and Pharmacokinetic  modeling of receptor occupancy of CD86, 
administration of the second belatacept dose at the end of Week 1 (Day 7, +/- 1 day) will ensure 
that subjects achieve receptor occupancy of > 90% through  Week 4 post transplant, just as the 
Day 5 dose, in the phase 3 studies, was shown to achieve.
4.3.2 
Thymoglobulin
All subjects will receive Thymoglobulin in a dose of up to 1.5 mg/kg by i.v. infusion on Day 1 
(Day  of  Transplant) and  daily  thereafter  (or  less  frequently,  as  tolerated)  to  reach  a  total 
cumulative dose between 3.0 and 5.5 mg/kg. Premedication with i.v. methylprednisolone (as per 
Section 4.3.5) is required, as well as acetaminophen and/or antihistamine, per local practice, are 
recommended to reduce the risk of infusion reactions.
The  initial  Thymoglobulin  infusion  (Day1)  should  be  administered  over  a  period  of  at  least 
6 hours, to be initiated intraoperatively, after premedication with methylprednisolone and prior to 
vascular reperfusion of the allograft. Subsequent doses should be administered over a period of
at least 4 hours, each to begin after methylprednisolone premedication. For subjects randomized 
to  
receive belatacept,  please  
refer  
to Section  4.3.1for  guidance  as  
to the  appropriate  sequence
and timing in which the Thymoglobulin  and  belatacept doses are to be  
infused (when  both are 
given on the same day).
At  the  discretion  of  the  Investigator,  Thymoglobulin  doses  may be  given  daily (or  less 
frequently,  as  
tolerated),  as  
long  as  
the  
total  number  of  days of  
induction  does  not  exceed  10 
days and the cumulative dose does not exceed 5.5 mg/kg.
Prior  to  administration  of  each  dose,  hematology  lab  values  must  be  reviewed  by  the 
Investigator.  If  the  absolute  lymphocyte  count  is  <  100/mm
3,  Thymoglobulin  will  not  be 
administered any further. If the platelet count is < 80,000/mm
3, the dose of Thymoglobulin will 
be  decreased  by  50%.  
If  
the  platelet count  
is  <  50,000/mm
3,  Thymoglobulin  will  be  withheld 
until laboratory values return to acceptable levels for Thymoglobulin infusion.
Thymoglobulin should be administered using a 0.22-micron filter through a peripheral or central
vein  only.  Each  
reconstituted  Thymoglobulin  vial  
(25  mg  or  5  mg/mL)  should  be  diluted  
to  a 
recommended volume of 50 mL with NSS or D5W.
For additional information on Thymoglobulin, see the package insert.
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4.3.3 
Everolimus
For subjects randomized to the EVL treatment group of the study, EVL will be given at an initial 
dose of 3.0 mg/day (1.5 mg bid) starting on Day 3. In subjects who experience DGF, defined as 
the requirement for acute dialysis during the first post transplant week, initiation of EVL may be 
delayed up to Day 7. In order to guide dose modifications, EVL pre-dose trough levels should be 
obtained from the local laboratory per the Time and Events Schedule (Table 5.1-2, Table 5.1-3) 
and  4  
to  5  days  after  any  change  
in  dose.  The  dosing  will  be  adjusted  
to  keep  pre-dose  
(C0) 
levels  at 6 to 10 ng/mL  
for the  
initial 3  months post-transplantation and at 4 to 8 ng/mL after 3 
months and for the remainder of the study.
As a guide to dose adjustment: EVL pharmacokinetics are dose-proportional. Therefore, the dose 
should be increased or decreased in proportion to the desired change in trough level. As a general 
rule:
If the new dose of EVL is calculated to be more than 2-fold different from the current dose, the 
investigator may want to make the change in two increments/decrements rather than all at once 
(except when the current trough is < 3 ng/mL).
EVL may increase the incidence of hypercholesterolemia, hypertension, arthralgia, hypokalemia, 
thrombocytopenia,  anemia,  delayed  wound  healing,  perinephric  fluid  collection  (lymphocele), 
oral  ulcers,  acne,  interstitial  lung  disease,  and  pancreatitis.  In  such  cases,  the  dose  may  be 
reduced or withheld at the discretion of the investigator, as tolerated by the subject.
Subjects  unable  to  tolerate  the  reduced  dose  of  EVL  should  be  discontinued  from  assigned 
therapy,  after  which  they  may  be  converted to  alternative  therapy  per  the  investigator’s 
discretion.  All  subjects  will  be  followed  for  graft  and  survival  status  through  Month  24. 
Although discontinued  
from assigned therapy, they  should remain  
in the  study to complete the 
protocol-specified  period  of  follow-up.  Such  subjects  will  be  counted  in  
the  EVL  arm  of  
the 
study  
in  
ITT  analyses  but  may  also  be  evaluated  
in  other  sensitivity  analyses,  
for  example,  by 
censoring at the time of discontinuation from EVL.
For full prescribing information, see the package insert.
4.3.4 
Mycophenolate Mofetil
Subjects  randomized  to receive  MMF,  will  receiveMMF* daily,  in  2 divided  doses,  on  a 
consistent schedule in relation to time of day and meals. The dose should be between 0.5 - 2.0 g 
per day (0.25 to 1.0 g bid), and up to 3.0g per day  
in  African  American/Black subjects, at the 
investigator’s discretion.
The first dose of MMF should be administered preoperatively on the Day 1 (Day of Transplant). 
The MMF dose should be administered orally in  a capsule or solution formulation. Intravenous 
dosing  
is permitted, if  needed due to intercurrent illness, postoperative  
ileus, or other causes at 
New EVL dose = Current dose  ×  New target trough concentration
      Current trough concentration
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the investigator
's discretion. The recommended starting i.v. dose of MMF injection is 1 g twice 
daily as a  slow continuous  
i.v.  
infusion over  no  
less than 2  hours. Subsequent doses should  be 
administered orally as soon as the subject is able to tolerate medications by mouth.
The  dose  schedule  may  be  adjusted  on  the  basis  of  results  of  laboratory  tests  (eg,  decreased 
WBCs) and subject tolerability.
*Note: Mycophenolate sodium is not to be used as first line therapy for subjects randomized to 
the tacrolimus + MMF treatment group.
For subjects who develop nausea, diarrhea, or other MMF-related gastrointestinal adverse effects 
(eg,  symptoms  fully  assessed  and  deemed  not  
to  have  an  etiology other than intolerability to 
MMF),  the  MMF  dose  may  be  decreased  to  a  minimum  allowable  dose  of  0.5  g daily.  An 
attempt  should  be  made  to  divide  the  total  dose  of  MMF  into,  up  
to 4  daily  doses.  Subjects 
unable  to  tolerate  the  minimal protocol-defined dose  of  MMF  may  be  converted  to 
mycophenolate sodium  in  an  equivalent  dose,  where possible.  If  further  reductions  or 
interruptions are deemed necessary by the Investigator, the medical monitor should be contacted.
Subjects unable to tolerate the reduced dose of MMF or substitution with mycophenolate sodium 
in  an equivalent dose,  should  be  discontinued  
from  assigned  
therapy, after which they may be 
converted  
to  alternative  
therapy  per  
the  
investigator’s  discretion.  All  subjects  will  be  
followed 
for  graft  and  survival  status  
through  Month  24.  Although  discontinued  from  assigned  
therapy, 
they  should  
remain  on  
the  study  
to  complete  
the  protocol-specified  period  of  follow-up.  Such 
subjects will be counted in the TAC + MMF arm of the study in ITT analyses but may also be 
evaluated in other sensitivity analyses, for example, by censoring at the time of discontinuation 
from MMF or mycophenolate sodium.
For  full  prescribing information  for MMF and  mycophenolate sodium, see  the  respective 
package inserts.
4.3.5 
Tacrolimus
The  recommended  total  initial  dose  of  TAC  is  0.1  mg/kg/day  orally  in  2  divided  doses  and 
adjusted thereafter on the basis of therapeutic drug monitoring, to target pre-dose (approximately 
12-hour trough) blood concentrations of 4-11 ng/mL. Subjects randomized to the TAC treatment 
group, therapy with TAC may be initiated any time within the first 24 hours post-transplant, or 
delayed  pending  improvement  in  renal  function,  eg,  after  the  serum  creatinine  (SCr) 
concentration  has  decreased  
to ≤4  mg/dL  
(in  absence  of  dialysis).  
Initiation  of  dosing  may  be 
delayed  up  
to  Day  7,  if  in  
the  clinical  judgment  of  
the  investigator,  earlier  initiation  of  TAC 
therapy  is  not  in  the  best  interest  of  the  subject  due  
to  postoperative  impairment  of  allograft 
function.
Tacrolimus  trough  (pre-dose)  concentrations  should  be  monitored  per  the  Time  and  Events 
schedule (Refer  to Table  5.1-2).  More  frequent  monitoring  is  permitted  per  local  standard  of 
care.  Doses  of  TAC  should  be  taken  consistently, either  with  or without  food,  because  the 
presence and composition of food decreases its bioavailability.
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Dosing  should  be  titrated  based on  clinical  assessment  of  rejection  risk  and  tolerability, to 
maintain trough levels in the range of 4-11 ng/mL, wherever possible.
Acute overdosages of up to 30 times the intended dose have been reported. Almost all cases have 
been  asymptomatic  and  all  patients  recovered  with  no  sequelae. Based  on  the  poor  aqueous 
solubility and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus 
is not dialyzable to any significant extent. General supportive measures and treatment of specific 
symptoms should be followed in all cases of overdosage.
Subjects  who,  in  
the  clinical  judgment of  
the  investigator,  are unable  
to  
tolerate  maintenance 
therapy  with  TAC  should  be  discontinued  from  assigned  therapy, after which they may be 
converted to alternative therapy at the investigator’s discretion. All subjects will be followed for 
graft and survival status through Month 24. Although discontinued from assigned therapy, they 
should remain in the study to complete the protocol-specified period of follow-up. Such subjects 
will  be counted in the TAC arm of the study  
in the ITT analysis,  but may also  be evaluated  
in 
other sensitivity analyses, for example, by censoring at the time of discontinuation from TAC.
For full prescribing information, see the package insert.
4.3.6 
Corticosteroids
This  
is a rapid corticosteroid withdrawal trial; corticosteroids are to be administered during the 
first  week of  study  
treatment  only.  To  
reduce the  
risk  of  
infusion  
reactions,  prior to  beginning 
each  Thymoglobulin  infusion  all subjects  will  receive  premedication  with  methylprednisolone 
(as the sodium succinate), to be administered i.v. over approximately 30 minutes, as follows:
1st Dose of Thymoglobulin: 500 mg methylprednisolone i.v.
2nd Dose of Thymoglobulin: 250 mg methylprednisolone i.v.
3rd Dose of Thymoglobulin: 100 to150 mg methylprednisolone i.v.
Any additional doses of Thymoglobulin:
4th Dose of Thymoglobulin: 60 mg methylprednisolone i.v.
5th Dose and beyond of Thymoglobulin: 30  mg  methylprednisolone  
i.v. prior to each 
Thymoglobulin infusion
Day 4 to Day 10:
• Subjects completing Thymoglobulin induction before Day 7may receive prednisone, 
p.o. (or the equivalent) in lieu of the same dose of i.v. methylprednisolone:
o Day 4:60 mg prednisone p.o. (or equivalent)
o Days 5 through 7:30 mg prednisone p.o. daily (or the equivalent).
• Subjects  continuing to  receive  Thymoglobulin  induction  during  Days  4-10post-
transplant  should  still  be  pre-treated  with  methylprednisolone  
i.v.  as  
indicated  above  
in 
lieu of p.o. prednisone.
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• All  corticosteroids  are to  be  discontinued  by  Day  7,  except  for subjects  still  receiving 
Thymoglobulin  induction  between  Days  8  - 10;  those  subjects  must  discontinue 
corticosteroids after the final dose of Thymoglobulin induction has been completed.
For  additional  information  on methylprednisolone,  prednisone,  or  their  equivalents,  see  the 
respective package inserts.
4.3.7 
Prophylaxis After Transplantation
4.3.7.1 
Antiviral 
Antiviral  prophylaxis  
for  prevention  of  
infection  by  CMV  and  other  Herpesviruses  
is  
required 
for all subjects during the post-transplant period for at least 3 months, and should be initiated no 
later than Day 10.  The following are guidelines only; the specific choice of antiviral drug, and 
the dose and duration of the regimen prescribed, should be individualized for each subject on the 
basis  of  
level  of  
infection  
risk,  GFR,  and  other  clinical  considerations,  
in  accordance  with  
the 
local standard of care:
Table 4.3.7.1-1: 
Antiviral Prophylaxis for Prevention of Infection
Donor/Recipient CMV status at transplant
Antiviral drug and duration of prophylaxis
Donor seropositive / Recipient seropositive
Valganciclovir X 3 months
Donor seropositive / Recipient seronegative
Prohibited from study participation per eligibility 
criterion (1)(k) [See Section 3.3.2]
Donor seronegative / Recipient seropositive
Valganciclovir X 3 months
Donor seronegative / Recipient seronegative
Valganciclovir or acyclovir X 3 months
In  addition,  if  T  cell-depleting  agents  are  initiated  for  the  treatment  of  AR,  valganciclovir 
prophylaxis should be re-administered for 3 months per local standard of care.
For  subjects  who  are  allergic  to,  or  have  a  contraindication  for  valganciclovir,  the  medical 
monitor should be contacted.
4.3.7.2 
Pneumocystis jiroveci pneumonia (PJP)
Unless contraindicated, all subjects who participate in this  study must receive PJP prophylaxis 
with sulfamethoxazole/trimethoprim  
for 12  months  
following transplantation, and  
for 6  months 
following any additional courses of T cell-depleting agent used for treatment of AR. Dosing and 
administration  of  sulfamethoxazole/trimethoprim  are  to  be  determined  by  the  Investigator 
according to each subject’s level of renal function, and in a manner consistent with the package 
insert.
Subjects  with  
intolerance  
to  sulfa  drugs  or  
trimethoprim,  or  
for  whom  either  one  
is  otherwise 
contraindicated,  may  receive  prophylaxis with  inhaled  pentamidine,  or  orally  administered 
atovaquone or dapsone, at the investigator’s discretion.
For full prescribing information, see the respective package inserts.
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4.3.7.3 
Oral Moniliasis/Candidiasis 
It is recommended that subjects receive oral moniliasis prophylaxis for at least 10 days following 
transplantation as well as following treatment of AR, with 4 - 6 mL of nystatin oral suspension 
(400,000 to 600,000 units; one-half of the dose to each side of the mouth) four times daily. The 
preparation should be retained in the mouth for as long as possible before swallowing.
4.3.8 
Dose Modifications 
The dose of belatacept to be infused is based on the baseline (Day 1) body weight, and will not 
be  modified unless a change  
in body weight of≥10% of the Day 1 weight has occurred. If an 
adjustment has been made based upon a body weight change, this weight should be considered as 
a  new  baseline  weight.  No  further  adjustment  of  dose  based  upon  body  weight  is  required
thereafter, unless the subject experiences an additional body weight change ≥10% from the new 
baseline  weight. If  this  occurs,  the  dose  should  again  be  modified, starting  with the  next 
belatacept infusion, and that new weight should then be considered as the new baseline weight.
Doses of Thymoglobulin, MMF, EVL and TAC may be adjusted as described inSection 4.3. 
In  
the  absence  of  AEs  deemed  at  
least  possibly  related  
to  study  drug  
treatment,  subjects  will 
complete  their  scheduled  belatacept  infusions  as  prescribed  by  the protocol.  If  the  belatacept 
infusion  can  not  be  administered  within  
the  visit/infusion  window  defined  
in  
the  protocol,  
the 
infusion  should  be  skipped  and  the  next  infusion  administered  within  the  next  visit/infusion 
window.  
If  a  belatacept  
infusion  must  be  skipped,  
the  
investigator  should  contact  
the  medical 
monitor  
in  advance  
to  discuss  
the  circumstances.  
In  
the  event of  new,  serious,  and  unexpected 
toxicity potentially related to belatacept, study drug administration should be interrupted, and the 
medical monitor promptly notified by the investigator. The subject will be considered eligible to 
receive  additional study  drug only  after  discussion  with  the  medical  monitor.  Under  no 
circumstances  should  the  dose  of  belatacept  be  modified other  than  for  weight  changes,  as 
described  above.  Subjects  for  whom  belatacept  dosing  is  discontinued  should  be  placed  on 
alternative immunosuppressive regimen, to be determined at the discretion of the investigator.
In the event that a subject receives plasmapheresis for the treatment of AR, a discussion of risks 
and benefits between the investigator and the medical monitor should take place to determine the 
subject’s eligibility to remain in the study on assigned therapy.
4.4 
Blinding/Unblinding
Not applicable. This study is open label.
4.5 
Treatment Compliance
All medications specified in this protocol must be administered as described within the protocol. 
All  study  medications  and  concomitant  medication  usage  must  be reported  on  
the  appropriate 
case report form (CRF) pages and any deviations from specified administration should be clearly 
documented.
In  addition,  each  
time  study  medication  
is  dispensed,  compliance  should  be  
reinforced.  When 
study  drug  everolimus,  
tacrolimus,  or MMF  
is  returned,  compliance  should  be  assessed  based 
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upon  an  
interview  with  
the  subject  and  a  count  of  
the  
tablets  
returned.  Compliance  should  be 
between > = 80% and < = 120% of that prescribed. The investigator (or designee) should record 
the  amounts  of  study  medication  dispensed  and  returned  at each  visit,  as  well  as  document 
reasons  
for  non-compliance  
in  
the  source  document.  The  dates of  all  study  medication  dosing, 
including interruptions, missed doses or overdose, should be recorded on the eCRF. If the subject 
is not > = 80% compliant with recording study drug doses during the study, the period of non-
compliance  should  be  noted  as  a  protocol  deviation  and  the  sponsor  should  be  notified.  The 
subject should be educated on the importance of medication compliance and to record and report 
any missed doses.
4.6 
Destruction and Return of Study Drug
4.6.1 
Destruction of Study Drug
For  this  study,  study  drugs  (those  supplied  by  BMS  or  sourced  by  the  investigator)  such  as 
partially used study drug containers, vials and syringes may be destroyed on-site.
Any  unused  study  drugs  can  only  be  destroyed  after  being  inspected  and  reconciled  by  the
responsible  Study  Monitor  unless  study  drug  containers  must  be immediately  destroyed  as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics).
On-site destruction is allowed provided the following minimal standards are met:
• On-site disposal practices must not expose humans to risks from the drug.
• On-site  disposal  practices  and  procedures  are  in  agreement  with  applicable  laws  and 
regulations, including any special requirements for controlled or hazardous substances.
• Written procedures for on-site disposal are available and  
followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.
• Records  are  maintained  that  allow  for  traceability  of  each  container,  including  the  date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method  of  disposal,  ie,  incinerator,  licensed  sanitary  landfill,  or  licensed  waste  disposal 
vendor must be documented.
• Accountability and disposal records are complete, up-to-date, and available  
for the Monitor 
to review throughout the clinical trial period.
If  conditions  for  destruction  cannot  be  met  the  responsible  Study  Monitor  will  make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
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4.6.2 
Return of Study Drug
If  study  drug  will  not  be  destroyed  upon  completion  or  termination  of  the  study,  all  unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible Study Monitor.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
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5 STUDY ASSESSMENTS AND PROCEDURES
5.1 
Flow Chart/Time and Events Schedule 
Table 5.1-1: 
Screening and Baseline/Randomization Procedural Outline (IM103177)
Procedure
Screening
Period a
Baseline/ 
Randomization/ 
Day of Transplant
Notes
Day- 30 
Day 1
Informed Consent
X
Consent must be obtained prior to performance of any study-specific procedures.
Call IVRS
X
X
Upon signature of informed consent form, call IVRS to enroll subject & begin 
reporting of SAEs. On Day 1, prior to transplant surgery, call IVRS to randomize the
subject and for study drug dispensing; Section 4.2.
Confirm Inclusion/Exclusion 
Criteria
X
Section 3.3
Full Medical History
X
Sections 3.3 and 5.3
Physical Exam
X
Section 5.3
Neurological Exam
X
Section 5.3
Vital Signs/Weight/Height
X
X
Blood pressure (BP) (sitting position), heart rate, temperature & respiratory rate.
Weight to be used to calculate belatacept dose.
Height taken at baseline only; Section 5.3
12 Lead Electrocardiogram
(ECG)
X
If the subject has an ECG performed within 6 months of transplant, and the report is 
available, that is acceptable; Section 5.3
TB Infection Screening
X
Section 3.3
Chest X-Ray
X
Posterior-anterior and lateral views within 6 months prior to the date of transplant; 
Section 3.3
Adverse Event Monitoring 
X
Include evaluation of Neurologic signs and symptoms for CNS events and 
malignancies; Section 6.
Review Concomitant 
Medications
X 
Refer to Section 3.4for prohibited and/or restricted treatments
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Table 5.1-2: 
Procedural Outline - Year 1 of Treatment (IM103177)
Procedure
M1 
M 3
M 6
M 9
M 
12
Notes
W
1
W
2
W 
4
W
8
W
12
W 
16
W
20
W 
24
W 
28
W 
32
W 
36
W 
40
W 
44
W 
48
W 
52
D
7
D 
15
D 
29
D 
57
Belatacept 
Dispensing
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
For belatacept subjects only, 
call the IVRS for vial 
assignment.Section 4.2
Everolimus or 
Tacrolimus 
Dispensing
X
X
X
X
X
EVL or TAC subjects only, 
call the IVRS for container 
assignment. Section 4.2
Vital Signs/Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X* 
X* 
X 
X* 
X* 
X* 
X
All subjects will have BP 
(sitting position), heart rate, 
temperature, respiratory rate 
& weight; belatacept subjects 
will have BP and heart rate 
also at 30 minutes after the 
EoI (end of infusion).
*Not required for TAC 
subjects completing the visit 
by phone.
Section 5.3
Physical Exam
X
X Section 5.3
Neurological Exam
X
X
Also required if change in 
neurologic status based on 
clinical signs and symptoms is 
observed; Section 5.3
Adverse Event 
Monitoring
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Include evaluation of 
Neurologic signs and 
symptoms for CNS events and 
malignancies; Section 6.
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Table 5.1-2: 
Procedural Outline - Year 1 of Treatment (IM103177)
Procedure
M1 
M 3
M 6
M 9
M 
12
Notes
W
1
W
2
W 
4
W
8
W
12
W 
16
W
20
W 
24
W 
28
W 
32
W 
36
W 
40
W 
44
W 
48
W 
52
D
7
D 
15
D 
29
D 
57
Peri-Infusional AE 
Monitoring
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Belatacept randomized 
subjects only. Following 
every belatacept infusion, 
subject must be contacted 
within 48 hours to determine 
if they had any adverse events 
within 24 hrs of their infusion; 
Section 6.7.1.
Review 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Refer to Section 3.4for 
prohibited and/or restricted 
medications
LOCAL LABS
Serum Creatinine
X 
X 
X 
X 
X 
X 
X
X
X
Also must be obtained at time 
of suspected AR, PML or 
PTLD; Sections 5.3.6,5.3.7
and 5.3.8.
Hematology w/diff
Required 
on days 
when 
Thymo-
globulin 
infused
Lymphocyte, platelet, and 
neutrophil counts must be 
evaluated by Investigator 
prior toeach Thymoglobulin 
infusion; Section 4.3.2and 
5.3.6
Pregnancy Test 
X 
X 
X 
X 
X 
X 
X 
X 
X* 
X* 
X 
X* 
X* 
X* 
X
All WOCBP:
Negative pregnancy test is 
required prior to dosing at all 
study visits. 
*Not required for TAC 
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Table 5.1-2: 
Procedural Outline - Year 1 of Treatment (IM103177)
Procedure
M1 
M 3
M 6
M 9
M 
12
Notes
W
1
W
2
W 
4
W
8
W
12
W 
16
W
20
W 
24
W 
28
W 
32
W 
36
W 
40
W 
44
W 
48
W 
52
D
7
D 
15
D 
29
D 
57
subjects completing the visit 
by phone; Section 3.3.3and 
5.3.
Everolimus Trough 
X* 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
For everolimus subjects only: 
Section 4.3.3
- Hold morning dose until 
trough level is drawn. 
- Also obtained at time of 
suspected AR, PML, or PTLD 
(Sections 5.3.7and 5.3.8) and 
4-5 days after any change in 
dose (Sections 4.3.3 and
5.3.6)
*Week 1 trough sample 
collection is not required if 
subject does not start 
everolimus prior to Week 1 
visit.
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Table 5.1-2: 
Procedural Outline - Year 1 of Treatment (IM103177)
Procedure
M1 
M 3
M 6
M 9
M 
12
Notes
W
1
W
2
W 
4
W
8
W
12
W 
16
W
20
W 
24
W 
28
W 
32
W 
36
W 
40
W 
44
W 
48
W 
52
D
7
D 
15
D 
29
D 
57
Tacrolimus Trough 
X* 
X 
X 
X 
X 
X 
X 
X
X
X
For tacrolimus subjects only:
Section 4.3.5
- Hold morning dose until 
trough level is drawn. 
- Also obtained at time of 
suspected AR, PML, or PTLD
(Sections 5.3.6,5.3.7and 
5.3.8) and after any change in 
dose
*Week 1 trough sample 
collection is not required if 
subject does not start 
tacrolimus prior to Week 1 
visit.
CENTRAL LABS
Urine collection 
X 
X
X
X
Section 5.3.6.1
Hematology w/diff
X 
X
X
X Section 5.3.6.1
Hemoglobin A1c
X
X
X Section 5.3.6.1
Chemistry Panel 
(Fasting)
X
X
X
X
X
Nothing to eat/drink, except 
water, for 8 hours prior to 
laboratory collection; 
Section 5.3.6.1
Lipid Panel 
(Fasting)
X
X
 
X
X
Nothing to eat/drink, except 
water, for 8 hours prior to 
laboratory collection; Section 
5.3.6.1
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5.2 
Study Materials
The following study materials will be provided at the study start:
• On-Site Investigator File (OSIF)
• Pharmacy Logs
• BMS-224818 Investigator Brochure
• Site manual of operation for the IVRS
• Registration worksheets for IVRS
• Case Report Form (CRF) instructions
• Laboratory kits and laboratory manual
• Pregnancy surveillance forms
• Any other materials as locally required or agreed.
The central laboratory will provide all laboratory-related materials. The investigator will need to 
have a centrifuge, a freezer (-20ºC or below), appropriate containers and dry ice for shipment and 
storage  of  blood  and  plasma  samples.  Enough  dry  ice,  when  indicated,  should  be  utilized  to 
allow samples to arrive at their designated laboratory in a frozen state.
5.3 
Safety Assessments
Safety  assessments  will  be  performed  throughout  the  study  and  at  early  termination/ 
discontinuation, as specified  
in the Time and Events Schedule (Table 5.1-1, Table 5.1-2, Table 
5.1-3).
Data  
for  
the  procedures  and  assessments  specified  
in  
this  protocol  should  be  submitted  on  
the 
CRF. Lab assessments that are performed and sent to central vendor do not need to be recorded 
on the CRF. However, any local lab assessments which are not performed by the central vendor 
but are part of the required study procedures should be entered into the database and recorded on 
the specified CRF page.
Additional  procedures  and  assessments  may  be  performed  as  part of  the  standard  of  care. 
However, data for those assessments should remain in the subject’s medical file and should not 
be provided unless specifically requested by the Sponsor.
5.3.1 
Imaging Assessment for the Study
Not applicable.
5.3.2 
Visit Windows
For the purpose of this study, “Week” refers to the end of treatment week (eg. Week 4 = Day 29, 
Week 8 = Day 57, etc). Visit windows are provided for site staff and subject convenience. After 
Day 1, it is recommended, whenever possible, that visits be scheduled Monday through Thursday 
as  permitted  by  
the  visit  window,  
to  allow  for  
the  
timely  shipment  of  samples  
to  
the  central 
laboratory. See Table 5.3.2-1:
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Table 5.3.2-1: 
Visit windows for study procedures and infusion (when applicable)
Visit/Infusion
Visit Window
Day 1
Day of Transplant; seeSection 4.3for details regarding the timing of the 
initial dose relative to kidney transplantation and temporal sequence of 
study drugs.
Week 1 (Day 7)
Target date ±1 day
Week 2 (Day 15)
Target date ±2 days
Week 4 - Month 6
Target date ±3 days
Month 7 - Month 24
Target date ±5 days
Early Termination (ET)
Within 14 days after discontinuation of study drug. If the visit cannot be 
completed within the window (eg, due to hospitalization, etc), the visit 
should be completed as soon as possible thereafter.
Follow-up 8, 12, 24 weeks
Target date from date of last dose of study drug ±5 days
Phone  visits  for  subject  randomized  to  receive  TAC  may  commence  after  the  Month  6  visit 
(excluding visits for months 9, 12, 15, 18, 21, and 24, which should be completed in the office). 
Subjects will  be contacted to assess  
for AEs and  concomitant  medications. Each of these visits
should occur within the prescribed visit window.
5.3.3 
Vital Signs
Vital  signs  (body  temperature,  respiratory  rate,  blood  pressure [BP],  and  heart  rate) will  be 
recorded as outlined in Table 5.1-1, Table 5.1-2and Table 5.1-3. Arterial systolic and diastolic 
BP and  radial  artery  pulse  rate  will  be  measured and  recorded  in  the  seated  position;  supine 
determinations are acceptable if the subject is unable to sit.
Subjects randomized to a belatacept treatment group will have vital signs measured prior to the 
belatacept infusion and both BP and heart rate measured 30 minutes after the end of the infusion. 
When the subject  
is unable to remain seated for at least 60 minutes, and the dose of belatacept 
must be administered while supine, then both pre- and post-infusion vital signs may be obtained 
in this position.
Results  
from  any  vital  signs  determination  
that  
the  
Investigator  considers  clinically  significant 
mustbe recorded on the appropriate AE page of the CRF.
5.3.4 
Physical Measurements
A 12-lead electrocardiogram (ECG) should be performed at screening. If the subject has an ECG 
performed within 6 months of transplant, and the report is available, those results are acceptable
for use in lieu of a Screening Visit ECG. 
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Body weight and height will be recorded at the scheduled visits, as outlined in Table 5.1-1, Table 
5.1-2,  and Table  5.1-3.  The  following  guidelines  will  aid  in  the  standardization  of  these 
measurements:
• The same scale should be used to weigh a given subject throughout the study 
• Scales should be calibrated and reliable; scales should be zeroed just prior to each subject’s 
weigh-in session 
• A subject should void just prior to being weighed
• Whenever possible, weight should be recorded before a subject’s meal (if applicable) and at 
approximately the same time each day
• A subject should be minimally clothed (ie, no shoes or heavy over garments).
5.3.5 
Physical Examination
Physical  examinations  may  be  performed  by  a  Doctor  of  Medicine,  Doctor  of  Osteopathy, 
Physician’s Assistant or Nurse Practitioner. Subjects will undergo a routine physical examination 
during screening and at specified visits as outlined in Table 5.1-1, Table 5.1-2, and Table 5.1-3.
5.3.6 
Laboratory Assessments
Blood and urine samples will be obtained as outlined in Table 5.1-1, Table 5.1-2, and Table 5.1-
3 for clinical  
laboratory  evaluations.  A central  
laboratory  vendor will  be utilized  
for this  study 
and a laboratory manual will be provided to each site. Subjects should be fasting for a minimum 
of 8 hours prior to specified fasting blood draws. However, if a subject is not fasting at a given 
visit, the blood draw should still be performed, and the non-fasting status should be documented. 
Analysis  of  clinical laboratory  specimens  will  be  performed  by a  central  or  
local  
laboratory  as 
specified below.
5.3.6.1 
Central Laboratory
• Hematology: complete blood count (CBC with platelet) with differential, HbA1c
• Chemistry  panel  (Fasting*):  sodium,  potassium,  chloride,  bicarbonate, calcium;  glucose, 
BUN,  serum  creatinine,  uric  acid,  ALT,  AST,  LDH,  alkaline  phosphatase,  total  protein, 
albumin, total bilirubin, phosphorous and magnesium, cGFR
• Lipid panel (Fasting*): total cholesterol, LDL, HDL, triglycerides
• Single voided  urine  specimen  for  urinalysis  (UA)  and  urine  protein-to-creatinine  ratio 
(U
Pr/Cr).  The  analytes  
tested  for  are  
to  
include:  dipstick  protein  glucose  and  occult  blood; 
urine protein and creatinine concentrations and, where available, calculation of the UPr/Cr. If 
results  from  the  UA  are  positive  for  occult  blood,  glucose  or  protein,  microscopic 
examination of the urine sediment will be performed
• Serum total IgG concentration and those of its 4 subclasses. The same samples for serum IgG 
determination  are  also  to  be  collected  at  the  time  of  serious  infections,  CNS  events, 
malignancies, graft loss and clinically suspected AR. When the PI is notified of, or, for any 
other reason suspects that a subject has experienced any of these events, a blood sample for 
serum IgG determination should be collected as per the laboratory manual. Site may also be 
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• Pregnancy  Test  
(serum/urine):  A  pregnancy  
test  
(minimum  sensitivity  25  
IU/L  of β-HCG) 
must be performed at a local laboratory for all WOCBP within 24 hours prior to the first dose 
of study medication (baseline or Day 1). Pregnancy testing must be performed in all WOCBP 
within 24 hours prior to dosing at all other study  visits. Urine pregnancy testing kits will be 
provided by a central  
laboratory and processed at the site; serum pregnancy tests should  be 
performed at a local laboratory, if necessary. If a female subject becomes pregnant, she will 
be discontinued from study medication.
• Evaluation  of  suspected  episodes  of  acute  rejection  will  require  real  time  assessment  of 
serum  creatinine  concentrations as  well  as that  of belatacept and  everolimus blood  levels 
(belatacept/everolimus treated  subjects  only)  or  TAC  trough  levels  (TAC  treated  subjects 
only) and the histopathologic findings from renal biopsies; these will be evaluated locally to 
guide patient management (see Sections 5.3.7 and 5.3.8). 
Results from any laboratory test (including local laboratory tests) that the Investigator considers 
clinically-significant mustbe recorded on the appropriate AE page of the CRF.
5.3.6.3 
Collection, Shipping and Transport
Collection,  processing,  transport,  and  storage  of  local  laboratory  clinical  specimens  will  be 
performed based on study site practices. Collection, processing, transport, and storage of central 
laboratory  clinical specimens  will  be  detailed  in  a  separate  manual  to  be  provided  to  the 
investigator at or before the time of study initiation. 
5.3.7 
Assessment of Clinical Suspicion of Acute Rejection
In this protocol, acute rejection is defined as a clinical (“clinically suspected”) and pathological 
(biopsy proven) event. In addition to identification, on an allograft biopsy, of findings consistent
with either cell- or antibody-mediated acute rejection, confirmation requires that at least one of 
the clinical criteria listed below be met:
• An unexplained increase in serum creatinine concentration of≥25% from a recent baseline 
value.
“Recent baseline” serum creatinine is defined as the average of the 3 most recent serum 
creatinine concentrations that were available prior to the value that prompted clinical 
suspicion of acute rejection and were determined by a local laboratory. These 3 serum 
creatinine concentrations must have been obtained from samples drawn on different days 
and prior to initiation of the first treatment in any course of dialysis that the subject receives.
• An unexplained decrease in urine output
• Fever and allograft tenderness that is otherwise clinically unexplained
• During the  first  14  days  post-transplant,  an  otherwise  unexplained,  persistent  elevation  in 
serum creatinine in the presence of clinical suspicion of acute rejection
OR
• Acute rejection that is: (a) clinically suspected for any other reason(s); and (b) is treated. 
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Unless  a  biopsy  is  medically  contraindicated  due,  for  example, to  a risk  of  hemorrhage  that 
cannot  be  satisfactorily  mitigated  by  administration  of  fresh  frozen  plasma  or  plasma  factor 
concentrates, no subject should be treated for AR without having a biopsy performed to confirm 
the diagnosis. If a subject is treated for AR without biopsy confirmation, this should be clearly 
indicated on the appropriate CRF pages.
Prior  
to obtaining  any  biopsy  
for  suspected  AR,  
the  presence  of  other  clinical  conditions  that 
could adversely affect renal function should be ruled out, including those affecting the patency of 
the renal artery and vein, obstruction (hydronephrosis), intravascular volume depletion, infection 
and drug-associated nephrotoxicity.
Notes:
♦Acute  
rejection  will  not  be  
reported  as  an  AE  or  SAE  
in  
this  study,  see Section  6.  These 
events will be collected on separate CRFs.
♦Routine or surveillance biopsies performed according to local practice and in the absence of 
clinical suspicion of acute rejection are NOT permitted per protocol.
5.3.8 
Renal Biopsy Procedure
All biopsy procedures and pathology assessment are to be performed locally by the site. Central 
pathology  for  assessment  of  AR  will  not  be  part  of  
this  study. However,  non-histopathologic 
assessments  of  biopsy  
tissue  will  be  performed,  
for  example,  
immunohistochemistry  and  RNA 
expression,  when  residual  tissue  is  available  in  the  form  of  a  paraffin  block  and/or  (2-3) 
unstained slides that can be sent to BMS. 
For all biopsy specimens, the tissue should be stained and graded according to the 2007 update to 
the  Banff  97  classification  of  kidney  transplant  pathology
54,55.  Grading  of  allograft  biopsies 
should be performed locally in order to guide acute treatment decisions.
5.3.9 
Follow-up Biopsy of a Documented Acute Rejection
Subjects  may  have  a  follow-up  renal  allograft  biopsy  performed after  a  documented  acute 
rejection episode. 
Hospitalization intended for the biopsy procedures alone, and not complicated or prolonged due 
to other adverse events, will not be considered a SAEs (see Section 6)
5.3.10 
Treatment of Acute Rejection
Prior to initiation of treatment for suspected AR, ensure that:
a) Local  blood  samples  are  collected  
for  measurement  of  serum  creatinine  concentration,  and 
trough levels of EVL or TAC (if applicable).
b) Central laboratory samples are collected for immunogenicity, CMV/EBV/BK viral load, IgG 
& subclasses 1-4 and biomarkers (see Section 5.6). 
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The  severity  of  acute  
rejection  will  be  determined  using  
the  2007  update  
to  
the  Banff  9754,55
classification,  which  will  also  serve  as  a  guide  to  treatment  of  any  episode  that  is  biopsy 
confirmed.
Guidelines  
for the treatment  of acute  
rejection  according  
to the Banff  97  classification  and  
the 
2007 update are provided  below,  
in  bullets, and  
in Figure 5.3.10-1and Figure 5.3.10-2. To the 
extent  clinically  feasible,  these guidelines  are  intended  to  standardize  the  treatment  of  acute 
rejection across clinical sites so as to improve interpretability of data. It is recognized, however, 
that the guidelines may not be applicable to all clinical situations, such that deviations from them 
may be required in individual cases. The guidelines are summarized below:
• Subjects  with  acute  rejection  of  Banff  severity  grades  up  to  and  including  IIA  should  be 
treated initially with methylprednisolone (as the sodium succinate), 250 - 500 mg i.v. per day 
for 3 consecutive days. Corticosteroids should then be tapered per investigator’s discretion.
• Subjects with acute rejection of Banff severity grades IIB and III should be treated initially 
with  ATGAM,  Thymoglobulin,  ATG-Fresenius-S,  or  OKT3.  Use  of  other  polyclonal 
antilymphocyte  preparations  or  polyclonal  antithymocyte  globulins  is  permitted  in  regions 
where  market  authorization  exists,  and  if  they  are  indicated  for  the  treatment  of  acute 
rejection in kidney transplantation. Use of Campath 1-H is not permitted in this protocol, as it 
is not indicated for use in kidney transplantation.
• Subjects  with  acute  rejection that  is  either unresponsive  to,  or  worsening  despite  initial 
corticosteroid therapy should have a repeat, percutaneous allograft biopsy performed before 
initiating  treatment  for  steroid-resistant  acute  rejection.  Subjects  may  be  treated  with 
Thymoglobulin,  ATGAM,  OKT3,  ATG-Fresenius-S,  or  other  approved agents  as  noted 
above.  Following the  
last dose of anti-rejection medication, steroids should then  be tapered 
per investigator’s discretion. 
• CMV and  PJP  prophylaxis must be  administered  as  detailed  in Section  4.3.7whenever
T-cell-depleting agents are utilized to treat AR.
The  guidelines  for  
treatment  of  Banff grades IA  
- IIA  acute  
rejection  are  presented  
in  Figure 
5.3.10-1, and those for gradesIIB - III, in Figure 5.3.10-2:
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5.3.11 
Neurological Examination
A neurologic assessment (history and examination) will be performed at designated time points 
(seeTable 5.1-1, Table 5.1-2and Table 5.1-3). A neurologist is not required for this assessment. 
Neurological examinations  may  be performed  by  a Doctor of  Medicine, Doctor of Osteopathy, 
Physician’s  Assistant  or  Nurse  Practitioner.  The  neurologic  history  will  include  
the  subject’s, 
other  family  members’,  or  other  caretaker’s description  of  neurological  symptoms,  such  as: 
personality,  memory,  headaches,  seizures,  impairment  of  consciousness,  swallowing,  vision, 
hearing,  language  function,  coordination,  gait,  weakness,  alterations  in  sensation or sphincter 
function, or appearance of involuntary movements.
The  neurologic  exam  will  include  assessment  of  mental  status,  gait,  speech,  cranial  nerves, 
cerebellar  function,  deep  
tendon  
reflexes,  sensory  function  and  motor  
function. The  onset  and 
duration of  any  new  symptoms, and  
their  relationship  
to  any  intercurrent  medical  illnesses  or 
recent medications, may also be relevant.
Any  new  or  worsening  findings  should  be  reported  as  an  adverse event  and  evaluated  with 
additional diagnostic modalities and/or neurologic consultation, as considered appropriate by the 
investigator. In cases of unexplained neurological findings, magnetic resonance imaging (MRI), 
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computed tomography (CT), and/or cerebrospinal fluid (CSF) examination for John Cunningham 
(JC)  virus  should  be  considered.  
In  any  such  case,  
the  medical  monitor  
(or designee)  must  be 
contacted.
Supplemental CRF  
forms will be provided to collect information confirming completion of the 
neurologic assessment.
5.3.12 
Definition of Graft Loss
In  
this  study,  graft  
loss  
is  defined  as  either  functional  
loss or  physical  
loss.  Functional  
loss  
is 
defined as meeting any of the criteria:
• Regularly scheduled or chronic dialysis treatments over a period of ≥56 days.
• Re-transplantation (either preemptive or if first criterion above is met and subject is waiting 
for transplant).
Physical graft loss is defined as surgical excision (nephrectomy).
5.3.13 
Suspicion of PTLD
Specific surveillance for PTLD will be incorporated for all subjects in this trial. 
CNS imaging and/or neurologic consultation should be considered for any subject with a new or 
worsening neurologic finding.
For subjects who undergo biopsy for suspicion of PTLD, it is recommended that tissue from the 
biopsy  specimen  be  evaluated  for  CD3,  CD20,  CD79-a  and  EBER.  Additionally,  locally 
prepared  slides,  as  well  as  a  portion  of  
the  
tissue  and/or  unstained  slides will be  
requested for 
standardized assessment by a central pathologist. Instructions for the preparation and shipment of 
biopsy specimens to the PTLD central pathologist will be provided to each investigator.
In subjects with suspected PTLD, a blood sample should be obtained for determination of anti-
viral  T-cell  responses  (U.S.  sites  only)  as  well  as  for  belatacept and  everolimus blood  levels
(belatacept/everolimus treated subjects only) or TAC trough levels (TAC treated subjects only) 
at the time the event is suspected.  However, in subjects with suspected PTLD, the management 
of overall immunosuppression will be at the discretion of the investigator. The Medical Monitor 
should  be  advised  of  the  planned  strategy  for  the  management  of  belatacept  and  other 
immunosuppressants.
The Medical Monitor must also be notified of all confirmed cases of PTLD.
5.3.14 
Diagnosis and Treatment of Hypertension
Hypertension  will be  evaluated,  defined  and  
treated  
in  
this  protocol  according  
to  
the  Seventh 
Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment 
of High Blood Pressure guidelines  
for subjects with renal transplants56. Accordingly, in adults, 
pre-hypertension  
is  defined  as SBP ≥130  mm  Hg  or  DBP ≥80  mm  Hg,  and  hypertension  as 
SBP≥140  mm Hg or DBP ≥ 90  mm Hg. In addition, subjects who do not meet these  
levels of 
SBP or DBP, but are receiving medication(s) for the management of hypertension, and/or those 
with a prior medical history of hypertension, are also to be considered as having hypertension. 
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Per  the  guidelines  included  in  the Seventh Report of the Joint National Committee on the 
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure57in the  absence  of 
compelling data for renal transplant recipients, no particular class of antihypertensive drugs can 
be considered superior to any other. Therefore, subjects should be treated per the investigator’s 
discretion and in accordance with local standards of care to reach the target blood pressure goals.
The  intensity  of  an  anti-hypertensive  treatment  regimen  is  defined  as  the  total  number  of 
antihypertensive  medications  used  to  control  hypertension.  In  subjects  with  hypertension, 
whether  adequately  controlled  or  not, all  antihypertensive  medications  will  be  counted  in 
determining  
the  presence  of  hypertension  and  
the  
intensity  of  
the  
treatment  
regimen,  since  
the 
antihypertensive  effects  will  be  considered  present  regardless  of  the  ostensible  indication  for 
which they were prescribed.
5.3.15 
Diagnosis of New Onset Diabetes After Transplant
A subject who did not have diabetes prior to transplant and receives an anti-diabetic medication 
for a duration of at least 30 days will be considered to have new onset diabetes after transplant 
(NODAT). All cases of NODAT should be reported to BMS as an adverse event.
Additionally,  a  subject  who meets  the  criteria  below  (set forth  by  the  American  Diabetes 
Association57), and did not have diabetes prior to transplant will be considered to have new onset 
diabetes. These criteria are summarized as:
1. Hemoglobin  A1C  ≥6.5%, when  performed  in  a  laboratory  using  a  method  that  is  NGSP 
certified and standardized to the DCCT assay.
2. In  the  presence  of  symptoms  characteristic  of  diabetes  mellitus,  a  casual  plasma  glucose 
concentration ≥200  mg/dL  (11.1 mmol/L).  Casual  is defined  as  any  time  of  day  without 
regard  to  time  since  last meal.  Symptoms  of  characteristic  of  diabetes  include  polyuria, 
polydipsia, and unexplained weight loss.
or
3. Fasting Plasma Glucose (FPG) ≥126 mg/dL (7.0 mmol/L)*. Fasting is defined as no caloric 
intake for at least 8 h.
or
4. Two (2)-h post-load blood glucose concentration ≥200 mg/dL (11.1 mmol/L) during an Oral 
Glucose  Tolerance  Test  (OGTT)*. The  test  should  be  performed  as  described  by  WHO, 
using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
*In  the  absence  of  unequivocal  hyperglycemia,  criteria  1  through 3  should  be  confirmed  by 
repeat testing.
Any new or worsening findings must be recorded on the appropriate AE page of the CRF.
5.3.16 
Treatment for Dyslipidemia
Clinical practice guidelines for the management of dyslipidemias in renal transplant subjects are 
available from  
the  National Kidney  Foundation  Kidney  Disease  Outcomes  Quality  
Initiative
58. 
Subjects  should  be  treated  in  a  manner  consistent  with  these  guidelines  (see 
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Table 5.3.16-1) and local standard of care:
Table 5.3.16-1: 
Guidelines for the Treatment of Dyslipidemias in Renal Transplanta
Definition of
Dyslipidemia 
Goal 
Initiate
Increase 
Regimen
If Not at 
Goal 
Alternative
TGs ≥500 mg/dL
(≥5.65 mmol/L)
TGs < 500 mg/dL
(< 5.65 mmol/L)
TLC
TLC + 
Fibrate or 
Niacin
Fibrate or 
Niacin
LDL 100 - 129 mg/dL
(2.59 - 3.35 mmol/L)
LDL < 100 mg/dL
(< 2.59 mmol/L)
TLC
TLC + 
Statin
Bile Acid 
Sequestrant or 
Niacin
LDL ≥130 mg/dL
(≥3.36 mmol/L) 
LDL < 100 mg/dL
(< 2.59 mmol/L)
TLC + 
Statin
TLC + 
Increased 
Statin Dose 
Bile Acid 
Sequestrant or 
Niacin
TGs ≥200 mg/dL (≥2.26 mmol/L) 
AND non-HDL ≥130 mg/dL 
(≥3.36 mmol/L)
Non-HDL < 130 mg/dL
(< 3.36 mmol/L)
TLC + 
Statin
TLC + 
Increased 
Statin Dose 
Fibrate or 
Niacin
a Notes:
1. Modified from NKF-K/DOQI guidelines58. ‘Statin’ refers to a class of compounds that inhibit the enzy
me 
3-hydroxy-3-methylglutaryl  coenzyme  A  reductase  (HMG-CoA)  inhibitor.  It  is  recommended  that  the 
maximum doses of statins be reduced in subjects receiving tacrolimus. The addition of a third agent that is 
also metabolized by the cytochrome P450 system increases the risk of myositis and rhabdomyolysis, and 
therefore, such combinations should be avoided. The effects of sirolimus on statins are unknown. Refer to 
the appropriate package insert for specific recommendations.
2. The NKF-K/DOQI guidelines recommend gemfibrozil as the fibrate of choice as it does not require dose 
modification for renal insufficiency.
3. All subjects  who exceed any stated threshold value for dyslipidemia should begin recommended therapy, 
which should then be titrated to lower the elevated fasting lipid concentration(s) to the above target level(s).
Non-HDL  =  non-high-density  lipoprotein,  LDL  =  low-density  lipoprotein,  NKF-K/DOQI  =  National  Kidney 
Foundation  Kidney  Disease  Outcomes  Quality  Initiative,  TGs  =  
triglycerides,  and  TLC = therapeutic  
lifestyle 
changes (eg, diet and exercise).
Intensity of treatment regimen is defined as the total number of antihyperlipidemic medications 
used  to  control  dyslipidemia.  Each  drug  prescribed as  an  antihyperlipidemic  agent  will  be 
counted  
individually.  For  example:  concomitant  use  of  a  statin and  an  agent  of  another  class 
(e.g., ezetimibe),or combination therapy (e.g., a statin and ezetimibe in one pill) will be counted 
as 2 medications.
All  prescribed  antihyperlipidemic  medications  will  be  counted  as  having  been  given  for
treatment of  dyslipidemia  in  subjects  with  dyslipidemia  regardless  of  the  degree  of  control 
achieved,  and  independent  of  the  intended  indication, since  the lipid-lowering  effects  are 
expected to be present in any case.
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Any new or worsening findings must be recorded on the appropriate AE page of the CRF.
5.3.17 
Follow-up Safety Period
NOTE:  Withdrawal  of  a  subject  from  study  medication  does  not  imply  that  the  subject  is 
withdrawn from the study. All subjects will be followed for full duration of the protocol for graft 
and survival status (See Section 3.6).
8-Week Post Last Dose Safety Follow-up Visit
All  subjects  should  complete  
the  8-Week  Post  Last  Dose  Safety  Follow-up  Visit, this  visit 
may be conducted by phone. The following procedures are required:
♦Assess for AEs
♦Pregnancy Test (WOCBP only)
♦Concomitant medications 
Belatacept-treated subjects who discontinue belatacept or complete the study and return to 
standard of care, the following blood sample is also required at the 8-Week Post Last Dose 
Safety Follow-up Visit:
♦Immunogenicity 
12-Week and 24-Week Post Last Dose Safety Follow-up Visits 
Belatacept-treated subjects who discontinue belatacept or complete the study and return to 
standard of care should complete the 12-Week and 24-Week Post Last Dose Safety Follow-
up visits, the following procedures are required:
♦Assess for AEs
♦Immunogenicity sample collection
A ±5 day window will be allowed for each follow-up visit.
5.4 
Efficacy Assessments
Only data  
for the procedures and assessments specified  
in this protocol should  be submitted to 
BMS on a case report form. Data from additional procedures and assessments performed as part 
of standard of care should remain in the subject’s medical record and should not be provided to 
BMS, unless specifically requested.
 
 
 
 
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6 
ADVERSE EVENTS
An Adverse Event (AE)is defined as any new untoward medical occurrence or worsening of a 
preexisting  medical condition  
in a clinical  
investigation  subject administered an  
investigational
(medicinal) product and that does not necessarily have a causal relationship with this treatment. 
An  AE  can  
therefore  be  any  unfavorable  and  unintended  sign  
(such  as  an  abnormal  
laboratory 
finding),  symptom,  or  disease temporally  associated  with  the  use  of  investigational  product, 
whether or not considered related to the investigational product.
The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE). The casual relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not  related:  There  is  not  a  reasonable  causal  relationship  between  study  drug 
administration and the AE.
The  term  "reasonable  causal  relationship"  means  there  is  evidence  to  suggest  a  causal 
relationship.
Adverse  events  can  be  spontaneously  reported  or  elicited  during  open-ended  questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs.)
Note: Acute rejection will not be reported as an AE or SAE in this study. These events will be 
collected on separate CRFs.
6.1 
Serious Adverse Events
A Serious Adverse Event (SAE)is any untoward medical occurrence that at any dose: 
• results in death
• is life-threatening (defined as an event in which the subject was at risk of death at the time of 
the  event;  
it  does  not  
refer  
to  an  event  which  hypothetically  might  have  caused  death  
if  
it 
were more severe)
• requires  inpatient  hospitalization  or  causes  prolongation  of  existing  hospitalization 
(seeNOTEbelow)
• results in persistent or significant disability/incapacity
• is a congenital anomaly/birth defect 
• is  an  
important  medical  event  
(defined  as  a  medical  event(s)  
that  may  not  be  
immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific  judgment,  may  jeopardize  the  subject  or  may  require intervention  [eg,  medical, 
surgical]  to  prevent  one  of  the  other  serious  outcomes  listed  in  the  definition  above.) 
Examples of such events include, but are not limited to, intensive treatment in an emergency 
room  or  at  home  for allergic  bronchospasm;  blood  dyscrasias  or  convulsions  that  do not 
result  in  hospitalization.) Potential  drug  induced  liver  injury (DILI)  is  also  considered  an 
important medical event. (See Section 6.6for the definition of potential DILI.)
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Suspected  
transmission  of  an  
infectious  agent  
(eg, pathogenic  or  nonpathogenic)  via  
the  study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential DILI are not always serious by regulatory 
definition, these events must be handled as SAEs. (See Section 6.1.1 for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy should be reported 
as  SAE.  For  example,  if  death,  which  is  a  study  endpoint, occurred  due  to  anaphylaxis, 
“anaphylaxis” must be reported. (See Section 6.1.1 for reporting details.)
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies:
−a  visit  
to  
the  emergency  room  or  other  hospital  department  <  24  hours,  
that  does  not 
result in admission (unless considered an important medical or life-threatening event)
−elective surgery, planned prior to signing consent
−admissions as per protocol for a planned medical/surgical procedure
−routine  health  assessment  requiring  admission  for  baseline/trending  of  health  status 
(eg, routine colonoscopy)
−medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases
−admission  encountered  for  another  life  circumstance  that  carries  no  bearing  on  health 
status  and  requires  no  medical/surgical  intervention  (eg,  lack of  housing,  economic 
inadequacy, caregiver respite, family circumstances, administrative reason).
6.1.1 
Serious Adverse Event Collection and Reporting
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not  related  to  study  drug,  must  be  collected,  including  those  thought  to  be  associated  with 
protocol-specified procedures.
All  SAEs  must  be  collected  that  occur  during  the  screening  period  and  within  56  days  of 
discontinuation of dosing. If applicable, SAEs must be collected that relate to any later protocol-
specified procedure (eg, a follow-up skin biopsy).
All events of death, graft loss, malignancy, PTLD, and serious infections (ie, otherwise meeting 
SAE reporting requirements) must be reported to BMS for all randomized subjects until the end 
of the study, irrespective of study drug discontinuation or investigator-deemed causality.
The investigator should report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure.
An SAE report should be completed for any event where doubt exists regarding its seriousness.
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If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship should be specified in the narrative section of the SAE Report Form.
SAEs,  whether  
related  or  not  
related  
to  study  drug,  and  pregnancies  must  be  
reported to  BMS 
(or designee) within  24  hoursof  awareness  of  
the  event.  SAEs  must  be  
recorded  on  
the  SAE 
Report Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms). When 
using  paper  forms,  the  reports  are  to  be  transmitted  via  email or  confirmed  facsimile  (fax) 
transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number:  Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. The paper forms should be used and submitted immediately, only 
in  
the  event  
the  electronic  system  
is  unavailable  
for  
transmission.  When  paper  
forms  are  used, 
the original paper forms are to remain on site.
SAE  Telephone  Contact (required  for  SAE  and  pregnancy  reporting):  Refer  to  Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports should include the same investigator term(s) initially reported.)
If  an  ongoing  SAE  changes  
in  
its  
intensity  or  
relationship  
to  study  drug  or  
if  new  
information 
becomes  available,  a  follow-up  SAE  report  should  be  sent  within  24  hours  to  the  BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs should be followed to resolution or stabilization.
6.2 
Nonserious Adverse Events
Anonserious adverse eventis an AE not classified as serious.
6.2.1 
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE  information  should  also  be  collected  from  the  start  of  a  placebo lead-in  period  or  other 
observational period intended to establish a baseline status for the subjects.
Nonserious  AEs  should  be  followed  
to  
resolution  or  stabilization,  or  
reported  as  SAEs  
if  
they 
become  serious  (see Section  6.1.1).  Follow-up  is  also  required  for  nonserious  AEs  
that  cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic).
Completion  of  supplemental  CRFs  may  be  requested  for  AEs  and/or  
laboratory  abnormalities 
that are reported/identified during the course of the study.
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6.3 
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (paper or electronic) as appropriate:
• Any  abnormal  laboratory  test  result  that,  in  the  opinion  of  the  investigator, is  clinically 
significant or meets the definition of an SAE 
• Any abnormal laboratory test result that required the subject to have study drug discontinued 
or interrupted
• Any  abnormal  
laboratory  
test  
result that  
required  
the  subject  
to  
receive  specific  corrective 
therapy.
It  
is  expected  
that, wherever  possible,  
the  clinical  event  
rather  
than  
the  
laboratory  abnormality 
would  be  used  by  
the  reporting  investigator:  e.g.,  “anemia”  instead  of  
the  corresponding  low 
hemoglobin value.
6.4 
Pregnancy
If,  
following  
initiation of the  
investigational product, it is subsequently discovered that a study 
subject  
is pregnant or may  have  been pregnant at the time of  
investigational product exposure, 
including during at least 6 half lives after product administration, the investigational product will 
be permanently discontinued in an appropriate manner (eg, dose tapering if necessary for subject 
safety).
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject  unless  contraindicated  by  pregnancy  (eg,  x-ray  studies).  Other  appropriate  pregnancy 
follow-up procedures should be considered if indicated.
The  
investigator  must  
immediately  notify  
the  BMS  of  
this  event and  complete  and  forward  a 
Pregnancy Surveillance  Form to BMS (or designee) within 24  hours of awareness of the  event 
and in accordance with SAE reporting procedures described in Section 6.1.1.
Follow-up  
information  
regarding  
the  course of  
the  pregnancy,  
including  perinatal  and  neonatal 
outcome  and,  where  applicable,  offspring  information  must  be  reported  on  the  Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
For  women  participating  at  US  
investigative  sites  who  become  pregnant  while using  MMF  or 
EC-MPS/MPA in this study, the investigator should report the pregnancy to the Mycophenolate 
Pregnancy Reference Registry and should strongly encourage the patient to enroll in the registry.
6.5 
Overdose
An overdose is defined as the accidental or intentional ingestion of any dose of a product that is 
considered both excessive and medically important.
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However,  for  reporting  purposes, alloccurrences  of  overdose  (for the  investigational  drugs 
belatacept and everolimus) must be reported as SAEs(see Section 6.1.1for reporting details).
6.6 
Potential Drug Induced Liver Injury (DILI)
Wherever  possible,  
timely  confirmation  of  initial liver-related  
laboratory  abnormalities  should 
occur  prior  to  the  reporting  of  a  potential  DILI  event.  All  occurrences  of  potential  DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
Potential drug induced liver injury is defined as:
a) A serum AT (ALT or AST) elevation > 3 times ULN
AND 
b) A  serum  total  bilirubin  >  2  times  ULN,  without  initial  findings  suggestive  of  cholestasis 
(e.g., an elevated serum alkaline phosphatase),
AND 
c) No  other  immediately  apparent  possible  causes  of  AT  elevation  and  hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic.
6.7 
Other Safety Considerations
Any  significant  worsening  noted  during  interim  or  final  physical  examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
6.7.1 
Events of Special Interest (ESI)
Additional CRFs or appropriate source documentation  may  be required  
for  
further clarification 
for the following “events of special interest”:
• PTLD
• PML
• Malignancies (other than PTLD) including non-melanoma skin carcinomas
• TB Infections (serious and non-serious)
• CNS Infections (serious and non-serious)
• Viral Infections (serious)
• Infusion related reactions
• Other reason deemed necessary by the Sponsor
To monitor and better understand these risks, BMS,  
its collaborators and/or its agents  may use 
collected blood samples for JCV, EBV and other immune function-related tests.
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7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
A  Data  Monitoring  Committee  (DMC)  will  be  convened  to  provide  oversight  of  benefit-risk 
considerations  for  patients  in  the  study  and  if  necessary  make recommendations  to  BMS  to 
ensure the ongoing safety of study subjects.
At  periodic  intervals,  the  DMC  will  review  the  accumulated  safety  and  efficacy  data  on  key 
outcomes,  in  unblinded  fashion,  including death,  graft  loss,  acute  rejection,  infections,  and 
malignancies;  these  data  will  be  reviewed  for  the  overall  population  as  well  as  relevant 
subgroups.  The  DMC  will  then  provide  to  BMS  their  assessment  of  the  emerging balance 
between benefits and risks, and recommendations regarding the further conduct of the study.
A DMC Charter will be prepared, which will include full details of the Committee’s membership 
and responsibilities, and how it will function; this will include the frequency of routine meetings, 
the types of data outputs to be provided for their review, and criteria for convening any ad hoc 
safety reviews. Appropriate updates will be made to the protocol, as well.
8 STATISTICAL CONSIDERATIONS
8.1 
Sample Size Determination
This study is descriptive in nature and is not powered to show statistically significant treatment 
differences  
for any outcome  measure. A  sample of  approximately 70 subjects, randomized  
in  a 
1:1 ratio to the belatacept + EVL and TAC + MMF groups, is planned.
Assessment of clinical suspicion of acute rejection can be found in Section 5.3.7. As an endpoint, 
acute rejection events in this study will be those that are CSBPAR.
If the true probability of CSBPAR  
in the  belatacept + EVL treatment group  
is 3.8%, a sample 
size of 35 subjects allows the estimation of the population proportion (πp) with a 95% CI
ǂof 0.2 
% to 16.4% around the observed proportion of CSBPAR. If the rate is 3%, in the TAC +MMF 
treatment group, then the 95% CI
ǂaround the estimate would be 0.1 % to 15.1 %, for lower and 
upper limits, respectively.
For the secondary endpoint of assessing the difference in the incidence of CSBPAR at 6 months 
post-transplantation between the TAC + MMF and belatacept + EVL groups, respectively, with 
120 subjects per treatment group, if the observed incidences of CSBPAR (conservatively based 
on  study  IM103034)  are  3%  and  3.8%, the  2-sided  95%  confidence  interval  (CI)* of  the 
differences between the observed incidence rates can be summarized as in Table 8.1-1.
Table 8.1-1: 
Confidence Intervals* for the Difference between Two Proportions
Difference of Treatments 
(assumed proportions)
Lower 95% Confidence 
Limit
Upper 95% Confidence 
Limit
Half Width
TAC + MMF (3%)   
vs 
Bela + EVL (3.8%)
- 13.2%
11.3%
12.25%
ǂ Confidence Interval Method: Clopper-Pearson
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*Confidence Interval Method: Score (Wilson)
8.2 
Populations for Analyses
• The  primary  endpoint  will  be initially  assessed  on  the  ITT population  in  each  treatment 
group.  The  
ITT population  will  consist of  all  
randomized  and  
transplanted  subjects  
treated 
with at least one dose of Thymoglobulin and one dose of study treatment, either belatacept or 
TAC,  and  will  be  
included  
in  
the  safety  and  efficacy  analysis  data  sets.  
In  
these  analyses, 
CSBPARs  occurring  after  discontinuation  from  assigned  therapy  will  be  counted  in  the 
treatment arm to which the subject was originally randomized.
• Additionally,  
for  CSBPAR,  a  sensitivity  analysis  will  be  performed  with  
right  censoring  at 
the time of discontinuation from the assigned therapy.
• An as-treated analysis will be based on the treatment regimen received. Analysis of treatment 
differences  in  
the  rates  of  CSBPAR  will  only include  
those  subjects  who  remain  on  
their 
original therapy  
from the beginning, through the designated analysis time point(s) (e.g., the 
Months 6, 12 and 24 study visits) for these above mentioned analyses. Treatment differences 
in the rates of CSBPAR will also be performed using a per protocol efficacy dataset.
−This is defined as the set of all data derived from that subset of subjects once treated, are 
followed  up  consistently  with  all  study  criteria  to  
the  extent that  no  relevant  protocol 
deviations have been identified.
The  primary  analysis  will  be  done  on  the  ITT  population  and  the  sensitivity  analyses  on  the 
primary endpoints will be done in the As Treated, as well as the Per Protocol population.
8.3 
Endpoints
All  primary  and  secondary  endpoints  listed  below  will  be  assessed  and  described  for each 
treatment group.
8.3.1 
Primary Endpoint(s)
• The incidence of CSBPAR at 6 months post-transplant, in the individual treatment groups:
−Belatacept + EVL
−TAC + MMF
8.3.2 
Secondary Endpoint(s)
The two treatment groups will be compared for all secondary endpoints.
Acute Rejection
• Treatment differences in the incidence of CSBPAR at 6, 12 and 24 months post-transplant, in 
the belatacept + EVL versus TAC + MMF treatment groups;
• Time to CSBPAR;
• Treatment  differences  in  the  severity  grades  and  therapeutic modalities  used  to  treat all 
episodes of CSBPAR at 6, 12, and 24 months post-transplant;
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−Severity: To be assessed by the local pathologist, using the 2007 update to the Banff 97 
classification of renal allograft pathology;
−Treatment regimen:  Categorical  analysis  of  CSBPAR  episodes  by  treatment  received, 
including: a) corticosteroids; b) T-cell depleting agent(s); c) renal replacement therapy; d) 
plasmapheresis; e) IVIg; f) rituximab.
Subject and graft survival
• Proportion of all subjects who survive with a functioning graft at 6, 12 and 24 months post-
transplant;
• Proportion of all subjects who experience death by 6, 12 and 24 months post-transplant;
• Proportion of all subjects who experience graft loss by 6, 12 and 24 months post-transplant;
• Time to event analysis of death and graft loss.
Renal Function
• Absolute  (mean  and  median)  cGFR  values  at  3,  6,  12  and  24  months  post-transplant,  as 
determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula;
• The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant;
• Slope of the change in cGFR from Month 3 to Months 6, 12 and 24 post-transplant;
• Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.
Donor Specific Anti-HLA Antibodies (DSA)
• Percentage  of  subjects  with,  and  titers  of  pre-existing  (pre-transplant)  and de novo(post-
transplant)  DSA  on Day  1 (pre-transplant,  pre-dose),  and  at  Months  12  and  24 post-
transplant;
• Characterization  of  any de novoDSA  detected  by  IgM  and  IgG subclasses,  and  by  the 
presence or absence of complement fixing properties.
Safety and tolerability of each treatment regimen
• Incidence of all AEs and SAEs at 6, 12 and 24 months post-transplant;
• Incidence of ESI at 6, 12 and 24 months post-transplant;
• Description and incidence of clinically significant changes in vital signs;
• Description and incidence of laboratory test abnormalities.
Cardiovascular and metabolic co-morbidities
• Incidence of NODAT at 6, 12 and 24 months post-transplant;
• Absolute  (mean  and  median)  values  for  SBP  and  DBP  at  3,  6,  12  and  24 months  post-
transplant;
• Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant;
• Absolute  (mean  and  median)  values  at  3,  6,  12  and  24  months  post-transplant,  and  mean 
change from baseline levels at Months 12 and 24, for the following fastinglipid levels:
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• Descriptive summaries of graft and subject survival, by treatment group
−at Month 12 in subjects with and without AR by Month 6 and 
−at Month 24 in subjects with and without AR by Month 12
• Descriptive summaries of infection and malignancy, by treatment group
−at Month 12 in subjects with and without AR by Month 6 and 
−at Month 24 (by subjects with and without AR by Month 12
In  addition,  Kaplan-Meier  (KM)  cumulative  event  rates  will  also  be  performed  by  treatment 
groups.
8.4.2.2 
Subject and Graft Survival
The  endpoint  of  subject  and  graft  survival  at  6,  12  and  24  months  post-transplant  will  be 
summarized  within  each  treatment  group  using  point  estimates  of  the proportion  of  subjects 
surviving  with  a  
functioning  graft,  and  
the  corresponding  95%  CIs.  The  proportion  of  subjects 
who  die,  proportion  of  subjects  who  have  a  graft  loss,  and  the proportion  of  subjects  who 
experience the following outcomes will each be summarized using point estimates and 95% CI 
within each treatment group.
• Overall graft loss rates at 6, 12 and 24 months
• Rates of death with a functioning graft at 6, 12 and 24 months;
• Rates of pure (death-censored) graft loss at 6, 12 and 24 months.
8.4.2.3 
Renal Function
Calculated GFR at Months 3, 6, 12, and 24 and change in cGFR from Month 3 to Months 6, 12 
and  24,  respectively,  will  be  descriptively  summarized.  For  a  subject  who  has  one  or  more 
missing  values  for  cGFR  due  
to  a  graft  loss  or  death,  
the  missing  values  will  be  imputed  as 
“zero”. 
A linear mixed effects model will be used to analyze changes from Month 3 cGFR. Details of the 
analyses will be available in the Statistical Analysis Plan.
Population-mean  slopes  will  be  estimated  for  each  treatment  group.  In  addition,  the  95% 
confidence intervals will also be obtained for each mean slope. Intercepts will be summarized in 
the same manner.
In  addition,  urinary  protein to  creatinine  ratios,  to  be  obtained  from  single-voided  urine 
specimens at 3, 6, 12 and 24 months post-transplant, will be descriptively summarized.
8.4.2.4 
Donor Specific Antibodies
The  percentage  of  subjects  with  detectable DSA  on  Day  1,  and  of de novoDSA  at  12  and  24 
months post-transplantation will be descriptively summarized by treatment group. The data from 
the  DSA  assessments  will  be  cross-matched  with  the  number  of  donor  /  recipient  HLA 
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mismatches  
to  confirm  
the  anti-donor  status  of  any  detected  anti-HLA  antibodies.  The  
results 
will be categorized according to the results obtained by flow cytometry, as follows:
• Mean Florescent Intensity (MFI) > 2000 = Positive
• MFI 1000-2000 = Potentially Positive
• MFI < 1000 = negative
8.4.2.5 
Cardiovascular and Metabolic Co-morbidities
Descriptive  summaries of SBP and DBP will  be  provided  by treatment group at Months 6, 12, 
and  24.  
In  addition,  
the  changes  
from  
the  
last  measurement  obtained prior to transplant to the 
subsequent  measurements  obtained  at  each  subsequent  (post-transplant)  time  point  will  be 
summarized.
Changes  in  each  of  the  fasting  lipid  variables  (total  cholesterol,  HDL  cholesterol,  LDL 
cholesterol and TG) between the last value obtained prior to the transplant and results at Months 
12 and 24 will be descriptively summarized.
The incidence of NODAT at 6, 12 and 24 months post-transplantation will be summarized along 
with the corresponding 95% CIs.
Changes from baseline in fasting glucose and HbA1C levels will be descriptively summarized at 
Months 6, 12 and 24.
Additionally,  descriptive  summaries  of  antihypertensive  and  antihyperlipidemic therapies  will 
also be provided. Details of the analyses will be available in the Statistical Analysis Plan.
8.4.3 
Safety Analyses
Safety analysis will be based on all randomized, transplanted, and treated subjects. All AEs will 
be summarized and  
listed  by treatment groups. SAEs  and  AEs that result  
in discontinuation of 
the study drug will also be tabulated in detail. Laboratory marked abnormalities, defined as those 
identified  as  “critically”  out  of range  per  the  central  laboratory  manual,  will  be  summarized 
descriptively. There will be no statistical testing of group differences with respect to frequencies 
of adverse events or laboratory marked abnormalities or changes in clinical laboratory tests from 
baseline (last measurement prior to randomization).
All  safety  summaries  except  those  for  reports of  death,  graft  loss,  PTLD,  malignancies,  and 
serious infections, will be based only on data at the scheduled analysis time point applying ‘last 
dose  date  +  56’  cut  counting  rules.  For  events  of  death,  graft loss,  PTLD,  malignancies,  and 
serious  
infections,  
two  different  summaries  will  be  prepared.  The  
first  summary  will  be  based 
only  on  data  at  
the  scheduled  analysis  
time  point  applying  
‘last  dose  date  +  56’  cut  counting 
rules. The secondary summary will be based on all available data at the scheduled analysis time 
point without applying ‘last dose date + 56’ cut counting rules.
The frequencies and incidence rates using person-year method with exposure will be summarized 
by treatment groups.
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9
STUDY MANAGEMENT
9.1 
Compliance
9.1.1 
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and  be prepared  by, BMS. The  
investigator should  not implement any 
deviation  or  change  to  
the  protocol  without  prior  review  and  documented  approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects.
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to  obtaining  
IRB/IEC  approval/favorable  opinion,  as  soon  as  possible  
the  deviation  or  change 
will be submitted to:
• IRB/IEC for review and approval/favorable opinion
• BMS
• Regulatory Authority(ies), if required by local regulations
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Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If  an  amendment  substantially  alters  the  study  design  or  increases  the  potential  risk  to  the 
subject: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable  opinion;  
(2)  
the  
revised  
form  must  be  used  
to obtain  consent  
from  subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2 
Monitoring
Representatives  of  BMS  (or  designee)  must  be  allowed  to  visit  all  study  site  locations 
periodically to assess the data quality and study integrity. On site they will review study records 
and  directly  compare  
them  with  source  documents,  discuss  
the  conduct  of  
the  study  with  
the 
investigator, and verify that the facilities remain acceptable.
In addition, the study may be evaluated by BMS internal auditors (or designee) and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The  investigator  must  notify  BMS  promptly  of  any  inspections  scheduled  by  regulatory 
authorities, and promptly forward copies of inspection reports to BMS.
9.1.3 
Investigational Site Training
Bristol-Myers Squibb will provide quality  
investigational staff training prior to study initiation. 
Training  topics  will  include  but  are  not  limited  to:  GCP,  AE  reporting,  study  details  and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2 
Records
9.2.1 
Records Retention
The  
investigator  must  
retain  all  study  
records and  source  documents  for  
the  maximum  period 
required  by  applicable  regulations  and  guidelines,  or  institution  procedures,  or  for  
the  period 
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If  the  investigator  withdraws  from  the  study  (eg,  relocation,  retirement),  
the  records  shall  be 
transferred  
to  a  mutually  agreed  upon  designee  
(eg,  another  
investigator, IRB).  Notice  of  such 
transfer will be given in writing to BMS.
9.2.2 
Study Drug Records 
It  is  the  responsibility  of  the  investigator  to  ensure  that  a  current  disposition  record  of 
investigational  product  
(those  supplied  by  BMS)  
is  maintained at  each  study  site  where  study 
drug and  the  following  non-investigational product(s): methylprednisolone,  prednisone  or 
equivalent,  mycophenolate  mofetil,  mycophenolate  sodium or  equivalents are  inventoried  and 
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dispensed. Records or logs  must comply with applicable regulations  and guidelines and  
should 
include:
• amount received and placed in storage area
• amount currently in storage area
• label identification number or batch number 
• amount dispensed to and returned by each subject, including unique subject identifiers
• amount transferred to another area/site for dispensing or storage
• nonstudy disposition (eg, lost, wasted) 
• amount destroyed at study site, if applicable
• amount returned to BMS
• retain samples for bioavailability/bioequivalence, if applicable
• dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form.
BMS  
(or  designee)  will provide  forms  
to  
facilitate  
inventory  control  
if the  
investigational  site 
does not have an established system that meets these requirements.
9.2.3 
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or  entered  as  a  control  
in  
the  
investigation.  Data  
that  are  derived  from  source  documents  and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For  sites  using  
the  BMS  electronic  data  capture  
tool,  electronic  CRFs  will  be  prepared  for  all 
data collection fields except for fields specific to SAEs and pregnancy, which will be reported on 
the paper or electronic SAE form and Pregnancy Surveillance form, respectively. Spaces may be 
left  blank  only  
in  
those  circumstances  permitted  by  study-specific  CRF  completion  guidelines 
provided by BMS.
The  confidentiality  of  records  that  could  identify  subjects  must  be  protected,  respecting  the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs.
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated  by the  
investigator or qualified physician who  
is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form. For electronic CRFs, review 
and approval/signature is completed electronically through the BMS electronic data capture tool.
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The investigator  must  retain  a  copy  of  the  CRFs  including  records  of  the  changes  and 
corrections.
Each  individual electronically  signing  electronic  CRFs  must  meet  BMS  
training  requirements 
and  must  only  access  the  BMS  electronic  data  capture  tool  using  the  unique  user account 
provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3 
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report.
For this protocol, the Signatory Investigator will be selected considering the following criteria:
• National Coordinating Investigator
• Subject recruitment (eg, among the top quartile of enrollers)
• Regional  representation  (eg,  among  top  quartile  of  enrollers  from  a  specified  region  or 
country)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study require approval by BMS prior to publication or presentation 
and  must  adhere  
to  BMS’s publication  
requirements  as  set  forth  
in  
the  approved  clinical  
trial 
agreement  (CTA).  All  draft  publications,  including  abstracts  or  detailed  summaries  of  any 
proposed presentations, must be submitted to BMS at the earliest practicable time for review, but 
at any event not less than 30 days before submission or presentation unless otherwise set forth in 
the  CTA.  BMS shall  have  the  right  to  delete  any  confidential  or proprietary  information 
contained in any proposed presentation or abstract and may delay publication for up to 60 days 
for purposes of filing a patent application.
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10 GLOSSARY OF TERMS
Term
Definition
Adverse Reaction
An adverse event that is considered by either the investigator 
or BMS as related to the investigational product
Unexpected Adverse Reaction An adverse reaction, the nature or severity of which is not 
consistent with the applicable product information 
(eg, Investigator Brochure for an unapproved investigational 
product)
Serious Adverse Event 
Serious adverse event defined as any untoward medical 
occurrence that at any dose: results in death; is life 
threatening (defined as an event in which the subject was at 
risk of death at the time of the event; it does not refer to an 
event which hypothetically might have caused death if it 
were more severe), requires insubject hospitalization or 
causes prolongation of existing hospitalization; results in 
persistent or significant disability/incapacity, is a congenital 
anomaly/birth defect; is an important medical event (defined 
as a medical event(s) that may not be immediately life 
threatening or result in death or hospitalization but, based 
upon appropriate medical and scientific judgment, may 
jeopardize the subject or may require intervention 
[eg, medical, surgical] to prevent one of the other serious 
outcomes listed in the definition above). Examples of such 
events include, but are not limited to, intensive treatment in 
an emergency room or at home for allergic bronchospasm; 
blood dyscrasias or convulsions that do not result in 
hospitalization.). For reporting purposes only, BMS also 
considers the occurrence of pregnancy, overdose (regardless 
of association with an AE), and cancer as important medical 
events.
Casual blood glucose 
concentration
Blood glucose test at any time of the day without regard to 
time since last meal. 
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11 LIST OF ABBREVIATIONS
Term
Definition
AE
adverse event
ALT
alanine aminotransferase
APC
antigen presenting cell
AR
acute rejection
AST
aspartate aminotransferase
AT
Aminotransaminases (ALT and AST)
β-HCG
beta-human chorionic gonadotrophin
BCAR
biopsy confirmed acute rejection
BID, bid
bis in die, twice daily
BKV
B.K.( patient
's initials, in whom it was first detected) Virus
BMI
body mass index
BMS
Bristol-Myers Squibb
BMS-224818 
LEA29Y (belatacept)
BP
blood pressure
BPAR
Biopsy-proven acute rejection
BUN
blood urea nitrogen
C
Celsius
C0
concentration pre-dose, trough
CAN
chronic allograft nephropathy
CBC
complete blood count
CD
cluster of differentiation
CFR
Code of Federal Regulations 
cGFR
calculated glomerular filtration rate
CI
confidence interval
CKD
chronic kidney disease
Cmin, CMIN 
minimum observed concentration
CMV
Cytomegalovirus
CNI
calcineurin inhibitor
CNS
Central nervous system
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Term
Definition
CRF
Case Report Form, paper or electronic
CS
Corticosteroids
CsA
cyclosporine (cyclosporin)
CSBPAR 
Clinically-suspected biopsy-proven acute rejection
CSF
cerebral spinal fluid
CTA
clinical trial agreement
CXR
chest x-ray
CYP
cytochrome p-450
D
Day
D5W
dextrose 5% in water for injection
de novo
from the beginning (Latin)
DBP
diastolic blood pressure
DGF
delayed graft function
DILI
drug induced liver injury
dL
Deciliter
DMC
Data Monitoring Committee
DSA
donor specific antibody
EBV
Epstein-Barr virus
EBNA
Epstein-Barr nuclear antigen
EBER
Epstein-Barr virus-encoded small RNAs
ECD
extended criteria donor
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
eg
exempli gratia (for example)
eGFR
estimated glomerular filtration rate
EoI
end of infusion
ESI
Events of Special Interest
ESRD
end-stage renal disease
ET
Early Termination
EVL
everolimus
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Term
Definition
F
Fahrenheit
FDA
Food and Drug Administration
FPG
Fasting Plasma Glucose
FSGS
focal segmental glomerulosclerosis (FSGS)
FSH
follicle stimulating hormone
FU
follow-up
g
Gram
GCP
Good Clinical Practice
GFR
glomerular filtration rate
h
Hour
HbA1c
hemoglobin A1c
HBV
hepatitis B virus
HCV
hepatitis C virus
HDL
high-density lipoprotein
HIV
Human Immunodeficiency Virus
HLA
human leukocyte antigen
HR
heart rate
HRT
hormone replacement therapy
HUS
hemolytic uremic syndrome
ICF
informed consent form
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
Ig
Immunoglobulin
IGRA
interferon- gamma release assay
IHC
immunohistochemistry
IL
Interleukin
IL-2R
Interluekin-2 receptor
IL2RA
Interluekin-2 receptor alpha chain
IMP
investigational medicinal products
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Term
Definition
INH
Isoniazid
IP
investigational product
IRB
Institutional Review Board
ITT
intent-to-treat
IU
International Unit
IV, i.v.
Intravenous
IVIg
Intravenous immune globulin
IVRS
interactive voice response system
JCV
John Cunningham virus
K3EDTA 
potassium ethylenediaminetetraacetic acid
KDIGO
Kidney Disease Improving Global Outcomes
KDOQI
Kidney Disease Outcomes Quality Initiative
kg
Kilogram
ΚΜ 
Kaplan-Meier
L
Liter
LD
living donor
LDH
lactate dehydrogenase
LDL
low-density lipoprotein
LI
less intensive
LTE
long-term extension
mAb
monoclonal antibody
MDRD
Modification of Diet in Renal Disease (study)
MFI
mean fluorescent intensity
mg
Milligram
MI
more intensive
min
minute
mL
milliliter
mm
millimeter
MMF
mycophenolate mofetil
mmHg
millimeters of mercury
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Term
Definition
MPA
mycophenolic acid
MPGN
membranoproliferative glomerulonephritis
MRI
magnetic resonance imaging
mTOR 
mechanistic target of rapamycin
mTORi 
mTOR inhibitor
μg
microgram
N
number of subjects or observations
ng
nanogram
NIMP
non-investigational medicinal product 
NKF-K/DOQI 
National Kidney Foundation Kidney Disease Outcomes Quality Initiative
NODAT
new onset diabetes after transplant
NS
0.9% normal saline solution
OGTT
Oral Glucose Tolerance Test
OPTN
Organ Procurement and Transplantation Network
OR
covariate-adjusted odds ratio
OSIF
on-site investigator file
p, πp
population sample proportion
PCR
polymerase chain reaction
PD
pharmacodynamics
PJP
Pheumocystis jiroveci pneumonia
PK
pharmacokinetics
PML
progressive multifocal leukoencephalopathy
PO
per os (by mouth route of administration)
PPD
purified protein derivative (tuberculin skin test)
PRA
panel reactive antibodies
PTLD
Post transplant lymphoproliferative disorder
RNA
ribonucleic acid
S1P
sphingosine-1-phosphate
SAE
serious adverse event
SBP
systolic blood pressure
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Term
Definition
SCD
standard criteria donors
SCr
serum creatinine
SD
standard deviation
SLAM
Signaling lymphocyte activation molecule
SmPC
Summary of product characteristics
SOP
Standard Operating Procedures
SRL
Sirolimus
SRTR
Scientific Registry of Transplant Recipients
SWFI
sterile water for injection
TAC
Tacrolimus
TB
Tuberculosis
TC
total cholesterol
T-cell
T lymphocyte cell
TG
triglyceride
TLC
therapeutic lifestyle changes
TNFα
Tumor Necrosis Factor alpha
Treg
regulatory T-lymphocyte cell
ULN
upper limit of normal
UNOS
United Network of Organ Sharing
UPr/Cr
urine protein/ creatinine ratio
UTI
urinary tract infection
VNS
vial-needle-syringe
W
Week
WB
whole blood
WBC
white blood cell
WHO
World Health Organization
WMD
weighted mean difference
WOCBP
women of childbearing potential
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APPENDIX 1 
CONTRACEPTION GUIDELINES
Investigators  are  expected to  communicate  
the  
importance  of  pregnancy  prevention  because  of 
the increased potential for an adverse reproductive outcome. The investigator shall describe the 
length of time that strict precautions against pregnancy must be observed and provide guidance 
on  
the  use  of  appropriate  methods  for  sexually  active  subjects  and  
their  partners.  Women  and 
men  who  are  not  capable  of  reproduction  or  choose  to  be  abstinent  shall  be  exempt  from 
following  the  pregnancy prevention  requirements  specified  below.  All  subjects  shall  be 
counseled on pregnancy prevention and follow pregnancy testing requirements as specified in the 
protocol. 
DURATION OF MANDATORY CONTRACEPTION:
For female subjects who meet the criteria for WOCBP: 
(Duration of treatment) plus 8 weeks after the last dose of study drug.
For male subjects who are sexually active with WOCBP: 
(Duration of treatment) plus 8 weeks after the last dose of study drug.
CONTRACEPTIVE METHODS:
A. HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly  effective  methods  of  contraception  have  a  
failure  
rate  of  <  1%  when  used  consistently 
and correctly. WOCBP and female partners of male subjects who are WOCBP (unless the male 
is azoospermic), are expected to use one of the highly effective methods of contraception listed 
below:
1) Male condoms with spermicide1
2) Hormonal  methods  of  contraception  including  combined  oral  contraceptive  pills,  vaginal 
ring, injectables, implants and intrauterine devices (IUDs) such as Mirena
®
3) IUDs, such as ParaGard®
4) Tubal ligation 
5) Vasectomy
1. Gabbay MB, Thomas J, Gibbs A, Hold P. A randomized crossover trial of the impact of additional spermicide on 
condom failure rates. Sex Transm Dis 2008; 35: 862–8.
Kestelman  P.  et.  al.,  Efficacy  of  the  Simultaneous  Use  of  Condoms  and  Spermicides  Family  Planning 
Perspectives.Vol 23 (5); October 1991. 
Studies that administer drugs known to be teratogenic or drugs that have not undergone requisite 
preclinical testing for teratogenicity require two forms of contraception for both WOCBP and 
female partners of male subjects who are WOCBP (unless the male is azoospermic).One method 
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must be highly effective and the second method may also be highly effective or selected from the 
list of other contraceptive methods in Section B. WOCBP are exempt from this requirement if a 
commitment to abstinence is made. 
B. OTHER CONTRACEPTIVE METHODS
1. Diaphragm with spermicide
2. Cervical cap with spermicide
3. Vaginal sponge
4. Male condom without spermicide
5. Progestin only pills
6. Female condom*
* A male and a female condom must not be used together
C. HORMONE BASED METHODS OF CONTRACEPTION
• The MST, which must consider a recommendation from the relevant clinical pharmacologist, 
must  agree  that  the  use  of  a  hormone-based  contraceptive  is  safe  and  efficacious  for 
WOCBP. A drug-drug interaction study should have been completed, if appropriate. Or there 
must  be  compelling  evidence  to  substantiate  that  the  investigational  product(s)  or 
concomitant  medications  will  not  adversely  affect  hormone  exposures  such  that  efficacy 
might be compromised or present present additional risk
• Female  partners  of  male  subjects  participating  in  the  study  may  use  hormone  based
contraceptives  as  one  of  the  acceptable  methods  of  contraception  since  they  will  not  be 
receiving  drug. If  a  woman  is  over  35  years  of  age  and  smokes,  consideration  should  be 
given  to  other  forms  of  birth  control  as  opposed  to  hormonal  contraception  containing 
estrogen, due to the potential increased risk of myocardial infarction 
D. ABSTINENCE
• Abstinence is defined as the complete avoidance of heterosexual intercourse.
• Abstinence is an acceptable form of contraception for all study drugs.
• It is not necessary to use a second method of contraception when abstinence is elected.
• Subjects  who  choose  abstinence  must  continue  to  have  pregnancy tests,  as  specified  in 
Section 4.3. 
• Acceptable  alternate  methods  of  highly  effective  contraception must  be  discussed  in  the 
event that the subject chooses to forego abstinence
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E. METHODS OF CONTRACEPTION WITH INSUFFICENT DATA TO 
SUPPORT EFFECTIVENESS 
• No method
• Withdrawal
• Rhythm
• Spermicide alone 
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SAP_001.pdf: 
Statistical Analysis Plan for 
 
Official Title of Study 
Evaluation of Acute Rejection Rates in de novo Renal Transplant Recipients Following 
Thymoglobulin Induction, CNI-free, Nulojix (belatacept) -based Immunosuppression 
 
NCT02137239 
26-June-2019 


STATISTICAL ANALYSIS PLAN
FOR CLINICAL STUDY REPORT
EVALUATION OF ACUTE REJECTION RATES IN DE NOVO RENAL TRANSPLANT 
RECIPIENTS FOLLOWING THYMOGLOBULIN INDUCTION, CNI-FREE, NULOJIX 
(BELATACEPT)-BASED IMMUNOSUPPRESSION
PROTOCOL(S) IM103177
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TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN FOR CLINICAL STUDY REPORT...................................1
TABLE OF CONTENTS 
.............................................. 
..............................................................2
LIST OF TABLES 
................................................. 
............................................................... 
......4
LIST OF FIGURES ....................................................................................................................4
2  
STUDY DESCRIPTION..........................................................................................7
2.1  
Study Design 
............................................................................................................7
2.2  
Treatment Assignment..............................................................................................8
2.3  
Blinding and Unblinding...........................................................................................8
2.4  
Protocol Amendments...............................................................................................8
2.5  
Safety Monitoring...................................................................................................10
3  
OBJECTIVES .................................................... ....................................................10
3.1  
Primary...................................................................................................................10
3.2  
Secondary...............................................................................................................10
4  
ENDPOINTS..........................................................................................................11
4.1  
Primary Endpoint....................................................................................................11
4.2  
Secondary Endpoint................................................................................................11
5  
SAMPLE SIZE AND POWER...............................................................................14
6  
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS 
FOR ANALYSES..................................................................................................15
6.1  
Treatment Regimens...............................................................................................15
6.2  
Populations for Analyses .................................... ....................................................15
7  
STATISTICAL ANALYSES..................................................................................15
7.1  
Modifications to the Analyses Specified in the Protocol..........................................15
7.2  
General Methods....................................................................................................18
7.3  
Study Conduct........................................................................................................19
7.4  
Extent of Exposure.................................................................................................19
7.4.1  
Subject Disposition.................................................................................................19
7.4.2  
Demographic and Baseline Characteristics............................................................20
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7.5  
Extent of Exposure.................................................................................................21
7.5.1  
Discontinuation of Study Therapy...........................................................................22
7.6  
Efficacy..................................................................................................................22
7.6.1  
Primary Endpoints..................................................................................................22
7.6.1.1  Acute Rejection.......................................................................................................22
7.6.2  
Secondary Endpoints..............................................................................................23
7.6.2.1  Subject and Graft Survival......................................................................................23
7.6.2.2  Composite Endpoints of CSBPAR, Death, or Graft Loss.........................................24
7.6.2.3  Renal Function.......................................................................................................24
7.6.2.4  Donor Specific Antibodies......................................................................................25
7.6.2.5  Cardiovascular and Metabolic Co-Morbidities.......................................................27
7.6.2.6  Subgroup Analyses.................................................................................................28
7.7  
Safety 
.....................................................................................................................28
7.7.1  
Adverse Events Analysis.........................................................................................29
7.7.1.1  All Adverse Events..................................................................................................29
7.7.1.2  Events of Special Interest........................................................................................29
7.7.1.3  Multiple Adverse Events .........................................................................................30
7.7.2  
Laboratory Test Analysis........................................................................................31
7.7.3  
Other Safety Considerations...................................................................................31
8  
CONVENTIONS....................................................................................................34
8.1  
Calculations of Key Measures.................................................................................35
8.2  
Analysis Period of Interest......................................................................................35
8.3  
Missing Data Handling...........................................................................................35
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8.4  
Day Ranges for Analysis Time Points.....................................................................36
8.5  
Counting Rules for Efficacy Analysis.....................................................................37
8.6  
Conventions for Descriptive Summaries.................................................................37
8.7  
Safety Data Conventions.........................................................................................37
8.8  
Counting Rules for Adverse Events........................................................................37
8.9  
Missing, Unknown or Partial Dates.........................................................................38
9  
CONTENT OF REPORTS ............................................ .........................................41
APPENDIX 1  
LIST OF ABBREVIATIONS.................................................................42
APPENDIX 2  
RELEVANT PROTOCOL DEVIATION CRITERIA............................44
APPENDIX 3  
LIST OF PERI-INFUSIONAL EVENTS................................................46
APPENDIX 4  
MARKED LABORATORY ABNORMALITY CRITERIA...................47
APPENDIX 5  
DOCUMENT HISTORY .......................................................................50
LIST OF TABLES
Table 2.4-1:  
Protocol Amendments..............................................................................9
Table 5-1:  
Confidence Intervals* for the Difference between Two Proportions........14
Table 7.2-1:  
Overview of Primary and Key Secondary Analyses 
................................19
Table 7.6.1.1-1:  
Overview of Sensitivity Analysis............................................................23
Table 7.6.2.3-1:  
Overview of Analysis: Renal Function ...................................................24
Table 7.6.2.6-1:  
Subgroup categories for Key Endpoints..................................................28
Table 8.4-1:  
Day Ranges for Analysis Time Points.....................................................36
Table 9-1:  
List of Abbreviations..............................................................................42
Table 9-2:  
Relevant Protocol Deviation Criteria......................................................44
Table 9-3:  
Document History 
..................................................................................50
LIST OF FIGURES
Figure 2.1-1:  
Study Design Schematic...........................................................................7
Figure 8.9-1:  
Missing or Partial Onset Dates of Adverse Events ..................................41
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Research Hypothesis:
A belatacept-based maintenance immunosuppressive regimen incorporating Thymoglobulin
induction, concomitant therapy with EVL, and rapid corticosteroid withdrawal will result in
acceptable rates of AR and overall safety  consistent with the  current standard of carein
recipients of living and standard criteria deceased donor kidneys.
Schedule of Analyses:
The primary analysis  of  
the  primary  endpoint  of  
the  
incidence  of clinically  suspected,  biopsy 
proven acute rejection (CSBPAR) will be conducted at 6 months post-transplantation, Secondary
analyses  of  CSBPAR  will  be  conducted  at  12  and  24  months  post-transplantation,  after  all 
randomized,  transplanted  and  treated  subjects  have  either  completed  the  24  months  study 
treatment period and the follow up period or been discontinued prematurely from the study.
Periodic analyses will also be scheduled to support Data Monitoring Committee (DMC) review.
Two locks are planned for the study: one for all data except immune cell phenotyping and urine 
proteomics data and one for immune cell phenotyping and urine proteomics data.
This statistical analysis plan describes the analysis of all the data.
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2  
STUDY DESCRIPTION
2.1  
Study Design
For  
reasons  described  below,  only  70  of  
the  originally  
targeted  240  subjects  were  enrolled,  as 
shown in Figure 2.1-1:
Figure 2.1-1:  
Study Design Schematic
Abbreviations: M: Month; CSBPAR: Clinically Suspected and Biopsy Proven Acute Rejection; eGFR: 
estimated Glomerular Filtration Rate; SCD: Standard Criteria Donor; LD: Live Donor; Bela: Belatacept; 
MMF: Mycophenolate Mofetil; EVL: Everolimus; TAC: Tacrolimus.
This  
is a randomized, open-label,  multicenter, parallel-group study that was to be conducted at 
approximately  20  sites  in  North  and  South  America  and  
the  European  Union.  Approximately 
240  subject  were  originally  targeted  for  enrollment.  However,  enrollment  was  prematurely 
terminated  as  of  31-December  2016  for  administrative  reasons  related  to  belatacept  supply 
constraints associated with transition to a new manufacturing process. At that time, 70 subjects 
(n=35 per group), had been enrolled, each scheduled to receive a de novo kidney transplant and 
to be randomized (stratified by study site/center) in a 1:1 ratio, to 1 of the following 2 treatment 
groups:
• Thymoglobulin + Belatacept + Everolimus.
• Thymoglobulin + Tacrolimus + MMF.
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All  subjects  randomized  on  or  prior  to  31  December  2016  were  to  remain  in  the  study  on 
assigned therapy to complete the protocol-specified period of study participation.
This is a rapid corticosteroid withdrawal trial: corticosteroids were to be administered during the 
first week of study treatment only and discontinued by Day 7, except for subjects still receiving 
Thymoglobulin induction between Days 8-10, who could continue to receive methylprednisolone 
intravenous prior to beginning their Thymoglobulin infusions on those days. The duration of the 
study  is  24  months,  with  a  subsequent  8-week post  last  dose  safety  follow-up  period  for  all 
subjects. In addition, belatacept-treated subjects who discontinue treatment or complete the study 
and do not continue treatment with commercially available Nulojix® thereafter, will be seen at 
12 and 24 weeks post last dose for the collection of PK and/or immunogenicity samples.
2.2  
Treatment Assignment
Approximately 70 subjects (n=35 per group) receiving de novokidney transplants from living or 
standard criteria deceased donors, were to be randomized (stratified by study site/center), in a 1:1 
ratio, to one of the 2 specified treatments groups. A randomization schedule was to be generated 
and kept by BMS.
At the time of enrollment, immediately after written informed consent wasobtained, and
before performing any study-specific procedures, the physician/coordinator was  to  contact
IVRS to enroll each subject into the centralized database. Each subject was to be assigned
a unique, sequential, 5-digit subject number beginning with 80001, 80002, 80003, etc. by the
interactive voice response system (IVRS) for identification throughoutthe study. This subject
number was not to be reused for any other participant in the study. SAE reporting was to
begin at the time of enrollment for all subjects, immediately after written informed consent
was obtained.
The subject could  be randomized once all entry criteria (inclusion and exclusion) had been
met. The physician/coordinator w a 
s 
  
t o contact IVRS prior to transplant surgery to randomize
each subject into the centralized database. 
  The collection of non serious AE information was 
to begin at initiation of study drug. The IVRS was also to be contacted at each visit to obtain
belatacept vial assignments  and each time  additional supplies of other investigational products 
were to be dispensed.
2.3  
Blinding and Unblinding
Not applicable. This is an open-label study.
2.4  
Protocol Amendments
The protocol has 7 amendments and 1 administrative letter issued. Thetable below summarizes
the main purposes of these amendments. See the amendments for further details.
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Table 2.4-1:  
Protocol Amendments
Amendment #
Main purpose of the amendment
Amendment #1
Modifications were made to the WOCBP definition.
Protocol  was updated  with  Neurological  Exam
requirements, modification of the clinical criteria and
monitoring of PTLD.
AdministrativeLetter 01
Clarify the Everolimus trough sampling sequence
during Year 1 of treatment.
Amendment #2
This amendment  
is  country  specific for  Argentina and 
Colombia only to incorporate post study drug access to 
satisfy MOH requirements in those countries.
Amendment #3
Modification of Study Design: Addition of Tacrolimus
arm. Updates to the research hypothesis and study
objectives. Revisions to eligibility criteria. Updates to
the primary and secondary endpoints and statistical
section to support the revised study design and to
eliminate theallowance of crossover subjects.
Amendment #4
Syntactical edits and clarifications in support the
revised study design articulated in IM103177 Revised
Protocol 03, incorporating  Amendment 04.  The
amendment removed an experimental treatment group:
Thymoglobulin + belatacept + mycophenolate mofetil
with rapid corticosteroid withdrawal, from the study
design to eliminate a potentially higher risk of acute
rejection.
Amendment #5
Clarification  of  antiviral  prophylaxis  requirement. 
Updates  treatment  and  rescreening  of  living  donor 
patients with a positive IGRA at screening.
Revise protocol with recent administrative changes.
Amendment #6
Decrease  number  of  sites  and  subjects.  Statistical 
Sample Size Considerations updated. Clarification that 
all  grades  of  acute  rejection  will  be  included  in 
analyses  of  the  primary  and  relevant  secondary 
endpoints.
Amendment #7
Clarify  timing  of  collection  of  belatacept  and 
comparator  blood  
levels  for  clinically  suspected  AR, 
PML  or  PTLD.  Update  Procedural  Outline  Tables 
5.1-2  and  5.1-3  to  allow  for  collection  of a  blood 
sample  for  determination  of  the  belatacept  or 
comparator  blood  level  at  the time  of  any  clinically 
suspected episode of acute rejection, PML or PTLD.
Provide  guidance  regarding  the  evaluation  and 
acceptable range for oral immunosuppressive treatment 
compliance.  The  
type  of  T-cell  
responses  
to  be  
tested 
for in cases of clinically suspected PTLD or PML was 
clarified  as  being  “anti-viral”,  
rather  
than  specifically 
“anti-EBV”  in  nature.   Made   modifications  to 
secondary  and  exploratory  endpoints  to  align  the 
analyses  of  acute  
rejection  with the  statistical analysis 
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Table 2.4-1:  
Protocol Amendments
Amendment #
Main purpose of the amendment
plan, and corrected minor formatting and typographical 
errors throughout the protocol.
2.5  
Safety Monitoring
An external Data Monitoring Committee (DMC) will reviewaccumulating safety and efficacy
data at intervals specified in aDMC Charter, and will provide recommendations to BMS
regarding the emerging benefit-risk profile of the drug in this indication, and subsequent study
conduct. Periodic analyses will be scheduled to support Data Monitoring Committee (DMC)
review. Further details regarding the DMC will be available in the DMC charter.
3  
OBJECTIVES
3.1  
Primary
The primary objective is to assess the incidence of clinically suspected and biopsy proven acute 
rejection (CSBPAR) at 6 months post-transplant in de novo renal allograft recipients treated with 
thymoglobulin  induction,  rapid  corticosteroid  withdrawal,  and  maintenance  belatacept  in 
combination with EVL, or maintenance TAC in combination with MMF.
3.2  
Secondary
The effects of eachimmunosuppressant regimen  on  the  rates  of  acute  rejection,  subject  and 
allograft  survival  and  allograft  
function  were  
to  be  evaluated as  
follows  
(endpoints  
to  measure 
these objectives are described in further detail in protocol Section 8.3):
• The frequency and severity of CSBPAR at 12 and 24 months post-transplant.
• Rates of subject and allograft survival at 6, 12 and 24 months post-transplant.
• Changes  in  renal  function  and  severity  of  proteinuria  at  3,  6, 12  and  24  months  post-
transplant.
• The  frequency  and  
type  of  donor-specific,  anti-HLA  antibodies  
(DSA)  detectable  prior  
to,
and at 12 and 24 months post-transplant.
• The safety and tolerability of each treatment regimen, as based upon the results of vital signs,
and safety laboratory assessments, and cumulative rates of adverse events reported at 3, 6, 
12 and 24 months post-transplant.
The frequency of cardiovascular and metabolic co-morbidities reported at 3, 6, 12 and 24 months 
post-transplant.
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− Treatment  regimen:  Categorical  analysis  of  CSBPAR  episodes  by  treatment  received, 
including:  a)  corticosteroids; b)  lymphocyte  depleting  therapy; c)  renal  replacement 
therapy; d) plasmapheresis; e) IVIg; f) rituximab.
Subject and Graft Survival
• Proportion of all subjects who survive with a functioning graft at 6, 12 and24 months
post- transplant.
• Proportion of all subjects who experience death by 6, 12 and 24 months post-transplant.
• Proportion of all subjects who experience graft loss by 6, 12 and 24 months post-transplant.
• Time to event analysis of death or graft loss.
Renal Function
• Absolute  (mean  and  median)  cGFR values  at  3,  6,  12  and  24  months  post-transplant,  as 
determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula.
• The mean changes from Month 3 cGFR at 6, 12, and 24 months post-transplant.
• Slope of the change in cGFR from Month 3 to Months 6, 12 and 24 post-transplant.
• The mean urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.
Donor Specific Anti-HLA Antibodies (DSA)
• The percentage of subjects with, and titers of pre-existing (pre-transplant) andde novo (post-
transplant) anti-HLA  DSA on Day 1  
(pre-transplant,  pre-dose), and at Months 12 and 24, 
respectively.
• Characterization of any de novoDSA detected by IgM and IgG classes, and by the presence 
or absence of complement fixing properties.
Safety and Tolerability of each Treatment Regimen
• Incidence of all AEs and SAEs at 6, 12, and 24 months post-transplantation.
• Incidence of ESI at 6 months, 12 months, and 24 months
• Description and incidence of clinically significant changes in vital signs.
• Description and incidence of laboratory test marked abnormalities.
Cardiovascular and Metabolic Co-Morbidities
• Incidence of New Onset Diabetes After Transplantation (NODAT) at6, 12, and 24  months 
post-transplant.
• Absolute (mean and median) values for Systolic Blood Pressure (SBP) and Diastolic Blood 
Pressure (DBP) at 3, 6, 12 and 24 months post-transplant.
• Mean changes from baseline for SBP and DBP atmonths 6, 12, and 24 post-transplant.
• Absolute  (mean  and  median)  values  at  3,  6,  12  and  24  months  post-transplant,  and  mean 
change from baseline levels at Months 12 and 24, for the following fasting lipid levels:
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6  
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES
6.1  
Treatment Regimens
Approximately 70 subjects (n=35 per arm) receiving de novo kidney transplants will be
randomized (stratified by study site/center) in a 1:1 ratio to 1 of the following 2 treatment
groups:
• Thymoglobulin + Belatacept + Everolimus.
• Thymoglobulin + Tacrolimus + MMF.
6.2  
Populations for Analyses
• The “Intent-to-Treat” (ITT) population includes all subjects who are randomized,
transplanted and treated with atleast one dose of thymoglobulin and one dose of
study treatment, either belatacept or TAC. Subjects will be grouped according to the
treatment to which they are randomized.
• The “As Treated“ (AT) population includes all subjects who are randomized, transplanted
and treated with at least one dose of thymoglobulin and one dose of study drug, either
belatacept or TAC. Subjects will be grouped according to the treatment which they actually
received. The  “As Treated” treatment group is the same as the “As Randomized” treatment 
group, except in cases where a subject received a different treatment from the one he/she was 
randomized to for the entire course of their participation  
in the  study. In this case, the  “As 
Treated” treatment group is set to the treatment the subject actually received. In cases where 
a subject received different treatments after randomization, then the “As Treated” treatment 
group  is  the  first  treatment  received.  Safety  reporting  will  be  done  in  the  “As  Treated” 
population.
• The “Per-Protocol” (PP) population includes all randomized subjects who do not violate
terms of the protocol that might affect key study outcomes. The protocol specific definitions
for “relevant” protocol deviations are described inAPPENDIX 2.
• The PK population includes subjects who receive at least one dose of belatacept and have at 
least 1 post baseline sample available for PK analyses.
7  
STATISTICAL ANALYSES
7.1  
Modifications to the Analyses Specified in the Protocol
Due  
to  
the  
reduction  
in  sample size  
resulting from  premature  
termination  of  enrollment  as  of 
31 December  2016,  it  has  been  deemed  appropriate  to  revise  selected  statistical  analyses 
specified in the study protocol Section 8. The following modifications to and clarifications of the 
analyses have been made:
1) All  analyses  will  be  performed  for  the  whole  study  treatment period  (i.e.  24  months), 
including analyses at 6 or 12 months.
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2) Treatment differences will be produced only for the endpoints specified in the sections of this 
SAP itemized below, instead for all study endpoints.
3) Analysis of acute rejections:
a) The  
treatment  differences  
in  
the  severity  grades  and  
therapeutic  modalities  will  not  be 
calculated.
b) The sensitivity analyses using the per-protocol population will be performed if there are 
at least 10% of subjects with a protocol deviation in either treatment groups.
c) The sensitivity analyses using the as-treated population will be performed if there are at 
least  10%  of  subjects  
in  either  
treatment  group  
for  whom the  as-randomized  
treatment 
group is different from the as-treated treatment group.
d) The sensitivity analysis using right censoring at the time of discontinuation from assigned 
therapy will not be produced. Acute rejections occurring more than 56 days after the last 
dose date will be flagged in the listing.
e) The  descriptive summaries  by treatment group  for  cGFR,  graft  and  subject  survival, 
donor specified antibodies,  
infection and  malignancy at Month 12 for subjects with and 
without AR by Month 6, and at Month 24 in subjects with and without AR by Month 12, 
will  not  be  produced.  The  information  regarding  these  parameters  will  be  included  in 
listings that correspond to the specific analyses of these endpoints.
4) Analysis of subject and graft survival:
a) A  listing  including  all  subjects  who  died  or  lost  their  graft  will  be  produced. 
Corresponding  summaries,  treatment  differences  and  time  to event analysis  will  be 
produced if there are at least 5 subjects across treatment groups who died or experienced 
graft loss during the 24 Month treatment period.
b) Any summaries mentioned above, if to be produced, will only be produced for the whole 
24 Month treatment period. The corresponding analyses at 6 and 12  months will  not be 
produced.
c) Subject and allograft survival rates among those subjects who did and those who did not 
experience CSBPAR. This analysis will be produced only if there are at least 5 subjects 
across  treatment  groups  who  died  or  experienced  graft  loss  during  the  24  month-
treatment period.
5) Analysis of the composite endpoints of CSBPAR, death, or graft loss will be produced only 
if  
there  is  at  least  one  CSBPAR  and  at  least  one  death  or  graft  loss.  These  analyses  will 
include the proportion of all subjects who experience CSBPAR, death, or graft loss at 12 and 
24 months and a time to event analysis of the composite endpoint of CSBPAR, death, or graft 
loss.
6) All  safety  analyses  will  only  be  produced  for  the  whole  24  Month  treatment  period.  The 
corresponding safety analyses at 6 and 12 months will not be produced.
7) Analysis  of  
immunogenicity:  The  protocol  specifies  summaries of  
titers  of  detectable  anti-
belatacept  antibodies  at  Weeks  8, 12,  and  24  post  study  termination  (subjects  who 
discontinue belatacept only). Instead of descriptive statistics, a listing will be provided for all 
positive subjects. Similarly, the analysis of descriptive statistics for titers of detectable anti-
belatacept antibody will not be produced.
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8) Analysis of any clinical consequences of CSBPAR (and associated changes in the expression 
of  exploratory  gene  sets  associated  with  acute  rejection) at  6, 12  and  24  months  post-
transplant will be presented as follow:
a) The extent to which renal function recovered to the pre-rejection baseline will include the 
serum creatinine values related to CSBPAR in the corresponding listing.
b) The percentage of subjects who, post-CSBPAR, are reported to have developed infection 
or malignancy will not be summarized. Instead, a listing will be provided.
c) The percentage of subjects with, and titers of detectable, de novo (post-transplant) anti-
belatacept antibodies will  not be summarized. Instead, this  
information will  be  
included 
in a  
listing of  
immunogenicity results with corresponding  belatacept concentrations and 
selected laboratory parameters and events of special interest.
d) The subject and graft survival rates among those subjects who did, and those who did not 
experience  CSBPAR will  be provided only  
if there are at if there are at least 5 subjects 
across  treatment  groups  who  died  or  experienced  graft  loss  during  the  24  month-
treatment period.
9) The summary of median fluorescence intensity (MFI) of anti-HLA donor specific antibodies
will not be produced. Instead, the number of subjects with DSA will be summarized.
10) Analysis of anti-viral T-cell responses will not be provided. The immune cell phenotypes will 
be  summarized  
for  all  subjects  and  by  acute  
rejection  status  
(subjects  experiencing  at least 
one  acute  rejection  vs  
those  without  any  acute  rejection).  A  corresponding  listing  will  be 
provided.
11) The patterns of protein excretion, by urinary proteomics will be summarized for all  
subjects 
and  by  acute  rejection  status  (subjects  experiencing  at  least  one  acute  rejection  vs  those 
without  any  acute  
rejection).  Proteins  
that  are  below  LLOQ  
in  more  
than  50%  of  samples 
will not be analyzed. A corresponding listing will be provided.
Due to the fact that some data were not collected, the following analyses cannot be produced:
1) Clinically  significant  changes  in  vital  signs  were  not  collected.  Thus,  they  will  not  be 
summarized.  
Instead,  a  summary  of  
the  number  of  subjects  with  systolic  or  diastolic  blood 
pressure  values  above  the  values  mentioned  in section 7.6.2.5will  be provided.  Also, 
investigators may have reported corresponding adverse events which will be summarized and 
listed as described in Section 7.7.
2) For  
the  analysis  of  any  clinical  consequences  of  CSBPAR,  and associated  changes  in  
the 
expression  of  exploratory  gene  sets  associated  with  acute  
rejection,  no  summary  or listing 
that includes gene expression will be provided.
3) The analysis on titers of DSA and of the characterization of any de  novo DSA detected by 
IgM and IgG classes, and  by the presence or absence of complement  
fixing properties will 
not be produced. Instead, the number of subjects with DSA will be summarized.
4) The  IHC  analyses  of  any  remaining  allograft  biopsy  tissue  samples  available  at  sites 
following  clinical  review  will  not  be  provided,  as  no  such  residual  tissue  samples  were 
submitted for this purpose.
The following analyses will not be provided as part of this analysis plan:
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done at the last dose date if the subject completed the 24 month-treatment period, unless specified
otherwise.
The following table provides an overview of the primary and key secondary analyses to be
performed.
* Confidence Interval Formula: Exact (Clopper-Pearson)
‡ Confidence Interval Method: Score (Wilson)
§ Using Cox Propotional Hazard model
7.3  
Study Conduct
All subjects with relevant protocol deviations that could affect efficacy will be identified. A 
list of these protocol deviation criteria  
is provided  
in APPENDIX 2. These protocol deviations 
are referred to as “relevant” protocol deviations in this document.
All  randomized  subjects  with  at  least  one  relevant  protocol  deviation  will  be  summarized  by 
treatment group and overall. They will also be listed.
The ITT analysis population will be used for these analyses.
7.4  
Extent of Exposure
7.4.1  
Subject Disposition
The disposition of subjects will be presented as follows:
Table 7.2-1:  
Overview of Primary and Key Secondary Analyses
Measure of Interest
Analysis Method
Proportion of subjects who experience a CSBPAR at
6, 12 and 24 months post-transplant
Point estimate of the proportion and 95% CI*
within each treatment group at 6 months.
Difference in the incidence of CSBPAR between
arms, at 6, 12 and 24 months post- transplant
Point estimate and 95% CI‡for the difference
between the two arms
Time to first CSBPAR
Kaplan-Meier (KM) estimates of survival functions. 
Hazard Ratio and 95% CI§
Proportion of Subjects who survive with a
functioning graft at 24 months post-transplant
Point estimate of the proportion and 95% CI*
within each treatment group at 24 months (to be 
produced if there are at least 5 subjects across 
treatment groups who died or experienced graft 
loss)
Time to death or graft loss
KM estimate of subject and graft survival Hazard Ratio 
and 95%CI§(to be produced if there are at least 
5 subjects across treatment groups who died or 
experienced graft loss)
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• Number of subjects enrolled at screening.
• Number of subjects randomized and transplanted, presented by randomized treatment group.
• Reasons for not being randomized.
• Number  of  randomized  and  transplanted  subjects  who  receive  at  least  1  dose  of 
Thymoglobulin and 1 dose of study treatment, either belatacept or TAC.
• Number  of  subjects  who  discontinued  
treatment  at  any  
time  during  
the  
two  years,  
together 
with reasons for discontinuation, as tabulated by randomized treatment group.
• Number of subjects continuing in the follow up phase.
• Number  of  subjects  who  discontinued  study  during  the  follow  up phase,  together  with 
reasons for discontinuation and tabulated by randomized treatment group.
For  the  items  above,  the  overall  disposition  combining  all  treatment groups  will  also  be 
presented.
A  corresponding  listing  of  subjects  who  discontinued  from  the  treatment  period  (including 
subjects randomized but not treated) and the follow up period will be provided, together with the 
reason for discontinuation.
The ITT analysis population will be used for these analyses.
Enrollment  at each  site  and  by  age group  will  be  summarized  as  specified  in  EudraCT 
requirements.
7.4.2  
Demographic and Baseline Characteristics
Demographic and baseline characteristics of recipients and donors will be summarized
descriptively by means and standard deviations for continuous variables, and frequency
distribution for categorical variables. Summaries will be performed based on all randomized
subjects (ITT population). No statistical testing will be performed to assess imbalances between 
the two treatment groups.
Baseline demographic characteristics include the following:
Donors and recipients
• Age in years.
• Weight in kg (recipients only).
• Height in cm at the Screening evaluation (recipients only).
• Body mass index (BMI, kg/m2) (recipients only).
• Gender: Male versus Female.
• Race.
• Ethnicity (recipients only. Only for USA subjects).
• Geographic Region (recipients only).
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• Previous number of transplant (recipients only).
Baseline Disease Characteristics include:
• # of HLA –A, –B, –DR, and total mismatches.
• Percent (%) Panel Reactive Antibodies (PRA) (recipients).
• Primary etiology of end stage renal disease (ESRD; recipients only).
• Specific Disease History (recipients).
• Primary cause of death (donors).
• Recipient and Donor EBV antibody serostatus.
• Recipient and Donor CMV antibody serostatus.
• Viral serology for Hepatitis B (donors).
• Viral serology for Hepatitis C (donors).
• T Cell Cross-match for Transplant (recipients).
• B Cell Cross-match for Transplant (recipients).
• Type of transplant (donors).
 
7.5  
Extent of Exposure
The extent of exposure to belatacept will be summarized in two different ways: by total number 
of active infusions and by length of exposure.
A  frequency  distribution  table  will  be  presented  summarizing  the  total  number  of  active 
infusions administered in the ranges of 5 infusions for the belatacept treatment group.
In addition, the length of exposure to the assigned treatment will be summarized and presented 
according to the  
following time  
intervals (in days): ≤28 (≤1  month), 29-84 (2-3 months), 85-
168  (4-6  months),  169-252  (7-9  months),  253-364  (10-12  months),  365-448  (13-15 months), 
449-532  (16-18  months),  533-616  (19-21  months),  617-728  (22-24 months), ≥729  (>  24 
months).  This  summary  will  also be  produced  for  
the  TAC  treatment  group.  The  number  of 
subjects in each category will be displayed.
For  belatacept, the  
length  of  exposure  will  be  calculated  as  
the  
last  
infusion  date  +  28  days  or 
death date (if earlier) minus first infusion date.
For TAC, the length of exposure will be calculated as the last infusion dose + 10 days or death 
date (if earlier) minus first dose date.
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All summaries of exposure (both for total number of infusions and length of exposure) will also 
include  a  summary  of  the  mean,  the  standard  deviation,  the  median  and  the  maximum  and 
minimum values (i.e. range).
These analyses will be produced using the as treated population.
7.5.1  
Discontinuation of Study Therapy
The ITT analysis population (defined in Section 6.2) will be used to summarize discontinuation
from study therapy by treatment group as indicated in Section 7.4.1as well as the reason for the
premature termination of study therapy.
7.6  
Efficacy
This section and its subsections describe the planned efficacy analyses based on data included at 
the time of the final database lock.
All  analyses  for  efficacy  endpoints  below  will  be  assessed  and  described  for  each  of  
the 
2 treatment groups and for the overall study population, unless otherwise specified.
7.6.1  
Primary Endpoints
7.6.1.1  Acute Rejection
Rates of acute rejection will  be summarized  by treatment group at Months 6, 12 and 24 using
point estimates of the proportion of subjects experiencing at least one CSBPAR, and the
corresponding 95% CIs. Two-sided 95% CIs will also be generated for the difference between 
the two treatment regimens. Descriptive statistics will be provided for the percentages of subjects 
with CSBPAR in each treatment group, including those for severity grade and treatment received 
(corticosteroids,  
lymphocyte depleting agents, renal replacement therapy, plasmapheresis, IVIg, 
rituximab).  All  grades  of  acute  rejection,  excluding  those  assessed  by  the  pathologist  as 
"borderline  changes"  (biopsy  findings  “suspicious”  for  acute  cellular  rejection  per  the  Banff 
criteria),  will  be  
included  
in  
the  analysis  of  
the  primary  and relevant  secondary  endpoints  for 
acute rejection. Sensitivity analyses will be performed, including acute rejections assessed by the 
pathologist as ‘borderline changes’ (biopsy findings “suspicious” for acute cellular rejection per 
the Banff criteria).
In  addition,  Kaplan-Meier  (KM)  cumulative  event  rates  will  also  be  performed  by  treatment 
groups  and  the  corresponding  hazard  ratio  will  be  calculated  using  cox  proportional  hazard 
model for the whole study treatment period (i.e. 24 months).
A  corresponding  
listing  
including  all  suspected  acute rejection  events,  
regardless  of  when  
they 
occurred, will be provided. All events occurring more than 56 days since last dose date will be 
flagged.
An  additional  listing  will  be  produced  including  subjects  who  post-CSBPAR,  are  reported  
to 
have developed infection or malignancy.
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Sensitivity analyses
Sensitivity analyses will be performed on the PP population as well as on the AT population for
the primary analysis, if  there  are  in  either  treatment  group  at  least  10%  of  subjects  with  a 
protocol  deviation  or  subjects  
for  which  
the  as-randomized  
treatment group  
is  different  
for  
the 
as-treated  
treatment  group,  
respectively. The table below is a summary of the analysis along
with the populations itwill be performed in.
Table 7.6.1.1-1:  
Overview of Sensitivity Analysis
Measure of Interest
Analysis Method
Sensitivity Analysis Population
Proportion  of  subjects  who
experience a CSBPAR at 6, 12 and
24 months post-transplant
Point estimate ofthe proportion and
95% CI* within each treatment
group at 6 months
AT and PP
Difference in the incidence of
CSBPAR between arms, at 6, 12
and 24 months post-transplant
Point estimate and 95% CI‡for the
difference between the two arms
AT and PP
Time to CSBPAR
Kaplan-Meier (KM) estimates of
survival functions
Hazard Ratio and 95% CI§
AT and PP
* Confidence Interval Formula: Exact (Clopper-Pearson)
‡ Confidence Interval Method: Score (Wilson)
§ Using Cox Propotional Hazard model
7.6.2  
Secondary Endpoints
7.6.2.1  Subject and Graft Survival
A listing will be provided of all subjects who died or experienced graft loss at any time during 
the study.  A  
listing of all  subjects with unknown  subject and graft survival  status at the end of 
the 
24 month-treatment period will be provided.
If there are at least 5 subjects across treatment groups who died or experienced graft loss during 
the 24 month-treatment period, the following analyses will be produced:
• The composite endpoints of patient and graft survival at 24 months respectively will be
summarized within each treatment groups, using point estimates of the proportion of subjects 
surviving with a functioning graft, and the corresponding 95% CIs. The point estimate and its 
95% CIs will also be generated for the difference between the two treatment regimens.
• The  proportion  of  subjects  who  die,  proportion  of  subjects  who have  a  graft  
loss,  and  
the 
proportion  of  subjects  who  experience  the  following  outcomes  will  each  be  summarized 
using point estimates and 95% CI within each treatment group.
− Overall graft loss rates at 24 months.
− Rates of death with a functioning graft at 24 months.
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− Rates of pure (death-censored) graft loss at 24 months.
• In addition, Kaplan-Meier (KM) estimates of cumulative subject and graftsurvival rates
will also be summarized.
• The  subject  and  allograft  survival  
rates  will  be  summarized  among  
those  subjects  who  did 
and those who did not experience CSBPAR. This analysis will be produced only if there are 
at least 5 subjects across treatment groups who died or experienced graft loss during the 24 
month-treatment period.
7.6.2.2  Composite Endpoints of CSBPAR, Death, or Graft Loss
The  composite  endpoints  of  CSBPAR,  death,  or  graft  
loss  will  be  analyzed  only  
if  
there  
is  at 
least one CSBPAR and at least one death or graft loss. These analyses will include the proportion 
of all subjects who experience CSBPAR, death, or graft loss at 12 and 24 months and a time to 
event analysis of the composite endpoint of CSBPAR, death, or graft loss.
7.6.2.3  Renal Function
The following table provides a summary/overview of the analysis performed.
Table 7.6.2.3-1:  
Overview of Analysis: Renal Function
Renal Function variable
Analysis
Time points for analysis
cGFR using MDRD formula
Descriptive summary of absolute
values for each Treatment group
Month 3, 6, 12, 24
Descriptive summary of change
from Month 3 values for each
Treatment group
Month 6, 12, 24
Fixed Effects repeated measure
model using Time and Treatment as
class variables and Month 3 cGFR
as a covariate
Month 6, 12, 24
Mixed effects using Time as
random variable and Treatment as
class variable. Analysis on absolute
cGFR value using Month 3 cGFR as
a covariate
Month 6, 12, 24
Urine protein/ creatinine ratio
(U
PR/CR)
Descriptive summary of absolute
values for each treatment group
Month 3, 6, 12, 24
Descriptive summary of change
from Month 3 values for each
Treatment group
Month 6, 12, 24
Fixed Effects repeated measure
model using Time and Treatment as
class variables and Month 3 cGFR
as a covariate
Month 6, 12, 24
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cGFR
Calculated GFR at Months 3, 6, 12, and 24 and change in cGFR from Month 3 to Months 6, 12 
and 24, respectively, will be descriptively summarized.
A  
linear  mixed effects  model will  be used to analyze changes  
from Month 3 cGFR. The  
linear 
mixed model for repeated measures with terms of Month 3 cGFR values, treatment, month, and 
interaction  of  treatment  by  month.  The  variable  month  will  be  categorical.  The  unstructured 
(UN)  covariance  structure  will  be  assumed.  
If  computation  convergence  becomes  an  
issue,  
the 
compound symmetric (CS) covariance structure will be used. For each time point, the difference 
between  treatment  arms  will  be  calculated  along  with  the  corresponding  95%  confidence 
intervals.
Population-mean  slopes  will  be  estimated  for  each  treatment  group.  In  addition,  the  95% 
confidence intervals will also be obtained for each mean slope. Intercepts will be summarized in 
the  same  manner.  This  analysis  will  be  based  on  a  linear  mixed model  including  terms  for 
treatment,  Month  3  cGFR,  treatment-by-month  interaction as  well as month  (continuous 
covariate) as fixed effects. The model will also include a random intercept and slope for month. 
Unstructured covariance structure will be used.
For all of the analyses above, for any subject who has one or more missing values for cGFR due 
to a graft loss or death, the missing values will be imputed as “zero”.
Urine Protein/Creatinine Ratio
Urinary protein to creatinine ratios, to be obtained from single-voided urine specimens at 3, 6, 12 
and 24 months post-transplant, will be descriptively summarized.
A linear mixed effects model will be used to analyze changes  
from Month 3 UPCR. The  
linear 
mixed model for repeated measures with terms of Month 3 UPCR values, treatment, month, and 
interaction  of  treatment  by  month.  The  variable  month  will  be  categorical.  The  unstructured 
(UN)  covariance  structure  will  be  assumed.  
If  computation  convergence  becomes  an  
issue,  
the 
compound symmetric (CS) covariance structure will be used. For each time point, the difference 
between  treatment  arms  will  be  calculated  along  with  the  corresponding  95%  confidence 
intervals.
7.6.2.4  Donor Specific Antibodies
The  percentage  of  subjects  with  detectable DSA  on  Day  1,  and  of de novoDSA  at  12  and  24 
months post-transplant will be descriptively summarized by treatment group. The data from the 
DSA assessments will be cross-matched with the number of donor/recipient HLA mismatches to 
confirm  the  anti-donor  status  of  any  detected  anti-HLA  antibodies.  The  results  will  be 
categorized according to the results obtained by flow cytometry, as follows:
• Median fluorescence intensity(MFI) > 2000 = Positive.
• MFI 1000-2000 = Potentially Positive.
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• MFI < 1000 = Negative.
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7.6.2.5  Cardiovascular and Metabolic Co-Morbidities
Blood pressure
Descriptive summaries of SBP and DBP will be provided by treatment group at Months 3,  6,
12, and 24. In addition, the changes from baseline (lastmeasurement prior to transplant) to the
subsequent  measurements obtained at  each  subsequent  (post-transplant)  time  points will  be 
summarized.
Percentage  of  patients  in each  treatment  group  with  blood  pressures  above  the  values  given 
below will be presented in a table to include results pre-transplant and at each subsequent Study 
Visit:
• > 130/80mmHg (pre-hypertension).
• > 140/90mmHg (hypertension).
Descriptive statistics regarding  the  number of antihypertensive medications received in each
group at  6,  12  and  24  months  will be provided to evaluate severity of hypertension per the
protocol definition (e.g. mean/median number of antihypertensive medications).
Lipids
Descriptive  summaries  of  fasting  lipid  parameters  (total  cholesterol,  HDL  cholesterol,  LDL 
cholesterol and TG) at Months 3, 6, 12, and 24 will be presented. Changes from baseline values 
(last  measurement  prior  to  transplantation)  for each  of  the  fasting  lipid  parameters  (total 
cholesterol,  HDL  cholesterol,  LDL  cholesterol  and  TG)  to  Month 12  and  Month  24  will  be 
descriptively summarized.
Descriptive statistics regarding the number of lipid-lowering medications received in each group 
at  6,  12  and  24  months  will  be provided  (e.g. mean/median  number  of  lipid-lowering 
medications).
Control of fasting blood glucose
Mean values and changes from baseline (last measurement prior to transplantation) in fasting 
blood glucose and HbA1C  
levels  
to  Month  6,  Month  12  and  Month  24  will  be  descriptively 
summarized.
New Onset Diabetes Mellitus After Transplantation (NODAT)
The incidence of NODAT at 6, 12, and 24 months post-transplantation will be summarized along
with the corresponding 95% CIs within each treatment regimen group.
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7.6.2.6  Subgroup Analyses
Subgroups analyses of key efficacy measures (primary endpoint of CSBPAR by Month 6 and
key secondary endpoints of CSBPAR by 12 and 24 months)  will  be  performed.  Similar 
analyses  will  be  performed  for  subject  and  graft  survival  by  Month  24  if  
there  are  at  least  5 
subjects  across  treatment  groups  who  died  or  experienced  graft loss  during  the  24  month-
treatment period (see Section 7.1).
Summary statistics for the above efficacy measures by treatment group will be presented for only
those subgroup categories that consist of 10% or more of the total studypopulation. No statistical
tests will be performed for subgroups.
Table 7.6.2.6-1:  
Subgroup categories for Key Endpoints
Type of Characteristic
Subgroup factor
Categories
Donor Characteristics
Donor Condition
Living Donor
Deceased Donor
Recipient Characteristics
Recipient Gender
Male
Female
Recipient Characteristics
Recipient Race
White
Black
Other
Recipient Characteristics
Recipient Diabetic Status
Diabetic
Non-Diabetic
7.7  
Safety
Safety analysis will be based on all randomized, transplanted, and treated subjects (as  
treated 
population). All AEs will be summarizedand listed by treatment groups. SAEs and AEs that
result in discontinuation of the study drug will also be tabulated in detail. Laboratory marked 
abnormalities that are determined as “critically” out of range per the central laboratory manual, 
will  be summarized descriptively. There will  be  no statistical testing  of  group differences with 
respect  to  frequencies  of  adverse  events  or  laboratory  marked  abnormalities  or  changes  in 
clinical laboratory tests from baseline (last measurement prior to first dose date/time).
All safety summaries except those for reports of death, graft loss, PTLD, malignancies, and
serious infections, will be based only on data available at each of the scheduled analysis time
points, applying ‘last dose date + 56’ cut counting rules. For events of death, graft loss, PTLD,
malignancies, and serious infections, two different summaries will be prepared. The first
summary will be based only on data available applying ‘last dose date + 56’ cut counting
rules. The second summary will be based on all available data without applying ‘last dose
date + 56’ cut counting rules.
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The frequencies and exposure adjusted incidence rates using person-year method will be
summarized by treatment regimen groups and overall.
7.7.1  
Adverse Events Analysis
7.7.1.1  All Adverse Events
Adverse Events are recorded by the investigators on the Serious and Non-Serious Adverse Event
page(s) of the CRF. All investigators are required to report the nature, the onset and resolution
date, intensity, action taken, treatment required for event, and their opinion regarding the
relationship between the AE and the study medication.
Summary information (the number and percent of subjects by treatment) will be tabulated for:
• All AEs including clinical and laboratory adverse events.
• Most common AEs (reported in at least 5% of subjects in any treatment group).
• Treatment Related AEs.
• Serious adverse events (SAE).
• SAEs/AEs leading to discontinuation of study therapy.
• Adverse events categorized by severity.
• Serious  adverse  events  and  related  serious  adverse  events  with death  as  an  outcome 
following EudraCT.
Summaries will be presented by treatmentgroups and categorized by System Organ Classes
(SOCs) and Preferred Terms (PTs).
Listings for deaths, AEs, SAEs, and AEs/SAEs leading to discontinuation of  study therapy
will be provided. Detailed conventions for counting events are provided in Section 8.8.
Incidence rates for AEs/SAEs will beprovided, where exposure (in days) ofa subject is
calculated from the randomization to the event date, or the last dose date +56 whichever is the
earlier. The incidence rate = 100 * number of subjects with specified AEs/SAEs/total exposure
in years which is computed as total exposure in days divided by 365.25. For asubject who had
multiple occurrences of a specific event, the first occurrence date of the event will be the event
date.
7.7.1.2  Events of Special Interest
The following adverse events of special interest, as obtained from the additional CRF pages or
appropriate  source  documentation  will  be  listed  or  both  listed and  summarized  by treatment 
group, as specified below:
• Serious Infections (listing and summary).
• PTLD (listing).
• PML (listing).
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• Malignancies (other than PTLD) including non-melanoma skin carcinomas (listing).
• TB Infections (serious and non-serious) (listing).
• CNS Infections (serious and non-serious) (listing).
• Viral Infections (serious) (listing and summary).
• Infusion related reactions within 24 hours since belatacept infusion (listing and summary).
The conventions for counting adverse events are provided in Section 8.8. Listings of all adverse
events will also be based on all available data up to database lock.
Incidence rates will be calculated for SAEs and AEs of clinical interest for  the  Month  24 
analysis. The numerator is the number of subjects having the first occurrence of the event
within the period specified. The denominator is the overall total exposure in years (total
exposure days/365.25) within the period specified. However, for these summaries subjects
experiencing the event of interest will have their exposure censored at the time of the first
occurrence of the event. The resulting incidence rate is multiplied by 100to express the rate
per 100 person-year of exposure. Subjects for whom the time of onset of the first occurrence of
the AE of interest is in a given interval will not be included in the exposureand incidence 
rates in later intervals.
7.7.1.3  Multiple Adverse Events
Descriptive summaries of adverse events that takes into account the number of times that an
AE was reported by individual patient, will be provided. In order to prepare these summaries,
the AE data will be processed according to standard BMS algorithms tocategorizeeach line of
patient data as a new occurrence or a continuation of an existing event. This determination will
be based upon onset and resolution dates. All continuations of an existing event will be collapsed 
into a unique AE record. Each line of patient AE data will represent a uniqueAE record and will
contain the earliest onset day, the latest resolution day (if available),highest intensity, treatment
ever required, the maximum severity observed, the last known assessed relationship to study
medication by the investigator as well as highest action taken in the orderof (highest to
lowest): drug discontinued, drug interrupted, dose reduced, dose increase, and none.
This data will be presented as the rate per 100 years of patient exposure. Exposure to study
medication will be calculated according to approved standard BMS algorithms as well.
As an example,  if 10  patients  report  8  unique episodes  of headache  and had  a combined
cumulative exposure of 40 years to study medication, the incidence rate isreported as
8/40*(100) or 20 cases per 100 patient years of exposure.
The summary information will be tabulated for:
• The total number and incidence rate (exposure adjusted) of occurrences for all AEs occurring 
in at least 5% of the subjects in Safetypopulation (defined inSection 6.2)
• All AEs and SAEs:
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− the total number of events and incidence rate (exposure adjusted) at every6-month time
intervals.
− the  number  of  subjects  experiencing  an  AE  once  or  more  than  once  (analysis  to  be 
produced only for AEs).
A listing of all unique AE records will be also provided.
EudraCT Summaries:
Exposure adjusted event summaries including multiple occurrences of unique adverse events for 
EudraCT  reporting  requirements  will  be  presented  by  treatment. These  summaries  include 
serious adverse events, drug related serious adverse events and non-serious adverse events using 
a global cutoff of 5 percent.
7.7.2  
Laboratory Test Analysis
Laboratory marked  abnormalities  as  identified  using  pre-defined criteria  (seeAPPENDIX  4), 
will  be  descriptively  summarized  with  frequency  and  percentage.  All  laboratory  values  of  a 
laboratory analyte  will  be  listed  for  subjects  with  at  least  one  marked  abnormality  for  this 
parameter will be listed (independent of study period).
All  available  laboratory parameters included  in  the  Hematology  and  Chemistry  Panels  in 
protocol Section 5.3.6.1 will also be summarized over time (with mean, SD, median, minimum,
Q25, Q75, and maximum).
7.7.3  
Other Safety Considerations
Vital Signs
Body temperature (in degrees Celsius [oC]) and Heart rate (beats per minute) will be summarized
by treatment (withmean, SD, median, minimum, Q25, Q75 and maximum) at protocol-specified
intervals. The same analysis conventions will be followed as those for systolic and diastolic blood 
pressure (see Section 7.6.2.5).
Viral Loads and Immunoglobulins
Summaries  over time  will be  provided by  
treatment  group for  BK,  CMV  and  EBV  viral  
loads 
and Serum levels of IgG and IgG subclasses post-transplants.
 
 
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8  
CONVENTIONS
The conventions to be followed in the computation of summary measures of efficacy and safety
endpoints are described in this section.
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Acute Rejection
Any acute rejection-free subject who is not followed-up through the entire event-counting period
due to any reason will be considered as having no acute rejection during that period.
Renal Function
Missing cGFR values due to death or graft loss will be imputed with value of 0 and all other
missing values will remain missing.
8.4  
Day Ranges for Analysis Time Points
Subjects do not always adhere strictly to the visit schedule timing in the protocol. Therefore the
designation of the visits/months during the study will be based on the day of evaluation relative
to day 1 of the trial (first  dose  date  = study day 1) rather than the nominal visit/month
recorded in the case report form (CRF).
The following rules apply to the derived visits depending on the specific endpoint.  All 
endpoints analyzed over time will follow the analysis windowing specified in Table 8.4-1.
Table 8.4-1:  
Day Ranges for Analysis Time Points
At Month
Target Day
Day Range
1
28
1-56
3
84
57-112
6
168
141-196
9
252
225-280
12
364
337-392
15
448
421-476
18
532
505-560
21
616
589-644
24
728
701-756
Note: If a subject has more than one measurement recorded within the window for that time point, the measurement 
closest to the target day for that time point will be used. In any case in which both observations are equidistant from 
the target day, the later measurement will be used.
If data are collected at Month 2 (Week 8) then the day ranges are the following:
At Month
Target Day
Day Range
1
28
1-42
2
56
43-70
3
84
71-112
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At Month
Target Day
Day Range
...
In addition, the analyses for subject and graft survival, acute rejection related endpoints, NODAT 
and adverse events will follow the windowing below:
• Month 6: Defined as Day 1 to Day 168.
• Month 12: Defined as Day 1 to Day 364.
• Month 24: Defined as Day 1 to Day 728.
8.5  
Counting Rules for Efficacy Analysis
The counting rules for computingproportions for efficacy endpoints are laid out in this section.
For any endpoint under consideration, the end of the event-counting period will first be
determined for each subject. If a subject has atleast one episode of the event during this
event-counting period, then he/she will be included in the analysis and the episode with the most
severe grade will be counted. If there are multiple episodes with the same severity (grade), then
the calendar date of the occurrence of the first such event will be counted.For example, if a
subject had multiple episodes of a given event of varying degrees of severity, for the purpose of
estimating time to event the first occurrence will be used; however, for tabulation of severity, the
highest grade event will be included.
8.6  
Conventions for Descriptive Summaries
For the  descriptive  summaries  of BP parameters  and  laboratory  analytes of  interest (e.g. 
individual components of the fasting lipidprofile andmeasures of renal function) at any
given time point: If a subject has more than one measurement recorded during the corresponding
time-window, the result closest to the target day for that time point will be used. In any case in
which both observations are equidistant from the target day, the later measurement will be used.
Above convention will be followed unless noted otherwise.
8.7  
Safety Data Conventions
Safety data will be handled according to the BMS safety data convention standards and
Supplement to Safety Guidelines for BMS-224818.
8.8  
Counting Rules for Adverse Events
All adverse events (AE) are coded and grouped into Preferred Terms (PT) by System Organ
Class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA). Listings and
summaries will be based on the resulting SOCs and PTs.
A clinical AE is categorized as either a concomitant event (CE: an event indicated by the
investigator to be unrelated or not likely related to study  medication) oran adverse drug
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experience (ADE: an event indicated by the investigator to be certainly related, probably related,
or possibly related to study medication, or one with a missing relationship).
Investigator-identified laboratoryAEs are defined as laboratory abnormalities for which
investigators record information on the AE pages of the CRF. These particular events are those
that the investigator considered clinically significant.
For data analysis and reporting purposes, recurrent or continuing AEs, ifany, will be counted
only once based on the following factors, in order of precedence:
• Relationship: ADEs will take precedence over CEs.
• Intensity: the highest intensity event will be counted.
• Onset date and time: the first occurrence will be counted.
If the investigator does not report the intensity of an AE and it is not obtainable from subsequent
query, a classification in between severe and very severe will be assignedfor the purpose of
these counting rules. According to the AE dictionary, it is possible that different AEs may map to
the same preferred term. If two different AEs with the same preferred term are reported by the
same subject, only one will be counted.
Counting for the summaries of adverse events will begin immediately after  
first  dose  date.
For the summary of adverse events and serious adverse events, during the analysis time window,
the end of the event counting period will be determined as follows:
• For subjects  who did  not  discontinue  study  therapy  during  the specified  analysis time
window:
The end of analysis time window.
• For subjects who discontinued study therapy during the specified analysis time window:
The earlier of the following dates: The end of the analysis time window or 56 days after the
date of last dose of study medication.
For the summaries of adverse events of PTLD, malignancies, and serious infections, and for the
listings of AEs, SAEs, and laboratory AEs*, all AEs will be counted, including those occurring
after 56 days from the last dose date.
* Laboratory AE’s are clinically significant laboratory values per the assessment of the investigators as reflected in 
the adverse event records.
8.9  
Missing, Unknown or Partial Dates
No imputation of event dates will be performed on any efficacy endpoints, including acute
rejection, graft loss, death, laboratory measures and blood pressures, with the exception of cases
wherein the onset date of an episode related to acute rejection is unknown; in such cases, the date
of the first biopsy for that episode will be used as the onset date of the episode.
Missing Start Dates of study therapy
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No date imputation will be done for missing start dates of study therapy.
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Missing Start Dates of concomitant medications
If start date is missing then it will be imputed differently depending on whether the consent date
is available or not. If the consent date is available then the start date will be imputed by the
consent date. Otherwise, the start date will be imputed as 01 January 1900.
Partial Start Dates of concomitant medications
If a partial start date is available then it will be imputed by the earliest possible date based on the 
partial start date. For instance,  
if the available partial  start date is Year 2005, then the  
imputed 
start date will be 01 January 2005. However, if the available partial start date is May 2005, then 
the imputed start date will be 01 May 2005.
Missing or Continuing Stop Dates of concomitant medications
If a stop date is missing or treatment is continuing then it will be imputed as 31 December 2099.
Partial Stop Dates of concomitant medications
If a partial stop date is available then it will  be  
imputed by the  
latest possible date based on the 
partial stop date. For instance,  
if the available partial stop date is Year 2005, then the  
imputed 
stop  date  will be  31  December 2005.  However,  
if  
the  available  partial  stop  date  
is  May  2005, 
then the imputed stop date will be 31 May 2005.
Missing or Partial Onset Dates of Adverse Events
Before  
imputing any  missing or partial onset dates, two new dates will  be defined: a  surrogate 
date for each onset date (missing or partial), and an earliest possible date (EPD) for each partial 
onset  date.  The  surrogate  date  will  be  defined  as  the  first  non-missing  valid  date  from  the 
following list (in order of precedence):
• First active study medication date of any study medication,
• informed consent date, or
• visit date corresponding to the visit at which the  event was reported  
if a  valid  non-missing 
date is not available for any of these dates, the surrogate date will be set to missing.
The EPD is based on the partial onset date itself. For instance, if the available partial start date is 
Year 2005, then the EPD will be 01 January 2005. However, if the available partial start date is 
May 2005, then the EPD will be 01 May 2005.
If  
the  onset  date  
is  missing,  
then  
the  
imputed  onset  date  will be  
the  surrogate  date  as  defined 
above. If the surrogate date is missing, then the imputed onset date will be the visit date.
If the onset date is only partially available, the imputation of the onset date will follow different 
rules  depending  on  whether  the  surrogate  date  is  missing  or  not.  Partial  date imputation  is 
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APPENDIX 1  
LIST OF ABBREVIATIONS
Table 9-1:  
List of Abbreviations
Term
Definition
AE
Adverse Event
AR
Acute Rejection
BPAR
Biopsy proven AR
BMS
Bristol-Myers Squibb
BMS-224818
LEA29Y (belatacept)
BP
Blood Pressure
BUN
Blood Urea Nitrogen
cGFR
calculated Glomerular Filtration Rate
CI
Confidence Interval
CMV
Cytomegalovirus
CNI
Calcineurin inhibitor
CRF
Case Report Form
CsA
Cyclosporine A (cyclosporin)
CSR
Clinical study report
DBP
Diastolic Blood Pressure
DMC
Data Monitoring Committee
DSA
Donor Specific Antibodies
EBV
Epstein-Barr virus
EC-MPS
Enteric-coated Mycophenolate Sodium
GFR
Glomerular Filtration Rate
HbA1c
Hemoglobin A1c
HDL
High-density lipoprotein
HLA
Human Leukocyte Antigen
HUS
Hemolytic Uremic Syndrome
Ig
Immunoglobulin
ITT
Intent-To-Treat
IVRS
Interactive Voice Response System
LDL
Low-density lipoprotein
MedDRA
Medical Dictionary of Drug Regulatory Activities
MMF
Mycophenolate mofetil
MPA
Mycophenolic acid
MDRD
Modification of Diet in Renal Disease (study)
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Table 9-1:  
List of Abbreviations
Term
Definition
MTSOSD-59R
Modified Transplant Symptom Occurrence and 
Symptom Distress Scale-59R
NODAT
New Onset Diabetes After Transplantation
NULOJIX
Commercial belatacept
PD
Pharmacodynamics
PK
Pharmacokinetic(s)
PML
Progressive multifocal leukoencephalopathy
PTLD
Post-Transplant Lymphoproliferative Disorder
SAE
Serious Adverse Event
SBP
Systolic Blood Pressure
SCr
Serum Creatinine
TAC
Tacrolimus
TG
Triglyceride
UPCR
Urinary protein/creatinine ratio
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APPENDIX 2  
RELEVANT PROTOCOL DEVIATION CRITERIA
Table 9-2:  
Relevant Protocol Deviation Criteria
Per-ProtocolDeviation Code
Per-Protocol Deviation
Type
1.
Recipients with EBV serostatus
negative orunknown
Serious Breach
2.
Genetically-identical donor
recipient pairs (i.e., identical twins)
Serious Breach
3.
• Subjects with previous graft
loss due to AR
• Subjects with a positive T-cell 
or B-cell cross match
• Recipients of extended criteria 
deceased donor (ECD) kidney, 
as defined in the protocol
• Subjects receiving paired (dual 
or en bloc) kidney transplants
• CMV-negative subjects 
scheduled to receive a kidney 
from a CMV-positive donor
• Subjects with a past history of 
or current need of 
desensitization therapy
Subject Violation
4.
Any of the following conditions 
apply:
• Subjects with a recent (within 
3 months prior  to transplant) 
PRA ≥ 20%
• Donor age < 10 years Recipient 
age < 18 or > 75 at screening
Serious Breach
5.
Subjects with underlying renal
disease of:
• Primary focal segmental 
glomerulosclerosis
• Type I or II 
membranoproliferative 
glomerulonephritis
Atypical hemolytic uremic 
syndrome (HUS) / thrombotic 
thrombocytopenic purpura
Serious Breach
6.
Any of the following conditions 
apply:
• Subjects receiving maintenance 
immunosuppressive agents for 
other indications, such as 
Subject Violation
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Table 9-2:  
Relevant Protocol Deviation Criteria
Per-ProtocolDeviation Code
Per-Protocol Deviation
Type
treatment of autoimmune 
disease.
• Subjects received treatment 
other than assigned study 
medication
7.
Subjects with Body mass index
(BMI) > 35kg/m² for non-diabetic
and >30kg/m² for diabetic subjects
at screening
Serious Breach
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APPENDIX 3  
LIST OF PERI-INFUSIONAL EVENTS
List  of  peri-infusional  events  (infusion  related  reactions)  is  obtained  from  
the  preferred  
terms 
that  correspond  to  the  BMS  predefined  list  of  MedDRA  preferred terms  (Infusion  -related 
reactions-EU- SMQ_CODE  BMS03061). The peri-infusional events are those occurring within 
24  hours  of  Belatacept  administration  The  
latest  MedDRA  Version  of  
the  
list  of  events  at  
the 
time   
of   
the   
database   
lock   
will   
be   
used.
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APPENDIX 4  
MARKED LABORATORY ABNORMALITY CRITERIA
Thresholds  
for defining  markedly abnormal  
laboratory analyte  values (per National Cancer Institute Common Terminology Criteria 
for Adverse Events (NCI CTCAE), version 4.0 (published 29-May-2009).
Analyte
Formatted Value  Code
Lower threshold for Marked Abnormality  
Upper threshold for Marked Abnormality
US 
conventional 
unit
Conventional 
units
SI Units
US 
conventional 
unit
Conventional 
units
SI Units
Hemoglobin  
Hemoglobin
HB
< 8.0g/dL   
< 8.0g/dL   
< 80g/L
More than 
4.0g/dL > 
ULN*
More than 
4.0g/dL > 
ULN*
More than 
40g/L > ULN
White blood cell 
(WBC) count
Leukocytes
WBC
< 2.0 x 10 *
9C/L
(10 * 9 C/L = 
10 * 3C/uL)
< 2,000/mm3
< 2.0 x 10 *
9C/L
Absolute 
lymphocytes
Lymphocytes 
(absolute)
LYMPA
< 0.5 x 10 *
9C/L
(10 * 9C/L = 
10 * 3C/uL)
< 500/mm3
< 0.5 x 10 *
9C/L
> 20 x 10 *
9C/L
> 20,000/mm3
> 20 x 10 *
9C/L
Absolute 
neutrophils
Neutrophils 
(absolute)
NEUTA
< 1.0 x 10 *
9C/L
(10 * 9C/L = 
10 * 3C/uL)
< 1,000/mm3
< 1.0 x 10 *
9C/L
Platelets  
Platelet Count
PLAT
< 50 x 10 *
9C/L
(10 * 9C/L = 
10 * 3C/uL)
< 50,000/mm3
< 50 x 10 *
9C/L
Serum creatinine  
Creatinine
CREAT
> 3.0mg/dL  
> 3.0mg/dL  
> 265umol/L
Urinary 
protein/creatinine 
ratio
Protein/Creatinine 
Ratio
PRCRR
≥
3500mg/mg 
creatinine
≥3.5g/mg 
creatinine
> 395mg/mmol 
creatinine
Serum sodium 
[Na]
Sodium, Serum
NA
< 130mEq/L  < 130mEq/L  < 130mmol/L  > 155mEq/L  > 155mEq/L  
> 155mmol/L
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Analyte
Formatted Value  Code  
Lower threshold for Marked Abnormality  
Upper threshold for Marked Abnormality
Serum potassium 
[K]
Potassium, Serum
K
< 3.0mEq/L  < 3.0mEq/L  < 3.0mmol/L  > 6.0mEq/L  
> 6.0mEq/L  
> 6.0mmol/L
Bicarbonate 
[HCO
3]
Bicarbonate
HCO3
< 11mEq/L  < 11mmol/L  < 11mmol/L
Serum calcium 
[Ca]
Calcium, Total
CA
< 7.0mg/dL  
< 7.0mg/dL  < 1.75mmol/L  > 12.5mg/dL  > 12.5mg/dL  
> 3.1mmol/L
Serum magnesium 
[Mg]
Magnesium, 
Serum
MG
< 0.8mEq/L  
< 0.9mg/dL  < 0.4mmol/L  > 2.5mEq/L  
> 3.0mg/dL  
> 1.23mmol/L
Serum phosphorus 
[P]
Phosphorus, 
Inorganic
PHOS
< 2.0mg/dL  
< 2.0mg/dL  < 0.6mmol/L
Serum albumin  
Albumin
ALB
< 2.0g/dL  
< 2.0g/dL  
< 20g/L
Serum uric acid  
Uric Acid
URIC
> 10.0mg/dL  > 10.0mg/dL  
> 0.59mmol/L
Fasting blood 
glucose
Glucose, Fasting 
Serum
GLUCF
< 40mg/dL  
< 40mg/dL  < 2.2mmol/L  > 250mg/dL  > 250mg/dL
≥14.0mmol/L
Cholesterol
Cholesterol, Total 
(TC)
CHOL
> 400mg/dL  > 400mg/dL  
> 10.3mmol/L
Triglycerides
Triglycerides, 
Fasting
TRIGF
> 500mg/dL  > 500mg/dL  
> 5.7mmol/L
Serum aspartate 
aminotransferase 
(AST)
Aspartate 
Aminotransferase 
(AST)
AST
> 5.0 x 
ULN*
> 5.0 x ULN  
> 5.0 x ULN
Serum alanine 
aminotransferase 
(ALT)
Alanine 
Aminotransferase 
(ALT) 
ALT
> 5.0 x 
ULN*
> 5.0 x ULN  
> 5.0 x ULN
Serum alkaline 
phosphatase
Alkaline 
Phosphatase 
(ALP)
ALP
> 5.0 x 
ULN*
> 5.0 x ULN  
> 5.0 x ULN
Serum total 
bilirubin
Bilirubin, Total
TBILI
> 3.0 x 
ULN*
> 3.0 x ULN  
> 3.0 x ULN
* ULN: Upper limit of laboratory reference range. Note: ULN should be in the same unit.
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** Threshold not defined in NCI CTCAE v. 4.0
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