A Randomized, Open-label, Parallel-group, Single-dose, Biocomparability Study of the Pharmacokinetics of Belatacept Drug Products Using Active Pharmaceutical Ingredient Manufactured by Process E Relative to Active Pharmaceutical Ingredient Manufactured by Process C in Healthy Subjects
Phase: PHASE1
Conditions: Renal Transplantation
Sponsor: Bristol-Myers Squibb



Clinical Protocol
IM103349
BMS-224818
belatacept
Revised Protocol No.: 02
Date: 27-Sep-2016
2
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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Clinical Protocol
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BMS-224818
belatacept
Revised Protocol No.: 02
Date: 27-Sep-2016
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 02
27-Sep-2016
Incorporates Amendment 02
Amendment 02
27-Sep-2016
The purpose of this protocol amendment is to add 30 replacement subjects 
who will be dosed. Audit and monitoring visits revealed major protocol 
deviations at Site 2. Due to the number and significance of these 
deviations, BMS does not believe that the data generated at this site should 
be included in the primary analysis.
Revised 
Protocol 01
06-Jan-2016
Incorporates Amendment 01 and Administrative Letter 01
Amendment 01
06-Jan-2016
The purpose of this protocol amendment is to fulfill the United States 
Food and Drug Administration (FDA) request to monitor subjects until 
titer and/or sero-status are judged to be stable by the investigator and to 
include an additional immunogenicity sample in the protocol. During 
review of this protocol for belatacept, the FDA requested that at the 
completion of the Day 71 visit, subjects that seroconvert will be asked to 
continue to participate until judged to be stable by the investigator and to 
add an immunogenicity sample on Day 15. In accordance with this, 
subjects who seroconvert will be asked to return for a visit approximately 
every 4 months after Day 71. These changes will apply to all current and 
future subjects after this amendment is approved.
Administrative 
Letter
06-Nov-2015
The purpose of this administrative letter was to clarify the units of 
measure for study drug dosage in Section 4 of the protocol, to clarify the 
subject numbers if replacement subjects are used in Section 4.4, and to 
update an inconsistency in Table 5.1-2 regarding the length of collection 
for nonserious adverse events (AEs) based on study duration. Both 
Treatment A and Treatment B will be dosed as 10 mg/kg, replacement 
subjects will be assigned the original subject’s number plus 500, and all 
nonserious AEs will be collected through Day 71.
Original 
Protocol
14-Sep-2015
Not applicable
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SYNOPSIS
Clinical Protocol IM103349
Protocol Title:  A Randomized, Open-label, Parallel-group, Single-dose, Biocomparability Study of the 
Pharmacokinetics of Belatacept Drug Products Using Active Pharmaceutical Ingredient Manufactured by 
Process E Relative to Active Pharmaceutical Ingredient Manufactured by Process C in Healthy Subjects
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s):  Each subject will be administered a single dose of Process E belatacept 10 mg/kg intravenous (IV) or 
Process C belatacept 10 mg/kg IV infused over 30 minutes according to a randomization schedule.
Study Phase:  1
Research Hypothesis:  The pharmacokinetics (PK) of belatacept manufactured by Process E (Process E belatacept) 
and by Process C (Process C belatacept) are comparable in healthy subjects, based on exposure as measured by area 
under the serum concentration-time curve (AUC) from time zero extrapolated to infinite time (AUC[INF]) and 
maximum observed serum concentration (Cmax).
Objectives:
Primary:
The primary objective of this study is to compare the PK of Process E belatacept relative to Process C belatacept 
following a single-dose IV infusion of 10 mg/kg in healthy subjects.
Secondary:
The secondary objectives are as follows:

To assess the safety of a single-dose IV infusion of 10 mg/kg Process E belatacept and 10 mg/kg Process C 
belatacept.

To assess the immunogenicity of Process E belatacept and Process C belatacept.
Study Design:  This is an open-label, randomized, parallel-group, single-dose, biocomparability study in healthy 
subjects. Due to a number of significant deviations that occurred at Site 2, 30 replacement subjects will be dosed. 
This protocol allows for replacement of subjects at sponsor discretion. The data from the 30 subjects who were 
enrolled and dosed at Site 2 will not be included in the primary analysis, and the data from the 30 replacement 
subjects to be dosed will be used for the primary analysis.
The initial plan was to dose approximately 146 subjects (approximately 73 in each cohort) in order to complete a 
minimum of 67 subjects per cohort. Given the protocol deviations at Site 2, the number of subjects dosed in this 
study has now increased to approximately 176 in order to ensure adequate sample size for the primary analysis. 
Subjects will undergo screening evaluations to determine eligibility within 28 days prior to dosing on Day 1. To 
allow for possible dropouts, an adequate number of subjects will need to meet the inclusion/exclusion criteria at 
screening so that 73 subjects per arm will be dosed on Day 1.
Subjects will enter the study site on Day -1 and remain confined until completion of the Hour 72 PK sample 
collection on Day 4. On Day 1, subjects will be randomly assigned within stratified weight categories in a 1:1 ratio 
to receive either Process E belatacept or Process C belatacept 10 mg/kg, IV infused over 30 minutes. Subjects will 
return to the study site for PK blood sample collections after they are furloughed on Day 4 from the study site.
Blood samples for measurement of serum belatacept concentrations and immunogenicity will be obtained according 
to the schedule in Table 5.5.1-1.
Blood samples for immunogenicity assessments will be drawn prior to dosing and after dosing on Days 15, 29, 43, 
57, and 71.
Subjects will be closely monitored for adverse events (AEs) throughout the study. Clinical laboratory tests, vital sign 
measurements, 12-lead electrocardiogram (ECG) measurements, and physical examinations will be performed at 
selected times following dosing. The approximate duration of the study is 99 days, including a 28-day screening 
period and a 71-day study period.
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Subjects who seroconvert and continue to have a high titer at study discharge that is considered to be significantly 
increased versus baseline will be asked to return for follow-up assessment(s) for anti-belatacept antibodies 
approximately every 4 months until their titers and/or sero-status are judged to be stable by the investigator.
Subjects will undergo study procedures according to the study design schematic (Figure 1).
Figure 1:
Study Design Schematic
Days -28 to -1
Day 1
Day 4
Days 5 to 71
Day 71
S, E
Ra
10 mg/kg IV
Process E belatacept
OR
10 mg/kg IV
Process C belatacept
Furlough
after Hour 72 PK 
sample
PKb: Days 8, 15, 22, 29,
36, 43, 57
IMG: Days 15, 29, 43, 57, 71
Dischargec
Serial PK sampling
Abbreviations: E = enrollment; IMG = immunogenicity; IV = intravenous; PK = pharmacokinetic; R = randomization; S = 
screening.
a Subjects randomly assigned within stratified weight categories in a 1:1 ratio.
b Subjects will return to the study site for collection of a single PK sample.
c Evaluations performed prior to study discharge, or for subjects who are prematurely discontinued.
Study Population:  Healthy male and female subjects, including women of childbearing potential, ages 18 to 
55 years inclusive, as determined by medical history, physical examination, vital signs, 12-lead ECGs, and clinical 
laboratory evaluations will be eligible to participate in the study. All subjects must weigh between 60.0 to 100.0 kg, 
inclusive.
Women of childbearing potential must not be breastfeeding or pregnant and must be using an acceptable method of 
contraception. Women of childbearing potential must have a negative pregnancy test within 24 hours prior to dosing 
with study drug.
Study Drug:  Includes investigational products (IP).
Study Drug for IM103349
Medication
Potency
IP/Non-IP
Process E Belatacept
250 mg/vial
IP
Process C Belatacept
250 mg/vial
IP
Abbreviation: IP = investigational product.
Study Assessments:

Safety Outcome Measures: Safety assessments will be based on medical review of AE reports and the 
results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests. The 
incidence of observed AEs will be tabulated and reviewed for potential significance and clinical 
importance.

Pharmacokinetic Measures: PK parameters (Cmax, time of maximum observed serum concentration 
[Tmax], AUC from time zero to the time of last quantifiable concentration [AUC(0-T)], AUC(INF), total 
body clearance (CLT), volume of distribution at steady state (Vss) and terminal half-life [T-HALF]) will be 
derived from serum concentration versus time data.

Immunogenicity Measures: Immunogenicity determination will be based on antibody specificity for 
anti-belatacept antibodies and their corresponding titers in serum over time.
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Statistical Considerations:
Sample Size:  The PK of Process E belatacept and Process C belatacept will be considered equivalent if the 
90% confidence intervals (CIs) for the ratios of geometric means (Process E belatacept relative to Process C 
belatacept) are contained within the equivalence interval 0.80 to 1.25 for both AUC(INF) and Cmax. If there is no 
difference in the PK of belatacept between the 2 manufacturing processes, then 67 subjects per treatment group will 
provide at least 99% and 99% power with respect to AUC(INF) and Cmax, respectively, to conclude equivalence 
between the 2 manufacturing processes. The overall power to conclude equivalence for both AUC(INF) and Cmax 
in this case is also at least 99%.
If the PK of Process E belatacept is 11% greater or 10% less than the PK of Process C belatacept, then 67 subjects 
per treatment group will provide at least 96% and 84% power with respect to AUC(INF) and Cmax, respectively, to 
conclude equivalence between the 2 manufacturing processes. The overall power to conclude equivalence for both 
AUC(INF) and Cmax in this case is at least 81%.
These calculations assume that log(AUC[INF]) and log(Cmax) of belatacept are normally distributed with 
intersubject coefficients of variation no greater than 20% and 26%, respectively, based on the results of 
Study IM103024.
To allow for possible dropouts, an adequate number of subjects will need to meet the inclusion/exclusion criteria at 
screening so that a total of 176 subjects will be dosed including the originally planned 146 subjects (73 subjects per 
arm) and the 30 replacement subjects.
Endpoints:  The primary endpoints are AUC(INF) and Cmax of belatacept. The secondary PK endpoints are Tmax, 
AUC(0-T), CLT, Vss, and T-HALF.
Safety endpoints include the occurrence of AEs, serious adverse events (SAEs), and AEs leading to discontinuation; 
results of clinical laboratory tests, vital sign measurements, ECG findings, and physical examinations; and marked 
abnormalities in clinical laboratory test results.
The immunogenicity endpoint includes the incidence of anti-belatacept antibodies.
Analyses:
The data from the 30 subjects who were enrolled and dosed at Site 2 will not be included in the primary analysis,
and the data from the 30 replacement subjects to be dosed along with the data from the initial 116 subjects who were 
enrolled and dosed at the other sites will be used for the primary analysis. Details on handling of the data from the 
30 subjects who were enrolled and dosed at Site 2 will be described in the statistical analysis plan.
Pharmacokinetic:  A linear fixed effect model with treatment as a fixed effect will be fitted to the log-transformed 
PK parameters AUC(INF), Cmax, AUC(0-T) for use in estimation of effects and construction of CIs. To assess 
comparability of Process E belatacept to Process C belatacept, point estimates and the 2-sided 90% CIs for treatment 
differences on the log scale will be exponentiated to obtain estimates for ratios of geometric means and respective 
90% CIs for belatacept AUC(INF), Cmax, and AUC(0-T) on the original scale. A sensitivity analysis comparing the 
PK between Process E and Process C may be performed by excluding patients who are positive for anti-belatacept 
antibodies. Biocomparability of Process E belatacept to Process C belatacept will be concluded if the 90% CIs for 
the ratios of geometric means for belatacept AUC(INF) and Cmax are contained within 80% to 125%.
All individual PK parameters will be listed for each analyte, including exclusions and reasons for exclusion from 
summaries. Summary statistics will be provided for each PK parameter by treatment, for belatacept. Geometric 
means and coefficients of variation will be presented for Cmax, AUC(0-T), AUC(INF), CLT, and Vss by treatment 
group. Medians and ranges will be presented for Tmax by treatment group. Mean and standard deviation will be 
provided by treatment group for T-HALF.
Plots of individual AUC(INF), Cmax, and AUC(0-T) combined with corresponding geometric means will be 
provided versus treatment.
Immunogenicity:  The incidence of positive response will be summarized in a table by study day and the 
corresponding titer values will be listed. The impact of anti-belatacept on PK parameters will also be evaluated in 
individual subjects.
Safety:  All recorded AEs will be listed and tabulated by system organ class, preferred term, and treatment. Vital 
signs and clinical laboratory test results will be listed and summarized by treatment. Any significant physical 
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examination findings, ECG recordings, and clinical laboratory results will be listed. The number and percentage of 
subjects with marked laboratory abnormalities will be summarized. Electrocardiogram recordings will be evaluated 
by the investigator and abnormalities, if present, will be listed. All SAEs reported though Day 101 after the dose of 
the study drug will be included in the SAE summary table. All nonserious AEs that are reported though Day 71 after 
the dose of the study drug will be included in the AE summary table. Data from any safety related procedure after 
Day 71 or nonserious AEs will continue to be collected in the source documents, but not captured in the electronic 
case report form.
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1. INTRODUCTION AND STUDY RATIONALE .................................................... 
1.1 Study Rationale ................................................................................................. 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives ......................................................................................................... 
1.3.1 Primary Objective .................................................................................... 
1.3.2 Secondary Objectives ............................................................................... 
1.3.3 Exploratory Objectives ............................................................................ 
1.4 Product Development Background ................................................................... 
1.4.1 Pharmacology .......................................................................................... 
1.4.2 Toxicity ..................................................................................................... 
1.4.3 Preclinical Metabolism and Pharmacokinetics ....................................... 
1.4.4 Clinical Pharmacology and Safety .......................................................... 
1.4.4.1 Pharmacokinetics of Belatacept ..................................................... 
1.4.4.2 Safety of Belatacept in Healthy Subjects ........................................ 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2. ETHICAL CONSIDERATIONS .............................................................................. 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3. INVESTIGATIONAL PLAN ................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Other Restrictions and Precautions ......................................................... 
3.5 Discontinuation of Subjects following any Treatment with Study Drug .......... 
3.6 Post Study Drug Follow-up .............................................................................. 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-up ..................................................................................... 
4. STUDY DRUG ......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.6 Blinding/Unblinding ......................................................................................... 
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4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
4.10 Retained Samples for Bioavailability/Bioequivalence ................................... 
5. STUDY ASSESSMENTS AND PROCEDURES .................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Imaging Assessment for the Study............................................................ 
5.3.2 Laboratory Test Assessments ................................................................... 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.5.1 Pharmacokinetics and Immunogenicity: Collection and Processing ...... 
5.5.2 Pharmacokinetic Sample Analyses .......................................................... 
5.5.3 Labeling and Shipping of Biological Samples ......................................... 
5.6 Biomarker Assessments .................................................................................... 
5.7 Exploratory Biomarker Assessments ................................................................ 
5.8 Outcomes Research Assessments ..................................................................... 
5.9 Other Assessments ............................................................................................ 
5.9.1 Immunogenicity Sample Analysis ............................................................ 
5.9.2 Immunogenicity Labeling and Shipping of Biological Samples .............. 
5.10 Additional Research Collection ...................................................................... 
6. ADVERSE EVENTS ................................................................................................ 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury ................................................................. 
6.7 Other Safety Considerations ............................................................................. 
7. DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES.......................................................................................................
8. STATISTICAL CONSIDERATIONS...................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoints ................................................................................... 
8.3.2 Secondary Endpoints ............................................................................... 
8.3.3 Exploratory Endpoint(s) .......................................................................... 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
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8.4.2 Efficacy Analyses ..................................................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Exploratory Biomarker Analyses ............................................................. 
8.4.7 Outcomes Research Analyses .................................................................. 
8.4.8 Immunogenicity Analyses ......................................................................... 
8.5 Interim Analyses ............................................................................................... 
9. STUDY MANAGEMENT ....................................................................................... 
9.1 Compliance ....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10. GLOSSARY OF TERMS ....................................................................................... 
11. LIST OF ABBREVIATIONS ................................................................................. 
12. REFERENCES ....................................................................................................... 
APPENDIX 1 DIAGNOSTIC CRITERIA FOR DRUGS AND ALCOHOL ABUSE 
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Overall, the percentage of healthy subjects that developed antibodies to belatacept can be high 
after receiving a single dose of belatacept, up to 100% with most subjects (67%) having 
neutralizing anti-belatacept antibodies. However, these findings are not clinically relevant 
because the incidence of drug-specific antibody formation in kidney transplant recipients is low 
when belatacept is a component of multi-dose, multi-drug immunosuppressive regimes.
A summary of the results of these studies is available in Section 5.5.1 of the IB.5
1.5
Overall Risk/Benefit Assessment
Belatacept represents a new class of therapeutic agents that target the blockade of CD28-B7 
(CD80, CD86) interactions, key costimulatory signals required for T-cell activation. Belatacept 
is approved for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. 
Overall, the data in the belatacept clinical development program, including 36-month results of 
Phase 3 trials, support a favorable risk-benefit profile for belatacept.
This study is in healthy male and female subjects, a population that would not receive any health 
benefit from participating in this study.
Although this single-dose study in healthy subjects should not pose an unacceptable health risk 
to participants (Section 1.4.4.2 includes a discussion of the safety of belatacept in healthy 
subjects), in order to minimize the overall risk to participating subjects, this protocol has 
inclusion and exclusion criteria appropriate to the population and proposed dosing, exclusionary 
screening tests (12-lead ECG, medical history, physical examination, and clinical laboratory 
assessments), and specific safety assessments at study discharge.
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 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).
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2.2
Institutional Review Board/Independent Ethics Committee
Prior to 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 investigator or 
BMS should also provide the IRB/IEC with a copy of the belatacept IB 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 
(as per country guidelines) 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 or its designee will provide the investigator with an appropriate (ie, Global or Local) 
sample informed consent form(s) (ICF) which will include all elements required by the ICH 
harmonised tripartite guideline E6(R1): Good Clinical Practice and applicable regulatory 
requirements. The sample ICF will adhere to the ethical principles that have their origin in the 
Declaration of Helsinki.
Investigators must:

Provide a copy of the ICF 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 
nontechnical and easily understood.

Allow time necessary for subject or subject’s legally acceptable representative to inquire 
about the details of the study.

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.

Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF 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.

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.

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 
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subject’s willingness to continue participation in the study. This communication should be 
documented.
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 United States, the subjects’ signed HIPAA Authorization.
The consent form(s) must also include a statement that BMS 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 an open-label, randomized, parallel-group, single-dose, biocomparability study in healthy 
subjects. Due to a number of significant deviations that occurred at Site 2, 30 replacement 
subjects will be dosed. Section 4.4 allows for replacement of subjects at sponsor discretion. The 
data from the 30 subjects who were enrolled and dosed at Site 2 will not be included in the 
primary analysis, and the data from the 30 replacement subjects to be dosed will be used for the 
primary analysis.
The initial plan was to dose approximately 146 subjects (approximately 73 in each cohort) in 
order to complete a minimum of 67 subjects per cohort. Given the protocol deviations at Site 2, 
the number of subjects dosed in this study has now increased to approximately 176 in order to 
ensure adequate sample size for the primary analysis. Subjects will undergo screening 
evaluations to determine eligibility within 28 days prior to dosing on Day 1. To allow for 
possible dropouts, an adequate number of subjects will need to meet the inclusion/exclusion 
criteria at screening so that 73 subjects per arm will be dosed on Day 1.
Subjects will enter the study site on Day -1 and remain confined until completion of the 
Hour 72 PK sample collection on Day 4. On Day 1, subjects will be randomly assigned within 
stratified weight categories in a 1:1 ratio to receive either Process E belatacept or Process C 
belatacept, 10 mg/kg, IV infused over 30 minutes. Subjects will return to the study site for PK 
blood sample collections after they are furloughed on Day 4 from the study site. Blood samples 
will be collected through Day 57 (approximately 5-6 half-lives) for PK analysis and through 
Day 71 (approximately 7-8 half-lives) for assessment of immunogenicity when drug 
concentrations are low and unlikely to interfere with analysis of anti-drug antibodies.
The PK and immunogenicity blood sample schedule is shown in Table 5.5.1-1. Blood samples 
for immunogenicity will be obtained prior to dosing and after dosing on Days 15, 29, 43, 57, and 
71.
The study design schematic is presented in Figure 3.1-1.
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Figure 3.1-1:
Study Design Schematic
Days -28 to -1
Day 1
Day 4
Days 5 to 71
Day 71
S, E
Ra
10 mg/kg IV
Process E belatacept
OR
10 mg/kg IV
Process C belatacept
Furlough
After Hour 72 PK 
sample
PKb: Days 8, 15, 22, 29, 36, 43, 57
IMG: Days 15, 29, 43, 57, 71
Dischargec
Serial PK sampling
Abbreviations: E = enrollment; IMG = immunogenicity; IV = intravenous; PK = pharmacokinetic; 
R = randomization; S = screening.
a Subjects randomly assigned within stratified weight categories in a 1:1 ratio.
b Subjects will return to the study site for collection of a single PK sample.
c Evaluations performed prior to study discharge, or for subjects who are prematurely discontinued .
Physical examinations, vital sign measurements, 12-lead ECGs, and clinical laboratory 
evaluations will be performed at selected times throughout the study. Subjects will be closely 
monitored for AEs throughout the study. Approximately 200 mL of blood will be drawn from 
each subject during the study.
The approximate duration of the study is a 28-day screening period, 71 study days per subject for 
a total of up to 99 days.
Subjects who seroconvert and continue to have a high titer at study discharge that is considered 
to be significantly increased versus baseline will be asked to return for follow-up assessment(s) 
for anti-belatacept antibodies approximately every 4 months until their titers and/or sero-status 
are judged to be stable by the investigator.
3.2
Post Study Access to Therapy
At the end of the study, BMS will not continue to provide BMS supplied study drug to 
subjects/investigators unless BMS chooses to extend the study. The investigator should ensure 
that the subject receives appropriate standard of care to treat the condition under study.
3.3
Study Population
For entry into the study, the following criteria MUST be met prior to dosing on Day 1. No 
exceptions will be granted.
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Signed written informed consent must be obtained from the subjects in accordance with 
requirements of the study center’s IRB/IEC prior to the initiation of any protocol-required 
procedures.
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2. Target Population
a) Healthy male and female subjects, including women of childbearing potential (WOCBP), 
as determined by no significant deviation from normal in history, physical examination, 
vital signs, ECGs, and clinical laboratory determinations.
b) Must weigh between 60.0 to 100.0 kg, inclusive.
c) Must 
have 
body 
mass 
index 
(BMI) 
of 
18.0 
to 
30.0 
kg/m2, 
inclusive; 
BMI=weight (kg)/[height (m)]2.
d) Subject re-enrollment: This study permits, at the discretion of the investigator, the 
re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, 
subject has not been randomized / has not been treated). If re-enrolled, the subject must 
be re-consented.
3. Age and Reproductive Status
a) Males and females, ages 18 to 55 years, inclusive.
b) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 
25 IU/L or equivalent units of human chorionic gonadotropin within 24 hours prior to the 
start of study drug.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug plus 5 half-lives of belatacept (50 days) plus 30 days 
(duration of ovulatory cycle) for a total of 80 days following treatment completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug(s) plus 
5 half-lives of the belatacept (50 days) plus 90 days (duration of sperm turnover) for a 
total of 140 days following treatment completion.
f)
Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However, WOCBP must still undergo 
pregnancy testing as described in this section.
g) Men must be willing to refrain from sperm donation for 140 days after dosing.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception. Highly effective methods of contraception 
have a failure rate of < 1% when used consistently and correctly.
At a minimum, subjects must agree to the use of 1 method of highly effective contraception as 
listed below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

Male condoms with spermicide

Hormonal methods of contraception including combined oral contraceptive pills, vaginal 
ring, injectables, implants and intrauterine devices (IUDs) such as Mirenaby WOCBP 
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subject or male subject’s WOCBP partner. 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 study drug

IUDs, such as ParaGard

Tubal ligation

Vasectomy

Complete Abstinence*
*Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an 
acceptable form of contraception for all study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly effective contraception must be 
discussed in the event that the subject chooses to forego complete abstinence.
3.3.2
Exclusion Criteria
1.
Target Disease Exceptions
a) Subjects with active tuberculosis (TB) requiring treatment; subjects with a history of 
active or latent TB without documented adequate therapy; subjects with current clinical, 
radiographic, or laboratory evidence of active or latent TB. All subjects will be required 
to have a negative QuantiFERON-TB Gold test at the screening visit. A 
QuantiFERON-TB Gold test performed within 4 weeks of dosing on Day 1 will be 
acceptable provided there is documentation of a negative result. All subjects will be 
required to have a negative chest x-ray [posterior-anterior and lateral views] for TB at the 
screening visit. A chest x-ray performed within the past 6 months will be acceptable 
provided written documentation of negative results is available.
b) History of malignancy or strong family history of malignancy.
c) History of herpes zoster.
d) Any acute or chronic bacterial infection in the previous 12 weeks.
e) Any recent infection requiring antibiotic treatment within 4 weeks of dosing.
f)
Known or suspected infection, including infection with human immunodeficiency virus 
(HIV), hepatitis B or C viruses.
g) Presence of any factors that would predispose the subject to develop infection (eg, rectal 
fissures, poor dentition, open skin lesions).
h) Known or suspected autoimmune disorder.
i)
Any history of known or suspected congenital or acquired immunodeficiency state or 
condition that would compromise the subject’s immune status.
2. Medical History and Concurrent Diseases
a) Any significant acute or chronic medical illness.
b) History of clinically relevant hypertension that requires treatment.
c) Any major surgery within 4 weeks of study drug administration.
d) Donation of blood to a blood bank or in a clinical study (except a screening or follow-up 
visit) within 4 weeks of study drug administration (within 2 weeks for plasma only).
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e) Blood transfusion within 4 weeks of study drug administration.
f)
Inability to tolerate IV medication.
g) Inability to be venipunctured and/or tolerate venous access.
h) Smoking within less than 6 months of study drug administration.
i)
Recent (within 6 months of study drug administration) drug or alcohol abuse as defined 
in DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse7 (Appendix 1).
j)
Any other sound medical, psychiatric, and/or social reason as determined by the 
investigator.
3. Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG or clinical laboratory determinations beyond what 
is consistent with the target population.
b) Any of the following on 12-lead ECG prior to study drug administration, confirmed by a 
repeat test.
i)
PR ≥ 210 msec
ii) QRS ≥ 120 msec
iii) QT ≥ 500 msec
iv) QT interval corrected with Fridericia’s method ≥450 msec
c) Screening or Day 1 predose systolic blood pressure > 140 mm Hg or diastolic blood 
pressure > 90 mm Hg, confirmed by repeat assessment.
d) Positive urine screen for drugs of abuse.
e) Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or -2 
antibody.
f)
Positive urine screen for cotinine.
g) Positive alcohol screening test.
h) Any of the following laboratory results outside of the range specified below prior to study 
drug administration, confirmed by repeat test
i)
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of 
normal (ULN)
ii) Total bilirubin > ULN
iii) Hemoglobin < 0.9 × lower limit of normal
iv) Creatinine > ULN
4. Allergies and Adverse Drug Reaction
a) History of allergy to belatacept or related compounds.
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
5. Other Exclusion Criteria
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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) Inability to comply with restrictions and prohibited activities/treatments as listed in 
Section 3.4.
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
WOCBP is defined as any female who has experienced menarche and who has not undergone 
surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. 
Menopause is defined as 12 months of amenorrhea in a woman over age 45 in the absence of 
other biological or physiological causes. In addition, females under the age of 55 years must 
have a documented serum follicle-stimulating hormone (FSH) level > 40 mIU/mL to confirm 
menopause.
Females 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 considered postmenopausal.

1 week minimum for vaginal hormonal products (eg, 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.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications taken prior to study drug administration in the study are 
described below. Medications taken within 4 weeks prior to study drug administration must be 
recorded on the case report form (CRF).
1) Prior exposure to abatacept and/or belatacept or leukocyte-depleting agents (eg, rituximab).
2) Exposure to any investigational drug within 4 weeks of study drug administration.
3) Use of any prescription drugs within 4 weeks prior to study drug administration except those 
medications cleared by the PPD medical monitor after consultation with the BMS 
clinical/medical monitor.
4) Use of any other drugs, including over-the-counter medications (OTC) and herbal 
preparations, including St John’s wort, within 1 week or 5 half-lives, whichever is longer, 
prior to study drug administration except those medications cleared by the PPD medical 
monitor after consultation with the BMS clinical/medical monitor.
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5) Administration of oral polio vaccine or live varicella vaccine to subjects or household 
contacts during the course of the study.
6) Vaccination with any live vaccine within the past 4 weeks prior to dosing and for 71 days 
post dosing.
No concomitant medications (prescription, OTC, or herbal) are to be administered during the 
study unless they are prescribed by the investigator for treatment of specific clinical events. Any 
concomitant therapies must be recorded on the CRF.
3.4.2
Other Restrictions and Precautions
1) Subjects are to refrain from strenuous exercise, contact sports, and sunbathing for the 
duration of the study.
2) Subjects are not permitted to consume alcohol-containing beverages from 3 days prior to first 
dose until clinic furlough.
3) Subjects are required to remain in the clinical facility at least 72 hours after dosing until 
furloughed.
4) Subjects are required to fast (nothing to eat or drink except water) for 4 hours before until 
2 hours after study drug administration.
5) On Day 1, all subjects will receive identical meals.

A standard light breakfast will be served approximately 2 hours postdose.

A standard lunch will be served approximately 4 hours postdose.

A standard dinner will be served approximately 8 hours postdose.

A standard light snack will be served approximately 12 hours postdose.
The food content of meals may vary on Days 2 through 4.
6) Subjects should maintain an upright (seated or reclining) position for at least 4 hours 
postdose on Day 1.
3.5
Discontinuation of Subjects following any Treatment with Study Drug
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment and/or participation in the study

Any clinical AE, laboratory abnormality or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
subject

Termination of the study by BMS

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Unblinding a subject for any reason (emergency or nonemergency)

Inability to comply with protocol

Discretion of the investigator

Pregnancy
In the case of pregnancy, the PPD medical monitor or designee must immediately notify the 
BMS medical monitor or designee of this event. In most cases, the study drug will be 
permanently discontinued in an appropriate manner. If the investigator determines a possible 
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favorable benefit/risk ratio that warrants continuation of study drug, a discussion between the 
investigator and the BMS Medical Monitor or designee must occur.
All subjects who discontinue the study drug should comply with protocol-specified follow-up 
procedures as outlined in Section 5. The only exception to this requirement is when a subject 
withdraws consent for all study procedures including post-treatment study follow-up or loses the 
ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness).
If study drug 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 CRF page.
3.6
Post Study Drug Follow-up
Subjects who discontinue study drug may continue to be followed.
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug 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 the 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. In 
the event that 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 3 documented phone 
calls, faxes, texts, or emails as well as lack of response by subject to 1 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.
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4.
STUDY DRUG
Study drug includes both investigational [medicinal] product (IP/IMP) and non-investigational 
[medicinal] product (Non-IP/Non-IMP) and can consist of the following:

All products, active or placebo, being tested or used as a comparator in a clinical trial.

Study required premedication.

Other drugs administered as part of the study that are critical to claims of efficacy 
(eg, background therapy, rescue medications).

Diagnostic agents: (eg, glucose for glucose challenge) given as part of the protocol 
requirements must also be included in the dosing data collection.
After at least a 4-hour fast, on Day 1 each subject will receive a single 10 mg/kg IV dose of 
either belatacept Process E or belatacept Process C infused over 30 minutes according to a 
randomization schedule:

Treatment A: belatacept 10 mg/kg IV, Process E belatacept

Treatment B: belatacept 10 mg/kg IV, Process C belatacept
Belatacept process E (Treatment A) or belatacept process C (Treatment B) will be administered 
intravenously, at a dose of 10 mg/kg using a calibrated, constant-rate infusion pump. The 
continuous infusion solution must be filtered upon administration using an in-line, sterile, 
nonpyrogenic, low-protein binding filter with a pore size of 1.2 microns. Belatacept infusion 
should be administered over a period of 30 minutes, in a fixed volume of 100 mL, using 
0.9% sodium chloride (normal saline) as diluent, to produce a final infusion concentration of 
2 mg/mL to 10 mg/mL. If normal saline cannot be obtained sites may use 5% dextrose in water 
as an acceptable alternative.
The time at the start of the infusion will be called “0” hour. The IV infusion of study drug will be 
administered with the subject in the seated or reclining position. At the end of the infusion, the 
line must be flushed per the belatacept pharmacy manual for this study. Any unused portion of 
the infusion solution should not be stored for reuse.
Belatacept infusion must be completed within 24 hours of reconstitution of the lyophilized 
powder, If not used immediately the infusion solution may be stored under refrigerated 
conditions: 2°C to 8°C (36°F to 46°F) and protected from light for up to 24 hours (4 of these 
hours may be at room temperature, 20°C to 25°C [68°F to 77°F], and normal light).
Product description and storage information is described in Table 4-1.
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Table 4-1:
Study Drugs for IM103349
Product Description 
Dosage Form
Potency
IP/Non-IMP
Blinded or Open 
Label
Packaging/Appearance
Storage Conditions
(per label)
Belatacept for IV 
infusion, 250 mg/vial 
(Process C)
250 mg vial
IP
Open label
White to off white, 
whole or fragmented 
cake in a vial.
Store refrigerated, 
2°C-8°C (36°F-46°F); 
Protect from light.
Belatacept for IV 
infusion, 250 mg/vial 
(Process E)
250 mg vial
IP
Open label
White to off white, 
whole or fragmented 
cake in a vial.
Store refrigerated, 
2°C-8°C (36°F-46°F); 
Protect from light.
Abbreviations: IP=investigational product; IV=intravenous.
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4.1
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. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
4.2
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.
4.3
Storage 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 the BMS medical monitor should be contacted immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert. 
Investigational product documentation (whether supplied by BMS or not) 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). Specific 
instructions for preparation, stability and administration of the IP will be provided in a separate 
document.
4.4
Method of Assigning Subject Identification
Enrolled subjects, including those not dosed, will be assigned sequential subject numbers starting 
with 00001, (eg, 00001, 00002, 00003.... 00010). Those enrolled subjects meeting inclusion and 
exclusion criteria will be eligible to be randomized. Randomization numbers will be assigned 
prior to dosing.
Previous studies indicate that in subjects who take belatacept, there is a trend in higher clearance 
with increasing body weight.4 In this study, the randomization will be stratified by weight 
categories: 60 to < 70 kg, 70 to < 80 kg, 80 to < 90 kg, and 90 to 100 kg. Within each weight 
category, subjects will be randomly assigned to Process E belatacept or Process C belatacept in 
1:1 ratio. Randomization numbers will be sequential within each weight category, starting with 
1001, 2001, 3001, and 4001 for each weight category, respectively.
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Subjects will not be replaced if they are discontinued from the study secondary to an AE unless 
the AE can be determined to be unrelated to treatment. If a subject is replaced after dosing then 
the replacement subject will be assigned the original subject’s number plus 500. The replacement 
subject will receive the same treatment as the subject being replaced but a new randomization 
number will be assigned to him or her. For example, Subject 4 would be replaced by Subject 
504.
4.5
Selection and Timing of Dose for Each Subject
Each subject will receive a single IV dose of either 10 mg/kg belatacept Process E or 10 mg/kg 
belatacept Process C infused over 30 minutes on Day 1.
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Study drug will be administered intravenously in the study site under the supervision of study 
personnel.
4.8
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 BMS 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 standard operating procedures 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 BMS 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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4.9
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.
4.10
Retained Samples for Bioavailability/Bioequivalence
Not applicable.
5.
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule
Study assessments and procedures are presented in Table 5.1-1 and Table 5.1-2.
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Table 5.1-1:
Screening Procedural Outline (IM103349)
Procedure
Screening
Visit
Day -28 to 
Day -2
Day -1
Visit
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol-specific informed consent is 
signed.
Inclusion/Exclusion Criteria
X
X
Medical History
X
Include any toxicities or allergy related to previous treatments. Screening medical 
history evaluation may occur on Day -1 if the screening physical examination occurs on 
Day -1 (See “Physical Examination” note below).
Admit to Clinical Facility
X
Safety Assessments
Physical Examination
X
X
If the screening physical examination is performed within 24 hours prior to dosing on 
Day 1 then a single examination may count as both the screening and prior to dosing 
evaluation.
Physical Measurements
X
X
Height and weight at screening; weight only Day -1. Body mass index will be calculated 
at screening and on Day -1.
Vital Signs
X
X
Includes body temperature, respiratory rate, and seated blood pressure and heart rate. 
Blood pressure and heart rate should be measured after the subject has been resting 
quietly for at least 5 minutes. Day -1 vital sign measurements must be reviewed prior to 
dosing on Day 1.
12-Lead ECGs
X
X
ECGs should be recorded after the subject has been supine for at least 5 minutes. Results 
must be reviewed prior to dosing on Day 1.
Chest X-ray
X
A posterior-anterior and lateral chest x-ray will be performed at enrollment. A chest 
x-ray performed within the past 6 months will be acceptable provided written 
documentation of negative results is available.
Laboratory Tests
X
X
Includes blood and urine samples. Subjects are required to fast for at least 10 hours prior 
to the collection of specimens for clinical laboratory tests. All clinical laboratory 
assessment must be available and reviewed by the investigator prior to dosing on Day 1.
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Table 5.1-1:
Screening Procedural Outline (IM103349)
Procedure
Screening
Visit
Day -28 to 
Day -2
Day -1
Visit
Notes
Serology
X
Includes hepatitis C antibody, hepatitis B surface antigen, and HIV-1 and -2 antibodies. 
Results must be available and reviewed prior to dosing on Day 1.
QuantiFERON-TB Gold Test
X
A QuantiFERON-TB Gold test performed within 4 weeks of dosing on Day 1 will be 
acceptable.
Urine Drug Test (including cotinine)
X
X
Results must be available and reviewed prior to dosing on Day 1.
Alcohol Test
X
X
A urine alcohol test will be performed. Results must be available and reviewed prior to 
dosing on Day 1.
Pregnancy Test
X
X
For WOCBP only; serum pregnancy test at screening and Day -1. Serum or urine 
pregnancy test at all subsequent time points during the study. Results must be reviewed 
prior to dosing on Day 1.
Follicle-stimulating Hormone
Women only. Refer to Section 3.3.3.
Adverse Event Reporting
Monitor for Serious Adverse Events
X
X
All SAEs must be collected from the date of subject’s written consent until 30 days after 
discontinuation of dosing or completion of the subject’s participation in the study if the 
last scheduled visit occurs at a later time.
Abbreviations: ECG = electrocardiogram; HIV = human immunodeficiency virus; SAEs = serious adverse events; WOCBP = women of childbearing potential.
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Table 5.1-2:
On Treatment Procedural Outline (IM103349)
Procedurea
Day 
1
Day 
2
Day 
4b
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Day 
43
Day 
57
Day 
71c
Notes
Safety Assessments
Physical Examination
X
X
Physical Measurements
X
Weight only
Vital Signs
X
X
X
X
X
X
Vital signs will be measured 
predose and within 30 minutes 
postdose on Day 1. Day 4 vital signs 
will be measured prior to furlough 
from study site. See note in 
screening procedures. 
12-Lead ECG
X
See note in screening procedures.
Laboratory Tests
X
X
X
X
See note in screening procedures 
and Section 5.3.2.
Pregnancy Test
X
X
X
X
Adverse Event 
Reporting
Monitor for Nonserious 
AEs
X
X
X
X
X
X
X
X
X
X
X
AEs will be reported from after dose 
of study drug through Day 71.
Monitor for SAEs
X
X
X
X
X
X
X
X
X
X
X
SAEs will be reported from 
subject’s written consent through 
Day 101.
Pharmacokinetic (PK) 
Assessments
Serial Blood PK 
Sampling for Belatacept
X
X
X
X
X
X
X
X
X
X
See Table 5.5.1-1.
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Table 5.1-2:
On Treatment Procedural Outline (IM103349)
Procedurea
Day 
1
Day 
2
Day 
4b
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Day 
43
Day 
57
Day 
71c
Notes
Immunogenicity
Assessments
Blood Sampling
X
X
X
X
X
X
Prior to dosing on Day 1.
See Table 5.5.1-1.
Subjects who seroconvert and 
continue to have a high titer at study 
discharge that is considered to be 
significantly increased versus 
baseline will be asked to return for 
follow-up assessment(s) for 
anti-belatacept antibodies 
approximately every 4 months until 
their titers and/or sero-status are 
judged to be stable by the 
investigator.
Clinical Drug Supplies
Randomize
X
Study Drug 
Administration
X
Supplied by BMS.
Abbreviations: AE = adverse event; ECG = electrocardiogram; PK = pharmacokinetic; SAE = serious adverse event.
a The window for Days 8 and 15 is ± 1. The window for Days 22, 29, 36, 43, and 57 is ± 2. The window for Day 71 is -2 days.
b Subjects will be furloughed from the clinic site after the Hour 72 PK sample on Day 4.
c Evaluations performed prior to study discharge, or for subjects who are prematurely discontinued.
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In the event multiple procedures are required at a single time point, the following is a list of 
procedures from highest priority to low:
1) PK sampling
2) Safety (ECG)
3) Safety (clinical laboratory tests)
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single screening or 
lead-in period will be permitted (in addition to any parameters that require a confirmatory value).
Any new result will override the previous result (ie, the most current result prior to enrollment) 
and is the value by which study inclusion will be assessed, as it represents the subject’s most 
current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1 may be repeated in an 
effort to find all possible well-qualified subjects. Consultation with the medical monitor may be 
needed to identify whether repeat testing of any particular parameter is clinically relevant.
5.2
Study Materials
The site will provide all required materials for the tests performed locally (ie, relevant clinical 
laboratory tests and urine drug screens). The site will have available a well-calibrated scale for 
recording body weight, a 12-lead ECG machine, and a calibrated sphygmomanometer and 
thermometer for vital signs assessments. A current and fully-stocked advanced cardiac life 
support cart will be immediately available on the premises. The site will have, a refrigerated 
centrifuge, a monitored and alarmed refrigerator, and freezer (-20°C [-68°F] or below), as well as 
containers and dry ice for shipment and storage of blood samples. The site will provide all 
materials required for accurate source documentation of study activities and for housing the 
subjects during the study. The site will source marketed product from a single commercial lot.
BMS or designee will provide a BMS-approved protocol and any amendments or administrative 
letters (if required), and IB. Case report forms (electronic or hard copy) will be provided by BMS 
or designee. BMS or the clinical facility will provide labels and tubes for the collection of blood 
samples for PK and immunogenicity analysis.
5.3
Safety Assessments
5.3.1
Imaging Assessment for the Study
Any incidental findings of potential clinical relevance found on a chest x-ray that are not directly 
associated with the objectives of the protocol should be evaluated and handled by the study 
investigator as per standard medical/clinical judgment.
5.3.2
Laboratory Test Assessments
A local laboratory will perform the analyses and will provide reference ranges for these tests. 
Results of clinical laboratory tests performed on Day -1 must be available prior to dosing.
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The following clinical laboratory tests will be performed:
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Serum Chemistry
AST
ALT
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase
Creatinine
Blood urea nitrogen
Uric acid
Fasting glucose
Total protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive 
on the dipstick
Serology
Serum for hepatitis C antibody, hepatitis B surface antigen, HIV-1 and -2 antibody (screening 
only)
Other Analyses
Test for drugs of abuse, including cotinine (urine or serum) (screening and Day -1)
Alcohol screening (urine) (screening and Day -1)
FSH (if necessary for confirmation of menopause at screening; see Section 3.3.3).
Pregnancy test (WOCBP only: screening, Day -1, Days 4, 29, 57, and 71)
QuantiFERON-TB Gold test (screening only)
Results of all laboratory tests required by this protocol must be provided to BMS, either recorded 
on the laboratory pages of the CRF or by another mechanism as agreed upon between the 
investigator and BMS (eg, provided electronically). If the units of a test result differ from those 
printed on the CRF, the recorded laboratory values must specify the correct units. Any abnormal 
laboratory test result considered clinically significant by the investigator must be recorded on the 
appropriate AE page of the CRF (See Section 6.3).
5.4
Efficacy Assessments
Not applicable.
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5.4.1
Primary Efficacy Assessment
Not applicable.
5.4.2
Secondary Efficacy Assessments
Not applicable.
5.5
Pharmacokinetic Assessments
Pharmacokinetics of belatacept will be derived from serum concentration versus time data. The 
pharmacokinetic parameters to be assessed include:
Cmax
Maximum observed serum concentration
Tmax
Time of maximum observed serum concentration
AUC(0-T)
Area under the serum concentration-time curve from time zero to time 
of last quantifiable concentration
AUC(INF)
Area under the serum concentration-time curve from time zero 
extrapolated to infinite time
Vss
Volume of distribution at steady state
CLT
Total body clearance
T-HALF
Half-life
Individual subject PK parameter values will be derived by noncompartmental methods by a 
validated PK analysis program. Actual times will be used for the analyses.
5.5.1
Pharmacokinetics and Immunogenicity: Collection and Processing
Table 5.5.1-1 lists the sampling schedule to be followed for the assessment of PK. Further details 
of blood collection and processing will be provided to the study site in the procedure manual.
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a The window for Days 8 and 15 is ± 1. The window for Days 22, 29, 36, 43, and 57 is ± 2. The window for Day 71 
is -2 days.
b This sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to the 
end of infusion). If the end of infusion is delayed to beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
5.5.2
Pharmacokinetic Sample Analyses
The serum samples will be analyzed for belatacept by a validated ligand binding assay using a 
validated enzyme-linked immunosorbent assay platform. The lower limit of quantification is 
3 ng/mL.
5.5.3
Labeling and Shipping of Biological Samples
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the procedure manual.
Table 5.5.1-1:
Pharmacokinetic and Immunogenicity Sampling Schedule for 
Belatacept
Study Day of 
Sample Collectiona
Event
Time
(Relative To The 
Start of Belatacept 
Infusion)
Hour: Min
PK Blood Sample 
for Belatacept
Immunogenicity 
Blood Sample
1
predose
00:00
X
X
00:15
X
EOIb
00:30
X
01:00
X
02:00
X
06:00
X
12:00
X
2
24:00
X
4
72:00
X
8
168:00
X
15
336:00
X
X
22
504:00
X
29
672:00
X
X
36
840:00
X
43
1008:00
X
X
57
1344:00
X
X
71
1680:00
X
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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.)
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 (See 
NOTE below)

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 6.6 for the definition of potential DILI).
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 (eg, death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as an SAE (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
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
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)

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the IB represent the Reference Safety Information to determine 
expectedness of SAEs for expedited 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 101 days of discontinuation of 
dosing.
The investigator must 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 must be completed for any event where doubt exists regarding its seriousness.
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 must 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 hours of awareness of the event. SAEs must be recorded on the SAE Report 
Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms). The preferred 
method for SAE data reporting collection is through the electronic case report form (eCRF). The 
paper SAE/pregnancy surveillance forms are only intended as a back-up option when the eCRF 
system is not functioning. In this case, the paper forms 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, electronic submission is the required 
method for reporting. In the event the electronic system is unavailable for transmission, paper 
forms must be used and submitted immediately. 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.
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If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports must 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, the SAE report must be updated and submitted within 24 hours to BMS 
medical monitor or designee using the same procedure used for transmitting the initial SAE 
report.
All SAEs must be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as a serious adverse event.
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 or identified during the course of the study.
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 laboratory test result that is clinically significant or meets the definition of an SAE

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives after product administration, the investigator must immediately notify the BMS 
medical monitor or designee of this event and complete and forward a Pregnancy Surveillance 
Form to the BMS medical monitor or designee within 24 hours of awareness of the event and in 
accordance with SAE reporting procedures described in Section 6.1.1.
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In most cases, the study drug will be permanently discontinued in an appropriate manner (eg, 
dose tapering if necessary for subject safety).
In the rare event that the benefit of continuing study drug is thought to outweigh the risk, after 
consultation with BMS, the pregnant subject may continue study drug after a thorough 
discussion of benefits and risk with the subject.
The investigator must immediately notify the BMS medical monitor or designee 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.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (See Section 6.1.1 for reporting details).
6.6
Potential Drug Induced Liver Injury
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 DILI is defined as:
1) Aminotransaminases (ALT or AST) elevation > 3 times ULN
AND
2) Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3) No other immediately apparent possible causes of aminotransaminase 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, ECGs, x-ray 
filming, or 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.
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7.
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable.
8.
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.2
Populations for Analyses

The Enrolled Population includes all subjects who sign an ICF.

The Randomized Population is a subset of the Enrolled Population including only subjects 
who were randomly assigned to a treatment. When using the Randomized Population, 
subjects will be presented in the treatment group they were randomly assigned to, even when 
the treatment they received was different.

The Treated Population is a subset of the Enrolled Population including only subjects who 
received at least 1 dose of study medication. All analyses using the Treated Population will 
be presented by randomized treatment group, except in cases where information was 
available which indicated that a subject received a different treatment for the entire course of 
their participation in the study. In this case, the safety data and PK data for those subjects 
will be presented by the treatment actually received.

The PK Population is a subset of the Treated Population. The PK population includes all 
subjects who received at least 1 dose of study medication and had any available 
concentration-time data.
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
The Evaluable PK Analysis Set is a subset of the PK Population. The Evaluable PK Analysis 
Set includes all subjects who have adequate PK profiles. All available concentration-time 
data and derived PK parameters will be reported, however only subjects with adequate PK 
profiles will be included in the summary statistics and statistical analyses.

The Immunogenicity Analysis Population: All treated subjects with at least 1 post-baseline 
immunogenicity result reported will be included in immunogenicity analysis.
8.3
Endpoints
8.3.1
Primary Endpoints
The primary endpoints are AUC(INF) and Cmax of belatacept.
8.3.2
Secondary Endpoints

The secondary PK endpoints are Tmax, AUC(0-T), CLT, Vss, and T-HALF of belatacept.

Safety endpoints include the occurrence of AEs, SAEs, and AEs leading to discontinuation; 
results of clinical laboratory tests, vital sign measurements, ECG findings, and physical 
examinations; and marked abnormalities in clinical laboratory test results.

The immunogenicity endpoint includes the incidence of anti-belatacept antibodies.
8.3.3
Exploratory Endpoint(s)
Not applicable.
8.4
Analyses
The data from the 30 subjects who were enrolled and dosed at Site 2 will not be included in the 
primary analysis, and the data from the 30 replacement subjects to be dosed along with the data 
from the initial 116 subjects who were enrolled and dosed at the other sites will be used for the 
primary analysis. Details on handling of the data from the 30 subjects who were enrolled and 
dosed at Site 2 will be described in the statistical analysis plan.
8.4.1
Demographics and Baseline Characteristics
Frequency distributions of gender and race will be tabulated. Summary statistics for age, body 
weight, height, and BMI will be tabulated.
8.4.2
Efficacy Analyses
Not applicable.
8.4.3
Safety Analyses
All recorded AEs will be listed and tabulated by system organ class, preferred term, and 
treatment. Vital signs and clinical laboratory test results will be listed and summarized by 
treatment. Any significant physical examination findings, ECG recordings, and clinical 
laboratory results will be listed. The number and percentage of subjects with marked laboratory 
abnormalities will be summarized. Electrocardiogram recordings will be evaluated by the 
investigator and abnormalities, if present, will be listed. All SAEs reported though Day 101 after 
the dose of the study drug will be included in the SAE summary table. All nonserious AEs that 
are reported though Day 71 after the dose of the study drug will be included in the AE summary 
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9.1.2.1
Source Documentation
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records, 
AE tracking/reporting, protocol required assessments, and/or drug accountability records.
When paper records from such systems are used in place of electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original.
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 and 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 study drug 
(inventoried and dispensed) is maintained at the study site to include the investigational product. 
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
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
retained 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 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. 
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
For this single site protocol, the principal investigator for the site will sign the clinical study 
report.
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 
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at any event not less than 30 days prior to 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
Complete Abstinence
If 1 form of contraception is required, complete abstinence is 
defined as complete avoidance of heterosexual intercourse 
and is an acceptable form of contraception for all study 
drugs. Female subjects must continue to have pregnancy 
tests. Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject 
chooses to forego complete abstinence.
If 2 forms of contraception are required, complete abstinence 
is defined as complete avoidance of heterosexual intercourse 
and is an acceptable form of contraception for all study 
drugs. Subjects who choose complete abstinence are not 
required to use a second method of contraception, but female 
subjects must continue to have pregnancy tests. Acceptable 
alternate methods of highly effective contraception must be 
discussed in the event that the subject chooses to forego 
complete abstinence.
Expanded definition Complete abstinence as defined as 
complete avoidance of heterosexual intercourse is an 
acceptable form of contraception for all study drugs. This 
also means that abstinence is the preferred and usual lifestyle 
of the patient. This does not mean periodic abstinence (eg, 
calendar, ovulation, symptothermal, profession of abstinence 
for entry into a clinical trial, postovulation methods) and 
withdrawal, 
which 
are 
not 
acceptable 
methods 
of 
contraception. Subjects who choose complete abstinence are 
not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. 
Acceptable 
alternate 
methods 
of 
highly 
effective 
contraception must be discussed in the event that the subject 
chooses to forego complete abstinence.
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11.
LIST OF ABBREVIATIONS
Term
Definition
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the serum concentration-time curve
AUC(INF)
area under the serum concentration-time curve from time zero 
extrapolated to infinite time
AUC(0-T)
area under the serum concentration-time curve from time zero to time of 
the last quantifiable concentration
BMI
body mass index
BMS
Bristol-Myers Squibb
CFR
Code of Federal Regulations
CI
confidence interval
CLT
total body clearance
Cmax
maximum observed serum concentration
CRF
case report form, paper or electronic
CTA
clinical trial agreement
DILI
drug induced liver injury
DSM IV
Diagnostic and Statistical Manual of Mental Disorders (4th Edition)
ECG
electrocardiogram
ECL
electrochemiluminescence
eCRF
electronic case report form
eg
exempli gratia (for example)
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
Investigator Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
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Term
Definition
ie
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal product
IND
Investigational New Drug 
IP
investigational product
IRB
Institutional Review Board
IU
International Unit
IUD
intrauterine device
IV
intravenous
L
liter
mg
milligram
mL
milliliter
mm Hg
millimeters of mercury
ng
nanogram
NHV
normal healthy volunteer
OTC
over the counter
PK
pharmacokinetic(s)
SAE
serious adverse event
TB
tuberculosis
T-HALF
half-life
Tmax
time of maximum observed serum concentration
ULN
upper limit of normal
Vss
volume of distribution at steady state
WOCBP
women of childbearing potential
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12.
REFERENCES
1
Horslen S, Barr ML, Christensen LL et al. Pediatric transplantation in the United States, 
1996-2005. Am J Transplant. 2007;7:1339-58.
2
Dharnidharka VR. Pediatric kidney transplantation literature review 2006. Pediatr 
Transplantation. 2007;11(4):354-65.
3
Nulojix (belatacept) [package insert]. Bristol-Myers Squibb Company (NJ); 2014 [cited 2015 
Jun 12]. Available from: http://packageinserts.bms.com/pi/pi_nulojix.pdf. 
4
Population pharmacokinetics and exposure-response analysis of belatacept (BMS-224818) in 
renal transplant patients. Bristol-Myers Squibb Company; 2009. Document Control No. 
930033188.
5
Belatacept Investigator Brochure, Version 18. Bristol-Myers Squibb Research and 
Development Company; 2015. BMS Document Control No. 930001192.
6
Department of Health and Human Services, Food and Drug Administration (US). Guidance 
for industry: Clinical pharmacology data to support a demonstration of biosimilarity for a 
reference product. May 2014.
7
American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th 
ed., text rev). Washington, DC: 2000.
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APPENDIX 1
DIAGNOSTIC CRITERIA FOR DRUGS AND ALCOHOL ABUSE
The following is taken from DSM-IV:
Diagnostic Criteria for Psychoactive Substance Dependence
A maladaptive pattern of substance use, leading to clinically significant impairment or distress as 
manifested by three (or more) of the following, occurring at any time in the same 12-month 
period:
1. Tolerance, as defined by either of the following:
a) A need for markedly increased amounts of the substance to achieve intoxication or 
desired effect,
b) Markedly diminished effect with continued use of the same amount of the substance.
2. Withdrawal, as manifested by either of the following:
a) The characteristic withdrawal syndrome for the substance,
b) The same (or closely related) substance is taken to relieve or avoid withdrawal 
symptoms.
3. The substance is often taken in larger amounts or over a longer period than was intended.
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.
5. A great deal of time is spent in activities necessary to obtain the substance (eg, visiting 
multiple doctors or driving long distances), use the substance (eg, chain-smoking) or recover 
from its effects.
6. Important social, occupational or recreational activities are given up or reduced because of 
substance use.
7. The substance use is continued despite knowledge of having a persistent or recurring 
physical or psychological problem that is likely to have been caused or exacerbated by the 
substance (e.g., current cocaine use despite recognition of cocaine-induce depression, or 
continued drinking despite recognition that an ulcer was made worse by alcohol 
consumption).
Criteria for Severity of Psychoactive Substance Dependence:
Mild: Few, if any, symptoms in excess of those required to make the diagnosis, and the 
symptoms result in no more than mild impairment in occupational functioning or in usual social 
activities or relationships with others.
Moderate: Symptoms or functional impairment between “mild” and “severe”.
Severe: Many symptoms in excess of those required to make the diagnosis, and the symptoms 
markedly interfere with occupational functioning or with usual social activities or relationships 
with others.
In Partial Remission: During the past six months, some use of the substance and some symptoms 
of dependence.
In Full Remission: During the past six months, either no use of the substance, or use of the 
substance and no symptoms of dependence.
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Diagnostic Criteria for Psychoactive Substance Abuse
A.
maladaptive pattern of psychoactive substance use, leading to clinically significant 
impairment or distress as manifested by one (or more) of the following, occurring at any 
time in the same 12-month period:
1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, 
school, or home (e.g., repeated absences or poor work performance related to substance 
use; substance-related absences, suspensions, or expulsions from school, neglect of 
children or household).
2. Recurrent substance use in situations in which it is physically hazardous (eg, driving an 
automobile or operating a machine when impaired by substance use).
3. Recurrent substance-related legal problems (eg, arrests for substance-related disorderly 
conduct).
4. Continued substance use despite having persistent or recurrent social or interpersonal 
problems caused or exacerbated by the effects of the substance (eg, arguments with 
spouse about consequences of intoxication, physical fights).
B.
The symptoms have never met the criteria for substance dependence for this class of 
substance
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