Clinical trial NCT02213068
Conditions: Transplant; Failure, Kidney EBV
Keywords: Kidney Renal Transplant EBV Immunosuppressants Belatacept
Sponsor: Lorenzo Gallon
Start date: 2014-07-01; Completion date: 2020-09-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is being done to investigate the impact of changing immunosuppressive medications from tacrolimus (Prograf®) to belatacept (Nulojix®) between three (3) and six (6) months after kidney transplantation. The immune system is the body's defense against infection and other disease. After transplantation, the body sees the new organ as "foreign" and tries to destroy or "reject" it. Immunosuppressive medications help to prevent the immune system from attacking the transplanted organ. The primary purpose of this research study is to evaluate the effects of three (3) different immunosuppressive treatments on rejection in post-transplant kidney recipients. This study will test whether switching from tacrolimus to belatacept will improve long-term kidney function.

Three of the immunosuppressants used in this study- mycophenolic acid (MPA), mycophenolate mofetil (MMF) and tacrolimus- are medications approved by the United States Food and Drug Administration (FDA) to be used after transplant. All of these medications have been routinely used in kidney recipients here at Northwestern University.

Belatacept (the "study drug") has been approved by the FDA for use at the time of transplant. However, the use of belatacept in this study is considered investigational as it has not been FDA approved for use beginning at 3 months after transplant.

This study will involve 51 adult kidney transplant recipients at Northwestern.

Detailed description:
Immunosuppressive therapy with the calcineurin inhibitors (CNI) cyclosporine (CsA) and Tacrolimus (Tac), have radically changed the field of organ transplantation. Ironically, although extensively and effectively used for kidney transplantation and other solid organ transplants, CsA and Tac cause important adverse renal side effects: acute and chronic renal dysfunction, hemolytic-uremic syndrome, hypertension, electrolyte disturbances and tubular acidosis. Chronic nephrotoxicity from CNI has been implicated as a principal cause of post-transplant renal dysfunction and it is characterized by an irreversible and progressive tubular atrophy, interstitial fibrosis, and focal hyalinosis of small renal arteries and arterioles. Attempts to minimize CNIs and their known toxicities have been marginally successful due to unacceptable rates of acute rejection and drug toxicity. Patients are converted to alternative immunosuppressive therapy related to CNI side effects including neurotoxicity, nephrotoxicity, cardiovascular (HTN, hyperlipidemia), metabolic (NODAT), and cosmetic side effects. Furthermore, this class of medications is associated also, by blocking Interleukin 2 (IL2) production, with negative impact on regulatory T cells (Tregs) generation (an important subpopulation of T helper cells that has been associated with positive immunomodulation and donor specific hypo-responsiveness).

Until the approval of Belatacept for adult EBV+ renal transplant recipients, there have been limited alternative immunosuppressive agents available to mitigate drug induced renal impairment. The phase III drug trials of Belatacept in combination with MMF and corticosteroids have resulted in significant and sustained improvement in glomerular filtration rate (GFR) at one year through three years post transplant. The overall safety of belatacept compared to cyclosporine in de novo transplant recipients was similar. However, there was an increased rate and severity of early acute rejection and post-transplant lymphoproliferative disorder (PTLD) of the central nervous system in patients treated with belatacept.

In a phase II switch study conducted by Bristol Myers Squibb (BMS), the incidence of acute rejection at 24 months post conversion was similar in patients remaining on CNI (4%) compared to those converted to belatacept (7%). There were no reported cases of post-transplant lymphoproliferative disorder (PTLD) in this patient population as of two years post randomization. However, one belatacept patient from Mexico developed tuberculosis and there were more non-serious fungal infections in the belatacept treated patients.

Mechanistically, CD28 (Cluster of Differentiation 28) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) are important for the function of regulatory T cells (Tregs). Belatacept binds to CD80/CD86 (Cluster of Differentiation 80/Cluster of Differentiation 86) ligands on antigen presenting cells (APCs) preventing CD28 to bind with these ligands and deliver the costimulatory signal to activate the T Cell. CTLA-4 is a related receptor expressed on activated T cells that also recognizes CD80/CD86 (Cluster of Differentiation 80/Cluster of Differentiation 86) and is thus termed co-inhibitory. It transmits both cell intrinsic and cell extrinsic negative signals that impair activation.

Investigation of the effect of early conversion to Belatacept at month 3 post-transplant on the subpopulations of T cells and B cells and peripheral blood and allograft biopsy-derived gene expression subpopulation profiles are planned. Optimization of the Belatacept immunosuppressive regimen to achieve good long term renal function and improved graft survival requires understanding the relationships of these cell populations to clinical outcomes.

Arms: arm 1: subjects continue MPA per SOC, receive bimonthly infusions of belatacept while gradually reducing and then discontinuing tacrolimus:

Belatacept: 5 mg/kg IV on Day 1, 15, 29, 43, and 57 post-conversion, then monthly thereafter.

Tacrolimus tapered over one month as follows:

Days 1- 14: SOC administration Day 15 (\~ 2 weeks into study): 40-60% of the previous dose Day 21 (\~ 3 weeks into study): 20-30% of the previous dose Day 30 (about 1 month): discontinue

MPA: administered according to SOC arm 2: Belatacept: 5 mg/kg IV on Day 1, 15, 29, 43, and 57 post-conversion, then monthly thereafter.

Tacrolimus tapered over one month as follows:

Days 1- 14: SOC administration Day 15 (\~ 2 weeks into study): 10% of the previous dose Day 21 (\~ 3 weeks into study): 20% of the previous dose Day 30 (\~ 1 month into study): 20% of the previous dose Target trough level ≤ 5 mg per ml of tacrolimus thereafter. arm 3: Standard of Care treatment regimen:

Tacrolimus: administered orally twice daily (BID) The total initial dose of Tacrolimus is given at 0.1 mg/kg in two divided doses to achieve a stable 12-hour trough level of 8 - 12 ng/mL on Days 1 through 30, with dose reduction to achieve a 12-hour trough target of 5 - 10 ng/mL thereafter.

MPA: dosed orally per package insert beginning on the day of transplantation. Methylprednisolone as sodium succinate is administered as 500 mg IV, 250 mg IV, 125 mg IV, on Days 0, 1, and 2 without corticosteroid taper.

MPA dose adjustments for gastrointestinal side effects or leukopenia will be made at the discretion of the investigator.
Interventions: intervention 1: belatacept intervention 2: Tacrolimus intervention 3: MPA
Intervention descriptions: intervention 1: Please reference Arm description for belatacept + MPA and Arm description for Arm belatacept + Low-Dose Tac for details on this intervention intervention 2: Please see Arm Descriptions for both Standard of Care Arm Tacrolimus + MPA standard treatment regimen and belatacept + Low-Dose Tac for details on this intervention intervention 3: Please see Arm Descriptions for both Standard of Care Arm Tacrolimus + MPA standard treatment regimen and belatacept + MPA for details on this intervention

Protocol documents:
Prot_SAP_000.pdf: 
Gallon Belatacept IND STU00085274 
Version Date 12/20/19 
Page 1 of 22 
RANDOMIZED CONVERSION OF EBV+ KIDNEY TRANSPLANT 
RECIPIENTS OF LIVING OR STANDARD CRITERIA DONORS AT THREE 
MONTHS POST TRANSPLANTATION TO BELATACEPT WITH MPA OR 
BELATACEPT WITH LOW-DOSE TACROLIMUS (50% OF DOSE) 
COMPARED TO PATIENTS REMAINING ON CENTER SPECIFIC 
STANDARD THERAPY OF TACROLIMUS AND MPA 
 
 
 
 
Prepared by 
Lorenzo Gallon, MD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Northwestern University 
Feinberg School of Medicine 
Division of Organ Transplantation 
 
RANDOMIZED CONVERSION OF EBV+ KIDNEY TRANSPLANT 
RECIPIENTS OF LIVING OR STANDARD CRITERIA DONORS AT THREE 
MONTHS POST TRANSPLANTATION TO BELATACEPT WITH MPA OR 
BELATACEPT WITH LOW-DOSE TACROLIMUS (50% OF DOSE) 
COMPARED TO PATIENTS REMAINING ON CENTER SPECIFIC 
STANDARD THERAPY OF TACROLIMUS AND MPA 
 
 
Principal Investigator: 
 
 
 
 
 
 
 
 
 
 
Sub-Investigator: 
Lorenzo Gallon, MD 
Professor of Medicine 
Northwestern, University, Feinberg School of Medicine 
Nephrology Division 
Division of Organ Transplantation 
The Comprehensive Transplant Center 
676 N. St. Clair Street, Suite 1900 
Chicago, IL 60611 
(312) 695-4457 
l-gallon@northwestern.edu 
 
Joseph Leventhal, MD, PhD 
Associate Professor of Surgery 
Director, Kidney and Pancreas Transplantation 
Northwestern University, Feinberg School of Medicine 
Department of Surgery 
Division of Organ Transplantation 
The Comprehensive Transplant Center  
676 North St. Clair, Suite 1900 
Chicago, IL 60611 
312.695.9019(t) 
jleventh@nmh.org 
 
Funding: 
Bristol-Myers Squibb 
777 Scudders Mill Road, Mailstop P11-to 
Plainsboro, NJ 08536 
 
Study Product: 
IND Number:                                        
Belatacept/Nulojix 
 
122155 Nulojix 
 
Date: 
12/20/2019  


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CONFIDENTIAL 
 
This document is confidential and the property of the Division of Organ 
Transplantation- Feinberg School of Medicine.  No part of it may be transmitted, 
reproduced, published, or used by other persons without prior written 
authorization from the study sponsor. 
 
 


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Hypothesis  
Belatacept-based immunosuppressive therapy will result in improved renal function at 1 
year post transplant compared to the combination of tacrolimus & MPA in living donor 
or deceased donor kidney transplant recipients.  
 
Background and Rationale 
Immunosuppressive therapy with the calcineurin inhibitors (CNI) cyclosporine (CsA) and 
Tacrolimus (Tac), have radically changed the field of organ transplantation. Ironically, 
although extensively and effectively used for kidney transplantation and other solid organ 
transplants, CsA and Tac cause important adverse renal side effects: acute and chronic 
renal dysfunction, hemolytic-uremic syndrome, hypertension, electrolyte disturbances 
and tubular acidosis. Chronic nephrotoxicity from CNI has been implicated as a principal 
cause of post-transplant renal dysfunction and it is characterized by an irreversible and 
progressive tubular atrophy, interstitial fibrosis, and focal hyalinosis of small renal 
arteries and arterioles. Attempts to minimize CNIs and their known toxicities have been 
marginally successful due to unacceptable rates of acute rejection and drug toxicity.  
Patients are converted to alternative immunosuppressive therapy related to CNI side 
effects including neurotoxicity, nephrotoxicity, cardiovascular (HTN, hyperlipidemia), 
metabolic (NODAT), and cosmetic side effects.  Furthermore, this class of medications is 
associated also, by blocking IL2 production, with negative impact on regulatory T cells 
(Tregs) generation (an important subpopulation of T helper cells that has been associated 
with positive immunomodulation and donor specific hypo-responsiveness). 
 
Until the approval of Belatacept for adult EBV+ renal transplant recipients, there have 
been limited alternative immunosuppressive agents available to mitigate drug induced 
renal impairment.  The phase III drug trials of Belatacept in combination with MMF and 
corticosteroids have resulted in significant and sustained improvement in GFR at one 
year through three years post transplant.   The overall safety of belatacept compared to 
cyclosporine in de novo transplant recipients was similar. However, there was an 
increased rate and severity of early acute rejection and PTLD of the central nervous 
system in patients treated with belatacept. 
 
In a phase II switch study conducted by BMS, the incidence of acute rejection at 24 
months post conversion was similar in patients remaining on CNI (4%) compared to 
those converted to belatacept (7%).  There were no reported cases of PTLD in this patient 
population as of two years post randomization.  However, one belatacept patient from 
Mexico developed tuberculosis and there were more non-serious fungal infections in the 
belatacept treated patients. 
 
Mechanistically, CD28 and CTLA-4 are important for the function of Tregs. Belatacept 
binds to CD80/CD86 ligands on antigen presenting cells (APCs) preventing CD28 to 
bind with these ligands and deliver the costimulatory signal to activate the TCell. CTLA-
4 is a related receptor expressed on activated T cells that also recognizes CD80/CD86 and 
is thus termed coinhibitory.  It transmits both cell intrinsic and cell extrinsic negative 
signals that impair activation.   
 


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Investigation of the effect of early conversion to Belatacept at month 3 post-transplant on 
the subpopulations of T cells and B cells and peripheral blood and allograft biopsy-
derived gene expression subpopulation profiles are planned. Optimization of the 
Belatacept immunosuppressive regimen to achieve good long term renal function and 
improved graft survival requires understanding the relationships of these cell populations 
to clinical outcomes.  
 
Objectives  
The aims of the study are:  
 
1. To assess the incidence of acute rejection and change in renal function by 
calculated (MDRD) GFR of adult EBV seropositive renal transplant recipients of 
living or standard criteria donors converted from Tacrolimus to Belatacept or low 
dose Tacrolimus with Belatacept at three months post-operatively compared to 
renal transplant recipients randomized to remain on standard dose Tacrolimus and 
MPA for maintenance therapy at 1 year post-transplantation 
 
2. To evaluate the impact of three different maintenance immunosuppressive 
regimens (Tacrolimus and MPA, Belatacept and MPA and Low dose Tacrolimus 
and Belatacept) on subpopulation of T cells including regulatory T cells and B 
cell subpopulations at  baseline(conversion at 3 months post-transplant), 6, 12, & 
24 months post-transplant by flow cytometry analysis 
 
3. To evaluate the impact of the maintenance immunosuppressive regimens on 
allograft immunohistopathology and allograft biopsy-derived gene expression 
profiles in subpopulations at baseline (conversion at 3 months post-transplant),12 
months and 24 months post-transplant to coincide with one year SOC biopsy   
 
4. To evaluate the impact of the maintenance immunosuppressive regimens on gene 
expression profiles in the peripheral blood subpopulations at  baseline (conversion 
at 3 months post-transplant), 6, 12, & 24 months post-transplant 
 
Primary Endpoint 
1. Change in eGFR (MDRD) at 1 year post-transplant compared to baseline at 
month 3 (conversion) 
 
Secondary Endpoints 
1. Patient and graft survival 
2. Incidence and severity of biopsy proven acute rejection  
3. Incidence of new onset post-transplant diabetes mellitus 
4. Incidence, timing and severity of bacterial, viral and fungal infections 
5. Incidence, timing and severity of malignancies 
6. Incidence of hyperlipidemia 
 
 
 


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Treatments  (Group-Specific) 
 
All subjects (N=43) will be randomized (1:1) to one of two treatment arms after 
enrollment at “Visit 1” (a standard-of-care clinic visit approximately  90 days post-
transplant): 
 
1. Conversion from Tacrolimus to Belatacept (Belatacept + MPA) CLOSED TO 
ENROLLMENT 
2. Conversion to low-dose Tacrolimus and Belatacept (Belatacept + Low-Dose Tac) 
3. Maintain standard tacrolimus regimen (Tacrolimus + MPA) 
 
Subjects will be randomly assigned to one of the two groups, according to a computer-
generated list and block randomization scheme. This method ensures a balance in sample 
size across groups over time. All possible balanced combinations of assignment within 
the block (i.e., equal number for all groups within the block) will be calculated. Blocks 
are then randomly chosen to determine the patients’ assignment into the groups. 
 
The lower limit for thee tacrolimus trough will correspond to the lowest level of 
tacrolimus detectable by the assay run at Northwestern (2 ng/ml per Northwestern’s 
transplant pharmacist). 
 
This a novel evaluation of the belatacept + tacrolimus regimen; as such, we anticipate 
that the belatecept + tacrolimus combination  administered to subjects in Group 2 will 
provide sufficient immunosuppression in comparison with those receiving standard of 
care treatment. At the time of conversion (3 months post-transplant) induction therapy 
from time-of-surgery should still have a protective immunosuppressive effect.  
 
The treatment regimens/group are described below: 
Group 1 (belatacept + MPA): subjects continue MPA per SOC, receive bimonthly 
infusions of belatacept while gradually reducing and then discontinuing tacrolimus- 
CLOSED TO ENROLLMENT- based on DSMB recommendations-please see letter 
attached  
 
Belatacept: 5 mg/kg IV on Day 1, 15, 29, 43, and 57 post-conversion, then 
monthly thereafter. 
 
Tacrolimus tapered over one month as follows: 
Days 1- 14: SOC administration 
Day 15 (~ 2 weeks into study): 40–60% of the previous dose  
Day 21 (~ 3 weeks into study): 20–30% of the previous dose  
Day 30 (about 1 month): discontinue  
 
MPA: administered according to SOC   
 


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Group 2 (belatacept + Low calcineurin inhibitors (CNI) dose): subjects discontinue 
MPA, receive bimonthly infusions of belatacept while gradually reducing to a 
lowered dose of CNI.  
 
Belatacept: 5 mg/kg IV on Day 1, 15, 29, 43, and 57 post-conversion, then 
monthly thereafter. 
 
CNI tapered over one month as follows: 
Days 1- 14: SOC administration 
Day 15 (~ 2 weeks into study): 10% of the previous dose  
Day 21 (~ 3 weeks into study): 20% of the previous dose  
Day 30 (~ 1 month into study): 20% of the previous dose Target trough level ≤ 5 
mg per ml of tacrolimus thereafter. 
 
 
Group 3: (CNI + MPA standard treatment regimen) 
 
CNI:  administered to target therapeutic levels per institutional SOC 
 
 
MPA dose adjustments for gastrointestinal side effects or leukopenia will be made at the 
discretion of the investigator.   
 
 
Sample Collection (All Groups) 
During this switch subjects will be asked to have weekly labs to monitor bone marrow 
function and kidney function (routine post-transplant blood tests). 
 
All subjects regardless of the group to which they were randomized (Group 1, Group 2, 
Group 3) will have the same types of blood, urine and tissue samples collected for 
research at the same time points as described below and in Table 1. The study is designed 
so that all sample collection (blood, urine and tissue) corresponds with standard of care 
visit time points: 
 
Visit 1: ~ 3months after transplant, time of randomization  (± 30 Days) 
1) A standard of care kidney biopsy will be performed and additional tissue sample 
will be taken for research in this study if subject has agreed to the procedure. 
2) Subjects will have 50 mL of blood taken and 20cc of urine collected as well as 
vital signs, weight, and medical history taken.  
 
Visit 2: 6 months after transplant  (± 30 Days) 
1) Blood, urine and vitals will be  collected as in Visit 1  
 
 
Visit 3: 12 months after transplant (± 45 Days) 
1) A standard of care kidney biopsy will again be performed, and a tissue sample  
will be taken for research in this study if subject has agreed to the procedure. 


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2) Blood, urine and vitals will be collected as in Visit 1. 
 
Visit 4:  24 months after transplant (± 60 Days) 
1) A standard of care kidney biopsy will be performed and additional tissue sample  
will be taken for research in this study if subject has agreed to the procedure. 
2) Blood, urine and vitals will be collected as in Visit 1. 
 
 
 
 
Table 1: Schedule of Sample Collection and Analyses (All Groups) 
 
SAMPLES AND 
INFORMATION 
COLLECTED AT 
TRANSPLANT AND 
POST-TRANSPLANT 
TIME-POINTS 
Study 
“Baseline”= 
Randomization 
at 3 Months 
Post-
transplant 
SOC visit  
6 Months 
Post -
Transplant  
12 Months 
Post 
Transplant  
 
24 months  
Post  
Transplant 
Renal Bx. (SOC)) 
X 
 
X 
X 
MDRD for eGFR (SOC) 
X 
X 
X 
X 
HLA antibodies (SOC) 
X 
 
X 
X 
Clinical Data (SOC) 
X 
X 
X 
X 
Urine Protein/creatinine 
ratio (SOC) 
X 
X 
X 
X 
Gene expression blood* 
X 
X 
X 
X 
Gene expression Biopsy* 
X 
 
X 
 
Cellular Assays for T and 
B cells.* 
X 
X 
X 
X 
Flow Cytometry* 
X 
X 
X 
X 
*Indicates monitoring and testing completed for this study’s immunobiology research. 
 
The PI and fellow transplant nephrologists will determine how standard of care blood and 
serum samples are utilized and analyzed (routine laboratory tests, tacrolimus trough 
levels, etc.) at each specific visit according to routine transplant protocols. 
  
. 
 
Primary Safety Endpoints 
The primary safety endpoints will be assessed on the adverse events (AEs) and serious 
adverse events (SAEs) that are observed throughout the trial. 
 
Treatment of Acute Renal Allograft Rejection 
Rejection will be treated at the discretion of the investigator. 
 
Initial treatment for biopsy-confirmed acute rejection for all subjects will be pulse 
corticosteroids (methylprednisolone 500 mg IV x 3 days), tapered to a dose of 20 mg 


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prednisone by day 7, unless the severity of the initial episode warrants use of anti-T-
lymphocyte antibody (OKT3 or Thymoglobulin).  Recurrent rejection will be treated with 
anti-T-lymphocyte antibody (OKT3 or Thymoglobulin). 
 
Subject Selection and Withdrawal 
The study will be conducted at Northwestern Medicine/Northwestern University and 
subjects will be recruited from the patients seen in the Division of Solid Organ 
Transplantation.  We expect that 43 recipients will be prospectively studied. The study 
will be conducted in recipients of living donor kidneys and deceased donor kidneys.  
Patients who satisfy the following inclusion/exclusion criteria will be eligible for the 
study. 
 
Sample Size and Sample Size Justification  
43 adult (18 years old or >), de novo, EBV seropositive recipients of living or standard 
criteria deceased donor renal transplants will be randomized to one of two treatment 
arms.17 subjects/arm will be randomized into Group 2 and Group 3 (Group 1 is now 
closed to enrollment at 9 subjects) to evaluate the efficacy of conversion at three months 
post-transplantation from Tacrolimus to either: 
(1) Belatacept and MPA (closed to enrollment at 9 subjects) or  
(2) low-dose Tacrolimus with Belatacept as compared with  
(3) standard-dose Tacrolimus and MPA as assessed by the following primary 
endpoint: 
 
1. Change in eGFR (MDRD) at 1 year post-transplant compared to 
baseline at month 3 (conversion) 
 
Sample size was calculated based upon a hypothetical 20% improvement in renal 
function at one year and beyond in the Belatacept + MPA group vs. standard of care 
Tacrolimus + MPA group (accounting for 10% attrition). This is based upon our 
experience in a pilot study of CNI and steroid avoidance in de novo living donor 
transplant recipients (ATC, 2012).  
 
Recipient Inclusion Criteria 
1. Adult ≥ 18 years of age 
2. Male or Female 
3. EBV seropositive 
4. Recipient of renal transplant from living or deceased donor 
 
Recipient Exclusion Criteria 
1. Recipients with EBV serostatus negative or unknown 
2. History of acute rejection (AR) within 3 months prior to randomization 
3. History of antibody mediated rejection 
4. Positive T-cell lymphocytotoxic cross match 
5. Proteinuria >1 g/day or > 0.5 g/day if diabetic in two weeks prior to 
randomization 
6. Rejection on 3 month post-transplant screening biopsy 


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7. BK nephropathy at 3months post-transplant screening biopsy 
8. Positive pregnancy test at the time of randomization in female of child bearing 
potential 
9. History of previous transplant 
10. History of positive human immunodeficiency virus test 
11. History of positive HCV infection  
12. End Stage Renal Disease (ESRD) secondary to primary FSGS (focal segmental 
glomerulonephritis) 
13. Currently participating in or has participated in an investigational drug or 
medical device study within 30 days or five drug half-lives, whichever is 
longer, prior to enrollment into this study. Patients cannot be given another 
investigational agent during the course of this study (through 24 months +/- 
60 Days). Patients may participate in another concurrent study only if that 
study is a non-interventional, observational investigation 
 
 
Donor Inclusion/Exclusion Criteria 
Any donor who provides consent and is accepted per institutional requirements as a 
donor will meet donor inclusion/exclusion criteria for purposes of this protocol. 
Subject Recruitment and Screening 
The study will be conducted at Northwestern Medicine/ Northwestern University and 
subjects will be recruited from the patients seen in the Division of Solid Organ 
Transplantation.  We expect that 43 recipient patients to be prospectively studied.  
Early Withdrawal of Subjects 
When and How to Withdraw Subjects 
Subjects may withdraw from the clinical trial at any time for any reason with no 
prejudice to their medical care.. Subjects may also be stopped in the study without their 
consent if their medical care requires they be.  Also, the Institutional Review Board (IRB) 
may stop the study at any time and all subjects will be returned to taking tacrolimus and 
followed for safety.  Subjects will be informed of why they are being stopped. 
 
Subjects non-compliant with medications and clinic follow-ups will be withdrawn from 
the study. 
 
Subjects with post-transplant complications such as malignancy infections that require 
modification or withdrawal of maintenance immunosuppression will be withdrawn from 
the study. 
 
Subjects who withdraw early will be given the option to consent to the study team 
following and recording their SOC data from EMR after they have withdrawn. 


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Data Collection and Follow-up for Withdrawn Subjects 
When subjects have been withdrawn prematurely from the study, an attempt will be made 
to collect at least survival data on these subjects throughout the protocol defined follow-
up period. Such data is important to the integrity of the final study analysis, since early 
withdrawal could possibly be related to the safety profile of the study.  If a subject 
withdraws consent to participate in the study, attempts will be made to obtain permission 
to record at least survival data during the follow-up period of the protocol. 
 
Donors 
Blood samples from donor subjects, using a separate donor ICR, will also be obtained 
during standard-of-care follow-up appointments. These donor leukocytes will be used as 
stimulator cells in studies of functional activity of recipient T-cells. These samples will 
be processed in the principal investigator’s research laboratory. 
 
We aim to obtain samples from all living donors (up to 43  from recipients who end up 
enrolling and participating in the research study. 
 
Study Drugs 
Belatacept (Nulojix) 
Belatacept will initially be infused intraveneously at a dose of 5 mg/kg over a 30 minute 
period. This medication will be given in an open label fashion, according to package 
insert recommendations. The first dose of belatacept will be given at the time of 
randomization to those patients assigned to have tacrolimus switched to belatacept. 
 
More than 1000 kidney transplant patients have received belatacept in clinical trials. 
Patients in these trials received belatacept or cyclosporine (a marketed drug for 
comparison), in addition to basiliximab, MMF and steroids to prevent transplant rejection. 
In general, patients treated with belatacept had the same overall rate of side-effects, 
including infections and cancers, as patients who received cyclosporine. In the first 36 
months of follow-up in the three clinical trials done in kidney transplant patients, the 
frequency of side-effects was similar comparing belatacept and cyclosporine. The most 
commonly reported side-effects (in ≥ 20 % of subjects) among belatacept subjects were 
urinary tract infection, diarrhea, constipation, nausea, swelling, decrease in transplanted 
kidney function, fever, cough, high blood pressure, and low white blood cells count.   
 
Other previously reported side-effects included: Low levels of phosphorus, calcium,  low 
or high levels of potassium in blood; high levels of creatinine, glucose and cholesterol;  
vomiting, abdominal pain,  operation-site complications and pain,  low red blood cells  
count, blood or protein leaks in the urine,  low blood pressure; graft dysfunction, headache, 
back pain, and trouble sleeping. Some side effects were serious and required 
hospitalization.  Some were fatal. 
 
Post-transplant lymphoproliferative disorder (PTLD), a tumor of white blood cells that can 
occur after kidney transplantation, developed more frequently in patients who received 
belatacept (14 cases out of 949; 1.5% of subjects) than those who received cyclosporine (3 
cases out of 476; 0.6%).  In addition, more than half of the PTLD cases in belatacept 


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patients involved the brain (9 cases out of 14; 65% of belatacept patient), which is a higher 
proportion than expected.  A total of 11 of 17 subjects with PTLD died; 8 out of 14 in the 
belatacept group and 3 out of 3 in the cyclosporine group.   
 
PTLD is almost always associated with the Epstein Barr virus (EBV). EBV is the same 
virus that causes infectious mononucleosis or "the kissing disease." Most patients who 
receive a transplant have been exposed to EBV in the past and have antibodies that can 
fight the virus. These patients have a lower risk of PTLD than patients who don’t have 
antibodies to EBV. The risk of developing PTLD may also increase if subject is treated 
with certain potent immune suppressing therapies or have another type of infection called 
Cytomegalovirus (CMV). 
 
Progressive multifocal leukoencephalopathy (PML), a rare, often fatal, infection of the 
brain has occurred in 1 kidney transplant recipient and it was fatal.    
 
Neurological examinations will be performed to monitor the risk of developing PTLD and 
PML. 
 
Some patients in the kidney transplant study have received belatacept for up to 5 years. In 
general, the rate of side effects decreases over time.  
 
It is unknown if these side-effects are caused by belatacept, as some of these side-effects 
were reported by patients who received cyclosporine, and all patients received other 
immunosuppressive drugs. Similarly, there may be other side effects if belatacept that are 
unknown.   
 
There is limited information available regarding the effectiveness of vaccines in non-human 
primates and humans that have been treated with belatacept. No data are available on the 
effect of therapeutic vaccinations in subjects receiving belatacept. Due to the risk of 
infection, subjects should not receive any live vaccinations during the course of the study. 
Similarly, neither the varicella (chicken pox) nor the live oral polio vaccine should be given 
to anyone living in subject’s home due to the rare risk of transmitting the infection. 
 
 
Mycophenolic Acid (MPA/MMF) (Myfortic) 
MPA will be given at a dose of between 540mg to 1080 mg PO twice daily.  The first 
dose will be given on Day 0 (day of kidney transplant surgery).  This medication will be 
given in an open label fashion.  There will not be any change in the dose of MPA at the 
time of randomization unless indicated by medical reasons (i.e. Neutropenia, GI side 
effects.)  
 
 
Common side-effects are diarrhea, vomiting, and decrease in the number of red and/or 
white blood cell. Rarely, subjects may experience gastrointestinal bleeding. Cases of 
progressive multifocal leukoencephalopathy, a rare, often fatal, infection of the brain have 
been reported in patients taking MPA. 
 


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Tacrolimus (Prograf) 
Tacrolimus will be administered  to target therapeutic TAC level per institutional SOC, 
beginning Day 1 (post-operative Day 1). The dose will be modified to achieve 12 hour 
trough concentrations of 5-10 ng/ml. This medication will be given in an open label 
fashion. The dose may be modified for Group 2 subjects to maintain trough level of ≤ 5 
ng/mL. 
 
Common side-effects are decrease in kidney function, high blood pressure, diabetes, tremor 
(shaking of a body part), headache, nausea, vomiting, diarrhea, tingling in hand or feet and 
decrease in the number of red and/or white blood cells, increase in blood potassium levels 
and decrease in blood magnesium levels. 
 
Safety and Adverse Events 
For the purpose of this clinical trial, the National Cancer Institute Common Terminology 
Criteria for Adverse Events v4.0 (CTCAE), dated June 14, 2012, will be used to grade all 
adverse events. 
Recording of Adverse Events 
At each contact with the subject, the investigator/member of investigator’s team will seek 
information on adverse events by specific questioning and, as appropriate, by 
examination.  Information on all adverse events will be recorded in the source document, 
and also in the appropriate adverse event module of the case report form (CRF).  All 
clearly related signs, symptoms, and abnormal diagnostic procedures results should 
recorded in the source document, though should be grouped under one diagnosis. 
 
All adverse events occurring during the study period must be recorded.  The clinical 
course of each event should be followed until resolution, stabilization, or until it has been 
determined that the study treatment or participation is not the cause.  Serious adverse 
events that are still ongoing at the end of the study period must be followed up to 
determine the final outcome.  Any serious adverse event that occurs after the study period 
and is considered to be possibly related to the study treatment or study participation 
should be recorded and reported immediately. 
 
 
Definitions 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or 
worsens in severity during the course of the study.  Intercurrent illnesses or injuries 
will be regarded as adverse events.  Abnormal results of diagnostic procedures are 
considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 


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Serious Adverse Event 
Adverse events are classified as serious or non-serious. A serious adverse event is 
any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are 
clearly of major clinical significance. They may jeopardize the subject, and may require 
intervention to prevent one of the other serious outcomes noted above.  For example, 
drug overdose or abuse, a seizure that did not result in in-patient hospitalization, or 
intensive treatment of bronchospasm in an emergency department would typically be 
considered serious.  
 
Collection and Reporting  
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. To prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more adverse events. 
 
If known, the diagnosis of the underlying illness or disorder should be recorded, rather 
than its individual symptoms. The following information should be captured for all AEs: 
onset, duration, intensity, seriousness, relationship to investigation product, action taken, 
and treatment required. If treatment for the event was administered, it should be recorded 
in the medical record. The investigator must supply BMS and the IRB/IEC with any 
additional information requested, notably for reported deaths of subjects.  
Serious Adverse Event Collecting and Reporting  
Following the subject’s written consent to participate in the study, all SAEs, whether 
related or not related to study drug, must be collected, including those thought to be 
associated with protocol-specified procedures. All SAEs must be collected that occur 
within 30 days discontinuation of dosing. If applicable, SAEs must be collected that relate 
to any later protocol-specified procedure (eg, a follow-up skin biopsy).  
 
The investigator should report any SAE occurring after these time periods that is believed 
to be related to study drug or protocol-specified procedure. 
An SAE report should be completed for any event where doubt exists regarding its status 
of 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 should be specified in the narrative 
section of the SAE Report Form. 
 


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All SAEs, whether related or unrelated to belatacept, and all pregnancies must be 
reported to BMS (by the investigator or designee) within 24 hours.  
All SAEs should be reported via confirmed facsimile (fax) transmission, or scanned and 
reported via electronic mail to:  
SAE Email Address: Worldwide.Safety@BMS.com 
SAE Fax Number: <<609-818-3804>> 
 
For studies conducted under an Investigator IND, any event that is both serious and 
unexpected must be reported to the Food and Drug Administration (FDA) as soon as 
possible and no later than 7 days (for a death or life-threatening event) or 15 days (for 
all other SAEs) after the investigator’s or institution’s initial receipt of the 
information. BMS will be provided with a simultaneous copy of all adverse events filed 
with the FDA. SAEs should be reported on MedWatch Form 3500A, which can be 
accessed at: http://www.accessdata.fda.gov/scripts/medwatch/. 
 
MedWatch SAE forms should be sent to the FDA at: 
MEDWATCH 
5600 Fishers Lane 
Rockville, MD 20852-9787 
Fax: 1-800-FDA-0178 (1-800-332-0178) 
http://www.accessdata.fda.gov/scripts/medwatch/ 
All SAEs should simultaneously be faxed or e-mailed to BMS at: 
Global Pharmacovigilance & Epidemiology 
Bristol-Myers Squibb Company 
Fax Number: 609-818-3804 
Email: Worldwide.safety@bms.com 
If an ongoing SAE changes in its intensity or relationship to study drug or if new 
information becomes available, a follow-up SAE report should be sent within 24 hours to 
the BMS using the same procedure used for transmitting the initial SAE report. All SAEs 
should be followed to resolution or stabilization. 
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed 
otherwise in this protocol. Any condition responsible for surgery should be documented 
as an adverse event if the condition meets the criteria for an adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported 
as an adverse event in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for a preexisting condition.  Surgery will not be reported as an 
outcome of an adverse event if the purpose of the surgery was elective or 
diagnostic and the outcome was uneventful. 


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• Hospitalization or prolonged hospitalization required to allow efficacy 
measurement for the study. 
• Hospitalization or prolonged hospitalization for therapy of the target disease of 
the study, unless it is a worsening or increase in frequency of hospital admissions 
as judged by the clinical investigator. 
 
IRB Notification by Investigator 
Reports of all serious adverse events (including follow-up information) must be 
submitted to the IRB within 10 days of the investigator’s knowledge of the event if this 
event meets UPIRSO criteria.  Copies of each report and documentation of IRB 
notification and receipt will be kept in the regulatory binder for the clinical trial.   
 
FDA Notification by Investigator 
The principal investigator shall notify the FDA and study drug manufacturer by telephone 
or by facsimile transmission of any unexpected fatal or life-threatening experience 
associated with the use of the drug within 24 hours of the investigator’s knowledge of the 
event. 
 
If a previous adverse event that was not initially deemed reportable is later found to fit 
the criteria for reporting, the principal investigator will submit the adverse event in a 
written report to the FDA and study drug manufacturer as soon as possible, but no later 
than 15 calendar days from the time the determination is made. 
 
Stopping Rules 
Subjects diagnosed with two acute renal allograft rejection episodes post conversion from 
tacrolimus to belatacept will be stopped from participating in the study and will be 
switched back to tacrolimus. Subjects may be stopped from participating in the study and 
will be switched back to tacrolimus after a single episode of acute renal allograft rejection 
when appropriate.  
 
A subject’s ongoing immunosuppressive therapy will be determined by the PI and fellow 
transplant nephrologists if that subject develops significant side effects secondary to 
belatacept such as severe thrombocytopenia (platelets count <50, 000), post-transplant 
lymphoproliferative disorder (PTLD) or  progressive multifocal leukoencephalopathy 
(PML).. 
 
Subjects developing post-transplant infections (i.e., UTI, CMV,HSV, EBV, HCV, HBV, 
HIV,PCP), that in the opinion of the investigator are detrimental to the subject and their 
participation in this research trial, will be stopped from participating in this study. 
 
Patient Authorization: This study is to be conducted according to US and international 
standards of Good Clinical Practice (FDA Title 21 part 312 and International Conference 
on Harmonization guidelines), applicable government regulations and Institutional 
research policies and procedures. 
 


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This protocol and any amendments will be submitted to the Northwestern University 
Institutional Review Board (IRB), in agreement with local legal prescriptions, for formal 
approval of the study conduct.  The decision of the IRB concerning the conduct of the study 
will be made in writing to the investigator and a copy of this decision will be provided to 
the investigator before commencement of this study.  The investigator will place a list of 
IRB members and their affiliate in the regulatory binder for the clinical trial. All subjects 
for this study will be provided with a printed consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study. This consent form will be submitted with the protocol for review 
and approval by the IRB for the study.  The formal consent of a subject, using the IRB-
approved consent form, will be obtained before the subject is submitted to any study 
procedures. This consent form will be signed by the subject and the investigator-designated 
research professional obtaining the consent.  The subject will be given a signed copy of the 
informed consent for their records. 
 
Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study. This 
safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above, as well as the construction and implementation of a site data and 
safety-monitoring plan. Medical monitoring will include a regular assessment of the 
number and type of serious adverse events. 
 
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting 
condition should be recorded as an adverse event if the frequency, intensity, or the 
character of the condition worsens during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality will be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities 
that meet the definition of an adverse event will also be recorded and documented as an 
adverse event.  
 
Post-study Adverse Event 
All unresolved adverse events should be followed by the investigator for 90 days until the 
events are resolved, the subject is lost to follow-up, or the adverse event is otherwise 
explained.  At the last scheduled visit, the investigator should instruct each subject to 
report any subsequent event(s) that the subject, or the subject’s personal physician, 
believes might reasonably be related to participation in this study.   
 
The investigator will notify the drug manufacturer, IRB, and FDA of any death or 
adverse event occurring within one year after a subject has discontinued or terminated 
study participation that may reasonably be related to this study.  The drug manufacturer, 
IRB, and FDA will also be notified if the investigator should become aware of the 


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development of cancer or of a congenital anomaly in a subsequently conceived offspring 
of a subject that has participated in this study.  
 
 
Laboratory Test Abnormalities 
All laboratory test results captured as part of the study should be recorded following 
institutional procedures. Test results that constitute SAEs should be documented and 
reported as such. 
 
The following laboratory abnormalities should be documented and reported appropriately: 
• any laboratory test result that is clinically significant or meets the definition of an 
SAE 
• any laboratory abnormality that required the subject to have study drug 
discontinued or interrupted 
• any serious laboratory abnormality that required the subject to receive specific 
corrective therapy. 
 
Overdose 
In case of over dosage, it is recommended that the patient be monitored for any signs or 
symptoms of adverse reactions, and appropriate symptomatic treatment instituted. Limited 
data suggest that plasmapheresis may accelerate removal of belatacept from systemic 
circulation. 
 
 
Potential Drug-Induced Liver Injury (DILI) 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities 
should occur prior to the reporting of a potential DILI event. All occurrences of potential 
DILIs, meeting the defined criteria, must be reported as SAEs (see Section 7.2.1 for 
reporting details). 
Potential drug induced liver injury is defined as  
1. AT (ALT or AST) elevation > 3 times upper limit of normal (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 AT elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing 
chronic or acute liver disease, or the administration of other drug(s) known to be 
hepatotoxic. 
 
Other Safety Considerations 
Any significant worsening noted during interim or final physical examinations, 
electrocardiograms, X-rays, and any other potential safety assessments, whether or not 
these procedures are required by the protocol, should also be recorded as a non-serious or 
serious AE, as appropriate, and reported accordingly. 
 


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Non-Serious Adverse Events (NSAEs) 
All adverse events that do not meet any of the criteria for serious should be regarded as 
non-serious adverse events.  
 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
 
1. A visit to the emergency room or other hospital department lasting less than 24 
hours that does not result in admission (unless considered an “important medical 
event” or a life-threatening event) 
2. Elective surgery planned before signing consent 
3. Admissions as per protocol for a planned medical/surgical procedure 
4. Routine health assessment requiring admission for baseline/trending of health 
status (eg, routine colonoscopy) 
5. Medical/surgical admission for purpose other than remedying ill health state 
that was planned before study entry. Appropriate documentation is required in 
these cases 
6. 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).  
 
Non-Serious Adverse Events (NSAEs) Collecting and Reporting 
The collection of non-serious adverse event (NSAE) information should begin at initiation 
of study drug. NSAE 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. NSAEs should be followed to resolution or stabilization, or reported as SAEs if 
they become serious. Follow-up is also required for NSAEs that cause interruption or 
discontinuation of study drug, or those that are present at the end of study treatment as 
appropriate. All identified NSAEs must be documented appropriately. 
 
Data Handling and Record Keeping 
 
Data and Statistical Plan 
Sample size calculation of 43 subjects (17 subjects in Group 2 and Group 3, 9 subjects in 
Group 1, now closed to enrollment) has been conducted based upon a hypothetical 20% 
improved renal function at one year and beyond in the Belatacept + MPA group vs. 
standard dose Tacrolimus and MPA and a hypothetical 10% improvement in renal 
function in the Low dose Tacrolimus + Belatacept vs. standard of care Tacrolimus + 
MPA group accounting for 10% attrition .  This is based upon our experience in a 
recently completed pilot study of CNI and steroid avoidance in de novo living donor 
transplant recipients where iodothalamate GFR at one year was 53.6 +/- 12.5 cc/min in 
the CNI group vs. 65.7 +/- 9.2* in the CNI avoidance cohort. The anticipated incidence 
of acute rejection will be ≤ 7% in the belatacept treatment arm as reported in the Phase II 
belatacept switch study. We expect to recruit 17 subjects per study arm (9 subjects in 
Group 1, now closed to enrollment) to acquire a total of at least 15 subjects per study arm 
at the end of the study with a power of 90% and a two-sided tests at a significance level 
of 0.05. Reducing sample size will have no impact as the two remaining groups will still 
reach original target enrollment number and Group 1, which is now closed, will be 


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analyzed with the number of patients so far enrolled  (n = 9). Based upon our transplant 
center volume of approximately 160 living donor kidney transplants per year, we 
estimate that patient accrual for the study can be completed within 18 months. Pt follow-
up in this study will be for 21 months post-conversion (24 months post-transplantation). 
 
The normality of primary endpoint will be examined and when needed, appropriate 
transformations will be applied. The primary analysis to compare the mean change in 
eGFR from month 3 to 1 year and 24 months post-transplant between the two Belatacept 
arms and the standard care arm will be performed using the mixed effects model 
accounting for the correlations among repeated measures. We will include time, baseline 
eGFR, group indicators for the treatment and control arms, and their interaction term as 
covariates. The difference between the two treatment arms and the control arm in the 
change of eGFR will be examined by estimating the regression coefficients of the 
interaction between the group indicators and time. Dunnett tests will be used for 
investigating contrasts between each of the two belatacept arms and the standard of care 
control arm. This will reduce the chance of a false positive. 
 
Secondary binary endpoints including the incidence of acute rejection will be compared 
between two Belatacept arms and standard arm using the Fisher’s exact test due to the 
sparse cells expected. Secondary continuous endpoints including maintenance 
immunosuppressive regimens on allograft immunohistopathology and allograft biopsy-
derived gene expression profiles will be analyzed by mixed effects model described 
above to detect changes at 6, 12, and 24 months post-transplant.  
 
Due to the huge number of hypothesis testings (comparisons between treatment arms, 
between peripheral blood subpopulations, and over different time points) for all the 
endpoints,  we will control the false discovery rate (FDR) to be less than 0.125 to account 
for multiple comparisons using q-values (Storey, 2002).  
 
The relationship between patient and graft survival and treatment and standard arms will 
be studied with Kaplan-Meier estimation and a log-rank test. 
 
Recognizing that missing data due to dropout over time could bias study findings, we will 
compare outcomes between study completers and non-completers. If differences suggest 
selective dropout, adjusted analyses described by Robins et al [Robins JM, Rotnitzky A, 
Zhao LP. Analysis of semiparametric regression models for repeated outcomes in the 
presence of missing data. Journal of the American Statistical Association. 1995;90:106-
21] will be applied.  
 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA).  Those regulations require a signed subject authorization informing the subject 
of the following:  
• What protected health information (PHI) will be collected from subjects in this 
study 


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• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of 
subject authorization.  For subjects that have revoked authorization to collect or use PHI, 
attempts will be made to obtain permission to collect at least vital status (i.e. that the 
subject is alive) at the end of their scheduled study period. 
 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  
Source data are contained in source documents   Examples of these original documents, 
and data records include: hospital records, clinical and office charts, laboratory notes, 
memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, 
recorded data from automated instruments, copies or transcriptions certified after 
verification as being accurate and complete, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, biopsy slides, subject files, and records kept at the 
pharmacy, at the laboratories, and at medico-technical departments involved in the 
clinical trial. The primary data collection instrument for this study will be OTTR 
electronic notes.  
 
  
 
Records Retention 
It is the investigator’s responsibility to retain study essential documents for at least 2 
years on site after the last approval of a marketing application in their country and until 
there are no pending or contemplated marketing applications in their country or at least 2 
years have elapsed since the formal discontinuation of clinical development of the 
investigational product. After two years of on-site storage, all files relating to this project 
will be sent offsite for an additional 13 years. 
 
Ethical Considerations 
This study is to be conducted according to US and international standards of Good 
Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations and Institutional research policies and 
procedures. 
 
This protocol and any amendments will be submitted to a properly constituted 
independent Institutional Review Board (IRB), (Northwestern University Institutional 
Review Board), in agreement with local legal prescriptions, for formal approval of the 
study conduct.  The decision of the IRB concerning the conduct of the study will be made 
in writing to the investigator and a copy of this decision will be provided to the 
investigator before commencement of this study.  The investigator will place a list of IRB 
members and their affiliate in the regulatory binder for the clinical trial. 
 


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All subjects for this study will be provided with a copy of the consent form describing 
this study and providing sufficient information for subjects to make an informed decision 
about their participation in this study. This consent form will be submitted with the 
protocol for review and approval by the IRB for the study.  The formal consent of a 
subject, using the IRB-approved consent form, will be obtained before the subject is 
submitted to any study procedures. This consent form will be signed by the subject and 
the investigator-designated research professional obtaining the consent.  The subject will 
be given a signed copy of the informed consent for their records. 
 
Study Finances 
This study is financed by Bristol-Myers Squibb.  
 
Conflict of Interest 
Any investigator who has a conflict of interest with the study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by Northwestern 
University) must have the conflict reviewed by a properly constituted Conflict of Interest 
Committee with a Committee- sanctioned conflict management plan prior to participation 
in this study.  All Northwestern University investigators will follow the University 
conflict of interest policy.  The investigators will sign conflict of interest document 
number ORSP-100, as per Northwestern University IRB guidelines. 
 
Subject Stipends or Payments 
Subjects will be provided with parking voucher on study related visits. 
 
Publication Plan 
Findings from this study will be presented at scientific meetings as an abstract, a poster or 
oral presentation.  The findings may also be published in peer reviewed professional 
journals.  No subjects will be identified in any manner regardless of the way the results 
are presented to the scientific community and/or public. 

ICF_001.pdf: 
Permission to Take Part in a Human Research Study 
Do not sign this consent if today’s date is later than the stated expiration date above. 
 
 
 
 
            Recipient 
Gallon Bela IND STU85274  
Recipient ICF Version Date 3-3-2020                        Page 1 of 13 
 
 
Title Of Research Study: Randomized Conversion Of EBV + Kidney Transplant 
Recipients Of Living Or Standard Criteria Donors At Three Months Post Transplantation To 
Belatacept With MPA Or Belatacept With Low-Dose Tacrolimus (50% Of Dose) Compared 
To Patients Remaining On Center Specific Standard Therapy Of Tacrolimus And MPA 
 
Investigator:  Lorenzo Gallon, MD 
 
Sponsor: Northwestern University 
Supported By: Bristol-Myers Squibb 
 
 
Financial Interest Disclosure: 
The following disclosure is made to give you an opportunity to decide if this relationship will affect 
your willingness to take part in this research study:  
 
Your doctor, who is also the person responsible for this research study, is interested in both your 
clinical care and the conduct of this research study.  You have the right to discuss this study with 
another person who is not part of the research team before making your decision whether or not to 
be in the study. 
 
 
 
 
Why am I being asked to take part in this research study? 
You are being asked to take part in this study because you received a kidney transplant. 
 
What should I know about a research study? 
• 
Someone will explain this research study to you. 
• 
Whether or not you take part is up to you. 
• 
You can choose not to take part. 
• 
You can agree to take part and later change your mind. 
• 
Your decision will not be held against you. 
• 
You can ask all the questions you want before you decide. 
 
Why is this research being done? 
This study is investigating the impact of changing your current immunosuppressant medications to 
low calcineurin inhibitors (CNI) dose (for example, tacrolimus) with belatacept (Nulojix®) between 
three (3) and six (6) months after your transplant. The main purpose of this research study is to 
evaluate the effects of two (2) different immunosuppressive treatments on the occurrence of 
rejection episodes. The immune system is your body’s defense against infection and other 
disease. After transplant, the body sees the new organ as “foreign” and tries to destroy or “reject” 
Key Information:  
The first few pages of this document include a summary of this study to help you 
decide whether or not to participate. Detailed information is provided after the 
summary. 


Permission to Take Part in a Human Research Study 
Do not sign this consent if today’s date is later than the stated expiration date above. 
 
 
 
 
            Recipient 
Gallon Bela IND STU85274  
Recipient ICF Version Date 3-3-2020                        Page 2 of 13 
 
it. Immunosuppressive medications help to prevent your immune system from attacking your 
transplanted organ.  
 
Three of the immunosuppressants used in this study- mycophenolic acid (MPA), mycophenolate 
mofetil (MMF) and tacrolimus- are medications approved by the United States Food and Drug 
Administration (FDA) to be used after transplant to prevent your body from rejecting your 
transplanted kidney. These medications are routinely used by kidney recipients here at 
Northwestern University.  
 
In addition, belatacept (the “study drug”) has been approved by the FDA for use at the time of 
transplant. However, the use of belatacept in this study is considered experimental as it has not 
been FDA approved for use beginning at 3 months after transplant.  
 
How long will the research last and what will I need to do? 
Your participation in this study will last for 21 months after the time of enrollment.  
 
As a subject in this study, you will be asked to come to Northwestern Medicine’s Transplant Clinic 
(676 North St. Clair Street, Suite #1900), Chicago, IL.  About 3 months after your surgery, you will 
be assigned to one of two  study treatment groups: 
 
• 
Belatacept Group: In this group you will receive the study drug, Belatacept, with a 
low calcineurin inhibitors (low CNI) dose 
 
• 
Standard of Care Group: In this group you will receive standard of care 
immunosuppression treatment  
 
Your group will be assigned by chance using randomization, a process similar to the flip of a coin. 
Neither you nor your study staff will select the group to which you are assigned. 
 
If you are taking the study drug, you will be asked to have weekly labs to monitor blood counts and 
kidney function.  Throughout the study, the study staff and doctor will let you know when you 
should have labs drawn.  These tests are considered standard of care for patients who change 
immunosuppression medication after transplant. 
 
Regardless of the group to which you are assigned, you will have blood (3.5 Tablespoons) urine 
(1.5 Tablespoons) collected for research at your 3, 6, 12 and 24 month visits. 
 
Optional Tissue Collection and Biopsy 
We would like to collect an additional tissue sample for research during each of your standard of 
care (SOC) biopsies: 3 months, 12 months, and 24 months post-transplant. You will be able to tell 
us if you allow for this optional added tissue collection at the end of this consent form.  
 
More detailed information about the study procedures can be found under the section What 
happens if I say “Yes, I want to be in this research”? 
 
Is there any way being in this study could be bad for me? 
Immunosuppressant Treatment: Regardless of the group you are assigned to, you will be taking 
anti-rejection medications as part of this study. An increased risk of infection is a common side 
effect of all the immunosuppressant drugs in this study. These medications are also associated 
with a slightly increased risk of cancer because the immune system plays a role in protecting the 
body against some forms of cancer. 
 


Permission to Take Part in a Human Research Study 
Do not sign this consent if today’s date is later than the stated expiration date above. 
 
 
 
 
            Recipient 
Gallon Bela IND STU85274  
Recipient ICF Version Date 3-3-2020                        Page 3 of 13 
 
Optional Tissue collection and biopsies: The most common complication of a kidney biopsy is 
bleeding. Bleeding that is serious enough can require a blood transfusion. 
 
More detailed information about the risks of this study can be found under “Is there any way 
being in this study could be bad for me? (Detailed Risks)” 
 
Will being in this study help me in any way? 
We cannot promise any benefits to you or others from your taking part in this research. However, 
possible benefits include improved long-term kidney function. In addition, taking part in this study 
may help doctors establish new standard of care immunosuppression therapies that have better 
long-term kidney results.   
 
What happens if I do not want to be in this research? 
Taking part in research is completely voluntary. You decide whether or not to participate. If you 
choose to not to take part, there will be no penalty to you or loss of benefit to which you are 
entitled.   
 
Instead of being in this research study, your choices may include treatment with other medications 
available either by prescription from your doctor or from other studies. 
 
 
 
Who can I talk to? 
If you have questions, concerns, or complaints, or think the research has hurt you, talk to 
Lorenzo Gallon, MD, the person in charge of this research study. You can call him at (312) 695-
4457. If problems arise evenings or weekends, you may call (312) 695-8900 and ask to speak to 
the kidney research coordinator on call. 
 
This research has been reviewed and approved by an Institutional Review Board (IRB). You may 
talk to them at (312) 503-9338 or irb@northwestern.edu if: 
• 
Your questions, concerns, or complaints are not being answered by the research team. 
• 
You cannot reach the research team. 
• 
You want to talk to someone besides the research team. 
• 
You have questions about your rights as a research participant. 
• 
You want to get information or provide input about this research. 
 
How many people will be studied? 
This study will involve 51 adult kidney transplant recipients at Northwestern Medicine’s Transplant 
Clinic. 
 
What happens if I say “Yes, I want to be in this research”? 
As a subject in this study, you will be asked to come to Northwestern Medicine’s Transplant Clinic 
(676 North St. Clair Street, Suite #1900), Chicago, IL. About 3 months after your surgery, you will 
be assigned to one of two study treatment groups. Your group will be assigned by chance using 
randomization, a process similar to the flip of a coin. Neither you nor your study staff will select the 
group to which you are assigned. 
Detailed Information: 
The rest of this document includes detailed information about this study (in addition to the 
information listed above). 


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The two treatment groups are described below: 
Group 
Medicatio
ns 
Belatacept 
CNI 
(calcineurin inhibitors) 
MPA/MMF* 
Belatacept 
Group 
Belatacept 
+ Low CNI 
Dose  
Loading dose: Belatacept 
given via IV every other week 
for the first 5 visits 
 
You will then continue to 
receive Belatacept IV monthly 
for 19 months 
Reduced slowly over 
the first month 
 
From Day 30 until the 
end of the study, you 
will maintain a target 
trough level ≤ 5 mg/mL 
 
Stopped at time 
of 
randomization. 
Standard 
of Care 
Group 
CNI + 
MPA/MMF 
N/A 
Given according to 
standard of care dosing 
guidelines 
Given according 
to standard of 
care dosing 
guidelines 
 
*MPA/MMF 
dose changes 
will be made for 
diarrhea or low 
white blood 
count 
 
Additional Standard of Care Labs for Belatacept Group  
Subjects in the Belatacept Group will be asked to have weekly labs to monitor blood counts and 
kidney function.  Throughout the study, the study staff and doctor will let you know when you 
should have labs drawn.  These tests are considered standard of care for patients who change 
immunosuppression medication after transplant. 
 
Study Visit Schedule for All Subjects  
Regardless of the group to which you are assigned you will have blood, urine and tissue samples 
collected for research as outlined: 
 
Time 
(Month) 
Blood Draw 
Urine 
Sample 
Biopsy 
3 
3.5 
tablespoons 
1.5 
tablespoons 
During your standard of care kidney biopsy, with your permission, 
an additional tissue sample will be collected for research 
6 
3.5 
tablespoons 
1.5 
tablespoons 
No biopsy sample 
12 
3.5 
tablespoons 
1.5 
tablespoons 
During your standard of care kidney biopsy, with your permission, 
an additional tissue sample will be collected for research 
24 
3.5 
tablespoons 
1.5 
tablespoons 
During your standard of care kidney biopsy, with your permission, 
an additional tissue sample will be collected for research 
 
Blood and Urine Collection 
We will collect and store a sample of your blood and urine from each study visit.  From your blood, 
we plan to examine the genes behind your body’s immune response (how your body recognizes 
and protects itself from germs and other things that seem foreign and unsafe). In addition, we will 


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Recipient ICF Version Date 3-3-2020                        Page 5 of 13 
 
examine your white blood cell function.  From your urine, we plan to examine proteins to see if they 
can give us new information about how well your kidneys work.  
 
Optional Tissue Collection and Biopsy 
We would like to collect an additional tissue sample for research during each of your standard of 
care (SOC) biopsies: 3 months, 12 months, and 24 months post-transplant. You will be able to tell 
us if you allow for this optional added tissue collection at the end of this consent form.  
  
End of Study Procedures 
Regardless of the group to which you are assigned, you will be scheduled for a standard of care 
clinic visit at 24 months after transplant, and this will be the last time we collect samples for this 
study.  At this time you will talk with the study physician about whether you are going to stay on the 
medicine you were taking for the study, or whether you will switch to another anti-rejection  
medication.  
 
What are my responsibilities if I take part in this research? 
If you take part in this research, you will be responsible to:  
● 
Follow the instructions of your study doctor. 
● 
Come to all your scheduled study visits and procedures. 
● 
If you see a doctor outside the research study, tell the doctor you are in a research study. 
● 
Do not change any of your other medications or start any new medications without checking 
with your study doctor and your medical practitioner. 
● 
Tell the study staff if you wish to stop being in the study. 
 
What happens if I say “Yes”, but I change my mind later? 
You can leave the research at any time; it will not be held against you. 
 
If you decide to leave the research, contact the study doctor or the study staff. You will be asked 
for further information or samples. Already collected information may not be removed from the 
research study database and will continue to be used to complete the research analysis. 
 
Choosing not to be in this study or to stop being in this study will not result in any penalty to you or 
loss of benefit to which you are entitled.  Specifically, your choice not to be in this study will not 
negatively affect your right to any present or future medical treatment. 
 
Data and samples collected and analyzed prior to when you withdraw from the study will be used. 
If you choose to withdraw and your samples and they have not yet been analyzed, you can choose 
to have your samples destroyed. If you stop being in the research, already collected data may not 
be removed from the study database. You will be asked whether the investigator can collect data 
from your routine medical care.  
 
If you agree, this data will be handled the same as research data 
 
Detailed Risks: Is there any way being in this study could be bad for me? 
Taking part in this study may involve the following risks from the study procedures: 
 
Blood Draws 
The risks of drawing blood include a bruise at the point where the blood is taken, redness and 
swelling of the vein and infection. There is a rare chance of getting dizzy or fainting. Care will be 
taken to avoid these complications. 
 


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Biopsies and the Collection of Additional Tissue Samples for Research 
When patients have kidney tissue samples taken, 3 – 4 out of 100 people have bleeding in the 
kidney (3.5% chance) and 2 – 3 out of 100 people have bleeding around the kidney (2.5% chance). 
Bleeding in or around the kidney can lead to a fall in blood pressure and rise in heart rate. One out 
of 100 people who have a transplant kidney biopsy require a blood transfusion or placement of a 
urinary catheter (1% chance). In 1 out of 1,000 people, a kidney biopsy may lead to a need for 
surgery or loss of the kidney (0.1% chance). Additional risks include pain and/or bleeding at the 
site of the biopsy, infection, discomfort, and blood-stained urine. 
 
You will receive a shot of medicine that numbs the biopsy area before the biopsy.  The risks of 
local anesthetics include infection or burning sensations around the area of the shot, and allergic 
reactions to the medication (such as a rash). You will be asked about any allergies before the 
biopsy. 
 
Risks of Belatacept (Nulojix) 
Some patients in kidney transplant studies have received belatacept for up to 13 years, and in 
general, the rate of side effects decreases over time.  About 1000 kidney transplant patients have 
received belatacept in clinical trials comparing belatacept and the approved drug cyclosporine. 
They received one drug or the other, in addition to basiliximab, MMF and steroids, to prevent 
transplant rejection.   In general, patients treated with belatacept had the same overall rates of side 
effects, including infections and cancers, as patients who received cyclosporine.  In the first 36 
months of follow-up in the three trials done in kidney transplant patients, the frequencies of side 
effects in the groups taking belatacept and cyclosporine were similar.  Some side effects were 
serious and required hospitalization. Some were fatal. 
 
 
The most commonly-reported side effects (in ≥ 20 % of subjects) among belatacept subjects were:  
• 
Urinary tract infection 
• 
Diarrhea, constipation, or nausea 
• 
Swelling 
• 
Decreased transplanted kidney function 
• 
Fever or cough 
• 
High blood pressure 
• 
Decreased white blood cell count 
 
 The following occurred in 10-20% of patients:  
• 
Infections 
• 
Low levels of phosphorous, calcium, or potassium in blood 
• 
High levels of potassium in the blood (which can cause nausea and an irregular heartbeat) 
• 
Increased creatinine, glucose and cholesterol 
• 
Vomiting with abdominal pain 
• 
Operation-site complications and pain 
• 
Decreased red blood cell counts 
• 
Blood or protein in the urine 
• 
Low blood pressure 
• 
Graft dysfunction 
• 
Headache 
• 
Back pain 
• 
Trouble sleeping 
 
PML  
Rarely, progressive multifocal leukoencephalopathy (PML) has occurred in kidney transplant 


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recipients and in patients taking belatacept as part of multi-drug immunosuppressive regimens. 
One kidney transplant recipient developed PML, an often fatal infection of the brain.   There was 
one occurrence of PML in these clinical trials.   
 
PTLD 
Post-transplant lymphoproliferative disorder (PTLD) occurs when tumors of white blood cells start 
to grow after transplantation.  PTLD developed in 14 out of 949 patients who received 
belatacept and in 3 out of 949 patients who received cyclosporine.  In addition, 9 of the PTLD 
cases in belatacept patients involved the brain, and this was a higher number than expected.  
 
PTLD is almost always linked to the Epstein - Barr virus (EBV). EBV is the same virus that causes 
infectious mononucleosis, or “the kissing disease.”  You have a higher risk of PTLD if you don’t 
have EBV antibodies. Most transplant patients have been exposed to EBV before, and have 
antibodies that can fight the virus, thus making them less likely to develop PTLD.  You are being 
approached for this study because you have been exposed EBV.     
 
Overall, it is unknown if these side effects are caused by belatacept, as some of these side effects 
were reported by patients who received cyclosporine, and all patients received other 
immunosuppressive drugs.  Similarly, there may be other side effects of belatacept that are 
unknown.  Therefore, if you experience these or any other symptoms, notify your study doctor or 
study staff as soon as possible. 
 
Risks of Tacrolimus  
Common side effects of tacrolimus include:  
• 
High blood pressure 
• 
High blood sugar and diabetes  
• 
Increased kidney function blood tests 
• 
Trembling 
• 
Headaches 
• 
Burning in the hands and/or feet and itchy skin 
• 
Increased levels of potassium, cholesterol and/or triglyceride levels in the blood 
• 
Unsteady movements or clumsiness 
• 
Thickening of the heart muscle 
• 
Trouble sleeping 
• 
Abdominal pain, diarrhea, or nausea 
• 
Infection 
Less common but more serious side effects include:  
• 
Inflammation of the lung tissue 
• 
BK nephropathy (a kind of kidney infection)  
• 
Posterior reversible encephalopathy syndrome (PRES): a combination of side effects 
including headaches, confusion, seizure, and vision problems 
• 
Progressive multifocal leukoencephalopathy (PML), a serious infection that can lead to 
disability or death.  
Risks of Mycophenolic Acid (MPA, or Myfortic®) or Mycophenolate Mofetil (MMF, or 
CellCept®) 
More common side effects include: 
• 
Infections (CMV or urinary tract infections) 
• 
Constipation, diarrhea, nausea, or vomiting 
• 
Low white blood cell count 
• 
Low red blood cell count 


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Recipient ICF Version Date 3-3-2020                        Page 8 of 13 
 
 
Genetic Information 
As part of this study, information about your genes and your immune response to the study 
medications will be taken from your blood samples. Any information that could be used to identify 
you will be kept in password-protected computers, or in files stored in locked offices to ensure that 
your personal information is only accessible to project staff. 
 
 
Unforeseen Risks: 
In addition to the risks listed above, the study drugs and procedures may have unknown side 
effects. There is always the possibility that you will have a reaction that is currently not known or 
not expected. All drugs have the risk of causing an allergic reaction that, if not treated promptly, 
could be life-threatening. It is important that you report any and all symptoms or possible reactions 
to your study doctor or nurse. You will be monitored for side effects by study staff and the study 
doctor.  Based on unforeseen risks, you could be withdrawn from the study. 
 
This study involves the use of your identifiable, personal information and there is a chance that a 
loss of confidentiality could occur. The researchers have procedures in place to lessen the 
possibility of this happening.  See the section below titled: “What happens to the information 
collected for the research?”.  
 
What do I need to know about reproductive health/sexual activity if I am in this 
study? 
The procedures in this research are known to harm a pregnancy or fetus in the following ways: 
Mycophenolic acid (MPA) and mycophenolate mofetil (MMF) are known to increase the risk of loss 
of a pregnancy and to cause congenital birth defects.   
The research may also hurt a pregnancy or fetus in ways that are unknown. These may be a minor 
inconvenience or may be so severe as to cause death. The effects of belatacept and tacrolimus on 
human sperm and eggs have not been studied and the effects on the developing fetus using these 
study drugs during pregnancy and risk of birth defects are also unknown and may be 
unforeseeable. 
 
You should not be or become pregnant, father a baby, breastfeed or donate eggs/sperm while on 
this research study. 
 
If you are sexually active, both men and women should use at least one effective means of birth 
control while participating in this research study. According to the World Health Organization and 
the United States Center for Disease Control and Prevention, the most effective forms of birth 
control include complete abstinence, surgical sterilization (both male and female), intrauterine 
devices (IUDs), and the contraceptive implant.  The next most effective forms of birth control 
include injectables, oral contraceptive pills, the contraceptive ring, or the contraceptive patch.  
Acceptable but least effective methods of birth control include male condoms (with or without 
spermicide) and female condoms. 
 
If you or your partner become pregnant while taking part in this research study or for 6 weeks after 
you complete the study, it is important that you tell the study doctor or other research team 
member immediately. You may be required to stop participation in this study; however, other 
treatment options will be discussed with you at that time if necessary. 
 
 
 


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Recipient ICF Version Date 3-3-2020                        Page 9 of 13 
 
If you or your partner [are/is] considered to be postmenopausal, you are not required to use 
contraception while taking part in this research study. Postmenopausal women rarely become 
pregnant. If you or your partner become pregnant while participating in this research study or for 6 
weeks after you complete the study, it is important that you tell the study doctor or other research 
team member immediately. You may be required to stop participation in this study; however, other 
treatment options will be discussed with you at that time if necessary. 
 
Will it cost me anything to participate in this research study? 
Taking part in this research study may lead to added costs to you. 
 
If you are assigned to the Belatacept Group, you will receive belatacept, the study drug, free of 
charge, for the duration of the study. However, the cost of the belatacept infusion procedure will be 
billed to you or to your health insurance company. 
 
There will be other tests and procedures that are part of your routine medical care that are not part 
of research: 
• 
Routine blood and urine tests  
• 
Drug levels when a immunosuppression medicine is changed   
 
You and your insurance company will be charged for the health care services that you would 
ordinarily be responsible to pay. In some cases, insurance will not pay for services ordinarily 
covered because these services were performed in a research study. You should check with your 
insurance to see what services will be covered by your insurance and what you will be responsible 
to pay. 
 
Will being in this study help me in any way?  
We cannot promise any benefits to you or others from your taking part in this research. However, 
possible benefits include improved long-term kidney function. In addition, taking part in this study 
may help doctors establish new standard of care immunosuppression therapies that have better 
long-term kidney results.   
 
 
 
What happens to the information collected for the research? 
Efforts will be made to limit the use and disclosure of your personal information, including research 
study and medical records, to people who have a need to review this information. We cannot 
promise complete secrecy. Organizations that may inspect and copy your information include the 
IRB and other representatives of this institution, Bristol-Myers Squibb and its partners and 
contractors and the US Food and Drug Administration. 
 
De-identified specimens retained after the study for future research (an optional element of this 
study),  will be stored, in the Tarry Building, 14th floor, 303 E. Chicago Avenue, Chicago, IL 60611, 
until they are used up.  
 
The sponsor, monitors, auditors, the IRB, the Northwestern University Office for Research Integrity, 
the US Office of Research Integrity (ORI), the US Office for the Protection of Human Research 
Protections (OHRP), the US Food and Drug Administration (FDA) may be granted direct access to 
your medical records to conduct and oversee the research. By signing this document, you are 
authorizing this access. We may publish the results of this research. However, we will keep your 
name and other identifying information confidential. 
 


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Recipient ICF Version Date 3-3-2020                        Page 10 of 13 
 
A description of this clinical trial will be available at http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time. 
 
Data Sharing  
De-identified data from this study may be shared with the research community at large to advance 
science and health. We will remove or code any personal information that could identify you before 
files are shared with other researchers to ensure that, by current scientific standards and known 
methods, no one will be able to identify you from the information we share. Despite these 
measures, we cannot guarantee anonymity of your personal data. 
 
Can I be removed from the research without my OK? 
The person in charge of the research study or the sponsor can remove you from the research 
study without your approval. 
 
We will tell you about any new information that may affect your health, welfare, or choice to stay in 
the research. 
 
What else do I need to know? 
 
If you become ill or get injured as a result of this study (medications, devices or procedures), you 
should seek medical treatment through your doctor or treatment center of choice. You should 
promptly tell the study doctor about any illness or injury.   
 
The hospital [university, researchers] will not pay for medical care required because of a bad 
outcome resulting from your taking part in this research study. This does not keep you from 
seeking to be paid back for care required because of a bad outcome. 
 
Travel Expenses:   
You will receive a voucher for free parking for your study visits. This voucher is only valid if you 
park in the 222 E. Huron Street Garage which is connected to the Galter Pavilion (clinics) and the 
Feinberg Pavilion (hospital) by the street overpass on the second floor. The garage is also known 
as “University Parking Garage A.”  If you park in any other garage, this parking voucher will not be 
valid and you will need to pay for your own parking. If you do not drive in for your study visits, the 
study staff will discuss other options of equal value. 
 
Genetic Information: 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it 
illegal for health insurance companies, group health plans, and most employers to discriminate 
against you based on your genetic information. This law generally will protect you in the following 
ways: 
• 
Health insurance companies and group health plans may not request your genetic 
information that we get from this research. 
• 
Health insurance companies and group health plans may not use your genetic 
information when making decisions regarding your eligibility or premiums. 
• 
Employers with 15 or more employees may not use your genetic information that we get 
from this research when making a decision to hire, promote, or fire you or when setting 
the terms of your employment. 
 
Be aware that this federal law does not protect you against genetic discrimination by companies 
that sell life insurance, disability insurance, or long-term care insurance. 
 


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            Recipient 
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Recipient ICF Version Date 3-3-2020                        Page 11 of 13 
 
 
Tissue or blood samples stored for future research 
Allowing for the storage and future testing of your tissue and blood samples will involve no cost to 
you. Your samples will be used only for research and will not be sold. The research done with your 
tissue and blood samples may lead to the development of new products in the future. No 
compensation will be given to you now or in the future for use of these samples. 
 
 
 
HIPAA Authorization 
We are committed to respect your privacy and to keep your personal information confidential.  
When choosing to take part in this study, you are giving us the permission to use your personal 
health information that includes health information in your medical records and information that can 
identify you. For example, personal health information may include your name, address, phone 
number or social security number. Your health information we may collect and use for this research 
includes: 
• 
Results of physical examinations 
• 
Medical history 
• 
Lab tests, or certain health information indicating or relating to a particular condition as well 
diaries and questionnaires 
• 
Records about study medication or drugs 
• 
Records about study devices 
• 
Genetic health information: information about your genes and your immune response to the 
study medications will be taken from your blood samples. 
• 
Records about radiological tests and results 
• 
Records about medical procedures and results 
• 
Records about microbiology tests and results 
• 
Records about pathology tests and results 
• 
Records about imaging tests and results 
 
During this study, you may be coming to a Northwestern Memorial Healthcare Corporation entity 
(for example, Northwestern Memorial Hospital, Prentice Women’s Hospital) for research 
appointments or to get clinical services, such as lab tests, needed for the study.  When that 
happens, you will be scheduled for these services through the NMHC computer system.  When a 
clinical exam or lab is done by NMHC or one of its employees for the purpose of this research 
study, that information will be kept in both NMHC’s clinical records and in the study records. 
 
The following clinical providers may give the researchers information about you:  all current and 
previous health care providers, including but not limited to the Shirley Ryan AbilityLab (SRALAB), 
Northwestern Medical Group (NMG), Northwestern Memorial Hospital (NMH), and Northwestern 
Lake Forest Hospital (NLFH). 
 
Once we have the health information listed above, we may share some of this information with the 
following offices or entities outside of Northwestern University and its clinical partners (or affiliates):  
the Northwestern University Institutional Review Board Office and Office for Research Integrity; the 
US Office of Research Integrity; the US Office for Human Research Protections; the US Food and 
Drug Administration.   
 
Any research information shared with outside entities will not contain your name, address, 
telephone or social security number or any other personal identifier unless disclosure of the 
identifier is necessary for review by such parties or is required by law or University policy [except 


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that such information may be viewed by the Study sponsor and its partners or contractors at the 
Principal Investigator’s office]. 
 
 
• 
Authorized members of the Northwestern University workforce, who may need to see 
your information, such as administrative staff members from the Office for Research, 
Office for Research Integrity and members of the Institutional Review Board. 
• 
Clinical affiliates, including but not limited to the Shirley Ryan AbilityLab (SRALAB), 
Northwestern Medical Group (NMG), Northwestern Memorial Hospital (NMH), 
Northwestern Lake Forest Hospital (NLFH), and the Ann & Robert H. Lurie Children’s 
Hospital of Chicago (Lurie Children’s).  Your participation in this clinical trial may be 
tracked in an electronic database and may be seen by investigators running other trials 
that you are enrolled in and by your healthcare providers.  
• 
Clinical affiliates, including but not limited to Northwestern Medical Group (NMG), 
Northwestern Memorial Hospital (NMH), and Northwestern Lake Forest Hospital 
(NLFH), for purposes including, but not limited to, the affiliate’s provision of care to you 
and/or the affiliate’s scheduling of appointments and/or billing activities. 
• 
Other University research centers and University contractors who are also working on 
the study, 
• 
Study monitors and auditors who make sure that the study is being done properly,  
• 
Pharmaceutical Company (“Bristol Myers Squibb”), who is a funding entity for the study, 
and that company’s contractors and partners. 
• 
Government agencies and public health authorities, such as the Food and Drug 
Administration (FDA) and the Department of Health and Human Services (DHHS). 
Those persons who get your health information may not be required by Federal privacy laws (such 
as the Privacy Rule) to protect it.  Some of those persons may be able to share your information 
with others without your separate permission. 
 
The results of this study may also be used for teaching, publications, or presentations at scientific 
meetings. If your individual results are discussed, your identity will be protected by using a study 
code number rather than your name or other identifying information.  Examples of identifying 
information include medical record number, Social Security number, and address. 
 
Unless you revoke your consent, it will not expire. 
 
Although you may revoke consent to participation in this research at any time and in any format, 
you must revoke authorization for use or disclosure of your health information in writing. To revoke 
your authorization, write to: 
 
PI’s Name: Lorenzo Gallon, MD 
Institution: Northwestern University 
 
Department:  Comprehensive Transplant Center 
Address: 676 North St. Clair Street, Suite #1900, Chicago, IL 60611 
 
You do not have to authorize the use or disclosure of your health information; however, you will not 
be allowed to take part in this research study. If you do not authorize the use or disclosure of your 
health information, it will not affect your treatment by health care providers, or the payment or 
enrollment in any health plans, or affect your eligibility for benefits. 
 
 


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Recipient ICF Version Date 3-3-2020                        Page 13 of 13 
 
Optional Elements: 
The following research activities are optional, meaning that you do not have to agree to them in 
order to participate in the research study. Please indicate your willingness to participate in these 
optional activities by placing your initials next to each activity. 
I agree 
I disagree  
_______ 
 
 
_______ 
The researcher may collect extra tissue during my routine 3-
month, 12-month and 24-month post-transplant kidney biopsy 
procedures.  
_______ 
 
 
_______ 
The researcher may contact me in the future to see whether I am 
interested in participating in other research studies by the 
Principal Investigator of this study. 
_______ 
 
 
 
 
 
_______ 
The researcher may retain any leftover blood or tissue samples 
taken during the study. These samples may be used for other 
research not related to this study. These samples will be retained 
in non-identifiable form, meaning that there will be no information 
associated with the blood or samples that will allow anyone to 
readily ascertain my identity.  
 
 
 
 
Your signature documents your permission to take part in this research. You will be provided a 
copy of this signed document. 
 
_____________________________________________________  
__________ 
Subject’s Name (printed)   
 
 
 
 
 
 
Date 
 
 
_____________________________________________________  
__________ 
Subject’s Signature  
 
 
 
 
 
 
 
Date 
 
 
_____________________________________________________  
__________ 
Name (printed) of Person Obtaining Consent 
 
 
 
 
Date 
 
 
____________________________________________________ 
 
__________ 
Signature of Person Obtaining Consent  
 
 
 
 
Date