Clinical trial NCT04046549
Conditions: Allografts Rejection; Transplant, Kidney Transplant Rejection Kidney Transplantation
Keywords: Renal allograft dysfunction Cell-mediated rejection Antibody mediated rejection Immunosuppression Acute rejection VIB4920 MEDI4920 Belatacept Thymoglobulin Methylprednisolone Corticosteroids
Sponsor: Amgen
Start date: 2019-10-30; Completion date: 2023-03-22
Enrollment: 25 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the efficacy, safety and tolerability of dual costimulation blockade with VIB4920 in combination of belatacept in adult male or female recipients of a renal allograft from a deceased, living unrelated or human leukocyte antigen (HLA) non-identical living related donor.

Detailed description:
Study with completed results acquired from Horizon in 2024.

Arms: arm 1: Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept (with Thymoglobulin and corticosteroids) and will be discharged on Day 3/4 at the discretion of the investigator. Participants will return to the study center to receive study drugs (VIB4920 and /or belatacept) weekly for 2 visits, then every 2 weeks for 5 visits, and then monthly for 9 visits for safety monitoring.
Interventions: intervention 1: Belatacept intervention 2: VIB4920 intervention 3: Thymoglobulin intervention 4: Methylprednisolone
Intervention descriptions: intervention 1: Protocol versions 1 through 4: Belatacept 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4 (timing is at investigator's discretion), and at the end of Weeks 2, 4, 8 and 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48. intervention 2: Protocol versions 1 and 2: VIB4920 1500 mg by IV infusion on post-op Days 1 and 14, and at the end of Weeks 4, 6, 8 and 10; then 1500 mg every 4 weeks from Week 12 to Week 48.

Protocol versions 3 and 4: VIB4920 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4 (timing is at investigator's discretion), Week 2, and at the end of Weeks 4, 6, 8, and 10; then 1500 mg every 4 weeks from Week 12 to Week 48. intervention 3: Protocol versions 1 and 2: Thymoglobulin 3.0 mg/kg by intravenous (IV) infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0) (1 dose).

Protocol versions 3 and 4: Thymoglobulin 1.5 mg/kg by intravenous infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4. intervention 4: Protocol versions 1 and 2: Methylprednisolone by IV infusion (500, 250, 125 and 60 mg on Days 0, 1, 2 and 3, respectively) followed by oral administration of prednisone 30 mg per day on Days 4, 5, and 6.

Protocol versions 3 and 4: Methylprednisolone by IV infusion (500, 250, 125 and 60 mg on Days 0, 1, 2 and 3, respectively) followed by oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to at least 20 mg per day on Day 8, to at least 10 mg per day on Day 15, and to at least 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.

Protocol documents:
Prot_000.pdf: 
Protocol v4.0 Final 23Jul2021 
 
VIB4920.P2.S1 
1 
 
  
 
 
 
  
 
A PHASE 2A SINGLE-ARM, PROSPECTIVE, OPEN-
LABEL PILOT STUDY TO EVALUATE THE SAFETY 
AND EFFICACY OF DUAL COSTIMULATION 
BLOCKADE WITH VIB4920 AND BELATACEPT FOR 
PROPHYLAXIS OF ALLOGRAFT REJECTION IN 
ADULTS RECEIVING A KIDNEY TRANSPLANT 
 
Sponsor Protocol Number: VIB4920.P2.S1 
 
Application Number: IND 141544 
 
Investigational Product: VIB4920 
 
Sponsor: Viela Bio, Inc.  
 
Medical Monitor: 
 
 
Contract Research Organization: CTI Clinical Trial & Consulting Services 
 
Protocol Version number: Final Protocol v4.0  
 
Date: 23 Jul 2021 
 
Protocol History: Protocol v1.0; Amendment 1, v2.0, Amendment 2 v3.0 
 
 
 
 
 
 
 
 
 
PPD


Protocol v4.0 Final 23Jul2021 
 
VIB4920.P2.S1 
2 
 
  
 
Summary of Changes 
 
 
Protocol Number: VIB4920.P2.S1 
Application Number: IND 141544 
Investigational Product: VIB4920 
Protocol Version Number: Final Protocol v4.0 
Protocol Version History: Protocol v1.0; Amendment 1, v2.0; Amendment 2, v3.0 
 
Section, Page 
Protocol v3.0 Text 
Modified Text 
Rationale for 
Change  
Synopsis, 
Methodology, Page 
11 
Subjects who are 
unwilling to comply with 
study schedule after early 
discontinuation of 
treatment should undergo 
End-of-Treatment/End-
of-Study visit at time of 
discontinuation and 
undergo complete safety 
follow up at 4, 8, and 12-
weeks after end treatment 
visit. 
Subjects who are unwilling to 
comply with study schedule 
after early discontinuation of 
treatment should undergo End-
of-Treatment/End-of-Study 
visit at time of discontinuation 
and undergo complete safety 
follow up at 4, 8, and 12-weeks 
after End-of-Treatment visit. 
Correct error in 
previous protocol 
terminology.  
Section 7.1, 
Overall Study 
Design, Page 32 
 
 
The study will be 
conducted at two centers 
in the United States in a 
total of approximately 20 
patients meeting all 
inclusion and exclusion 
criteria. 
 
The study will be conducted at 
approximately four centers in 
the United States in a total of 
approximately 20 patients 
meeting all inclusion and 
exclusion criteria.  
Update to reflect 
current number of 
sites expected to 
participate. 
Table 2, Schedule 
of Assessments  
Screening Period, 
Footnote o, Page 
37 
 
Prior and concomitant 
meds will be recorded 
from 30 days prior to 
administration of 
VIB4920 and through the 
end of the study. 
 
Prior and concomitant meds 
will be recorded from 30 days 
prior to administration of 
VIB4920 and through the end 
of the study. Medications 
administered in the 
perioperative period solely for 
the conduct of surgery, such as 
anesthesia- related 
medications, electrolytes and 
intravenous fluids, do not need 
to be collected. Any transplant 
related medications, such as 
immunosuppressive drugs, 
administered during this period 
should be collected.   
Clarify the 
concomitant 
medications that are 
to be collected and 
excluding 
perioperative, 
standard of care 
medications.  




Protocol v4.0 Final 23Jul2021 
 
VIB4920.P2.S1 
4 
 
  
 
Section, Page 
Protocol v3.0 Text 
Modified Text 
Rationale for 
Change  
administered during this period 
should be collected.   
Section 8.4.1, 
Biological 
Samples, Page 45 
If consent is withdrawn, 
any samples collected 
prior to that time may still 
be given to and used by 
the Sponsor but no new 
data or samples will be 
collected unless 
specifically required to 
monitor safety of the 
subject. 
If consent is withdrawn, any 
samples collected prior to that 
time may still be given to and 
used by the Sponsor but no 
new samples will be collected 
unless specifically required to 
monitor safety of the subject. 
Clarify data may still 
be collected from 
subjects who 
withdraw consent 
based on previously 
provided samples; 
however, no 
additional samples 
will be collected.  
Section 9.2, 
Concomitant 
Medications, Page 
49 
Prior and concomitant 
meds will be recorded 
from 30 days prior to 
administration of 
VIB4920 and through the 
end of the study. 
 
Prior and concomitant meds 
will be recorded from 30 days 
prior to administration of 
VIB4920 and through the end 
of the study. Medications 
administered in the 
perioperative period solely for 
the conduct of surgery, such as 
anesthesia- related 
medications,  electrolytes and 
intravenous fluids, do not need 
to be collected. Any transplant 
related medications, such as 
immunosuppressive drugs, 
administered during this period 
should be collected.   
Update for 
consistency with 
revisions throughout 
the protocol. 
Section 10.1.3, 
VIB4920 
Inspection, Page 50 
Refer to the Product 
Complaint section for 
further instructions 
(Section   11.1.7). 
Refer to the Product Complaint 
section for further instructions 
(Section   10.1.7). 
Correct error in the 
referenced section of 
the protocol. 
Section 10.1.7, 
Reporting Product 
Complaints, Page 
52 
 
 
 
Email:  
Productcomplaints 
@VielaBio.com  
Phone:  
+1 (240) 575-6744    
+1 (240) 329-0283    
+1 (240) 920-0066   
Mail:  Viela Bio, Inc.   
Attn: Quality Assurance 
and Compliance   
One MedImmune Way,   
Gaithersburg, MD USA 
20878
Email: 
ClinicalProductComplaints 
@horizontherapeutics.com 
 
Phone: 1-866-479-6742 
 
Update to reflect 
current product 
complaint report 
contacts.  
Section 11.1.12, 
 
, Page 58 
 
 
 will be 
 
 will be 
collected from 
 
Update for 
consistency with 
CCI
CCI
CCI
CCI














Protocol v4.0 Final 23Jul2021  
 
VIB4920.P2.S1 
11 
 
  
 
4. Patients with known immunodeficiency. 
5. Patients with medical history of confirmed venous thromboembolism, arterial thrombosis, 
coagulopathy or known platelet disorders. 
6. Patients with risk factors for venous thromboembolism or arterial thrombosis (e.g., 
immobilization or major surgery within 12 weeks before screening), prothrombotic status 
(including but not limited to congenital or inherited deficiency of antithrombin III, protein C, 
protein S, or confirmed diagnosis of antiphospholipid syndrome). 
7. Patients requiring treatment with antithrombotic drugs (clopidogrel, prasugrel, warfarin, 
others). Low-dose aspirin treatment (up to 100 mg/day) is allowed. 
8. Patients requiring long-term systemic anticoagulation after transplantation, which would 
interfere with obtaining biopsies. 
9. Patients with poor vascular access such that IV administration of the study medications may be 
compromised.  
10. Patients with any contraindication to kidney biopsy. 
11. CMV-seronegative recipients of a CMV-seropositive donor kidney, or unknown CMV 
serostatus. 
12. EBV-seronegative or with unknown EBV serostatus. 
13. Receipt of live (attenuated) vaccine within the 4 weeks before screening. 
14. Patients with high potential of graft loss due to recurrence of underlying kidney disease. 
15. Prior solid organ transplant or potential to require a concurrent organ or cell transplant.  
16. Previous treatment with belatacept. 
17. Previous treatment with CD40 or anti-CD40L agents. 
18. Use of B cell depleting therapy (e.g., rituximab), non-depleting B cell directed therapy (e.g., 
belimumab) or abatacept within 1 year prior to enrollment. 
19. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of 
enrollment, whichever is longer. 
20. At screening blood tests, any of the following: 
a. Aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN) 
b. Alanine aminotransferase (ALT) > 2.5 × ULN 
c. Alkaline phosphatase (ALP) > 2.5 × ULN 
d. Total bilirubin (TBL) > 2 × ULN 
e. Hemoglobin < 75 g/L 
f. Neutrophils < 1.5 × 109/L 
g. Platelets < 100 × 109/L 
21. Patients with severe systemic infections, current or within the 2 weeks prior to transplant 
surgery. 
22. Positive test for chronic hepatitis B infection at screening or within the last 12 months, defined 
as either (1) positive hepatitis B surface antigen [HBsAg] or (2) a positive hepatitis B core 
antibody [anti-HBc] PLUS negative hepatitis B surface antibody [anti-HBs]. Note that subjects 
with a positive anti-HBs ONLY or a positive anti-HBc PLUS positive anti-HBs AND negative 
HBsAg are eligible to enroll. 
23. Positive test for hepatitis C virus antibody at screening or within the last 12 months. 
24. Positive test for HIV antibody at screening or within the last 12 months. 
25. History of or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test (for 
recipients of living donor kidneys) at screening, unless previously treated for latent 
tuberculosis. Subjects with an indeterminate QuantiFERON®-TB Gold test result can repeat the 






Protocol v4.0 Final 23Jul2021  
 
VIB4920.P2.S1 
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Statistical methods: 
 
The primary and secondary efficacy endpoints will be analyzed descriptively by calculating the 
proportion of incidence and the corresponding 80% exact confidence interval. The safety endpoints 
will be summarized descriptively as well. The number and percentage of subjects reporting treatment 
emergent- AEs will be summarized by system organ class and preferred terms, by severity, and by 
relationship to the investigational product. The number and percentage of subjects reporting SAEs and 
AESIs will be summarized. Laboratory, vital sign, and ECG measurements, as well as their changes 
from baseline, at each visit and shift from baseline, if applicable, will be summarized descriptively. 
 


Protocol v4.0 Final 23Jul2021  
 
VIB4920.P2.S1 
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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................8 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............15 
LIST OF TABLES .....................................................................................................20 
LIST OF FIGURES ....................................................................................................20 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................21 
5. 
INTRODUCTION ......................................................................................................24 
5.1. 
Background .................................................................................................................24 
5.1.1. 
Dual co-stimulatory blockade in mice ........................................................................24 
5.1.2. 
Dual co-stimulatory blockade in NHP ........................................................................25 
5.1.3. 
Costimulatory blockade in human kidney transplantation .........................................25 
5.1.3.1. 
Blocking the CD28-CD80/86 pathway .......................................................................25 
5.1.3.2. 
Blocking the CD40-CD40L pathway .........................................................................26 
5.2. 
Safety experience ........................................................................................................27 
5.2.1. 
Belatacept ...................................................................................................................27 
5.2.2. 
VIB4920 .....................................................................................................................27 
5.2.3. 
Dual co-stimulatory blockade .....................................................................................28 
5.3. 
Rationale for the Study ...............................................................................................29 
5.4. 
Rationale for Endpoints ..............................................................................................29 
5.5. 
Rationale for Dose(s) Selected ...................................................................................29 
5.6. 
Rationale for Study Population ...................................................................................30 
6. 
STUDY HYPOTHESES AND OBJECTIVES ..........................................................30 
6.1. 
Primary Hypothesis ....................................................................................................30 
6.2. 
Secondary Hypothesis ................................................................................................30 
6.3. 
Primary Objective .......................................................................................................30 
6.4. 
Secondary Objectives .................................................................................................30 
6.5. 
Exploratory Objectives ...............................................................................................31 
7. 
INVESTIGATIONAL PLAN .....................................................................................31 
7.1. 
Overall Study Design ..................................................................................................31 
7.2. 
Number of Subjects ....................................................................................................33 
7.3. 
Treatment Assignment ................................................................................................33 


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7.4. 
Dose Adjustment Criteria ...........................................................................................33 
7.5. 
Criteria for Study Termination ...................................................................................33 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................41 
8.1. 
Subject Inclusion Criteria ...........................................................................................41 
8.2. 
Subject Exclusion Criteria ..........................................................................................41 
8.3. 
Reasons for permanent study drug discontinuation ....................................................43 
8.4. 
Withdrawal of Informed Consent for Data and Biological Samples ..........................44 
8.4.1. 
Biological Samples .....................................................................................................44 
8.4.2. 
Samples Obtained for Future Research ......................................................................45 
9. 
TREATMENT OF SUBJECTS ..................................................................................45 
9.1. 
Description of Study Drugs ........................................................................................45 
9.2. 
Concomitant Medications ...........................................................................................48 
9.3. 
Prohibited Medications ...............................................................................................48 
9.4. 
Treatment Compliance ................................................................................................48 
9.5. 
Randomization and Blinding ......................................................................................48 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................49 
10.1. 
VIB4920 .....................................................................................................................49 
10.1.1. 
VIB4920 Packaging and Labeling ..............................................................................49 
10.1.2. 
VIB4920 Storage ........................................................................................................49 
10.1.3. 
VIB4920 Inspection ....................................................................................................49 
10.1.4. 
VIB4920 Preparation ..................................................................................................49 
10.1.4.1. 
Dose Preparation Steps ...............................................................................................49 
10.1.4.2. 
Intravenous administration .........................................................................................50 
10.1.5. 
VIB4920 Accountability .............................................................................................51 
10.1.6. 
VIB4920 Handling and Disposal ................................................................................51 
10.1.7. 
Reporting Product Complaints ...................................................................................51 
10.2. 
Belatacept ...................................................................................................................51 
10.2.1. 
Supply .........................................................................................................................51 
10.2.2. 
Storage/Handling ........................................................................................................51 
10.2.3. 
Preparation for Administration ...................................................................................52 
10.3. 
Thymoglobulin ...........................................................................................................53 
10.3.1. 
Supply .........................................................................................................................53 
10.3.2. 
Storage/Handling ........................................................................................................53 


Protocol v4.0 Final 23Jul2021  
 
VIB4920.P2.S1 
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10.3.3. 
Instructions for Dilution and Administration .............................................................54 
10.3.3.1. 
Reconstitution .............................................................................................................54 
10.3.3.2. 
Dilution .......................................................................................................................54 
10.3.3.3. 
Infusion .......................................................................................................................54 
10.4. 
Corticosteroids ............................................................................................................55 
11. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................55 
11.1.1. 
Informed Consent .......................................................................................................55 
11.1.2. 
Demographic/Medical History ...................................................................................55 
11.1.3. 
Background (donor and recipient) ..............................................................................55 
11.1.4. 
Vital Signs ..................................................................................................................55 
11.1.5. 
Physical Examination .................................................................................................55 
11.1.6. 
Electrocardiogram (ECG) ...........................................................................................56 
11.1.7. 
Laboratory Assessments .............................................................................................56 
11.1.7.1 
Hematology .................................................................................................................56 
11.1.7.2 
Blood Chemistry .........................................................................................................56 
11.1.7.3 
Immunoglobulins ........................................................................................................56 
11.1.7.4. 
Coagulation Parameters ..............................................................................................56 
11.1.7.5. 
Urinalysis ....................................................................................................................57 
11.1.8. 
Viral Serology .............................................................................................................57 
11.1.9. 
Pregnancy Screen ........................................................................................................57 
11.1.10. 
Spot Urine Protein Creatinine Ratio ...........................................................................57 
11.1.11. 
Renal Function ............................................................................................................57 
11.1.12. 
 ................................................................................................57 
11.1.13. 
Pharmacokinetics ........................................................................................................57 
11.1.14. 
 ..........................................................................................................57 
11.1.15. 
Donor-specific Antibodies ..........................................................................................58 
11.1.16. 
Immunogenicity ..........................................................................................................58 
11.1.17. 
Exploratory Biomarkers ..............................................................................................58 
11.1.18. 
 ..............................................................................................58 
11.1.19. 
Estimate of Blood Volume to be Collected Per Study Visit .......................................58 
11.1.20. 
Prior & Concomitant Medications ..............................................................................59 
11.1.21. 
Cytomegalovirus Prophylaxis .....................................................................................60 
11.1.22. 
Pneumocystis jirovecii (Pneumocystis carinii) pneumonia prophylaxis ....................60 
CCI
CCI
CCI


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11.1.23. 
Prophylaxis and treatment of oral Candida ................................................................60 
11.1.24. 
Surveillance Biopsy ....................................................................................................60 
12. 
ASSESSMENT OF EFFICACY ................................................................................60 
12.1. 
Histological Grading of Acute Allograft Rejection ....................................................60 
12.2. 
Handling of Acute Rejection Episodes .......................................................................61 
12.3. 
Allograft Loss .............................................................................................................61 
13. 
ASSESSMENT OF SAFETY .....................................................................................61 
13.1. 
Delayed Graft Function ..............................................................................................62 
13.2. 
Adverse and Serious Adverse Events .........................................................................62 
13.2.1. 
Definition of Adverse Events .....................................................................................62 
13.2.1.1. 
Adverse Event (AE) ....................................................................................................62 
13.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................63 
13.2.1.3. 
Adverse Events of Special Interest (AESIs) ...............................................................63 
13.3. 
Relationship to Investigational Product ......................................................................64 
13.4. 
Relationship to Protocol Procedures ...........................................................................65 
13.5. 
Recording Adverse Events .........................................................................................65 
13.5.1. 
Assessment of Severity ...............................................................................................65 
13.5.2. 
Pregnancy ...................................................................................................................66 
13.5.3. 
Time Period for Collection of Adverse Events ...........................................................66 
13.5.4. 
Follow-up of Unresolved Adverse Events ..................................................................66 
13.6. 
Reporting Serious Adverse Events .............................................................................66 
14. 
STATISTICS ..............................................................................................................67 
14.1. 
General Considerations for Data Analysis .................................................................67 
14.1.1. 
Analysis Set ................................................................................................................67 
14.1.1.1. 
Safety analysis set .......................................................................................................67 
14.1.1.2. 
Efficacy evaluable set .................................................................................................67 
14.1.1.3. 
Pharmacokinetic analysis set ......................................................................................67 
14.1.2. 
Procedure for Accounting for Missing Data ...............................................................67 
14.2. 
Statistical Methods ......................................................................................................68 
14.2.1. 
Efficacy .......................................................................................................................68 
14.2.1.1. 
Primary Efficacy Endpoint .........................................................................................68 
14.2.1.2. 
Primary Efficacy Analysis ..........................................................................................68 
14.2.1.3. 
Secondary Efficacy Endpoints ....................................................................................68 


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14.2.1.4. 
Secondary Efficacy Analyses .....................................................................................68 
14.2.2. 
Safety ..........................................................................................................................68 
14.2.2.1. 
Safety Endpoints .........................................................................................................68 
14.2.2.2. 
Safety Analysis ...........................................................................................................69 
14.2.2.3. 
Immunogenicity ..........................................................................................................69 
14.2.3. 
Analysis of Pharmacokinetics .....................................................................................69 
14.2.4. 
Exploratory endpoints: ................................................................................................70 
14.2.5. 
Interim Analysis ..........................................................................................................70 
14.2.6. 
Sample Size and Power Considerations .....................................................................70 
15. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................70 
15.1. 
Study Monitoring ........................................................................................................70 
15.2. 
Audits and Inspections ................................................................................................71 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................72 
17. 
ETHICS ......................................................................................................................72 
17.1. 
Ethics Review .............................................................................................................72 
17.2. 
Ethical Conduct of the Study ......................................................................................72 
17.3. 
Written Informed Consent ..........................................................................................72 
18. 
DATA HANDLING AND RECORD KEEPING ......................................................73 
18.1. 
Inspection of Records .................................................................................................73 
18.2. 
Retention of Records ..................................................................................................73 
19. 
PUBLICATION POLICY ..........................................................................................73 
20. 
LIST OF REFERENCES ............................................................................................74 
APPENDICES ...............................................................................................................................77 
APPENDIX 1. 
MENT..................................................................78 
APPENDIX 2. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS 
DISEASE (NIAID) AND FOOD AND ALLERGY ANAPHYLAXIS 
NETWORK (FAAN) GUIDANCE FOR ANAPHYLAXIS DIAGNOSIS ...............79 
APPENDIX 3. AN APPROACH TO MANAGEMENT OF ANAPHYLACTIC AND 
HYPERSENSITIVITY REACTIONS .......................................................................80 
APPENDIX 4. ACTIONS REQUIRED IN CASES OF INCREASES IN LIVER 
BIOCHEMISTRY AND EVA
 .......................................81 
 ..................................................................82 


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LIST OF TABLES  
Table 1: 
Abbreviations and Specialist Terms ...........................................................................21 
Table 2:  
Schedule of Assessments - Screening Period .............................................................35 
Table 3:  
Schedule of Assessments  Treatment period (Day 0 to Week 24) ...........................37 
Table 4:  
Schedule of Assessments  Treatment period (Week 28 to Week 48) and 
Post-treatment Safety Follow-up ................................................................................39 
Table 5:  
Treatment Schedule ....................................................................................................47 
Table 6: 
Estimate of Total Blood Volume to be collected per study visit ................................59 
 
LIST OF FIGURES  
Figure 1: 
Study Design ...............................................................................................................34 




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Abbreviation or Specialist Term 
Explanation 
HLA 
Human leukocyte antigen 
HSA 
Human serum albumin 
HSV 
Herpes simplex virus 
ICF 
Informed consent form 
ICH 
International Council for Harmonization 
IV 
Intravenous 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
JCV 
JC virus  
mAb 
Monoclonal antibody 
MAD 
Multiple-ascending dose 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities  
MMF 
Mycophenolate mofetil 
mTOR Inhibitor 
Mammalian target of rapamycin  
NHP 
Non-human primates 
NS 
Sodium chloride  
NOAEL 
No observed adverse effects level 
OAE 
Other adverse event 
PBMC 
Peripheral blood mononuclear cells 
PI 
Principal Investigator 
The investigator who leads the study conduct at an 
individual study center. Every study center has a principal 
investigator. 
PK 
Pharmacokinetics  
PRA 
Panel Reactive Antibody test 
RA 
Rheumatoid arthritis  
RNA 
Ribonucleic acid 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SAD 
Single-ascending dose 
SC 
Subcutaneous  
SID 
Subject identifier  


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Abbreviation or Specialist Term 
Explanation 
SWFI 
Sterile water for injection 
TAC 
Tacrolimus 
TB 
Tuberculosis 
TBL 
Total bilirubin  
tBPAR 
Treated biopsy-proven acute rejection 
TCR  
T-cell receptor 
TEAE 
Treatment emergent adverse event 
ULN 
Upper limit of normal 
USP 
United States Pharmacopeia  
VZV 
Varicella zoster virus 


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VIB4920.P2.S1 
24 
 
  
 
5. 
INTRODUCTION  
5.1. 
Background   
Post transplantation immunosuppressive management has reduced rates of acute rejection and 
improved 1-year outcomes; however, all-cause graft failure at 5 years is still approximately 28% 
for deceased donor and 16% for living donor transplants (Wang, Skeans et al. 2016). Calcineurin 
inhibitors (CNIs) and corticosteroids, often used as maintenance immunosuppression in kidney 
transplant patients, are associated with toxicities and side effects that contribute to decreased 
renal function and increased morbidity and mortality (Naesens, Kuypers et al. 2009). These long-
term outcomes indicate a need for selective immunomodulators which may improve long-term 
patient and allograft survival by avoiding the chronic toxicities of nonselective 
immunosuppressive therapies. 
Rejection of organ allografts is mediated by interactions of both innate and adaptive immune 
systems, with T cells having a central role mainly due to their ability to recognize foreign antigen 
fragments resulting in T cell activation, clonal expansion, differentiation into effector cells, and 
destruction of the transplanted organ. Another important mechanism is T cell-dependent B cell 
activation and differentiation that leads to production of alloantibodies and alloantibody 
mediated rejection. For optimal activation, T cells require simultaneous engagement of the high-
affinity antigen-specific T-cell receptor (TCR) and signaling through costimulatory molecules 
(Zhang, Pierson et al. 2015). The cluster of differentiation (CD)28-CD80/86 and CD40-CD40L 
pathways are two of the most important pathways shown to have a pivotal role in transplantation 
(Adams, Ford et al. 2016). 
Targeting CD40L for the prevention of transplant rejection has been considered since the mid-
1990s. In a landmark study, an anti-CD40L monoclonal antibody induced markedly prolonged 
survival of fully disparate murine cardiac allografts in both naive and sensitized hosts (Larsen, 
Alexander et al. 1996). Further studies confirmed a beneficial effect of anti-CD40L on graft 
survival using various rodent models: recurrence of diabetes in islet isografts in rats with 
autoimmune diabetes (Kover, Geng et al. 2000), corneal transplants in mice (Qian, Boisgerault et 
al. 2001) and limb allografts in mice (Tung, Mackinnon et al. 2003). 
A number of studies in non-human primates (NHP) have also established the utility of anti-
CD40L monoclonal antibodies in prevention of transplant rejection for kidney (Kirk, Harlan et 
al. 1997, Kirk, Burkly et al. 1999), (Preston, Xu et al. 2005), (Kanmaz, Fechner et al. 2004, 
Schuler, Bigaud et al. 2004), (Pearson, Trambley et al. 2002), skin (Elster, Xu et al. 2001) and 
(Xu, Montgomery et al. 2003), in islet transplant (Kenyon, Chatzipetrou et al. 1999, Kenyon, 
Fernandez et al. 1999) and heart transplant (Pierson, Chang et al. 1999). However, in many 
settings CD40L blockade alone was not uniformly sufficient to prevent acute or chronic 
rejection, suggesting that adjunct treatment may be required to fully control T cell 
recognition/activation. These observations led to the exploration of dual costimulatory blockade 
to prevent allograft rejection.  
5.1.1. 
Dual co-stimulatory blockade in mice  
In one of the very first publications describing the effect of dual costimulatory blockade in 
animals (Larsen, Elwood et al. 1996), mice receiving cardiac allografts were treated with 
CTLA4-Ig or anti-CD40L antibody alone or in combination. Anti-CD40L alone prolonged 


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cardiac allograft survival but only the combination of CTLA4-Ig and anti-CD40L prevented 
allograft loss during the observation period. Animals treated with the combination of CTLA4-Ig 
and anti-CD40L had no chronic vascular rejection and were histologically free of lymphocytic 
infiltration, fibrosis and had no coronary arterial intimal lesions. No adverse events (AEs) were 
reported with the dual costimulatory blockade in this study (Larsen, Elwood et al. 1996). In a 
similar murine cardiac allograft model, (Shirasugi, Adams et al. 2002) dual costimulatory 
blockade with CTLA4-Ig and anti-CD40L resulted in long-term acceptance of cardiac allografts. 
No AEs were reported other than the transplant rejection. 
5.1.2. 
Dual co-stimulatory blockade in NHP  
Dual co-stimulatory blockade with CTLA4-Ig and anti-CD40 ligand has been tested in NHPs. In 
a kidney transplant model, a brief perioperative treatment of donor kidney sensitized animals 
with CTLA4-Ig or anti-CD40 ligand (5C8) alone led to rejection-free survival of 20 98 days 
compared to 5-8 days in control animals (Kirk, Harlan et al. 1997). Two animals received a 
combination regimen, one rejected at 32 days and the second at 100 days post transplantation. 
Retreatment of the latter animal with the same regimen fully reversed rejection. Extending the 
treatment period from 14 to 28-days post-transplantation extended renal allograft survival for up 
to 9 months without any further intervention (Knechtle, Kirk et al. 1999) demonstrating that the 
combination of CTLA4-Ig and anti-CD40L is more effective than either agent alone in 
preserving renal allograft survival without the need for chronic immunosuppression. 
In another study of kidney transplant in rhesus monkeys, dual costimulatory blockade with 
CTLA4-Ig and anti-CD40L or anti-CD40 improved allograft survival compared to CTLA4-Ig 
alone with the two longest allograft survivals observed in animals receiving CTLA4-Ig plus anti-
CD40L (Pearson, Trambley et al. 2002). Dual costimulatory blockade, but not CTLA4-Ig 
monotherapy, also prevented the development of donor-specific antibodies in recipient monkeys. 
5.1.3. 
Costimulatory blockade in human kidney transplantation  
5.1.3.1. 
Blocking the CD28-CD80/86 pathway  
Belatacept (Nulojix®) is a fusion protein of human IgG1 linked to the extracellular domain of 
CTLA-4 that blocks costimulation and inhibits T-cell activation. It is U.S. Food and Drug 
Administration-approved for prophylaxis of organ rejection in adult patients receiving a kidney 
transplant for use in combination with basiliximab induction, mycophenolate mofetil (MMF), 
and corticosteroids (Food and Drug Administration 2017). The pivotal phase III clinical trial 
(The Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression 
Trial [BENEFIT]) found that compared to cyclosporine, belatacept was associated with superior 
renal function and similar patient/graft survival at 1 year after kidney transplantation, despite a 
higher rate (approximately 17%) of early acute rejection (Vincenti, Charpentier et al. 2010). In 
addition to the higher rate of acute rejection, the histologic severity of the rejections appeared to 
-
term efficacy in preserving renal function compared to CNIs, the high rate of acute kidney 
rejections has limited its use.  
Early biopsy proven acute rejection (BPAR) was reduced following T cell depleting induction 
therapy followed by CNI-free and steroid-free maintenance with belatacept and sirolimus or 
everolimus. Ferguson et al compared two belatacept-based regimens (belatacept + MMF and 


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belatacept + sirolimus) to tacrolimus + MMF. All subject received Thymoglobulin (6 mg/kg) and 
a 4-day course of corticosteroids as induction therapy (Ferguson, Grinyo et al. 2011). Eighty-
nine patients were randomized and transplanted. At month 6, acute rejection occurred in 4 
patients in the belatacept-MMF, 1 in the belatacept-sirolimus group and 1 in the tacrolimus-
MMF group. Most acute rejections occurred in the first 3 months. More than two-thirds of 
patients in the belatacept groups remained on CNI- and steroid-free regimens at 12 months and 
the estimated glomerular filtration rate was 8 10 mL/min higher with either belatacept regimen 
than with tacrolimus-MMF. Overall safety was comparable between groups (Ferguson, Grinyo et 
al. 2011).  
Wojciechowski et al reported low acute rejection rate (comparable to that seen in patients 
receiving calcineurin inhibitor-based regimens) with belatacept and everolimus maintenance 
following induction with a reduced dose Thymoglobulin (3 mg/kg) regimen. Graft function 
remained excellent at 1 year (Wojciechowski, Chandran et al. 2017).  
Importantly, in both studies approximately 38% of patients receiving sirolimus or everolimus did 
not tolerate their mTOR inhibitor and had to be converted to another immunosuppressant. 
Kirk et al investigated a belatacept-based regimen without CNIs or steroids using alemtuzumab 
induction, monthly belatacept and daily sirolimus (Kirk, Guasch et al. 2014). The regimen was 
successful in preventing clinical allograft rejection; none of the 20 patients experienced BPAR, 
nor did any patient develop donor specific antibodies (DSA) within the first year. Subclinical 
rejection was detected on surveillance biopsy in the first year in 3 patients. All maintained stable 
function, remained on protocol therapy, and resolved their histological findings on subsequent 
surveillance biopsies. Ten patients elected oral immunosuppressant weaning, seven of whom 
were maintained rejection-free on monotherapy belatacept. All three patients who failed weaning 
responded to conventional treatment and achieved stable allograft function (Kirk, Guasch et al. 
2014). 
5.1.3.2. 
Blocking the CD40-CD40L pathway  
The experience with blocking the CD40-CD40L ligand pathway in human transplantation is 
limited. Preliminary results with BG9588 (hu5C8, a humanized anti-CD40L monoclonal 
antibody [mAb]) in combination with MMF in kidney transplantation showed mild, steroid-
sensitive acute rejection early in the post-transplant period in 5/7 patients, including two who 
received hu5C8 as monotherapy. These mild rejection episodes have been easily reversed with 
steroids and long-term good renal function was achieved in all patients (Kirk, Knechtle et al. 
2001). The study drug was well tolerated during the infusion but thromboembolic events in this 
study and other studies with hu5C8 in non-transplant indications led to discontinuation of hu5C8 
development. 
Recently, CFZ533 a fully human, Fc-silenced, nondepleting, IgG1 mAb against CD40 was 
compared to tacrolimus following basiliximab induction in patients receiving kidney transplants. 
Six-month interim results demonstrated comparable efficacy on the composite endpoint of 
treated biopsy-proven acute rejection, graft loss, or death (21.2 vs. 22.2%) and better renal 
function (55.8 vs. 45.5 mL/min) with CFZ533 vs. tacrolimus, respectively, with fewer infectious 
complications in the CFZ533 group (Nashan, Tedesco et al. 2018). 


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These studies demonstrate that combining belatacept with an mTOR inhibitor effectively 
prevents kidney allograft rejection without CNIs or steroids when used following T cell 
depleting induction with alemtuzumab or Thymoglobulin and that selected, immunologically 
low-risk patients can be maintained safely on once monthly intravenous (IV) belatacept. 
Experience with blocking the CD40-CD40L pathway in human kidney transplant is limited but 
early results show promising efficacy. These data together with the existing preclinical evidence 
supporting the synergistic effect of simultaneously blocking the CD28-CD80/86 and CD40-
CD40L pathways provide the scientific and clinical foundation for the rationale of combining 
belatacept and VIB4920 to prevent allograft rejection and preserve renal function without the use 
of conventional immunosuppression. 
5.2. 
Safety experience  
5.2.1. 
Belatacept  
Belatacept (Nulojix) is approved for prophylaxis of organ rejection in adult patients receiving a 
kidney transplant. The use of belatacept is contraindicated in transplant recipients who are 
Epstein-Barr virus (EBV)-seronegative or with unknown serostatus due to the increased risk of 
developing posttransplant lymphoproliferative disorders, predominantly involving the central 
nervous system. As with all immunosuppressants there is an increased risk of infections, 
including serious and opportunistic infections with belatacept. However, in clinical trials the rate 
of infections was not higher than in the control arm receiving cyclosporine (Food and Drug 
Administration 2017). In a long term, 7-year follow up of the BENEFIT study, the most common 
AEs in each of the groups were serious infections with cumulative incidence rates of 10.7% for  
belatacept, and 13.3% cyclosporine (Vincenti 2016). 
In the pivotal clinical trials belatacept was used after induction therapy with basiliximab. Recent 
exploratory studies used induction therapy with the T cell depleting agents alemtuzumab or 
Thymoglobulin, at standard (6 mg/kg) or reduced (3 mg/kg) doses. Although the studies were 
limited in size and were not designed to formally assess safety, no unanticipated toxicity was 
observed in any of these studies (Kirk, Guasch et al. 2014, Grinyo, Del Carmen Rial et al. 2017, 
Wojciechowski, Chandran et al. 2017). 
5.2.2. 
VIB4920  
Several repeat-dose studies (maximum weekly dosing duration of 6 months) and one single dose 
study were conducted in cynomolgus monkeys to evaluate the safety, pharmacokinetics, and 
pharmacodynamics of CD40L inhibition by IV or subcutaneous (SC) administration of VIB4920 
(formerly MEDI4920) or its parent molecule. The no observed adverse effect levels (NOAELs) 
for repeat-dose studies were the highest doses tested for most of the studies: 150 mg/kg weekly 
IV or SC and 300 mg/kg weekly IV for the 5-week studies; 250 mg/kg weekly SC for the 6-
month study. The NOAEL for the single-dose study was 600 mg/kg IV. Weekly IV 
administration of 150 or 300 mg/kg VIB4920 for 6 months resulted in early euthanasia of one 
animal at 150 mg/kg/dose on Day 92 associated with declining clinical condition, adverse 
clinical pathology changes, and microscopic evidence of inflammatory cell infiltrates in multiple 
tissues. In addition, one animal dosed at 300 mg/kg/dose had enlarged spleen with nodular and 
abnormal appearance at scheduled necropsy on Day 192. Microscopically, increased amounts of 
inflammatory cell infiltrates in multiple organs and tissues were present in this animal and a 


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systemic opportunistic fungal infection was detected; this was considered secondary to the 
pharmacology of VIB4920. Therefore, no NOAEL was established for IV dosing in the 6-month 
study. However, the NOAEL for the SC cohort in the 6-month study was 250 mg/kg weekly. 
The safety of VIB4920 was evaluated in single ascending dose clinical study in healthy subjects 
and in a multiple ascending dose study in patients with active rheumatoid arthritis (RA). Overall, 
VIB4920 was well tolerated with a balanced distribution of treatment-emergent adverse events 
(TEAEs) observed between placebo and the active dose groups in both studies. There were no 
infusion-related reactions, severe infections or deaths (Albulescu, Müller-Ladner et al. 2018).  
The most common TEAEs reported in the multiple-ascending dose (MAD) study in RA were 
diarrhea, hyperhidrosis, upper respiratory tract infection and urinary tract infection, each 
occurring in 3 patients (7.1%). One grade 4 serious adverse event (SAE) of encephalitis was 
reported in the 1500 mg VIB4920 dose group, occurring after 6 doses of study drug. No 
etiological infectious agent was identified, and the event was considered unrelated to VIB4920. 
Several months after discontinuing VIB4920 similar symptoms recurred and patient was 
subsequently diagnosed with metastatic melanoma of the brain. Notably, no clinically significant 
coagulation or platelet function abnormalities were observed following treatment with VIB4920 
in either study. 
Previous human studies with anti-CD40L monoclonal antibodies identified an increased risk of 
thromboembolic events linked to concurrent antibody-mediated binding to both CD40L and 
FcgRIIa on adjacent platelets resulting in thrombosis (Kawai, Andrews et al. 2000). To avoid the 
safety complications associated with mAb based targeting of CD40L, VIB4920 was developed 
by an alternate approach using a non-antibody based structure that does not contain an Fc region, 
and therefore is unlikely to induce adverse platelet responses. Accordingly, no thromboembolic 
events or clinically important abnormal platelet or coagulation parameters were noticed in any of 
the NHP or human studies with VIB4920 (see VIB4920 Investigators Brochure for additional 
details). 
5.2.3. 
Dual co-stimulatory blockade  
There is no clinical experience with dual co-stimulatory blockade in humans.  
No serious toxicity signal was reported from murine studies spanning various organ 
transplantation models. Several studies tested simultaneous blockade of the CD28-CD80/86 and 
CD40-CD40L pathways in NHP. In a kidney transplant model, the combination of CTLA4-Ig 
and anti-CD40 ligand (5C8) was well tolerated with no increase in opportunistic infections or 
lymphoproliferative diseases. One animal treated with combination costimulatory blockers 
developed shigella and campylobacter enterocolitis. This pathogen is common in rhesus 
monkeys and untreated animals from the same colony were also infected with the same 
pathogens (Kirk, Harlan et al. 1997). Importantly, neither drug affected peripheral T cell or B 
cell counts and no T cell activation or cytokine release occurred, and no clinically important 
alterations in peripheral blood were noted. Additionally, the dual costimulatory blockade did not 
alter in vitro T cell responsiveness, as they exhibited strong reaction to donor and third party 
cells but without allograft rejection (Pearson, Trambley et al. 2002, Xu, Montgomery et al. 
2003).  


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In another study of kidney transplant in rhesus monkeys, dual costimulatory blockade with 
CTLA4-Ig and anti-CD40L or anti-CD40 significantly improved allograft survival compared to 
CTLA4-Ig (Pearson, Trambley et al. 2002). In this study all three cytomegalovirus (CMV) 
negative recipients receiving kidneys from CMV positive donors developed CMV infection. One 
of these monkeys were treated with anti-CD40 monotherapy and two with the combination of 
CTLA4-Ig and anti-CD40L. None of the CMV positive recipients in any treatment group had 
CMV infection post-transplant. No other toxicity was reported from this study (Thompson, 
Cardona et al. 2011). 
5.3. 
Rationale for the Study  
This is the first evaluation of the efficacy and safety of VIB4920 + belatacept in its target 
indication: prevention of allograft rejection in solid organ transplantation. This study will allow 
to assess the potential of VIB4920 + belatacept to replace standard immunosuppression with a 
CNI, MMF and corticosteroids in terms of anti-rejection efficacy, while preserving renal 
function with an acceptable safety and tolerability profile. Results of this study will be used to 
inform the dose and regimen selection for investigation in later phases of clinical development. 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP) and 
all applicable regulatory requirements.  
5.4. 
Rationale for Endpoints   
The primary and secondary efficacy endpoints are consistent with well-established precedents by 
global health authorities for clinical development of immunosuppressive regimens in de novo 
kidney transplantation. 
5.5. 
Rationale for Dose(s) Selected   
In this study, we propose to use T cell depleting induction therapy followed by a combination of 
belatacept (blocking the CD28-CD80/86 pathway) and VIB4920 (blocking CD40 ligand). T cell 
depletion will be used to reduce the acute T cell mediated response and protect against acute 
rejection in the immediate post-transplant period. Thymoglobulin will be administered at its 
approved dosing regimen for prophylaxis of acute rejection in patients receiving a kidney 
transplant. Following induction, belatacept will be combined with VIB4920 starting on Day 1 
post-transplant to maximize the impact of dual costimulatory blockade on the alloimmune 
response against the graft. Belatacept will be administered at its approved dosing regimen. 
VIB4920 will initially be given at the highest dose and frequency used in the Phase 1b 
rheumatoid arthritis study (1500 mg IV every 2 weeks) with an additional dose administered at 
Day 3 or Day 4. The initial higher dose of VIB4920 and the additional dose at Day 3 or 4 is 
chosen because the early postoperative period in kidney transplant is characterized by a 
hyperacute inflammatory environment with upregulation of both cell-bound and soluble CD40L 
and more frequent administration of VIB4920 may be required to achieve the necessary CD40L 
blockade. In addition, administering the VIB4920 and belatacept on the same schedule 
maximizes the dual co-stimulatory blockade. Moreover, the first three months post-transplant is 
also the period when most acute rejections occurred in the belatacept studies, therefore it is 
prudent to provide higher doses during this period. After 12 weeks the dosing frequency will be 
changed to every 4 weeks. This dosing regimen is expected to provide VIB4920 concentrations 


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above IC67 during the first 12 weeks and between IC50 and IC67 between Week 12 and 48. The 
prolonged duration of clinical and biomarker responses in RA at these drug levels further support 
the less intensive administration regimen after Week 12. 
5.6. 
Rationale for Study Population   
The study population is low immunological risk adult recipients of a first kidney allograft from a 
standard criteria deceased donor, living unrelated or human leukocyte antigen (HLA) non-
identical living related donor, typical for early development studies of new immunosuppression 
regimens in kidney transplantation. 
This is a single-arm, open-label exploratory study without a concurrent control group. The 
results of this study will be interpreted in the context of efficacy results from patients in 
randomized, controlled trials treated with a Food and Drug Administration (FDA)-approved 
standard-of-care composed of tacrolimus (TAC), MMF and corticosteroids and outcomes of 
standard of care therapies in current clinical practice. Results of this study will be used to inform 
the dose and regimen selection for investigation in later phases of clinical development. 
 
6. 
STUDY HYPOTHESES AND OBJECTIVES  
6.1. 
Primary Hypothesis  
Blockade of the CD40/CD40L pathway with VIB4920, and blockade of the CD28-CD80/86 
pathway with belatacept, will prevent renal allograft rejection (treated biopsy-proven acute 
rejection (tBPAR)) without traditional maintenance immunosuppression.  
6.2. 
Secondary Hypothesis  
Dual costimulation blockade with multiple doses of VIB4920 + belatacept is well tolerated and 
has an acceptable safety profile. 
6.3. 
Primary Objective  
The primary objective is to demonstrate that when added to standard-of-care induction regimen 
that includes Thymoglobulin® (anti-thymocyte globulin [rabbit]) and corticosteroids, dual 
costimulation blockade with multiple doses of VIB4920 + belatacept, started at the time of 
kidney transplant surgery and repeated every 2-4 weeks post-transplantation, prevents composite 
efficacy failure (tBPAR of grade 1A or higher, graft loss or death) at Week 24 post-
transplantation in the majority of subjects 
 
6.4. 
Secondary Objectives  
The secondary study objectives are to:  
1. Evaluate individual components (and combinations of the individual components) of the 
composite efficacy endpoint at Weeks 12, 24 and 48 post-transplantation. 


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2. Evaluate safety and tolerability of dual costimulation blockade with VIB4920 + 
belatacept in subjects receiving a kidney transplant. 
3. Evaluate the pharmacokinetics and immunogenicity (ADA) of VIB4920. 
6.5. 
Exploratory Objectives  
The exploratory study objectives are to: 
1. Evaluate renal function at Weeks 4, 12, 24 and 48 post-transplantation using estimated 
glomerular filtration rate (eGFR) by MDRD formula (eGFRMDRD) in subjects receiving a 
kidney transplant. 
2. Understand changes in 
 and 
 in blood related 
to pharmacology of VIB4920. 
3. Evaluate the 
 of 
 on 
.  
 
7. 
INVESTIGATIONAL PLAN  
7.1. 
Overall Study Design  
This is a Phase 2a, single-arm, open-label pilot study to evaluate the efficacy, safety and 
tolerability of dual costimulation blockade with VIB4920 + belatacept in adult male or female 
recipients of a renal allograft from a deceased, living unrelated or HLA non-identical living 
related donor. The basic scheme is presented in Figure 1. 
The study will be conducted at approximately four centers in the United States in a total of 
approximately 20 patients meeting all inclusion and exclusion criteria. Eligible patients are males 
or females, aged 18-70, who are low immunologic risk candidates (no donor-specific antibodies 
and a negative cross-match testing by T- and B- cell flow or by virtual cross-match) undergoing 
a first renal transplantation from a standard criteria deceased donor, or HLA non-identical living 
related donor. 
Immunosuppression will be achieved by administration of VIB4920 + belatacept (with 
Thymoglobulin and corticosteroids) according to the following regimen: 
 
Thymoglobulin 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the 
day of transplantation surgery (Day 0) , prior to VIB4920+belatacept infusion on 
post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-
op Day 3 or 4. Adjustments in the total dose of 6 mg/kg or frequency of delivery are 
allowed for clinical cause (i.e., thrombocytopenia). Reasons for adjustments should 
be clearly stated in the medical record and appropriate case report form.   
 
Methylprednisolone by IV infusion (500, 250, 125 and 60 mg on Days 0, 1, 2 and 3, 
respectively) followed by oral administration of prednisone 30 mg per day on Days 4, 
5, 6 and 7. Subjects may be tapered to at least 20 mg per day on Day 8, to at least 10 
mg per day on Day 15, and to at least 5 mg per day on Day 22. Discontinuation of 
prednisone should occur following the post-op Day 28 visit.  
CCI
CCI
CCI
CCI
CCI


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32 
 
  
 
 
VIB4920 1500 mg by IV infusion on post-op Day 1, repeated on post-op Day 3 or 4 
s discretion), Week 2, and at the end of Weeks 4, 6, 8 and 
10; then 1500 mg every four weeks from Week 12 to Week 48. 
 
Belatacept 10 mg/kg by IV infusion on post-op Day 1, repeated on post-op Day 3 or 4 
mg/kg IV every four weeks from Week 16 to Week 48. 
Subjects with evidence of renal allograft dysfunction (rising serum creatinine not attributable to 
technical complications) and/or evidence of cell-mediated or antibody mediated rejection on 
biopsy will be treated with additional immunosuppression, as clinically indicated and according 
to standard care at each participating clinical site. Whether to continue VIB4920+belatacept will 
be determined based on the histologic grade of the rejection and the clinical response to 
immunosuppressive therapy, as defined below.   
Written informed consent and any locally required authorization (e.g., data privacy) will be 
obtained from the subject prior to performing any protocol-related procedures, including 
screening evaluations. Patients may be screened between Day -28 and Day -1 prior to 
transplantation, with eligibility reconfirmed on Day 0 prior to induction of anesthesia for 
transplant surgery and prior to administration of Thymoglobulin or methylprednisolone. Subjects 
will be admitted to the transplant center for administration of VIB4920 and belatacept, 
observation and assessment of safety/tolerability and may be discharged after administration of 
belatacept+VIB4920 on Day 3 or 4 (at the discretion of the investigator) following completion of 
all scheduled Visit 4 assessments. Subjects will return to the study center for safety monitoring 
on Day 7 and for administration of study medication(s) and safety monitoring on Week 2; then 
every 2 weeks for 5 visits (at the end of Weeks 4, 6, 8, 10 and 12), and then monthly for 9 visits 
(at the end of Weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48). All subjects will be followed on 
study through Week 48 for acute rejection, graft survival and patient survival. Subjects who 
prematurely discontinue treatment with VIB4920 and/or belatacept will undergo an End-of-
Treatment visit at time of discontinuation and follow Schedule of Assessments through Week 48 
and at least three months after last dose with VIB4920 and/or belatacept completing the study 
with End of Study visit. Subjects who are unwilling to comply with study schedule after early 
discontinuation of treatment should undergo End-of-Treatment/End-of-Study visit at time of 
discontinuation and undergo complete safety follow up at 4, 8, and 12-weeks after end treatment 
visit. Subjects who wish to prematurely discontinue study participation should be asked to 
undergo an End-of-Study visit assessment before withdrawing consent.   
A graft core biopsy must be performed within 48 hours for all cases of suspected acute rejection 
(based on the investigator's clinical judgment), regardless of initiation of anti-rejection treatment. 
Biopsies will be read by local pathologist according to Banff criteria 2017 (Haas, Loupy et al. 
2018) and will be used to guide patient management. In addition, all subjects will undergo 
surveillance renal biopsies following reperfusion of the allograft on Day 0 and again at the end of 
Week 24. 
 Subjects with mild cellular rejection (Banff Grade 1A or 1B) will be treated with 
corticosteroids and continue treatment with VIB4920 + belatacept. 
 Subjects with Banff Grade 2A lesions will be treated with corticosteroids, then re-
biopsied 
, and will continue treatment with VIB4920 + 


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33 
 
  
 
belatacept if the repeat biopsy shows resolution of acute rejection or transitioned to 
standard of care immunosuppression for persistent or worsening lesions. 
 Subjects 
discontinue treatment with VIB4920, with subsequent management at the discretion 
of the investigator.  
Following completion of all required evaluations at the Week 48 visit, subjects will be followed 
for an additional 12 weeks for safety while receiving standard of care management at the 
 
7.2. 
Number of Subjects  
Eligible patients (i.e., meeting all inclusion and exclusion criteria) will be included in the study 
until a total of 20 patients undergo the scheduled kidney transplant surgery with intention to treat 
with the revised full-dose  regimen of Thymoglobulin, extended steroids, and an additional 
dose of VIB4920 on Day 3 or 4, and receive at least one dose of VIB4920.  
7.3. 
Treatment Assignment  
This is a single-arm, open-label exploratory study. All eligible patients will be treated with the 
same VIB4920/belatacept/Thymoglobulin/corticosteroids regimen detailed in Section 9.1. 
7.4. 
Dose Adjustment Criteria  
Not applicable. 
7.5. 
Criteria for Study Termination  
Periodic reviews of all available safety data will be conducted by the Sponsor. The Sponsor 
reserves the right to temporarily suspend or permanently terminate this study at any time. The 
reasons for temporarily suspending or permanently terminating the study may include but are not 
limited to the following: 
1. The incidence or severity of AEs in this or other studies indicates a potential health 
hazard to subjects. 
2. Subject enrollment is unsatisfactory. 
3. Non-compliance that might significantly jeopardize the validity or integrity of the study. 
4. Sponsor decision to terminate development of the investigational product for this 
indication. 
A decision to terminate may also be made by health authorities, regulatory bodies, or a specific 
Institutional Review Board (IRB) or ethics committee. 
 
 


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VIB4920.P2.S1
 
 
34 
 
 
  
 
Figure 1: 
Study Design  
  
 
 
 
 
 
 
 
 
 
 
 




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36 
 
 
  
 
a Date of birth, sex, race and ethnicity.  
b The following recipient background information should be collected: end-stage renal disease leading to transplantation, current dialysis (none, hemodialysis, peritoneal dialysis) 
and dialysis start date, highest PRA, most recent PRA and HLA type. 
c The following should be collected from donors: sex, race, ethnicity, transplant donor type (living related, living unrelated, deceased heart beating, deceased non-heart beating). 
d Medical history includes all ongoing conditions and relevant/significant medical history (including all major hospitalizations and surgeries), as determined by the Investigator. 
e Screening viral serology includes: CMV, EBV, HCV, HBsAg, HIV. 
f The history of or active tuberculosis (TB) should be recorded. For recipients of living donor kidneys, a QuantiFERON®-TB Gold test should be performed at screening, unless 
previously treated for latent tuberculosis. Subjects with an indeterminate QuantiFERON®-TB Gold test result can repeat the test, but if the repeat test is also indeterminate, they 
are excluded. Other standard of care methods performed for determining the TB status (e.g., chest X-rays) are permitted. 
g Serum 
 (females of childbearing potential only). 
h Vital signs will include blood pressure, heart (pulse) rate, respiratory rate, and body temperature. 
i At screening, a symptom-directed physical examination will be completed. Abnormalities will be recorded on the medical history eCRF page. 
j The hematology panel will include a complete blood count, with differential (including basophils, eosinophils, lymphocytes, monocytes, and neutrophils), hemoglobin, 
hematocrit, platelets and white blood cell count. 
k Chemistry and renal profile will include creatinine, blood urea nitrogen, fasting glucose, total protein and electrolytes (including sodium, potassium, chloride, calcium, 
bicarbonate and phosphorus). Hepatic profile will include albumin, total bilirubin, indirect bilirubin, AST, ALT, ALP and gamma glutamyl transferase. 
l Coagulation parameters will include prothrombin time and partial thromboplastin time. 
 
 
 
o  Prior and concomitant meds will be recorded from 30 days prior to administration of VIB4920 and through the end of the study. Medications administered in the perioperative 
period solely for the conduct of surgery, such as anesthesia-related medications,  electrolytes and intravenous fluids, do not need to be collected. Any transplant related 
medications, such as immunosuppressive drugs, administered during this period should be collected.  
p All AEs that occur between written informed consent signature and the end of the safety follow-up, whether or not related to the study drug, must be recorded in the eCRF.  Note: 
allograft rejection is a primary study endpoint to be reported as a study outcome, not as an adverse event. Instances of acute rejection that meet serious criteria should be captured 
on the Suspected Acute Rejection and Kidney Allograft Biopsy eCRFs as outlined in Section 12.2. Non-serious electrolyte abnormalities requiring an intervention observed 
within 30 days of transplantation need not be recorded as adverse events. If the electrolyte abnormality or the therapeutic intervention to correct it meets criteria for a serious 
adverse event it must be reported as an SAE during the entire study. 
 
 
 
CCI










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8. 
SELECTION AND WITHDRAWAL OF SUBJECTS  
8.1. 
Subject Inclusion Criteria  
Subjects must meet all of the following criteria to be eligible for study inclusion: 
1. Written informed consent and any locally required authorization (e.g., data privacy) 
obtained from the patient prior to performing any protocol-related procedures, including 
screening evaluations. 
2. Male or female recipients aged 18-70. 
3. Recipients of a first renal transplant from a standard criteria deceased, living unrelated or 
HLA non-identical living related donor. 
4. Recipients who are at low immunologic risk: 
a. No DSA, and 
b. Negative cross-match testing (by T- and B- cell flow or by virtual cross-match). 
5. Recipients with up to date vaccination as per local immunization schedules. 
6. A female subject is eligible if she is: 
a. Not pregnant or nursing. 
b. Of non-childbearing potential (i.e., post-menopausal defined as having been 
amenorrheic for at least 1 year prior to screening, or has had a bilateral tubal ligation 
at least 6 months prior to screening, or has had a bilateral oophorectomy or 
hysterectomy).  
c. Of childbearing potential, must have a negative serum pregnancy test within 48 hours 
prior to surgery and be using an effective method of contraception (per site specific 
recommendations) which must be continued for at least 6 months after the final dose 
of investigational product.  
7. Nonsterilized male subjects who are sexually active with a female partner of childbearing 
potential must use a condom with spermicide from Day 0 through to the end of the study 
and must agree to continue using such precautions for at least 6 months after the final dose of 
investigational product. 
8.2. 
Subject Exclusion Criteria  
Subjects meeting any of the following criteria will be considered ineligible for this study: 
1. Patients receiving an allograft from an ABO-incompatible donor. 
2. Patients treated with systemic immunosuppressive drug therapy for more than a total of 2 
weeks within 24 weeks prior to ICF signature. 
3. Patients who have undergone lymphodepleting therapy (e.g., Thymoglobulin, 
alemtuzumab). 
4. Patients with known immunodeficiency. 


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5. Patients with medical history of confirmed venous thromboembolism, arterial 
thrombosis, coagulopathy or known platelet disorders. 
6. Patients with risk factors for venous thromboembolism or arterial thrombosis (e.g., 
immobilization or major surgery within 12 weeks before screening), prothrombotic status 
(including but not limited to congenital or inherited deficiency of antithrombin III, 
protein C, protein S, or confirmed diagnosis of antiphospholipid syndrome). 
7. Patients requiring treatment with antithrombotic drugs (clopidogrel, prasugrel, warfarin, 
others). Low-dose aspirin treatment (up to 100 mg/day) is allowed. 
8. Patients requiring long-term systemic anticoagulation after transplantation, which would 
interfere with obtaining biopsies. 
9. Patients with poor vascular access such that IV administration of the study medications 
may be compromised.  
10. Patients with any contraindication to kidney biopsy. 
11. CMV-seronegative recipients of a CMV-seropositive donor kidney, or unknown CMV 
serostatus. 
12. EBV-seronegative or with unknown EBV serostatus. 
13. Receipt of live (attenuated) vaccine within the 4 weeks before screening. 
14. Patients with high potential of graft loss due to recurrence of underlying kidney disease. 
15. Prior solid organ transplant or potential to require a concurrent organ or cell transplant.  
16. Previous treatment with belatacept. 
17. Previous treatment with CD40 or anti-CD40L agents. 
18. Use of B depleting therapy (e.g., rituximab), non-depleting B cell directed therapy (e.g., 
belimumab) or abatacept within 1 year prior to enrollment. 
19. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-
lives of enrollment, whichever is longer. 
20. At screening blood tests, any of the following: 
a. Aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN) 
b. Alanine aminotransferase (ALT) > 2.5 × ULN 
c. Alkaline phosphatase (ALP) > 2.5 × ULN 
d. Total bilirubin (TBL) > 2 × ULN 
e. Hemoglobin < 75 g/L 
f. Neutrophils < 1.5 × 109/L 
g. Platelets < 100 × 109/L 
21. Patients with severe systemic infections, current or within the 2 weeks prior to transplant 
surgery. 
22. Positive test for chronic hepatitis B infection at screening or within the last 12 months, 
defined as either (1) positive hepatitis B surface antigen [HBsAg] or (2) a positive 
hepatitis B core antibody [anti-HBc] PLUS negative hepatitis B surface antibody [anti-


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HBs]. Note that subjects with a positive anti-HBs ONLY or a positive anti-HBc PLUS 
positive anti-HBs AND negative HBsAg are eligible to enroll. 
23. Positive test for hepatitis C virus antibody at screening or within the last 12 months. 
24. Positive test for HIV antibody at screening or within the last 12 months. 
25. History of or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at 
screening (for recipients of living donor kidneys), unless previously treated for latent 
tuberculosis. Subjects with an indeterminate QuantiFERON®-TB Gold test result can 
repeat the test, but if the repeat test is also indeterminate, they are excluded. Other 
standard of care methods performed for determining the TB status (e.g., chest X-rays) are 
permitted.  
26. History of cancer, except as follows: 
a. In situ carcinoma of the cervix treated with apparent success with curative therapy > 
12 months prior to screening; or 
b. Cutaneous basal cell or squamous cell carcinoma treated with apparent success with 
curative therapy 
27. Any severe cardiovascular, respiratory, endocrine, gastrointestinal, hematological, 
neurological, psychiatric, or systemic disorder that could impact the evaluation of safety 
 
28. Any condition that, in the opinion of the investigator, would interfere with evaluation of 
the investigational product or interpretation of subject safety or study results. 
29. Lactating or pregnant females or females who intend to become pregnant anytime from 
signing the informed consent form (ICF) through 6 months after receiving the last dose of 
investigational product 
30. Known history of severe allergy or reaction to any component of the investigational 
product formulation or to any other biologic therapy. 
31. Unwilling or unable to comply with the protocol, complete study assessments, and 
complete the study period. 
8.3. 
Reasons for permanent study drug discontinuation  
Study drug must be discontinued if the investigator determines that continuing it would result in 
a significant safety risk for that subject. Reasons for study drug discontinuation are or can be:  
1. Failure to undergo the scheduled kidney transplant surgery. 
2. 
e 
course of IV corticosteroids. 
3. Any acute rejection of Banff Grade  2B or any antibody-mediated rejection. 
4. Subjects with graft loss must discontinue treatment with VIB4920. The allograft will be 
presumed to be lost based on whichever of the following occurs first: the day the subject 
starts dialysis and is not able to subsequently be removed from dialysis (for a period of at 


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least 56 consecutive days), the day of nephrectomy, or the day reversible loss of graft 
perfusion is demonstrated by appropriate imaging techniques. Primary graft non-function 
is a subset of graft loss. 
5. Withdrawal of consent from the study. 
6. Withdrawal of consent from further treatment with investigational product. 
7. AE or significant laboratory abnormality that, in the opinion of the investigator and/or the 
sponsor, warrants discontinuation of further dosing. 
8. Pregnancy or a decision to become pregnant. 
9. Hepatic function abnormality defined as any increase in ALT or AST to greater than 3 × 
ULN and concurrent increase in bilirubin to greater than 2 × ULN related to VIB4920. 
10. Anaphylaxis or a serious hypersensitivity reaction attributed to VIB4920. 
11. Any life-threatening or serious infection or opportunistic infection.  
12. Malignancy. 
Subjects who prematurely discontinue study drug will undergo an EOT visit and all Week 48 
safety assessments at the time of discontinuation. Subjects who discontinue study drug should 
NOT be considered withdrawn from the study until the Week 48 visit or until completion of the 
follow up period. A Study Drug Discontinuation form should be completed, giving the date and 
primary reason for stopping study treatment. 
For subjects who withdraw prematurely from the study, the reason(s) for withdrawal must be 
recorded on the appropriate page of the eCRF. If possible, any subject who is withdrawn from 
the study will have, at the time of withdrawal, all exit procedures performed (i.e., Week 48 safety 
assessments). All clinically significant abnormalities will be followed-up, if possible, until 
resolved to the satisfaction of the Investigator.  
Eligible subjects who fail to undergo the scheduled kidney transplant surgery and those who 
prematurely terminate study participation without receiving any dose of VIB4920 will be 
replaced. Subjects who prematurely terminate study participation for any other reason will not be 
replaced. 
For subjects who are lost to follow-up (i.e. those subjects whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the investigator should 
show "due diligence" by documenting in the source documents steps taken to contact the subject, 
e.g., dates of telephone calls, registered letters, etc. 
8.4. 
Withdrawal of Informed Consent for Data and Biological Samples  
8.4.1. 
Biological Samples  
Study data are protected by the use of a SID number, which is a number specific to the 
subject. The investigator is in control of the information that is needed to connect a study 
specific expiration 
date, but the subject may withdraw consent at any time by notifying the investigator. If 
consent is withdrawn, any samples collected prior to that time may still be given to and used 


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by the Sponsor but no new samples will be collected unless specifically required to monitor 
safety of the subject. 
8.4.2. 
Samples Obtained for Future Research  
Samples obtained for future research will be labeled with a sample identification number. If 
the subject withdraws consent for participating in future research, the sponsor will locate the 
 
If the subject consents to have his/her samples used for future research, this additional 
research may not start immediately and may start at any time during the storage period. The 
after the end of the study in which they were collected. If the subject chooses not to allow 
his/her study samples to be used for future research, the samples will be destroyed by the 
sponsor once they are no longer required for the main study. 
If consent is withdrawn, the sponsor and the investigator will ensure that these sample(s) are 
destroyed unless the identification number has been removed and the subject can no longer 
 for 
research, the sponsor is not required to destroy results of this research. In this case only the 
remaining sample(s) will be destroyed. 
 
9. 
TREATMENT OF SUBJECTS  
9.1. 
Description of Study Drugs  
All subjects will be treated with the same immunosuppression regimen consisting of: 
 Thymoglobulin 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the 
day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-
op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op 
Day 3 or 4. Adjustments in the total dose of 6 mg/kg or frequency of delivery are 
allowed for clinical cause (i.e., thrombocytopenia). Reasons for adjustments should 
be clearly stated in the medical record and appropriate case report form.   
 Methylprednisolone by IV infusion (500, 250, 125 and 60 mg on Days 0, 1, 2 and 3, 
respectively) followed by oral administration of prednisone 30 mg per day on Days 4, 
5, 6 and 7. Subjects may be tapered to at least 20 mg per day on Day 8, to at least 10 
mg per day on Day 15, and to at least 5 mg per day on Day 22. Discontinuation of 
prednisone should occur following the post-op Day 28 visit.  
 VIB4920 1500 mg by IV infusion on post-op Day 1, repeated on post-op Day 3 or 4 
Week 2, and at the end of Weeks 4, 6, 8 and 10; 
then 1500 mg every four weeks from Week 12 to Week 48. 
 Belatacept 10 mg/kg by IV infusion on post-op Day 1 (
Thymoglobulin infusion ends), repeated on post-op Day 3 or 4 (timing is at 


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every four weeks from Week 16 to Week 48. 
VIB4920 should be administered prior to belatacept. Timings of administration of each drug 
should be recorded. 
The treatment schedule is represented in Table 5. 




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9.2. 
Concomitant Medications  
Details regarding the name, medical indication, dose, route, and frequency of all prescription 
medications, over-the-counter medications, or alternative therapies taken within 30 days prior to 
administration of VIB4920 and through the end of the study will be recorded. Medications 
administered in the perioperative period solely for the conduct of surgery, such as anesthesia 
related medications, electrolytes, and intravenous fluids, do not need to be collected. Any 
transplant related medications, such as immunosuppressive drugs, administered during this 
period should be collected.  
9.3. 
Prohibited Medications  
The following concomitant medications are prohibited throughout the study: 
 Non-protocol specified immunosuppressives such as tacrolimus, cyclosporine, 
sirolimus, everolimus, azathioprine, MMF, mycophenolic acid, basiliximab, 
alemtuzumab, intravenous immunoglobulins or any other immunosuppressive for the 
prophylaxis of acute rejection which is or may become available on the market during 
the course of the study. However, as specified in the protocol, patients who develop 
grades of acute cellular or antibody medicated rejection that require alternative 
treatment may be withdrawn from the study regimen and treated as necessary. 
 Investigational drug therapy other than VIB4920. 
 Live (attenuated) vaccine. Immunization with any live or live attenuated vaccine (i.e., 
measles, mumps, rubella and polio vaccine, Bacillus Calmette-Guerin, typhoid, 
yellow fever, cold adapted live influenza strain vaccine, or any other vaccines not yet 
licensed but belonging to this category) is specifically excluded during the treatment 
period. 
 Biologics such as cytokine inhibitors, cytokine receptor inhibitors, B-cell depleting 
agents, etc. 
Use of any prohibited medication during the study will be recorded in the eCRF. Additionally, 
administration or subsequent changes (increased or decreased in dose and/or frequency) in all 
medications will be recorded in the eCRF throughout the study.  
9.4. 
Treatment Compliance  
Site staff will administer all study medications intravenously at the study center, except for 
prednisone (which will be self-administered by the subject at Days 4, 5 and 6). The dose and date 
of administration of each study medication must be recorded in the subject
eCRF. Treatment 
compliance for IV infused medications will be assessed based on this information. For oral 
prednisone, compliance will be assessed based on drug accountability (subjects will be required 
to return any unused medication at the following visit).  
9.5. 
Randomization and Blinding  
This is a single-arm, open-label study. No randomization or blinding will be used.  


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10. 
STUDY DRUG MATERIALS AND MANAGEMENT  
10.1. 
VIB4920  
VIB4920 is a CD40L antagonist comprised of two identical Tn3 modules fused to human serum 
albumin (HSA). Each Tn3 is an engineered form of the third Fn3 protein domain of human 
Tenascin C. Polyglycine linkers join the two Tn3 domains, and the second Tn3 domain to the 
HSA protein. Each Tn3 binds specifically to human CD40L and inhibits its interaction with 
human CD40. 
Each vial contains a nominal 500 mg of VIB4920. VIB4920 is formulated at 100 mg/mL in 10 
mM sodium monobasic/dibasic phosphate buffer, 250 mM sucrose, and 0.02% (weight/volume 
[w/v]) poloxamer 188, pH 7.4.  
10.1.1. 
VIB4920 Packaging and Labeling  
The investigational product will be appropriately labeled in accordance with national laws and 
regulations.  
VIB4920 is provided with three vials per kit.  
10.1.2. 
VIB4920 Storage  
All investigational product (VIB4920) supplied should not be shaken and requires no special 
biohazard handling. The investigational product must be stored at 2ºC to 8ºC (36ºF to 46ºF) in 
refrigerator with adequate temperature monitoring. Investigational product must not be frozen. It 
should be stored in the original outer package in a location with limited access.  
10.1.3. 
VIB4920 Inspection  
Each vial selected for dose preparation should be inspected. If there are any defects noted with 
the investigational product, the investigator and site monitor should be notified immediately. 
Refer to the Product Complaint section for further instructions (Section 10.1.7). 
10.1.4. 
VIB4920 Preparation  
The investigational product is supplied as a sterile liquid in a 6R glass vial at a nominal fill 
volume of 5.0 mL, stoppered with siliconized 20 mm Teflon-coated elastomeric stopper, and 
sealed with flip-off cap overseal.   
10.1.4.1. Dose Preparation Steps  
No incompatibilities between VIB4920 and the components recommended for IV infusion (i.e., 
polyolefin IV bags for IV infusion, non-diethylhexyl phthalate infusion lines, and syringes used 
for dose preparation) have been observed.  
VIB4920 does not contain preservatives and any unused portions must be discarded. Preparation 
of investigational product and IV bags is to be performed aseptically. Total in-use storage time 
from needle puncture of the investigational product vial to start of administration should not 
exceed 4 hours at room temperature or 24 hours at 2°C to 8°C (36°F to 46°F). DO NOT 
FREEZE. If storage time exceeds these limits, a new dose must be prepared from new vials. 


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Three vials, one 250 mL IV bag containing 0.9% (w/v) saline (weight/volume [w/v]), and one IV 
infusion pump is required for administration of each 1500 mg dose of VIB4920. 
The dose preparation steps are as follows: 
1. For each 1500 mg IV dose, 15.0 mL of 0.9% saline should be removed from a prefilled 
250 mL IV. 
2. 15.0 mL of VIB4920 will be obtained from three (3) 500 mg vials by withdrawing 5.0 
mL from each vial. Use a new needle for each withdrawal.  
3. Investigational product should be added to the saline bag. 
4. Gently mix the contents of the IV bag. The saline bag should then be inspected to ensure 
the solution is clear. 
During preparation of the investigational product for infusion, the capacity of the tubing should 
be calculated in order to adjust the volume of investigational product solution needed to 
prime the IV tubing. This step is also necessary because the same volume of saline will be 
needed to flush the IV tubing at the completion of the infusion in order to deliver the complete 
volume of investigational product solution. Because the IV tubing contains investigational 
product solution, the saline flush must be infused using the same infusion rate as that used for the 
investigational product solution in the infusion bag. 
For example, if the IV tubing capacity is 15 mL, the IV tubing should be primed with 15 mL of 
investigational product solution from the infusion bag before initiating the infusion. Once the 
infusion bag is empty, the IV tubing should be flushed with at least 15 mL of 0.9% saline (w/v) 
via the infusion pump at the same rate as dosing. 
The start time of the infusion will be the time when infusion of the investigational product 
solution from the infusion bag (with IV tubing primed with investigational product solution) is 
started. The stop time of the infusion will be the time when the IV tubing has been flushed with a 
volume of 0.9% normal saline equivalent to IV tubing capacity (e.g., 15 mL for the example 
above) to administer the residual investigational product solution. 
10.1.4.2. Intravenous administration  
An experienced and qualified staff member will place the IV access.  
VIB4920 will be infused using an IV infusion pump. Each subject must receive the entire 
volume of investigational product solution in the IV bag over at least 90 minutes (approximately 
2.8 mL/min). Investigational product must be infused through a low-protein binding 0.2- or 0.22-
-line filter. Vital signs will be obtained prior to the start of each VIB4920 infusion. 
A physician must be present at the site or immediately available to respond to emergencies 
during administration of investigational product. Fully functional resuscitation facilities should 
be available. 
Further information on VIB4920 preparation and administration is provided in the IP Manual. 


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10.1.5. 
VIB4920 Accountability  
Study site staff will maintain a record of the investigational product received, dispensed, 
administered and destroyed. All records will be maintained with controlled access. A study 
monitor will perform drug accountability and compliance monitoring during the study.  
The Investigator will administer the study product only to subjects included in this study and 
according to the procedures established in this study protocol. Each administration of study 
product will be documented and transferred to the eCRF. 
10.1.6. 
VIB4920 Handling and Disposal  
The Investigator or designee must return any unused vials of VIB4920 to Viela Bio, Inc. or 
designee regardless of whether the study was completed or terminated prematurely. At the time 
of return, the Investigator must verify that unused or partially used study products have been 
returned and that no study products remain at the site. As an alternative to returning unused study 
product at the end of the study, the Investigator may destroy unused study medication on site 
with agreement from Viela Bio, Inc. 
10.1.7. 
Reporting Product Complaints  
Any defects with the investigational product must be reported immediately to the Viela Bio, Inc. 
Product Complaint Department by the site with further notification to the site monitor. All 
defects will be communicated to Viela Bio, Inc. and investigated further with the Product 
Complaint Department. During the investigation of the product complaint, all investigational 
product must be stored at labeled conditions unless otherwise instructed.  
Viela Bio, Inc. contact information for reporting product complaints:  
Email: ClinicalProductComplaints@horizontherapeutics.com 
  
Phone: 1-866-479-6742 
 
10.2. 
Belatacept  
10.2.1. 
Supply  
Belatacept (NULOJIX®) lyophilized powder for intravenous infusion will be dispensed by the 
® is supplied as a single-use vial with a silicone-free 
disposable syringe in the following packaging configuration (Food and Drug Administration 
2017): 
Description  
NDC Number 
One 250-mg vial 
One 12 mL Syringe  
0003-0371-13
10.2.2. 
Storage/Handling  
NULOJIX® must be stored refrigerated at 2°-8°C (36°-46°F). Protect NULOJIX® from light by 
storing in the original package until time of use. 


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The reconstituted solution should be transferred from the vial to the infusion bag or bottle 
immediately. The NULOJIX® infusion must be completed within 24 hours of constitution of the 
NULOJIX® lyophilized powder. If not used immediately, the infusion solution may be stored 
under refrigeration conditions: 2°-8°C (36°-46°F) and protected from light for up to 24 hours (a 
maximum of 4 hours of the total 24 hours can be at room temperature: 20°-25°C [68°-77°F] and 
room light). 
10.2.3. 
Preparation for Administration  
If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-
free disposable syringe from inventory.  
1. Calculate the number of NULOJIX® vials required to provide the total infusion dose. 
Each vial contains 250 mg of belatacept lyophilized powder.  
2. Reconstitute the contents of each vial of NULOJIX® with 10.5 mL of a suitable diluent 
using the silicone-free disposable syringe provided with each vial and an 18- to 21-gauge 
needle. 
Suitable diluents include: sterile water for injection (SWFI), 0.9% sodium chloride (NS), 
or 5% dextrose in water (D5W). Note: If the NULOJIX® powder is accidentally 
reconstituted using a different syringe than the one provided, the solution may develop a 
few translucent particles. Discard any solutions prepared using siliconized syringes. 
3. To reconstitute the NULOJIX® powder, remove the flip-top from the vial and wipe the 
top with an alcohol swab. Insert the syringe needle into the vial through the center of the 
rubber stopper and direct the stream of diluent (10.5 mL of SWFI, NS, or D5W) to the 
glass wall of the vial.  
4. To minimize foam formation, rotate the vial and invert with gentle swirling until the 
contents are completely dissolved. Avoid prolonged or vigorous agitation. Do not shake.  
5. The reconstituted solution contains a belatacept concentration of 25 mg/mL and should 
be clear to slightly opalescent and colorless to pale yellow. Do not use if opaque 
particles, discoloration, or other foreign particles are present. 
6. Calculate the total volume of the reconstituted 25 mg/mL NULOJIX® solution required to 
provide the total infusion dose. Volume of 25 mg/mL NULOJIX® solution (in mL) = 
Prescribed Dose (in mg) ÷ 25 mg/mL 
7. Prior to intravenous infusion, the required volume of the reconstituted NULOJIX® 
solution must be further diluted with a suitable infusion fluid (NS or D5W). NULOJIX® 
reconstituted with:  
 SWFI should be further diluted with either NS or D5W  
 NS should be further diluted with NS  
 D5W should be further diluted with D5W 
8. From the appropriate size infusion bag or bottle, withdraw a volume of infusion fluid that 
is equal to the volume of the reconstituted NULOJIX® solution required to provide the 
prescribed dose. With the same silicone-free disposable syringe used for reconstitution, 


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withdraw the required amount of belatacept solution from the vial, inject it into the 
infusion bag or bottle, and gently rotate the infusion bag or bottle to ensure mixing. 
The final belatacept concentration in the infusion bag or bottle should range from 2 
mg/mL to 10 mg/mL. Typically, an infusion volume of 100 mL will be appropriate for 
most patients and doses, but total infusion volumes ranging from 50 mL to 250 mL may 
be used. Any unused solution remaining in the vials must be discarded. 
9. Prior to administration, the NULOJIX® infusion should be inspected visually for 
particulate matter and discoloration. Discard the infusion if any particulate matter or 
discoloration is observed. 
10. The entire NULOJIX® infusion should be administered over a period of 30 minutes and 
must be administered with an infusion set and a sterile, non-pyrogenic, low-protein-
binding filter (with a pore size of 0.2-1.2 µm). 
 The reconstituted solution should be transferred from the vial to the infusion bag 
or bottle immediately. The NULOJIX® infusion must be completed within 24 
hours of reconstitution of the NULOJIX® lyophilized powder. If not used 
immediately, the infusion solution may be stored under refrigeration conditions: 
2°-8°C (36°-46°F) and protected from light for up to 24 hours (a maximum of 4 
hours of the total 24 hours can be at room temperature: 20°-25°C [68°-77°F] and 
room light).  
 Infuse NULOJIX® in a separate line from other concomitantly infused agents. 
NULOJIX® should not be infused concomitantly in the same intravenous line 
with other agents. No physical or biochemical compatibility studies have been 
conducted to evaluate the coadministration of NULOJIX® with other agents. 
 VIB4920 should be administered prior to belatacept. Timings of administration of 
each drug should be recorded. 
10.3. 
Thymoglobulin  
10.3.1. 
Supply  
Thymoglobulin will be dispensed 
 is supplied as 
a single-use clear glass 10 mL vial containing 25 mg of lyophilized (solid) Thymoglobulin. Each 
carton contains one Thymoglobulin vial (NDC 58468-0080-1) (Food and Drug Administration 
2017). 
10.3.2. 
Storage/Handling   
 Store in refrigerator at 2°C to 8°C (36°F to 46°F).  
 Protect from light.  
 Do not freeze.  
 Do not use after the expiration date indicated on the label.  
 Reconstituted Thymoglobulin is physically and chemically stable for up to 24 hours 
at room temperature; however, room temperature storage is not recommended. As 


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54 
 
 
  
 
Thymoglobulin contains no preservatives, reconstituted product should be used 
immediately.  
 Infusion solutions of Thymoglobulin must be used immediately.  
 Any unused drug remaining after infusion must be discarded. 
10.3.3. 
Instructions for Dilution and Administration  
10.3.3.1. Reconstitution  
After calculating the number of vials needed, using aseptic technique, reconstitute each vial of 
Thymoglobulin with 5 mL of SWFI, USP. 
1. Allow Thymoglobulin vials to reach room temperature before reconstituting the 
lyophilized product.  
2. Aseptically remove caps to expose rubber stoppers.  
3. Clean stoppers with germicidal or alcohol swab.  
4. Aseptically reconstitute each vial of Thymoglobulin lyophilized powder with the 5 mL of 
SWFI.  
5. Rotate vial gently until powder is completely dissolved. Each reconstituted vial contains 
25 mg or 5 mg/mL of Thymoglobulin.  
6. Inspect solution for particulate matter after reconstitution. Should some particulate matter 
remain, continue to gently rotate the vial until no particulate matter is visible. If 
particulate matter persists, discard this vial. 
10.3.3.2. Dilution  
1. Transfer the contents of the calculated number of Thymoglobulin vials into the bag of 
infusion solution (saline or dextrose). Recommended volume: per one vial of 
Thymoglobulin use 50 mL of infusion solution (total volume usually between 50 to 500 
mL) 
2. Mix the solution by inverting the bag gently only once or twice. 
10.3.3.3. Infusion  
Administer Thymoglobulin under strict medical supervision in a hospital setting, and carefully 
monitor patients during the infusion.  
Thymoglobulin is less likely to produce side effects when administered at the recommended flow 
rate. 
1. 
a 0.22 micrometer filter into a high-flow vein. 
2. Set the flow rate to deliver the dose over a minimum of 6 hours for the single dose. 


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10.4. 
Corticosteroids  
Corticosteroids (methylprednisolone and prednisone) will be dispensed by the hospital pharmacy 
and administered in the protocol-specified dose regimen.  
11. 
STUDY ASSESSMENTS AND PROCEDURES  
11.1.1. 
Informed Consent  
All candidates for enrollment or legally authorized representative will sign an ICF prior to any 
screening activities. Informed consent must be obtained by the principal investigator or a 
designee, such as a sub-investigator, with IRB-approved qualifications. 
Each patient must be given the opportunity to ask questions and to understand the details of 
study participation.  
patient signing the ICF.  
After signing the ICF, each subject will be assigned an identification number that will be used on 
all subject documentation. Numbers will be assigned in ascending sequential order. This number 
will also correspond to the subject number entered on test materials. 
11.1.2. 
Demographic/Medical History  
Demographic information to be collected includes date of birth, sex, race and ethnicity.  
Medical history information to be collected includes all ongoing conditions and 
relevant/significant medical history (including all major hospitalizations and surgeries), as 
determined by the Investigator.  
11.1.3. 
Background (donor and recipient)  
The following background information should be collected from donors: sex, race, ethnicity, 
transplant donor type (living related, living unrelated, deceased heart beating, deceased non-heart 
beating). 
The following recipient background information should be collected: end-stage renal disease 
leading to transplantation, current dialysis (none, hemodialysis, peritoneal dialysis) and dialysis 
start date, highest Panel Reactive Antibody (PRA) test, most recent PRA and HLA type.  
11.1.4. 
Vital Signs  
Vital signs including systolic and diastolic blood pressure (mmHg), pulse rate (beats/min), 
respiratory rate (RR) (breaths/min), body temperature (ºC) and body weight (kg) will be 
measured using clinically acceptable methods and devices as defined in the schedule of events 
and IP Administration manual.  
11.1.5. 
Physical Examination  
A complete physical examination will be completed at screening, while symptom-directed 
physical examinations will be performed thereafter, as specified in the Schedule of Assessments. 


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A complete physical examination will include the examination of the following body systems: 
general appearance, skin, HEENT (head, ears, eyes, nose, throat), cardiovascular, pulmonary, 
abdomen, neurological, lymph nodes, spine and extremities (skeletal). As part of the complete 
physical examination, a clinical assessment will be performed and will include the evaluation of 
the subject for clinical signs of infection, allograft rejection, AEs, and change in renal function. 
Any abnormalities will be recorded on the Case Report Form (CRF). At screening, abnormalities 
will be recorded on the medical history eCRF page. Clinically significant changes from baseline 
physical examination that are detected during follow-up will be recorded as an AE on the 
appropriate eCRF pages.  
11.1.6. 
Electrocardiogram (ECG)  
A 12-lead electrocardiogram (ECG) will be performed. Each ECG will include ventricular heart 
rate and intervals (PR, QRS, QT, QTc). The PI will be responsible for providing an interpretation 
of the ECGs in terms of clinical significance to the subject (i.e., normal, abnormal but not 
clinically significant, abnormal and clinically significant.). Any abnormalities and clinical 
significance will be entered on the eCRF.  
11.1.7. 
Laboratory Assessments  
Blood and urine samples will be collected for laboratory safety tests as specified in the Schedule 
of Assessments. Laboratory testing is described below. For further details regarding laboratory 
assessments see the Study Laboratory Manual.  
11.1.7.1 
Hematology  
The hematology panel will include a complete blood count, with differential (including 
basophils, eosinophils, lymphocytes, monocytes, and neutrophils), hemoglobin, hematocrit, 
platelets and white blood cell count.  
11.1.7.2 
Blood Chemistry  
Chemistry and Renal Profile:  
 Creatinine, blood urea nitrogen, fasting glucose, total protein and electrolytes 
(including sodium, potassium, chloride, calcium, bicarbonate, and phosphorus)  
Hepatic Profile:  
 Albumin, total bilirubin, indirect bilirubin, AST, ALT, alkaline phosphatase (ALP), 
and gamma glutamyl transferase. 
11.1.7.3 
Immunoglobulins  
 
Total immunoglobulins, IgA, IgG and IgM. 
11.1.7.4. Coagulation Parameters  
Prothrombin time and partial thromboplastin time will be assessed.  


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11.1.7.5. Urinalysis  
The urinalysis will include protein, glucose, blood, ketones, leukocytes, and pH by dipstick 
analysis. Microscopy (crystals, casts, white blood cells, red blood cells) will also be performed if 
any abnormalities are observed. 
11.1.8. 
Viral Serology  
Serological tests for exposure to CMV, EBV, hepatitis C virus (HCV), HBsAg and HIV will be 
performed for recipient and donor at screening, if not conducted within the previous 12 months. 
Additionally, viral monitoring for BK polyoma virus, CMV and EBV will be conducted 
throughout the study, as specified in the Schedule of Assessments (Table 3 and  
Table 4). 
11.1.9. 
Pregnancy Screen  
Serum human chorionic gonadotrophin beta (h
) pregnancy test(s) will be completed for all 
females of childbearing potential during the screening period (before Day 0). Females screened 
within 1 week prior to Day 0 will not need to repeat the pregnancy test as part of the 
reconfirmation of eligibility. In the post-transplant period, serum or urine h
 pregnancy tests 
 as specified in the Schedule of Assessments 
(Table 3 and  
Table 4).  
11.1.10. 
Spot Urine Protein Creatinine Ratio  
Quantitation of proteinuria and urine protein:creatinine ratio by spot urine sampling will be 
performed as specified in the Schedule of Assessments (Table 3 and  
Table 4). 
11.1.11. 
Renal Function  
Renal function by 
 
 will be assessed at each study visit.  
11.1.12. 
  
 will be collected from 
 
 as designated in 
 and  
 may include, but is not limited to, 
 
 Details on drawing, handling, and shipping 
 will be detailed in the study Lab 
Manual. 
11.1.13. 
Pharmacokinetics  
Plasma samples to determine the concentration of VIB4920 will be taken according to the visits 
specified in the Schedule of Assessments (Table 3 and  
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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58 
 
 
  
 
Table 4) and measured using a validated immunoassay. Note: Samples for PK at V3, V4 and 
V10 are to be taken predose and within 10 minutes after the end of infusion.  
11.1.14. 
  
 will be performed to 
 in 
, as specified 
in the Schedule of Assessments (Table 2, Table 3, and  
Table 4). Blood will be 
 
 for processing to 
 
 
 
11.1.15. 
  
 will be collected at the timepoints specified in the Schedule of Assessments 
(Table 2, Table 3, and  
Table 4) for the 
 
  
11.1.16. 
Immunogenicity  
Plasma samples for immunogenicity (anti-drug antibodies to VIB4920) will be taken prior to 
drug administration according to the visits specified in Table 3 and  
Table 4 and assessed using a validated immunoassay. 
11.1.17. 
  
Plasma, serum, and urine samples will be collected according to the visits specified in Table 3 
and  
Table 4. Assessments include changes in 
 and 
 
 
11.1.18. 
  
A blood sample will be collected 
 
 
 The 
 may be used for 
 
 and 
, by tests 
including but not limited to 
 
11.1.19. 
Estimate of Blood Volume to be Collected Per Study Visit  
The estimated volume of blood to be collected from each subject at each visit (and across all 
visits) from screening to the last visit of the Safety Follow-up (FU3) is presented in Table 6. If 
repeats of any blood tests are required, the volume of blood collection will increase accordingly. 
 
 
 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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Table 6: 
Estimate of Total Blood Volume to be collected per study visit  
 
Study Period 
Approximate Volume (mL) 
Screening Period 
42
Day 0   
64
Day 1 
43
Day 3 or 4 
31
Day 7   
23
Week 2 ± 1 day 
40
Week 4 ± 2 days 
82
Week 6 ± 2 days 
12
Week 8 ± 2 days 
45
Week 10 ± 2 days 
29
Week 12 + 2 days
82
Week 16 ± 3 days
32
Week 20 ± 3 days
16
Week 24 +3 days
82
Week 28 ± 3 days 
32
Week 32 ± 3 days 
16
Week 36 ± 3 days
68
Week 40 ± 3 days
32
Week 44 ± 3 days
16
Week 48 +3 days
82
EOT 
78
End of Treatment + 4 weeks 
14
End of Treatment + 8 weeks
35
End of Treatment + 12 weeks
82
Total
995
The volume of blood was estimated assuming that a serum pregnancy test will be performed. Thus, the volume of 
blood to be collected may be less for subjects performing urine pregnancy tests. 
Total may be less than indicated for subjects with available serological tests for exposure to CMV, EBV, HCV, 
HBsAg and HIV performed within the 12 months prior to screening and those who prematurely discontinue study 
treatment.  
Total excludes the End-of-Treatment visit.  


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11.1.20. 
Prior & Concomitant Medications  
Details regarding the name, medical indication, dose, route, and frequency of all prescription 
medications, over-the-counter medications, or alternative therapies taken within 30 days prior to 
administration of VIB4920 and through the end of the study will be recorded. Medications 
administered in the perioperative period solely for the conduct of surgery, such as anesthesia 
related medications, electrolytes, and intravenous fluids do not need to be collected. Any 
transplant related medications, such as immunosuppressive drugs, administered during this 
period should be collected.  
11.1.21. 
Cytomegalovirus Prophylaxis  
CMV pre-emptive therapy or prophylaxis is recommended for all cases in which either the donor 
or the recipient tests positive for CMV. It is recommended that CMV prophylaxis be 
administered for a minimum of 14 weeks after transplantation. Prophylaxis with IV ganciclovir 
or oral valganciclovir is recommended and will be administered according to local practice, 
taking into account dose adjustments based on renal function. Cases of CMV negative donor 
kidneys transplanted into CMV negative recipients will be treated according to local practice. 
CMV prophylaxis is also recommended following any AEs requiring antibody treatment of acute 
rejection episodes. 
11.1.22. 
Pneumocystis jirovecii (Pneumocystis carinii) pneumonia prophylaxis  
All subjects will be treated according to local standard of care. The same prophylaxis strategy 
should be applied for all subjects at a given site. Starting prophylaxis with trimethoprim-
sulfamethoxazole when oral medication can be tolerated is recommended, continuing for the first 
6 months after transplantation. Aerosolized pentamidine or dapsone may be administered to 
subjects unable to tolerate trimethoprim-sulfamethoxazole. 
11.1.23. 
Prophylaxis and treatment of oral Candida  
All subjects will be treated according to local standard of care. The same prophylaxis strategy 
should be applied for all subjects at a given site. Nystatin suspension in a swish and swallow 
regimen, oral fluconazole or clotrimazole troches are recommended for the prophylaxis or 
treatment of oral thrush (Candida). 
11.1.24. 
Surveillance Biopsy  
A surveillance renal biopsy will performed following reperfusion of the allograft on Day 0 and 
again at the end of Week 24, as specified in the Schedule of Assessments (Table 3). Where 
necessary to minimize any potential risk associated with the biopsy, a CT guided biopsy may be 
ith the medical monitor. A CT scan 
utilizes ionizing radiation to provide imaging to guide the biopsy collection. There can be risks 
of radiation from the CT scan. The cumulative radiation exposure from this test is considered 
small. 


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12. 
ASSESSMENT OF EFFICACY  
Efficacy evaluation will be based on the assessment and recording of acute cellular rejection 
(tBPAR, BPAR, treated acute rejections) and antibody-mediated rejections, graft loss, death, de 
novo DSA and renal function throughout the study.  
12.1. 
Histological Grading of Acute Allograft Rejection  
Histological grading of acute allograft rejection from biopsy specimens and the diagnosis of 
antibody-mediated rejection will be based on Banff criteria 2017 (Haas, Loupy et al. 2018).  
12.2. 
Handling of Acute Rejection Episodes  
In all suspected acute rejection episodes, regardless of initiation of anti-rejection treatment, a 
graft core biopsy must be performed within 48 hours. Suspected rejections must be entered into 
in the corresponding eCRF pages (e.g., Suspected Acute Rejection eCRF, Kidney Allograft 
Biopsy eCRF, etc.) preferably within 24 hours. 
Acute rejections should be treated with bolus methylprednisolone (other corticosteroids are 
acceptable at an equivalent dose) according to local practice. Recommended treatment is with at 
least 3 boluses of IV methylprednisolone with a minimal dose of 250 mg/bolus or at least 2 
boluses of IV methylprednisolone with a minimal total dose of 750 mg.  
 Subjects with mild cellular rejection (Banff Grade 1A or 1B) will be treated with 
corticosteroids and continue treatment with VIB4920 + belatacept. 
 Subjects with Banff Grade 2A lesions will be treated with corticosteroids, then re-
biopsied 
, and will continue treatment with VIB4920 + 
belatacept if the repeat biopsy shows resolution of acute rejection or transitioned to 
standard of care immunosuppression for persistent or worsening lesions. 
 
discontinue treatment with VIB4920, with subsequent management at the discretion 
of the investigator. 
All medications used for the treatment of suspected or confirmed acute rejections must be 
recorded on the Immunosuppressive Therapies eCRF. 
12.3. 
Allograft Loss  
The allograft will be presumed to be lost based on whichever of the following occurs first: the 
day the subject starts dialysis and is not able to subsequently be removed from dialysis (for a 
period of at least 56 consecutive days), the day of nephrectomy, or the day reversible loss of 
graft perfusion is demonstrated by appropriate imaging techniques. Primary graft non-function is 
a subset of graft loss. 
 
13. 
ASSESSMENT OF SAFETY  
Safety assessments will consist of: 


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 Monitoring and recording all AEs and SAEs. Note: allograft rejection is a primary 
study endpoint to be reported as a study outcome, not as an adverse event. 
 Regular monitoring of hematology, blood chemistry, immunoglobulins, coagulation 
parameters and urine results  
 Regular monitoring of vital signs, body weight, physical condition, pregnancy (for 
females of childbearing potential) and concomitant medications 
 Viral monitoring: 
 Every 2 weeks up to Week 12 for BK virus and monthly thereafter 
 Monthly for EBV and CMV viremia up to Week 12 and every 3 months thereafter 
13.1. 
Delayed Graft Function  
Subjects are considered to have delayed graft function (DGF) when: 
 A dialysis is performed, where DGF is the reported reason (in this case, the end of 
DGF is considered the day the last dialysis session ends), and/or 
 DGF is reported as an AE (in this case, the end of DGF is considered the day the 
reported AE ends, unless there is also dialysis reported which then defines the day the 
DGF ends). 
In case a subject experiences DGF, the DGF is by definition starting at reperfusion after the 
transplantation procedure. If the graft dysfunction is starting later according to the investigator, 
then this condition is considered secondary graft dysfunction. 
DGF must be reported as an AE for subjects who experience DGF without requiring dialysis. In 
case DGF is reported as an AE and dialysis is also reported, the end of DGF is considered the 
day the last dialysis session ends. 
If Thymoglobulin or other prohibited medication is used to treat DGF, VIB4920 will be 
discontinued. 
13.2. 
Adverse and Serious Adverse Events  
13.2.1. 
Definition of Adverse Events  
13.2.1.1. Adverse Event (AE)  
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal product, whether or not considered related to the medicinal product. 
- 
existing condition. An abnormal laboratory finding (including ECG finding) that requires 
medical intervention by the investigator, or a finding judged by the investigator as medically 
significant should be reported as an AE. If clinical sequelae are associated with a laboratory 


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abnormality, the diagnosis or medical condition should be reported (e.g., renal failure, 
hematuria) not the laboratory abnormality (e.g., elevated creatinine, urine RBC increased). 
Abnormal laboratory values that are not, in the investigator's opinion, medically significant and 
do not require intervention should not be reported as AEs. 
All AEs occurring between written informed consent signature and the end of the safety follow-
up, whether or not they are related to the study, must be recorded in the eCRF.  
Adverse events may be treatment emergent (i.e., occurring after initial receipt of investigational 
product) or non-treatment emergent. A non-treatment-emergent AE is any new sign or symptom, 
disease, or other untoward medical event that begins after written informed consent has been 
obtained but before the subject has received investigational product. 
Elective treatment or surgery or preplanned treatment or surgery (that was scheduled prior to the 
subject being enrolled into the study) for a documented pre-existing condition that did not 
worsen from baseline is not considered an AE (serious or non-serious). An untoward medical 
event occurring during the prescheduled elective procedure or routinely scheduled treatment 
should be recorded as an AE or SAE. 
Instances of acute rejection are anticipated on this study and have reporting guidelines referenced 
in Section 12.2. Acute rejection and manifestations of symptoms stemming from acute rejection 
are not reportable as serious adverse events.  
 
Electrolyte abnormalities requiring an intervention are common during the peri-transplant period. 
Because they are expected they are not considered an untoward medical event. Therefore, non-
serious electrolyte abnormalities requiring an intervention observed within 30 days of 
transplantation need not be recorded as adverse events. If the electrolyte abnormality or the 
therapeutic intervention to correct it meets criteria for a serious adverse event it must be reported 
as an SAE during the entire study.  
13.2.1.2. Serious Adverse Event (SAE)  
An SAE is an AE occurring during any study phase (i.e., screening period, treatment period, or 
safety follow-up), and at any dose of the investigational product, that fulfills one or more of the 
following: 
 Results in death 
 It is immediately life-threatening 
 It requires in-patient hospitalization or prolongation of existing hospitalization 
 It results in persistent or significant disability/incapacity  
 Results in a congenital abnormality or birth defect 
 It is an important medical event that may jeopardize the subject or may require 
medical intervention to prevent one of the outcomes listed above. 
All SAEs that occur between written informed consent signature and the end of the safety 
follow-up, whether or not they are related to the study, must be recorded in the eCRF. SAEs 


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discretion. 
Note: allograft rejection is a primary study endpoint to be reported as a study outcome, not as an 
adverse event. Instances of acute rejection that meet serious criteria should be captured on the 
Suspected Acute Rejection and Kidney Allograft Biopsy eCRFs as outlined in Section 12.2.  
13.2.1.3. Adverse Events of Special Interest (AESIs)  
An AESI is one of scientific and medical interest specific to understanding of the 
investigational product and may require close monitoring and collecting additional 
information by the investigator. An AESI may be serious or nonserious. The rapid 
reporting of AESIs allows ongoing surveillance of these events in order to characterize 
and understand them in association with the use of this investigational product. 
The following AESIs will be particularly monitored in this study (see the Safety 
Handling Plan for instructions and timing on completing any additional information 
required for specific types of events related to the categories noted below): 
 Thrombotic and embolic events 
 Hepatic function abnormality (meeting the definition of H
Law, Appendix 4) 
 Anaphylaxis and clinically significant (CTCAE Grade 3 or higher) hypersensitivity 
reactions (Appendix 2) 
 Immune complex disease 
 Severe Infusion-related reactions (CTCAE Grade 3 or higher, Appendix 3) 
 Malignant neoplasm 
 Infections: 
 Clinically significant (CTCAE Grade 3 or higher)  
 Opportunistic infections associated with immunosuppression including but not 
limited to reactivation of latent viral infection [VZV/HSV/EBV/JCV/CMV and 
BK polyoma virus], fungal infections and TB. 
13.3. 
Relationship to Investigational Product  
The investigator is required to provide an assessment of relationship of AEs and SAEs to 
the investigational product.  
following tests are met: 
 An unreasonable temporal relationship between administration of the investigational 
product and the onset of the event (e.g., the event occurred either before, or too long 
after, administration of the investigational product for it to be considered product-
related) 
 A causal relationship between the investigational product and the event is biologically 
implausible (e.g., death as a passenger in an automobile accident) 


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 A clearly more likely alternative explanation for the event is present (e.g., typical 
adverse reaction to a concomitant drug and/or typical disease-related event) 
Individual AE/SAE reports will be consider
 
e been caused by the 
product under investigation (i.e., there are facts, evidence, or arguments to suggest possible 
causation). 
13.4. 
Relationship to Protocol Procedures  
The investigator is also required to provide an assessment of relationship of SAEs to protocol 
procedures on the SAE Report Form. This includes non-treatment-emergent SAEs (i.e., SAEs 
that occur prior to the administration of investigational product) as well as treatment-emergent 
SAEs. A protocol-related SAE may occur as a result of a procedure or intervention required 
during the study (e.g., blood collection, washout of an existing medication). The following 
guidelines should be used by investigators to assess the relationship of SAEs to the protocol: 
 Protocol related: The event occurred due to a procedure/intervention that was 
described in the protocol for which there is no alternative etiology present in the 
 
 Not protocol related: The event is related to an etiology other than the procedure/ 
intervention that was described in the protocol (the alternative etiology must be 
 record). 
13.5. 
Recording Adverse Events  
AEs spontaneously reported by the subject and/or in response to an open question from the study 
personnel or revealed by observation will be recorded during the study at the investigational site. 
For each AE, the investigator will evaluate and report the onset (date and time), resolution (date 
and time), severity, causality, action taken, serious outcome (if applicable), and whether or not it 
caused the subject to discontinue the study. The AE term should be reported in standard medical 
terminology when possible.  
13.5.1. 
Assessment of Severity  
Severity will be assessed according to the following scale: 
 Grade 1: An event of mild intensity that is usually transient and may require only 
minimal treatment or therapeutic intervention. The event does not generally interfere 
with usual activities of daily living. 
 Grade 2: An event of moderate intensity that is usually alleviated with additional 
specific therapeutic intervention. The event interferes with usual activities of daily 
living, causing discomfort but poses no significant or permanent risk of harm to the 
subject. 


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 Grade 3: A severe event that requires intensive therapeutic intervention. The event 
interrupts usual activities of daily living, or significantly affects the clinical status of 
the subject.  
 Grade 4: An event, and/or its immediate sequelae, that is associated with an imminent 
risk of death or with physical or mental disabilities that affect or limit the ability of 
the subject to perform activities of daily living (eating, ambulation, toileting, etc). 
 Grade 5: Death (loss of life) as a result of an event. 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Section 13.2.1.2.  An AE of severe intensity 
may not be considered serious. 
13.5.2. 
Pregnancy  
Should a pregnancy occur, it must be reported and recorded on a pregnancy form. Pregnancy in 
itself is not regarded as an AE unless there is a suspicion that an investigational product may 
have interfered with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality) must be followed up and documented even if the subject was 
discontinued from the study. Pregnancy outcomes for pregnant partners of male study 
participants must also be followed up and documented. 
birth should be recorded. No additional follow-up will be required.  
All reports of congenital abnormalities/birth defects are SAEs. Spontaneous miscarriages should 
also be reported and handled as SAEs. Elective abortions without complications should not be 
handled as AEs. 
13.5.3. 
Time Period for Collection of Adverse Events  
All AEs and SAEs occurring between written informed consent and the end of the safety follow-
up will be collected.  
13.5.4. 
Follow-up of Unresolved Adverse Events  
Any non-serious AEs that are unresolved at the last visit of the safety follow-up period will be 
followed up by the investigator for as long as medically indicated, but without further recording 
in the eCRF. Information on SAEs has to be collected until they resolve or become permanent. 
Viela Bio retains the right to request additional information for any subject with ongoing 
AE(s)/SAE(s) at the end of the study, if judged necessary.  
13.6. 
Reporting Serious Adverse Events  
All SAEs/AESIs (related and unrelated) will be recorded from written informed consent 
signature up to the end of the safety follow-up, whether or not they are related to the study. Any 
SAEs/AESIs considered related to the investigational product and discovered by the investigator 
at any time after the study should be reported. Note: allograft rejection is a primary study 
endpoint to be reported as a study outcome, not as an adverse event. Instances of acute rejection 


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67 
 
 
  
 
that meet serious criteria should be captured on the Suspected Acute Rejection and Kidney 
Allograft Biopsy eCRFs as outlined in Section 12.2.  
 
All SAEs/AESIs must be reported within 24 hours by submitting a SAE/AESI Report Form by 
email to:  
 
ICON Patient Safety  
Email: icon-mads@iconplc.com 
 
Alternatively, the SAE Report Form can be submitted by fax to:  
 
ICON Patient Safety  
Fax: 1-215-616-3096 
Additional follow-up information, if required or available, should all be reported within one 
business day of receipt, should be completed on a follow-up SAE/AESI form, placed with the 
original SAE/AESI information and kept with the appropriate section of the eCRF and/or study 
file. 
The designated sponsor representative (ICON) will work with the investigator to ensure that all 
the necessary information is provided within 1 calendar day of initial receipt for fatal and life-
threatening events and within 5 calendar days of initial receipt for all other SAEs/AESIs. 
Viela Bio, Inc. or designee is responsible for notifying the relevant regulatory authorities of 
certain events. It is the PI
Independent Ethics Committee 
(IEC) of all SAEs/AESIs that occur at his or her site. Investigators will also be notified of all 
unexpected, serious, drug-related events (7/15 Day Safety Reports) that occur during the clinical 
trial.  Each site is responsible for notifying its IRB or IEC of these additional SAEs/AESIs. 
14. 
STATISTICS  
14.1. 
General Considerations for Data Analysis  
For continuous data, number of observations, the mean, standard deviation, median, minimum 
and maximum will be reported. For categorical data, percent and frequency will be reported. 
Details of the statistical analysis will be specified in a separate Statistical Analysis Plan (SAP).  
14.1.1. 
Analysis Set  
14.1.1.1. Safety analysis set  
Safety analysis set includes all subjects who received any dose of IP.  The safety, 
pharmacodynamics, and anti-drug antibody analyses will be based on the safety analysis set. 
14.1.1.2.  Efficacy evaluable set   
Efficacy evaluable set includes all subjects who received the revised regimen of Thymoglobulin 
and steroids, and any dose of IP. The efficacy analysis will be based on the efficacy evaluable 
set. 


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14.1.1.3. Pharmacokinetic analysis set  
Pharmacokinetic (PK) analysis set includes all subjects who received IP and have at least 
one quantifiable plasma PK observation post-first dose. The PK analysis will be based on the PK 
analysis set. 
14.1.2. 
Procedure for Accounting for Missing Data  
All analyses will be based on actual observed data. Missing values will not be imputed.  
14.2. 
Statistical Methods  
14.2.1. 
Efficacy  
14.2.1.1. Primary Efficacy Endpoint  
The primary efficacy variable is the incidence of efficacy failure, defined as treated biopsy-
proven acute rejection (tBPAR) of grade 1A or higher, graft loss or death, at Week 24 post-
transplantation. For the primary analysis the acute rejection rating will be based on the consensus 
of the pathologists at the initial two participating sites. 
14.2.1.2. Primary Efficacy Analysis  
The primary efficacy endpoint will be analyzed descriptively. The incidence of efficacy failure, 
defined as tBPAR of grade 1A or higher, graft loss or death, at Week 24 post-transplantation will 
be calculated, and the corresponding 80% 2-sided exact confidence interval will be calculated. 
14.2.1.3. Secondary Efficacy Endpoints  
In addition to Week 24, the incidence of efficacy failure as defined in Section 14.2.1.2 will be 
analyzed at Week 12 and Week 48.  
The following secondary efficacy variables will be analyzed at Weeks 12, 24 and 48: 
 Incidence of tBPAR, graft loss, death or loss to follow-up (LTFU) 
 Incidence of antibody-mediated rejection 
 Incidence of tBPAR 
 Incidence of BPAR 
 Incidence of treated acute rejections 
 Proportion of subjects with dnDSA 
14.2.1.4. Secondary Efficacy Analyses  
The secondary efficacy endpoints will be analyzed in the same way as the primary efficacy 
endpoint, at Weeks 12, 24 and 48.    


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14.2.2. 
Safety  
14.2.2.1. Safety Endpoints  
Safety endpoints will include: 
 TEAEs and SAEs 
 TEAE of special interest 
 Thrombotic and embolic events 
 
 
 Anaphylaxis and clinically significant (CTCAE grade 3 or higher) 
hypersensitivity reactions 
 Immune complex disease 
 Severe infusion-related reactions (CTCAE Grade 3 or higher) 
 Malignant neoplasm 
 Infections: 
o Clinically significant (CTCAE Grade 3 or higher) infections 
o Opportunistic infections (including but not limited to reactivation of latent 
viral infection [varicella zoster virus (VZV), herpes simplex virus (HSV), 
Epstein-Barr virus (EBV), JC virus (JCV), cytomegalovirus (CMV), and 
BK polyoma virus], fungal infections and tuberculosis 
 Laboratory data (laboratory variables by visit, change from baseline of laboratory 
variables by visit) 
 Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, body 
temperature and body weight) by visit 
 ECG by visit 
14.2.2.2. Safety Analysis  
AEs will be coded using the most recent version of Medical Dictionary for Regulatory Activities 
(MedDRA). All TEAEs will be summarized overall and by MedDRA System Organ Class and 
Preferred Term, by severity and by relationship to investigational product. Specific AEs will be 
counted once for each subject for calculating rates, but will be presented in total in subject 
listings. In addition, if the same AE occurs multiple times within a particular subject, the highest 
severity and level of causality will be reported. In addition, SAEs and AEs of special interest 
(AESIs) will be summarized. Other safety parameters, including laboratory assessments, vital 
signs, and ECG, will be summarized by absolute value at each visit, together with the 
corresponding changes from baseline, and shift from baseline if applicable. 


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14.2.2.3. Immunogenicity  
The number and percentage of subjects who develop detectable ADA will be summarized. The 
impact of ADA on PK and the association with AEs and SAEs will be assessed if data allow. 
14.2.3. 
Analysis of Pharmacokinetics  
Descriptive statistics of the VIB4920 plasma concentration will be summarized over visits. 
Individual and mean plasma concentration-time profiles of VIB4920 will be generated. Non-
compartmental analysis will be performed. 
When possible, the following PK parameters will be accessed for VIB4920 concentration: 
maximum observed concentration (Cmax), area under the concentration-time curve (AUC), 
systemic clearance (CL), and terminal elimination half-life (t½). Additional PK parameters may 
be determined and reported as appropriate. Descriptive statistics for PK parameters will be 
provided.  
The potential PK exposure-response relationship for efficacy and safety outcomes with VIB4920 
when combined with belatacept will be evaluated in an exploratory manner. 
14.2.4. 
Exploratory endpoints:  
 Proportion of 
 60 mL/min at 12, 24 and 48 weeks 
 Changes in 
 between Week 4 and Week 24; Week 4 and Weeks 48; Week 
24 and Week 48 
 Changes over time in 
 to VIB4920 pharmacology or disease 
activity 
 Changes over time in the 
 
.  
14.2.5. 
Interim Analysis   
No interim analysis is planned for the study. 
14.2.6. 
Sample Size and Power Considerations  
Belatacept added to standard induction therapy (basiliximab, MMF, corticosteroids) resulted in 
efficacy failure in 21.7% of recipients of living- and standard criteria deceased-donor kidneys by 
1 year (Nulojix® USPI). With 20 subjects, if we observe 3 or fewer subjects with efficacy failure 
least 70%. 
 
CCI
CCI
CCI


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15. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS  
15.1. 
Study Monitoring  
Before an investigational site can enter a subject into the study, a representative of Viela Bio, 
Inc. or of the CRO will visit the investigational study site to: 
 Determine the adequacy of the facilities. 
 Discuss with the investigator(s) and other personnel their responsibilities with regard 
to protocol adherence, and the responsibilities of Viela Bio, Inc. or its representatives. 
This will be documented in a Clinical Study Agreement between Viela Bio, Inc. and 
the investigator. 
During the study, a monitor from Viela Bio, Inc. or representative will have regular contacts with 
the investigational site, for the following: 
 Provide information and support to the investigator(s). 
 Confirm that facilities remain acceptable. 
 Confirm compliance with the principles of GCP and regulatory requirements. 
 Review of written informed consent forms for subjects screened/enrolled 
 Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs, and that investigational product accountability 
checks are being performed. 
 Perform source data verification. This includes a comparison of the data in the case 
report forms with the subject
records relevant to the study for accuracy and completeness. This will require direct 
access to all original medical and other trial related records for each subject (e.g. 
clinic charts). 
 Record and report any protocol deviations not previously sent to Viela Bio, Inc. 
 Confirm AEs and SAEs have been properly documented on eCRFs and confirm any 
SAEs have been forwarded to Viela Bio, Inc. or representative and those SAEs that 
met criteria for reporting have been forwarded to the IRB. 
During scheduled monitoring visits, the Investigator and the investigational site staff must be 
available to meet with the study monitor in order to discuss the progress of the study, make 
necessary corrections to CRF entries, respond to data clarification requests and respond to any 
other study-related inquiries of the monitor. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
15.2. 
Audits and Inspections  
Authorized representatives of Viela Bio, Inc., a regulatory authority, an IEC or an IRB may visit 
the site to perform audits or inspections, including source data verification. The purpose of a 
Viela Bio, Inc. audit or inspection is to systematically and independently examine all study-


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related activities and documents to determine whether these activities were conducted, and data 
were recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of 
the International Council for Harmonization (ICH), and any applicable regulatory requirements. 
Initial IRB approval, and all materials approved by the IRB for this study including the patient 
consent form and recruitment materials must be maintained by the Investigator and made 
available for inspection. 
In addition to the above, representatives of Viela Bio, Inc.
auditing staff or government 
inspectors may review the conduct/results of the study at the investigational site.   
The investigator should contact Viela Bio, Inc. immediately if contacted by a regulatory agency 
about an inspection. The Investigator cooperates with the auditor(s), makes available to the 
auditor all requested documentation, and ensures that issues detected during the course of these 
audits are satisfactorily resolved.  The Investigator supplies Viela Bio, Inc. with copies of all 
documentation and correspondence related to regulatory agency audits as outlined in the Clinical 
Trial Agreement.  If the results of the audit result in a Form FDA-483 (or similar document from 
another regulatory agency), the Investigator promptly provides a copy to a Viela Bio, Inc. 
representative and a draft response to Viela Bio, Inc. prior to submission to the regulatory 
agency. 
 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE  
To ensure compliance with GCP and all applicable regulatory requirements, Viela Bio, Inc. may 
conduct a quality assurance audit. Please see Section 15.2 for more details regarding the audit 
process. 
17. 
ETHICS  
17.1. 
Ethics Review  
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC as appropriate. The investigator must submit 
written approval to Viela Bio, Inc. or representative before he or she can enroll any patient into 
the study. 
The PI is responsible for informing the IRB or IEC of any amendment to the protocol in 
accordance with local requirements. In addition, the IRB or IEC must approve all advertising 
used to recruit subjects for the study. The protocol must be re-approved by the IRB or IEC upon 
receipt of amendments and annually, as local regulations require. 
The PI is also responsible to adhere to requirements stipulated by the respective IRB/IEC and for 
providing the IRB/IEC with reports of any reportable serious adverse drug reactions from any 
other study conducted with the investigational product. Viela Bio, Inc. will provide this 
information to the PI. 


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Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
Copies of all correspondence between the Investigator and the IRB/IEC is provided to Viela Bio, 
Inc.
 
17.2. 
Ethical Conduct of the Study  
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP, applicable regulatory requirements 
and the Viela Bio, Inc.  policy on Bioethics. 
17.3. 
Written Informed Consent  
The PI(s) 
will ensure that the patient or 
legally authorized representative is given full and adequate oral and written information about 
the nature, purpose, possible risk and benefit of the study. Patients or legally authorized 
representative must also be notified that they are free to discontinue from the study at any time. 
Patients or legally authorized representative will be informed that their study record and medical 
records/documents that pertain directly to the study will be reviewed and possibly copied by 
Viela Bio, Inc. or its designee, or a governmental agency (such as the FDA), and that every effort 
will be made to maintain patient confidentiality. The patient or legally authorized representative 
should be given the opportunity to ask questions and allowed time to consider the information 
provided. 
The Informed Consent must be witnessed and dated by the Investigator or his/her designee, and 
 
 
 signed and dated informed consent must be 
obtained before conducting any study procedures. 
The PI(s) must maintain the original, signed ICF. A copy of the signed ICF must be given to the 
patient or legally authorized representative.  
Subjects may be re-screened within 30 days under the current and signed ICF. 
The informed consent document must be fully approved by an institutional review board (IRB) 
or an independent ethics committee (IEC) prior to its use with study participants. 
 
18. 
DATA HANDLING AND RECORD KEEPING  
18.1. 
Inspection of Records  
Viela Bio, Inc. will be allowed to conduct site visits to the investigation facilities for the purpose 
of monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. 


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18.2. 
Retention of Records  
The PI must maintain all documentation relating to the study for a period of 2 years after the last 
marketing application approval, or if not approved 2 years following the discontinuance of the 
test article for investigation. If it becomes necessary for Viela Bio, Inc. or the Regulatory 
Authority to review any documentation relating to the study, the Investigator must permit access 
to such records. 
 
19. 
PUBLICATION POLICY  
Publication of study data is addressed in the Clinical Trial Agreement between Viela Bio, Inc. 
and Investigator(s) and/or Institution(s).   
 
 


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20. 
LIST OF REFERENCES  
Adams, A. B., Ford, M. L. and Larsen, C. P. (2016). "Costimulation Blockade in Autoimmunity 
and Transplantation: The CD28 Pathway." J Immunol 197(6): 2045-2050. 
 
 
Albulescu, M., Müller-Ladner, U., Moate, R., et al. (2018). "VIB4920, a Novel, Engineered 
CD40L Antagonist Decreased Disease Activity and Improved Biomarkers of Immune Activation 
in Patients with Active Rheumatoid Arthritis in a Phase 1b, Multiple-Ascending Dose Proof-of-
Concept Study." Arthritis Rheumatol 70. 
 
 
Elster, E. A., Xu, H., Tadaki, D. K., et al. (2001). "Treatment with the humanized CD154-
specific monoclonal antibody, hu5C8, prevents acute rejection of primary skin allografts in 
nonhuman primates." Transplantation 72(9): 1473-1478. 
 
 
Ferguson, R., Grinyo, J., Vincenti, F., et al. (2011). "Immunosuppression with belatacept-based, 
corticosteroid-avoiding regimens in de novo kidney transplant recipients." Am J Transplant 
11(1): 66-76. 
 
 
Food and Drug Administration (2017). "NULOJIX (belatacept) for injection, for intravenous use. 
HIGHLIGHTS OF PRESCRIBING INFORMATION ". 
 
 
Food and Drug Administration (2017). "THYMOGLOBULIN (anti-thymocyte globulin [rabbit]) 
for intravenous use. HIGHLIGHTS OF PRESCRIBING INFORMATION ". 
 
 
Grinyo, J. M., Del Carmen Rial, M., Alberu, J., et al. (2017). "Safety and Efficacy Outcomes 3 
Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant 
Recipients: Results From a Phase 2 Randomized Trial." Am J Kidney Dis 69(5): 587-594. 
 
 
Haas, M., Loupy, A., Lefaucheur, C., et al. (2018). "The Banff 2017 Kidney Meeting Report: 
Revised diagnostic criteria for chronic active T cell mediated rejection, antibody-mediated 
rejection, and prospects for integrative endpoints for next-generation clinical trials." American 
Journal of Transplantation 18(2): 293-307. 
 
 
Kanmaz, T., Fechner, J. J., Jr., Torrealba, J., et al. (2004). "Monotherapy with the novel human 
anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model." 
Transplantation 77(6): 914-920. 
 
 
Kawai, T., Andrews, D., Colvin, R. B., et al. (2000). "Thromboembolic complications after 
treatment with monoclonal antibody against CD40 ligand." Nat Med 6(2): 114. 
 
 
Kenyon, N. S., Chatzipetrou, M., Masetti, M., et al. (1999). "Long-term survival and function of 
intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154." Proc Natl 
Acad Sci U S A 96(14): 8132-8137. 
 
 
Kenyon, N. S., Fernandez, L. A., Lehmann, R., et al. (1999). "Long-term survival and function 
of intrahepatic islet allografts in baboons treated with humanized anti-CD154." Diabetes 48(7): 
1473-1481. 


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Kirk, A. D., Burkly, L. C., Batty, D. S., et al. (1999). "Treatment with humanized monoclonal 
antibody against CD154 prevents acute renal allograft rejection in nonhuman primates." Nat Med 
5(6): 686-693. 
 
 
Kirk, A. D., Guasch, A., Xu, H., et al. (2014). "Renal transplantation using belatacept without 
maintenance steroids or calcineurin inhibitors." Am J Transplant 14(5): 1142-1151. 
 
 
Kirk, A. D., Harlan, D. M., Armstrong, N. N., et al. (1997). "CTLA4-Ig and anti-CD40 ligand 
prevent renal allograft rejection in primates." Proc Natl Acad Sci U S A 94(16): 8789-8794. 
 
 
Kirk, A. D., Knechtle, S. and Sollinger, H. (2001). Preliminary results of the use of humanized 
anti-CD154 in human renal allotransplantation. 
 
 
Knechtle, S. J., Kirk, A. D., Fechner, J. H., Jr., et al. (1999). "Inducing unresponsiveness by the 
use of anti-CD3 immunotoxin, CTLA4-Ig, and anti-CD40 ligand." Transplant Proc 31(3B 
Suppl): 27S-28S. 
 
 
Kover, K. L., Geng, Z., Hess, D. M., et al. (2000). "Anti-CD154 (CD40L) prevents recurrence of 
diabetes in islet isografts in the DR-BB rat." Diabetes 49(10): 1666-1670. 
 
 
Larsen, C. P., Alexander, D. Z., Hollenbaugh, D., et al. (1996). "CD40-gp39 interactions play a 
critical role during allograft rejection. Suppression of allograft rejection by blockade of the 
CD40-gp39 pathway." Transplantation 61(1): 4-9. 
 
 
Larsen, C. P., Elwood, E. T., Alexander, D. Z., et al. (1996). "Long-term acceptance of skin and 
cardiac allografts after blocking CD40 and CD28 pathways." Nature 381(6581): 434-438. 
 
 
Naesens, M., Kuypers, D. R. and Sarwal, M. (2009). "Calcineurin inhibitor nephrotoxicity." Clin 
J Am Soc Nephrol 4(2): 481-508. 
 
 
Nashan, B., Tedesco, H., van den Hoogen, M. W., et al. (2018). CD40 Inhibition with CFZ533 - 
A New, Fully Human, Non-Depleting, Fc Silent mAB - Improves Renal Allograft Function 
While Demonstrating Comparable Efficacy vs. Tacrolimus in De-Novo CNI-Free Kidney 
Transplant Recipients. 
 
 
Pearson, T. C., Trambley, J., Odom, K., et al. (2002). "Anti-CD40 therapy extends renal allograft 
survival in rhesus macaques." Transplantation 74(7): 933-940. 
 
 
Pierson, R. N., 3rd, Chang, A. C., Blum, M. G., et al. (1999). "Prolongation of primate cardiac 
allograft survival by treatment with ANTI-CD40 ligand (CD154) antibody." Transplantation 
68(11): 1800-1805. 
 
 
Preston, E. H., Xu, H., Dhanireddy, K. K., et al. (2005). "IDEC-131 (anti-CD154), sirolimus and 
donor-specific transfusion facilitate operational tolerance in non-human primates." Am J 
Transplant 5(5): 1032-1041. 


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Qian, Y., Boisgerault, F., Benichou, G., et al. (2001). "Blockade of CD40-CD154 costimulatory 
pathway promotes survival of allogeneic corneal transplants." Invest Ophthalmol Vis Sci 42(5): 
987-994. 
 
 
Sampson, H. A., Munoz-Furlong, A., Campbell, R. L., et al. (2006). "Second symposium on the 
definition and management of anaphylaxis: summary report--Second National Institute of 
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium." J Allergy 
Clin Immunol 117(2): 391-397. 
 
 
Schuler, W., Bigaud, M., Brinkmann, V., et al. (2004). "Efficacy and safety of ABI793, a novel 
human anti-human CD154 monoclonal antibody, in cynomolgus monkey renal 
allotransplantation." Transplantation 77(5): 717-726. 
 
 
Shirasugi, N., Adams, A. B., Durham, M. M., et al. (2002). "Prevention of chronic rejection in 
murine cardiac allografts: a comparison of chimerism- and nonchimerism-inducing costimulation 
blockade-based tolerance induction regimens." J Immunol 169(5): 2677-2684. 
 
 
Thompson, P., Cardona, K., Russell, M., et al. (2011). "CD40-specific costimulation blockade 
enhances neonatal porcine islet survival in nonhuman primates." Am J Transplant 11(5): 947-
957. 
 
 
Tung, T. H., Mackinnon, S. E. and Mohanakumar, T. (2003). "Long-term limb allograft survival 
using anti-CD40L antibody in a murine model." Transplantation 75(5): 644-650. 
 
 
Vincenti, F. (2016). "Belatacept and Long-Term Outcomes in Kidney Transplantation." N Engl J 
Med 374(26): 2600-2601. 
 
 
Vincenti, F., Charpentier, B., Vanrenterghem, Y., et al. (2010). "A phase III study of belatacept-
based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT 
study)." Am J Transplant 10(3): 535-546. 
 
 
Wang, J. H., Skeans, M. A. and Israni, A. K. (2016). "Current Status of Kidney Transplant 
Outcomes: Dying to Survive." Adv Chronic Kidney Dis 23(5): 281-286. 
 
 
Wojciechowski, D., Chandran, S., Yang, J. Y. C., et al. (2017). "Retrospective evaluation of the 
efficacy and safety of belatacept with thymoglobulin induction and maintenance everolimus: A 
single-center clinical experience." Clin Transplant 31(9). 
 
 
Xu, H., Montgomery, S. P., Preston, E. H., et al. (2003). "Studies investigating pretransplant 
donor-specific blood transfusion, rapamycin, and the CD154-specific antibody IDEC-131 in a 
nonhuman primate model of skin allotransplantation." J Immunol 170(5): 2776-2782. 
 
 
Zhang, T., Pierson, R. N., 3rd and Azimzadeh, A. M. (2015). "Update on CD40 and CD154 
blockade in transplant models." Immunotherapy 7(8): 899-911. 
 


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APPENDICES  
 
 


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APPENDIX 1. I
ENT  
 
I have received and read the latest version of the 
VIB4920 (formerly 
MEDI4920). I have read the protocol VIB4920.P2.S1 and agree to conduct the study as outlined. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol.  
 
______________ 
Site Number 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 
 
 
 
 


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APPENDIX 2. NATIONAL INSTITUTE OF ALLERGY AND 
INFECTIOUS DISEASE (NIAID) AND FOOD AND 
ALLERGY ANAPHYLAXIS NETWORK (FAAN) 
GUIDANCE FOR ANAPHYLAXIS DIAGNOSIS  
NIAID and FAAN define anaphylaxis as a serious allergic reaction that is rapid in onset and may 
cause death (Sampson, Munoz-Furlong et al. 2006). They recognize 3 categories of anaphylaxis, 
with criteria designated to capture from 80% of cases (category 1) to >95% of all cases of 
anaphylaxis (for all 3 categories).  
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-
uvula) AND AT LEAST ONE OF THE FOLLOWING 
a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours): 
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen 
lips-tongue-uvula) 
b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia) 
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in 
systolic BP 
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
 
 
 
 
 
 
 




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APPENDIX 4. ACTIONS REQUIRED IN CASES OF INCREASES IN 
LIVER BIOCHEMISTRY A
S 
LAW  
Introduction 
This Appendix describes the process to be followed to identify and appropriately report cases of 
biochemistries.  
During the study the investigator will remain vigilant for increases in liver biochemistry. The 
investigator is responsible for deter
criteria at any point during the study. 
The investigator participates, together with Viela Bio clinical project representatives, in review 
and assessment of cases meeting PHL criteria to agree whether 
HL criteria are met if there is no alternative explanation for the elevations in liver biochemistry 
other than Drug Induced Liver Injury (DILI) caused by the investigational product.  
The investigator is responsible for recording data pertaining to PHL/HL cases and for reporting 
adverse events (AE) and serious adverse events (SAE) according to the outcome of the review 
and assessment in line with standard safety reporting processes. 
 
Definitions 
 
Aspa
following the start of investigational product irrespective of an increase in alkaline phosphatase 
(ALP). 
 
investigational product, can be found to explain the combination of increases; e.g., elevated ALP 
indicating cholestasis, viral hepatitis, another drug.   
For PHL and HL the elevation in transaminases must precede or be coincident with (i.e., on the 
same day) the elevation in TBL, but there is no specified timeframe within which the elevations 
in transaminases and TBL must occur. 
 
To identify cases of PHL it is important to perform a comprehensive review of laboratory data 
for any subject who meets any of the following identification criteria in isolation or in 
combination: 
 
 
 AS
 
 
 


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The investigator will without delay review each new laboratory report and if the identification 
criteria are met will: 
 Notify the sponsor study representative 
 Determine whether the subject meets PHL criteria by reviewing laboratory reports 
from all previous visits 
 Promptly enter the laboratory data into the laboratory eCRF 
 
Follow-up 
 
If the subject does not meet PHL criteria the investigator will: 
 Inform the sponsor representative that the subject has not met PHL criteria 
 Perform follow-up on subsequent laboratory results according to the guidance 
provided in the Clinical Study Protocol. 
 
If the subject does meet PHL criteria the investigator will notify the sponsor study representative 
who will then inform the central study team. The medical monitor contacts the investigator, to 
-up and the 
continuous review of data. After this contact the investigator will: 
 Monitor the subject until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically 
indicated  
 Investigate the etiology of the event and perform diagnostic investigations as 
discussed with the medical monitor.  
 If at any time (in consultation with the medical monitor) the PHL case meets serious 
criteria, report it as an SAE using standard reporting procedures 
Cases  
The instructions in this section should be followed for all cases where PHL criteria are met. 
No later than 3 weeks after the biochemistry abnormality was initially detected, the medical 
monitor will contact the investigator to review available data and agree on whether there is an 
alternative explanation for meeting PHL criteria other than DILI caused by the investigational 
product. The medical monitor and safety physician will also be involved in this review together 
with other subject matter experts as appropriate.   
According to the outcome of the review and assessment, the investigator will follow the 
instructions below. 


Protocol v4.0 Final 23Jul2021  
 
 VIB4920.P2.S1 
 
84 
 
 
  
 
If there is an agreed alternative explanation for the ALT or AST and TBL elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for a SAE: 
 If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate eCRF 
 If the alternative explanation is an AE/SAE, record the AE /SAE in the eCRF 
accordingly and follow the sponsor standard processes 
If it is agreed that there is no explanation that would explain the ALT or AST and TBL 
elevations other than the investigational product: 
 
 
 
apply 
 As there is no alternative explanation for the HL case, a causality assessment of 
 
If, there is an unavoidable delay, of over 3 weeks, in obtaining the information necessary to 
assess whether or not the case meets the criteria for HL, then it is assumed that there is no 
alternative explanation until an informed decision can be made: 
 
causality assessment as per above 
 Continue follow-up and review according to agreed plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to 
determine whether HL criteria are met. Update the SAE report according to the 
outcome of the review 
 
-induced liver injury: Premarketing clinical 
 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM174090.pdf 


PPD
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Statistical Analysis Plan 
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VIELA BIO, INC. 
 
STATISTICAL ANALYSIS PLAN 
Investigational Product: 
VIB4920 
Protocol Number: 
VIB4920.P2.S1 
 
A PHASE 2A SINGLE-ARM, PROSPECTIVE, OPEN-LABEL 
PILOT STUDY TO EVALUATE THE SAFETY AND 
EFFICACY OF DUAL COSTIMULATION BLOCKADE WITH 
VIB4920 AND BELATACEPT FOR PROPHYLAXIS OF 
ALLOGRAFT REJECTION IN ADULTS RECEIVING A 
KIDNEY TRANSPLANT 
 
 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ...........................................................................................4 
1 
INTRODUCTION ......................................................................................................5 
2 
Study Overview ...........................................................................................................5 
2.1 
Study Objectives and Endpoints...........................................................................5 
2.2 
Study Design ...........................................................................................................6 
2.2.1 
Overview ...........................................................................................................6 
2.3 
Sample Size .............................................................................................................7 
3 
Statistical Methods ......................................................................................................7 
3.1 
General Considerations .........................................................................................7 
3.1.1 
Definition of Baseline .......................................................................................8 
3.1.2 
Analysis Windows ............................................................................................8 
3.2 
Protocol Deviations ................................................................................................8 
3.3 
Analysis Sets ...........................................................................................................9 
3.3.1 
Safety analysis set .............................................................................................9 
3.3.2 
Pharmacokinetics analysis set .........................................................................9 
3.4 
Study Subjects ........................................................................................................9 
3.4.1 
Subject Disposition...........................................................................................9 
3.4.2 
Demographics, Baseline Characteristics, and Medical History .................10 
3.4.3 
Study Drug Exposure ....................................................................................10 
3.4.4 
Prior and Concomitant Medications ............................................................10 
3.5 
Efficacy Analyses .................................................................................................11 
3.5.1 
Primary Efficacy Endpoint(s) and Analyses ...............................................11 
3.5.1.1 
Primary efficacy endpoint .......................................................................11 
3.5.1.2 
Primary efficacy analysis ........................................................................11 
3.5.2 
Secondary Efficacy Endpoints and Analyses ..............................................11 
3.5.2.1 
Secondary efficacy endpoints ..................................................................11 
3.5.2.2 
Secondary efficacy analysis .....................................................................12 
3.5.3 
Exploratory Efficacy Endpoints and Analyses ...........................................12 
3.5.3.1 
Exploratory efficacy endpoints ...............................................................12 
3.5.3.2 
Exploratory efficacy analysis ..................................................................12 
3.6 
Safety Analysis .....................................................................................................12 
3.6.1 
Adverse Events ...............................................................................................12 
3.6.2 
Clinical Laboratory Evaluation ....................................................................13 
3.6.3 
Other Safety Evaluations ..............................................................................14 
3.7 
Pharmacokinetics .................................................................................................15 
3.8 
Immunogenicity....................................................................................................15 
3.9 
Exploratory Analyses...........................................................................................16 
4 
Planned Analysis .......................................................................................................16 
4.1 
Primary Efficacy Analysis ...................................................................................16 
4.2 
Final Efficacy Analysis ........................................................................................16 
4.3 
Final Analysis .......................................................................................................17 
 
LIST OF TABLES 
Table 1 
Study Objectives and Endpoints.....................................................................5 
Table 2 
Laboratory Results Analysis .........................................................................13 


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Table 3 
Definition of ADA Status ...............................................................................16 
LIST OF FIGURES 
Figure 1 
Study Flow Diagram ..................................................................................7 
Figure 2 
Subject Disposition.....................................................................................9 


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LIST OF ABBREVIATIONS 
Abbreviation or Specialized Term 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
BPAR 
biopsy-proven acute rejection 
CMV 
cytomegalovirus  
CSR 
clinical study report 
CTCAE 
common terminology criteria for adverse events 
DGF 
delayed graft function 
 
 
HLA 
human leukocyte antigen 
IP 
investigational product 
IV 
intravenous 
PK 
pharmacokinetics 
PRA 
Panel Reactive Antibody test 
PT 
preferred term 
QTc 
corrected QT interval 
SAE 
serious adverse event 
SOC 
system organ class 
SPP 
statistical programming plan 
tBPAR 
treated biopsy-proven acute rejection 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
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1 INTRODUCTION 
This document describes the statistical analysis for protocol VIB4920.P2.S1, a Phase 2a, 
prospective single-arm, open-label pilot study to evaluate the efficacy, safety, and tolerability 
of dual costimulation blockade with VIB4920 + belatacept in adult male or female recipients 
of a renal allograft from a deceased, living unrelated, or human leukocyte antigen (HLA) 
non-identical living related donor. 
2 STUDY OVERVIEW 
2.1 
Study Objectives and Endpoints 
The objectives and corresponding endpoints are listed in Table 1 below: 
Table 1 
Study Objectives and Endpoints 
Primary objective 
Endpoints/variables 
• To demonstrate that, when added to standard-of-
care induction regimen that includes 
Thymoglobulin® (anti-thymocyte globulin 
[rabbit]) and corticosteroids, dual costimulation 
blockade with multiple doses of VIB4920 + 
belatacept, started at the time of kidney transplant 
surgery and repeated every 2-4 weeks post-
transplantation, prevents composite efficacy 
failure (tBPAR of grade 1A or higher, graft loss, 
or death) at Week 24 post-transplantation in the 
majority of subjects (≥ 17/20) 
• Incidence of efficacy failure, defined as treated 
biopsy-proven acute rejection (tBPAR) of grade 
1A or higher, graft loss, or death, at Week 24 
post-transplantation 
Secondary objectives 
Endpoints/variables 
• To evaluate individual components (and 
combinations of the individual components) of 
the composite efficacy endpoint at Weeks 12, 24, 
and 48 post-transplantation. 
• Incidence of efficacy failure, defined as treated 
biopsy-proven acute rejection (tBPAR) of grade 
1A or higher, graft loss, or death, at Weeks 12 and 
48 post-transplantation 
• Incidence of tBPAR, graft loss, death, or loss to 
follow-up at Weeks 12, 24, and 48 
post-transplantation 
• Incidence of antibody-mediated rejection at 
Weeks 12, 24, and 48 post-transplantation 
• Incidence of tBPAR at Weeks 12, 24, and 48 
post-transplantation 
• Incidence of BPAR at Weeks 12, 24, and 48 post-
transplantation 
• Incidence of treated acute rejections at Weeks 12, 
24, and 48 post-transplantation 
• Proportion of subjects with de novo 
donor-specific antibodies (dnDSA) at Weeks 12, 
24, and 48 post-transplantation 
• To evaluate safety and tolerability of dual 
costimulation blockade with VIB4920 + 
• Treatment-emergent adverse events and 
treatment-emergent serious adverse events (TEAE 
and TESAE) 


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Table 1 
Study Objectives and Endpoints 
belatacept in subjects receiving a kidney 
transplant 
• Treatment-emergent adverse events of special 
interest (TEAESI) 
• Laboratory data by visit 
• Vital signs data by visit 
• ECG data by visit 
• To evaluate the pharmacokinetics (PK) and 
immunogenicity (anti-drug antibodies [ADA]) of 
VIB4920 
• VIB4920 plasma concentration over visits 
• PK parameters 
• Proportion of subjects who develop detectable 
ADA 
Exploratory objectives 
Endpoints/variables 
• Evaluate 
 at Weeks 4, 12, 24, and 
 
 
 in subjects receiving a 
kidney transplant 
• Proportion of subjects with 
 at 
Weeks 12, 24, and 48 
• Changes in 
 between Week 4 and 
Week 24; Week 4 and Week 48; and Week 24 and 
Week 48 
• To understand 
in 
 
 and 
 in blood 
related to pharmacology of VIB4920 
• Changes over time in 
 related 
to VIB4920 pharmacology 
• To evaluate the 
 of 
 
 on 
 
• Changes over time in the 
 
 and 
 
 
ADA = anti-drug antibodies; dnDSA = de novo donor-specific antibodies; ECG = electrocardiogram; 
 
MDRD = modification of diet in renal disease; PK = pharmacokinetics; tBPAR = treated 
biopsy-proven acute rejection; TEAE = treatment-emergent adverse event; TEAESI = treatment-emergent 
adverse event of special interest; TESAE = treatment-emergent serious adverse event 
2.2 
Study Design 
2.2.1 
Overview 
This is a single-arm, open-label exploratory study. The study will be conducted at 2 centers in 
the United States in a total of approximately 20 subjects. All eligible subjects will undergo 
the scheduled kidney transplant on Day 0 and be treated with VIB4920 + belatacept (with 
Thymoglobulin and corticosteroids) according to the following regimen: 
• Thymoglobulin 1.5 mg/kg by intravenous (IV) infusion prior to reperfusion of the 
allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept 
infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion 
on post-op Day 3 or 4 
• Methylprednisolone by IV infusion (500, 250, 125 and 60 mg on Days 0, 1, 2 and 3, 
respectively) followed by oral administration of prednisone 30 mg per day on Days 4, 5, 6 
and 7. Subjects may be tapered to at least 20 mg per day on Day 8, to at least 10 mg per 
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day on Day 15, and to at least 5 mg per day on Day 22. Discontinuation of prednisone 
should occur following the post-op Day 28 visit. 
• VIB4920 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4 
(timing is at investigator’s discretion), Week 2, and at the end of Weeks 4, 6, 8, and 10; 
then 1500 mg every 4 weeks from Week 12 to Week 48. 
• Belatacept 10 mg/kg by IV infusion on post-op Day 1 (first dose ≥ 12 hours after 
Thymoglobulin infusion ends), repeated on post-op Day 3 or 4 (timing is at investigator’s 
discretion), and at the end of Weeks 2, 4, 8, and 12; then 5 mg/kg IV every 4 weeks from 
Week 16 to Week 48. 
VIB4920 should be administered prior to belatacept. The basic study flow diagram is 
presented in Figure 1Figure 1. 
Figure 1 
Study Flow Diagram 
 
2.3 
Sample Size 
The protocol was amended after 3 subjects were enrolled under the protocol v2.0. 
Approximately 20 subjects will be enrolled under protocol v3.0. 
Belatacept added to standard induction therapy (basiliximab, mycophenolate mofetil, 
corticosteroids) resulted in efficacy failure in 21.7% of recipients of living- and standard 
criteria deceased-donor kidneys by 1 year (Nulojix® USPI). With 20 subjects, if 3 or fewer 
subjects are observed with efficacy failure (ie, response rate ≥ 85%) at week 24, there is 
> 89% confidence that the response rate is at least 70%. 
3 STATISTICAL METHODS 
3.1 
General Considerations 
All statistical calculations will be primarily performed using SAS® System Version 9.4 or 
higher. Categorical data will be summarized by the frequency counts and percentage of 
subjects in each category. Continuous variables will be summarized by descriptive statistics, 
including number of observations, mean, standard deviation, median, first quartile, third 
quartile, minimum, and maximum. 


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3.1.1 
Definition of Baseline 
In general, baseline will be defined as the last non-missing valid observation prior to the first 
administration of VIB4920 or belatacept, whichever occurs first. In cases where baseline 
measurements are taken on the same day as investigational product (IP) and no times are 
reported, it will be assumed that these measurements are taken prior to IP being administered. 
For 
 the baseline will be defined as Week 4 
measurement. 
3.1.2 
Analysis Windows 
Analysis visit windows will be used for all visit-based assessments to map longitudinal 
observations to scheduled visits and, thereby, allow for by-visit analyses, since not all 
assessments are performed on the scheduled day. Unless otherwise specified, all longitudinal 
efficacy and safety data analyses will be based on the analysis visit windows. The analysis 
visit windows will be calculated by bisecting the interval between adjacent scheduled visit 
days and will be specified in the statistical programming plan (SPP). 
The actual assessment day will be mapped to the windows defined for each scheduled study 
visit with following rules:  
• If more than one assessment falls within a visit window, the closest non-missing 
assessment to the scheduled day will be used in the analysis. 
• If 2 non-missing assessment actual dates are equidistant from the target day, the later 
visit will be used in the analysis. 
• For retest values of laboratory data, the retest value (the last valid observation 
assessed on the same visit day) will be chosen. 
3.2 
Protocol Deviations 
All protocol deviations will be classified as either major protocol deviations or minor 
protocol deviations. The major protocol deviations are considered as the important protocol 
deviations, which may significantly impact the completeness, accuracy, and/or reliability of 
the study data, and may significantly affect a subject’s rights, safety, or well-being. All the 
protocol deviations will be listed, and the major protocol deviation will be summarized. Some 
classifications of major protocol deviations are listed below. 
• Did not meet inclusion criteria or met exclusion criteria. 
• Received prohibited concomitant medication. 
• Met IP discontinuation criteria but was not discontinued from the IP.  
• Serious breach of good clinical practice. 
The list may be updated and will be finalized and documented prior to the database lock. 
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3.3 
Analysis Sets 
3.3.1 
Safety analysis set 
The safety analysis set includes all subjects who received any dose of IP. The safety, 
pharmacodynamics, and anti-drug antibodies (ADA) analyses will be based on the safety 
analysis set. 
3.3.2 
Efficacy evaluable set  
Efficacy evaluable set includes all subjects who received the revised regimen of 
Thymoglobulin and steroids, and any dose of IP. The efficacy analysis will be based on the 
efficacy evaluable set. 
3.3.3 
Pharmacokinetics analysis set 
The pharmacokinetics (PK) analysis set includes all subjects who receive IP and have at least 
one quantifiable serum PK observation post-first dose. PK analyses will be based on the PK 
analysis set. 
3.4 
Study Subjects 
3.4.1 
Subject Disposition 
A summary of subject disposition will be presented using the categories presented in 
Figure 2. 
Figure 2 
Subject Disposition 
 
Completed VIB4920 treatment 
Completed belatacept treatment 
Treated with VIB4920 + 
belatacept 
Underwent transplant 
surgery 
Screened 
Underwent transplant surgery 
but not treated with VIB4920 + 
belatacept 
Screen failed with reasons 
Discontinued VIB4920 with 
reasons 
Discontinued belatacept with 
reasons 
Discontinued study with 
reasons 
Completed study 


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3.4.2 
Demographics, Baseline Characteristics, and Medical History 
The demographics (age, gender, race, ethnicity, height, weight, and body mass index) will be 
summarized. 
Subject background information, including end-stage renal disease leading to transplantation, 
current dialysis (none, hemodialysis, peritoneal dialysis), highest Panel Reactive Antibody 
(PRA) test, most recent PRA, and HLA type, will be summarized. Donor background 
information, including sex, race, ethnicity, transplant donor type (living related, living 
unrelated, deceased heart beating, deceased non-heart beating), will be summarized as well. 
Significant medical history finding will be summarized by MedDRA system organ class 
(SOC) and preferred term (PT). 
3.4.3 
Study Drug Exposure 
VIB4920 and belatacept 
The number of doses received, amount of the study drug received, durations of the study drug 
exposure, and treatment compliance will be summarized for VIB4920 and belatacept 
separately. 
• Durations of the study drug exposure = last dose date + 28 ‒ first dose date + 1. 
• The amount of study drug exposure: if a subject received partial dose at a dosing visit, 
then the amount of study drug at that dosing visit will be estimated based on the actual 
volume administered. 
• Treatment compliance for an individual subject = [Total number of doses received]/ 
[Total number of doses planned per protocol] ×100%. 
Thymoglobulin and corticosteroids 
Subjects will receive IV thymoglobulin1.5 mg/kg prior to reperfusion of the allograft on the 
day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 
1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4. 
Number (%) of subjects who received thymoglobulin will be summarized by Day. 
Subjects will receive methylprednisolone by IV infusion (500, 250, 125, and 60 mg on Days 
0, 1, 2, and 3, respectively) followed by oral administration of prednisone 30 mg per day on 
Days 4, 5, 6 and 7. Subjects may be tapered to at least 20 mg per day on Day 8, to at least 10 
mg per day on Day 15, and to at least 5 mg per day on Day 22. Discontinuation of prednisone 
should occur following the post-op Day 28 visit. The methylprednisolone and oral prednisone 
dose in mg/day will be summarized by Day (Days 0, 1, 2, 3, Day 4 - Day 7, Day 8 - Day14, 
Day 15 - Day 21, Day 22 - Day 28). The total corticosteroid dose in mg will also be 
summarized. 
3.4.4 
Prior and Concomitant Medications 
Number (%) of subjects who received prior medications and concomitant medications will be 
summarized by WHO Drug dictionary. At each level of summarization, a subject is counted 


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once if the subject reported one or more medications at that level. The prior and concomitant 
medications are defined as below. 
• Prior medications are defined as medications with a stop date occurring before the IP 
administration date. 
• Concomitant medications are defined as medications with a start date on or after the 
IP administration date or stop date occurring on or after the IP administration date. 
The missing start/stop date will be imputed as appropriate and the details of the imputation 
will be included in the SPP. 
Number (%) of subjects who received the following medications will be summarized. 
• Medications used for the treatment of suspected or confirmed acute rejections. 
• Prophylaxis medications for each of cytomegalovirus (CMV), Pneumocystis jirovecii 
pneumonia, and oral Candida. 
3.5 
Efficacy Analyses 
3.5.1 
Primary Efficacy Endpoint(s) and Analyses 
3.5.1.1 
Primary efficacy endpoint 
The primary efficacy endpoint is the incidence of efficacy failure, defined as treated 
biopsy-proven acute rejection (tBPAR) of grade 1A or higher, graft loss, or death at Week 24 
post-transplantation. 
3.5.1.2 
Primary efficacy analysis 
For the primary efficacy analysis, the acute rejection rating will be based on the consensus of 
the pathologists at the 2 participating sites. 
The primary efficacy endpoint will be analyzed descriptively. The incidence of efficacy 
failure, defined as tBPAR of grade 1A or higher, graft loss, or death at Week 24 
post-transplantation, and the corresponding 80% 2-sided exact confidence interval will be 
calculated. Missing data will not be imputed. 
3.5.2 
Secondary Efficacy Endpoints and Analyses 
3.5.2.1 
Secondary efficacy endpoints 
The secondary efficacy endpoints are as follows: 
• Incidence of efficacy failure defined as tBPAR of grade 1A or higher, graft loss, or 
death at Weeks 12 and 48 
• Incidence of tBPAR, graft loss, death, or loss to follow-up at Weeks 12, 24, and 48 
• Incidence of antibody-mediated rejection at Weeks 12, 24, and 48 


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• Incidence of tBPAR at Weeks 12, 24, and 48 
• Incidence of BPAR at Weeks 12, 24, and 48 
• Incidence of treated acute rejections at Weeks 12, 24, and 48 
• Proportion of subjects with de novo donor-specific antibodies at Weeks 12, 24, and 48 
3.5.2.2 
Secondary efficacy analysis 
The secondary efficacy endpoints will be analyzed in the same way as the primary efficacy 
endpoint. 
3.5.3 
Exploratory Efficacy Endpoints and Analyses 
3.5.3.1 
Exploratory efficacy endpoints 
The exploratory efficacy endpoints are as follows: 
• Proportion of subjects with 
 at 12, 24, and 48 weeks 
• Changes in 
 between Week 4 and Week 24; Week 4 and Weeks 48; and 
Week 24 and Week 48 
3.5.3.2 
Exploratory efficacy analyses 
Proportion of subjects with 
 and the 
 2-sided exact 
confidence interval will be calculated. The 
 will be summarized by visit. The 
missing 
 will not be imputed. 
3.6 
Safety Analysis 
3.6.1 
Adverse Events 
In general, if an adverse event (AE) onset is on or after the first dose of VIB4920 or 
belatacept, whichever occurs first, the AE will be considered as a treatment-emergent adverse 
event (TEAE). Otherwise, the AE will be considered as a non-TEAE. 
AEs will be coded using the most recent version of MedDRA. All TEAEs will be 
summarized overall and by MedDRA SOC and PT, by severity and by relationship to IP. 
Specific AEs will be counted once for each subject for calculating rates, but all events will be 
presented in subject listings. In addition, if the same AE occurs multiple times within a 
particular subject, the highest severity and level of causality will be reported. 
An overall summary table will be showing the number and percentage of subjects with at 
least one event in any of the following categories: TEAE, treatment-emergent serious adverse 
event (TESAE), TEAE with outcome of death, Grade 3 or higher TEAE, TEAE leading to 
discontinuation of VIB4920, TEAE leading to discontinuation of belatacept, VIB4920 related 
TEAE, belatacept related TEAE, VIB4920 related TESAE, and belatacept related TESAE. 
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The TEAEs, TESAEs, TEAEs resulting in death, Grade 3 or higher TEAEs, TEAE leading to 
discontinuation of VIB4920, TEAE leading to discontinuation of belatacept, VIB4920 related 
TEAE, belatacept related TEAE, VIB4920 related TESAE, and belatacept related TESAE 
will be summarized by SOC and PT. TESAEs will be summarized by serious adverse event 
(SAE) criteria as well. In addition, a summary of TEAEs sorted by frequency will be 
presented by PT. The treatment emergent non-SAE will also be summarized by SOC and PT. 
An adverse event of special interest (AESI) is one of scientific and medical interest specific 
to understanding of the IP. AESIs for this protocol include: 
• Thrombotic and embolic events 
• Hepatic function abnormality (meeting the definition of Hy’s Law) 
• Anaphylaxis and clinically significant (common terminology criteria for adverse 
events [CTCAE] Grade 3 or higher) hypersensitivity reactions 
• Immune complex disease 
• Severe infusion-related reactions (CTCAE Grade 3 or higher) 
• Malignant neoplasm 
• Infections: 
− Clinically significant (CTCAE Grade 3 or higher)  
− Opportunistic infections associated with immunosuppression, including (but not 
limited to): reactivation of latent viral infection (varicella zoster virus, herpes simplex 
virus, Epstein-Barr virus, JC virus, CMV, BK polyoma virus), fungal infections, and 
tuberculosis. 
Treatment-emergent adverse events of special interest will be summarized by SOC and PT. 
Listings will be provided for all TEAEs and non-treatment emergent AEs. 
3.6.2 
Clinical Laboratory Evaluation 
The analysis for the laboratory results are listed in Table 2. 
Table 2 
Laboratory Results Analysis 
Laboratory dataset 
Planned Analysis 
Hematology, Chemistry, 
and Coagulation 
• Summary of the toxicity grade defined using the national cancer institute’s 
common terminology criteria for adverse events (NCI CTCAE) 
• Summary of at least 2-grade shift from the baseline to the worst post-baseline 
toxicity grade  
• Summary of shift from the baseline relative to the normal range 
• Summary of observed values and changes from the baseline  


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Table 2 
Laboratory Results Analysis 
Laboratory dataset 
Planned Analysis 
• Summary of potential Hy’s law cases 
Urinalysis 
• Summary of observed values and changes from the baseline 
• Summary of shift from the baseline relative to the normal range 
Spot Urine Protein 
Creatinine Ratio 
• Summary of observed values and changes from the baseline 
• Proportion of subjects with urine protein/creatinine ratio CR < 0.5 
Immunoglobulins 
• Summary of observed values and changes from the baseline 
3.6.3 
Other Safety Evaluations 
Overdose 
The incidence of TEAEs associated with overdose will be summarized by MedDRA SOC 
and PT, if applicable. 
Delayed Graft Function 
Subjects are considered to have delayed graft function (DGF) when: 
• A dialysis is performed, where DGF is the reported reason, and/or 
• DGF is reported as an AE 
The proportion of subjects experienced DGF will be summarized. 
Vital Signs 
The observed values, along with the changes from baseline, will be summarized for systolic 
blood pressure, diastolic blood pressure, body temperature, heart rate, and respiratory rate. In 
addition, a summary of subjects with clinically significant vital signs values (meeting any of 
following criteria) will also be provided. 
Systolic blood pressure: < 90 mmHg, > 160 mmHg 
Diastolic blood pressure: < 60 mmHg, > 100 mmHg 
Heart rate: < 50 beats/min, > 100 beats/min 
Respiratory rate: < 12 breaths/min, > 23 breaths/min 
Temperature: < 36°C, >38°C 


Statistical Analysis Plan 
VIB4920 
VIB4920.P2.S1 
26May2020, Version 2.0 
 
CONFIDENTIAL AND PROPRIETARY 
Page 15 of 17 
 
 
Electrocardiogram 
The observed values, along with the changes from baseline, will be summarized for 
ventricular heart rate, PR interval, QRS duration, QT interval, and the corrected QT interval 
(QTc). The number (%) of subjects meeting the following criteria will be summarized: 
• QTc > 450 msec 
• QTc > 480 msec 
• QTc > 500 msec 
• QTc increases from baseline > 30 msec 
• QTc increases from baseline > 60 msec 
In addition, the overall clinical evaluation of electrocardiogram results (normal, abnormal, 
not clinically significant abnormal, clinically significant abnormal) will also be summarized. 
Physical Examination and Weight 
The clinically important abnormal findings from the physical examinations will be recorded 
as AEs. The observed values and the changes from baseline in the weight will be 
summarized. 
3.7 
Pharmacokinetics 
The PK components of the clinical study report (CSR) will be generated and reported by the 
PK group. 
VIB4920 plasma concentration will be summarized descriptively by visits. VIB4920 
concentration-time profiles will be generated. Noncompartmental analysis will be performed 
for VIB4920-treated subject. Descriptive statistics for PK parameters will be provided.  
Plasma concentration of VIB4920, summary statistics, PK profile, and the additional 
PK-related analyses will be reported either in the CSR or in a clinical PK report as an 
addendum to the CSR. 
The potential PK exposure-response relationship for efficacy and safety outcomes with 
VIB4920 when combined with belatacept, and as a monotherapy if feasible, will be evaluated 
in an exploratory manner. 
3.8 
Immunogenicity 
The ADA status in Table 3 will be summarized by the categories included in the table and the 
ADA titer may be summarized for ADA positive subjects. The impact of ADA on safety may 
be evaluated if needed. The ADA incidence rate may also be summarized, where the 
incidence is the proportion of the subjects with ADA positive post-baseline only or boosted 
their pre-existing ADA during the study period. The cutoff for the boosted ADA will be 
finalized and documented before the database lock. 


Statistical Analysis Plan 
VIB4920 
VIB4920.P2.S1 
26May2020, Version 2.0 
 
CONFIDENTIAL AND PROPRIETARY 
Page 16 of 17 
 
 
Table 3 
Definition of ADA Status 
ADA Status 
Definition 
Prevalence (Positive during the study) 
ADA positive observed at least once during the study (baseline 
included) 
Negative during the study 
ADA positive not observed at any visit during the study (baseline 
included) 
Baseline positive 
ADA positive observed at baseline regardless of the post-baseline 
ADA status 
Post-baseline positive 
ADA positive observed at least once during post-baseline 
regardless of the baseline ADA status 
Only baseline positive 
ADA positive observed at baseline but not observed at any time 
post-baseline 
Only post-baseline positive 
(treatment-induced) 
ADA positive not observed at baseline but observed at least once 
post-baseline  
Both baseline and post-baseline positive 
ADA positive observed at baseline and observed at least once 
post-baseline 
Persistent positive 
Treatment-induced ADA positive at ≥ 2 post-baseline 
assessments (with ≥ 16 weeks between first and last positive) or 
positive at last post-baseline assessment 
Transient positive 
Treatment-induced ADA post-baseline positive but does not fulfil 
the criteria of persistent positive 
ADA = anti-drug antibodies. 
3.9 
Exploratory Analyses 
The following exploratory endpoints may be summarized descriptively. 
• Changes over time in 
 related to VIB4920 pharmacology. 
• Changes over time in the 
, and 
 
 
4 PLANNED ANALYSIS 
4.1 
Primary Efficacy Analysis 
The primary efficacy analysis will be performed when all subjects have completed Week 24 
or withdrawn prior to Week 24 visit. All available data at the time of the data cut-off will be 
included in the analysis. 
4.2 
Final Efficacy Analysis 
The final efficacy analysis will be performed when all subjects have completed Week 48 or 
withdrawn prior to Week 48 visit. All available data at the time of the data cut-off will be 
included in the analysis. 
CCI
CCI
CCI




Signature Page for VV-CLIN-001786 v1.0
Signature Page for VV-CLIN-001786 v1.0
Approval
26-May-2020 12:23:45 GMT+0000
Approval
26-May-2020 15:31:26 GMT+0000
PPD
PPD