Clinical trial NCT01974206
Conditions: Kidney Transplantation Cytomegalovirus (CMV) Negative Recipients
Keywords: ASP0113 Cytomegalovirus (CMV) Kidney Transplantation
Sponsor: Astellas Pharma Global Development, Inc.
Start date: 2013-11-20; Completion date: 2020-11-05
Enrollment: 150 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence of cytomegalovirus (CMV) viremia in CMV-seronegative subjects receiving a kidney from a CMV-seropositive donor. This study also evaluated the safety of ASP0113 in this patient population.

Detailed description:
Participants were followed for one year after first study drug injection. This was the primary study period.

Participants were followed for 4.5 years after completion of the primary study to assess long-term safety of the vaccine.

Arms: arm 1: Participants received 1 mL of 5 mg/mL of ASP0113 via injection in the deltoid muscle alternating sides with each dose on days 30, 60, 90, 120 and 180 in relation to the day of transplant (Day 0). arm 2: Participants received 1 mL of 5 mg/mL of placebo via injection in the deltoid muscle alternating sides with each dose on days 30, 60, 90, 120 and 180 in relation to the day of transplant (Day 0).
Interventions: intervention 1: ASP0113 intervention 2: Placebo
Intervention descriptions: intervention 1: intramuscular injection intervention 2: intramuscular injection

Protocol documents:
Prot_000.pdf: 
A Randomized, Double-Blind, Placebo-Controlled, Phase 
2 Trial to Evaluate the Efficacy and Safety of a Vaccine, 
ASP0113, in Cytomegalovirus (CMV)-Seronegative 
Kidney Transplant Recipients Receiving an Organ from a 
CMV-Seropositive Donor
ISN/Protocol 0113-CL-2001
ClinicalTrials.gov Identifier: NCT01974206
Date of Protocol: Final Version 3.0, 06 Jan 2014
Sponsor: Astellas Pharma Global Development, Inc. (APGD)
1 Astellas Way
Northbrook, IL 60062


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL-
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 1 of 177
Version 3.0, Incorporating Substantial Amendment 2
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial 
to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, 
in Cytomegalovirus (CMV)-Seronegative Kidney Transplant 
Recipients Receiving an Organ from a CMV-Seropositive Donor
Protocol for Phase 2 Study of ASP0113
ISN/Protocol 0113-CL-2001
Version 3.0
Incorporating Substantial Amendment 2 [See Attachment 1]
06 January 2014
IND 11,381
EudraCT 2013-000464-29
Sponsor:
Astellas Pharma Global Development, Inc. (APGD)
1 Astellas Way
Northbrook, IL 60062
Document History:
Original Version 1.0 [29Apr2013]
Version 2.0 Incorporating Substantial Amendment 1 [13Aug2013]
---------------------------------------------------------------------------------------------------------------------
This confidential document is the property of the Sponsor.  No unpublished information contained in this 
document may be disclosed without prior written approval of the Sponsor.


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL-
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 2 of 177
Version 3.0, Incorporating Substantial Amendment 2
Table of Contents
I.
SIGNATURES ······················································································ 8
II.
CONTACT DETAILS OF KEY SPONSOR’S PERSONNEL···························10
III.
LIST OF ABBREVIATIONS AND DEFINITION OF KEY TERMS ··················11
IV.
SYNOPSIS··························································································17
V.  
FLOW CHART AND SCHEDULE OF ASSESSMENTS·································26
Table 1: Schedule of Assessments······································································27
Table 1a: Plasma Viral Load Schedule ································································28
Table 2:  Schedule of Assessments – Long-term Follow-up Period································32
1
INTRODUCTION·················································································33
1.1
Background ····················································································33
1.1.1
Non-clinical and Clinical Data·························································33
1.1.2
Clinical Data ·············································································34
1.1.3
Phase 1 (VCL-CB01-101) Results ····················································34
1.1.4
Phase 2 (CB01-202) Results ···························································35
Table 3:  Viral Load Endpoints after 12-Month Follow-up in the CB01-202 Study – Per 
Protocol Population ···········································································36
1.2
Summary of Key Safety Information for Study Drugs ···································37
1.3
Risk-Benefit Assessment·····································································37
2
STUDY OBJECTIVE(S), DESIGN, AND ENDPOINTS ··································38
2.1
Study Objectives ··············································································38
2.2
Study Design and Dose Rationale···························································38
2.2.1
Study Design·············································································38
2.2.2
Dose Rationale···········································································41
2.3
Endpoints·······················································································41
2.3.1
Primary Efficacy Endpoints····························································41
2.3.2
Secondary Efficacy Endpoints·························································41
2.3.3
Exploratory Efficacy Endpoints ·······················································41
2.3.4
Immunogenicity Variables ·····························································42
2.3.5
Safety Variables ·········································································42
3
STUDY POPULATION··········································································43
3.1
Selection of Study Population ·······························································43


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL-
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 3 of 177
Version 3.0, Incorporating Substantial Amendment 2
3.2
Inclusion Criteria··············································································43
3.3
Exclusion Criteria ·············································································44
4
TREATMENT(S)··················································································46
4.1
Identification of Investigational Product(s) ················································46
4.1.1
Test Vaccine(s) ··········································································46
4.1.2
Placebo····················································································47
4.2
Packaging and Labeling ······································································47
4.3
Study Drug Handling ·········································································47
4.4
Blinding ························································································48
4.4.1
Retention of the Assignment Schedule and Procedures for Treatment Code 
Breaking ··················································································48
4.4.2
Breaking the Treatment Code by the Sponsor ·······································48
4.5
Assignment and Allocation ··································································49
5
TREATMENTS AND EVALUATION························································50
5.1
Dosing and Administration of Study Drug(s) and Other Medication(s)················50
5.1.1
Dose/Dose Regimen and Administration Period ····································50
5.1.2
Increase or Reduction in Dose of the Study Drug ···································50
5.1.3
CMV Prophylactic Therapy····························································50
5.1.3.1
Viral Prophylaxis ··································································51
5.1.3.2
Pneumocystis jiroveci Pneumonia Prophylaxis ································51
5.1.3.3
Prohibited Concomitant Medication·············································51
5.1.3.4
Concomitant Medication (Drugs and Therapies) ······························51
5.1.4
Treatment Compliance··································································52
5.2
Demographics and Baseline Characteristics ···············································52
5.2.1
Demographics············································································52
5.2.2
Medical History··········································································52
5.2.3
Transplant Information ·································································52
5.2.4
Donor Information ······································································52
5.2.5
Recipient Information···································································53
5.3
Efficacy and Immunogenicity Assessments ···············································53
5.3.1
Primary Efficacy Assessment··························································53
5.3.2
Secondary Efficacy Assessments······················································53
5.3.3
Exploratory Efficacy Assessments ····················································53
5.3.3.1
Immunogenicity····································································54


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL-
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 4 of 177
Version 3.0, Incorporating Substantial Amendment 2
5.3.4
Resource Utilization and Patient Reported Outcomes ······························54
5.3.4.1
EQ-5D···············································································55
5.3.4.2
Kidney Transplant Questionnaire················································55
5.3.4.3
SF-12 Health Survey Version 2··················································55
5.3.4.4
Health Economic Assessment (HEA) ···········································55
5.4
Safety Assessment ············································································56
5.4.1
Vital Signs················································································56
5.4.2
Adverse Events ··········································································56
5.4.2.1
Adverse Events of Possible Hepatic Origin ····································57
5.4.3
Local Reactogenicity Assessments····················································57
5.4.4
Systemic Reactogenicity Assessments················································57
5.4.5
Laboratory Assessments································································57
5.4.6
Physical Examination···································································59
5.4.7
Home Health Care Service ·····························································60
5.4.8
Long Term Follow-Up··································································60
5.5
Adverse Events and Other Safety Aspects ·················································60
5.5.1
Definition of Adverse Events (AEs) ··················································60
5.5.2
Adverse Events of Special Interest ····················································61
5.5.2.1
Adverse Events Commonly Associated with Vaccines ·······················61
5.5.2.2
Infection ············································································61
5.5.2.3
Post-Transplant Lymphoproliferative Disorder (PTLD)······················61
5.5.3
Definition of Serious Adverse Events (SAEs) ·······································62
5.5.4
Criteria for Causal Relationship to the Study Drug ·································63
5.5.5
Criteria for Defining the Severity of an Adverse Event ····························63
5.5.6
Reporting of Serious Adverse Events (SAEs) ·······································64
5.5.7
Follow-up of Adverse Events··························································65
5.5.8
Monitoring of Common Serious Adverse Events ···································65
5.5.9
Procedure in Case of Pregnancy·······················································65
5.5.10
Emergency Procedures and Management of Overdose ·····························66
5.5.11
Supply of New Information Affecting the Conduct of the Study··················66
5.6
Test Drug Concentration ·····································································66
5.7
Other Measurements, Assessments or Methods ···········································66
5.7.1
Blood Sample for Future PGx Analysis (Retrospective PGx Analysis) ··········66
5.8
Total Amount of Blood·······································································67
6
DISCONTINUATION············································································67


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL-
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 5 of 177
Version 3.0, Incorporating Substantial Amendment 2
6.1
Discontinuation of Individual Subject(s)···················································67
6.1.1
Study and Treatment Discontinuation ················································68
6.2
Discontinuation of the Site···································································68
6.3
Discontinuation of the Study·································································68
7
STATISTICAL METHODOLOGY ···························································69
7.1
Sample Size····················································································69
7.2
Analysis Sets···················································································69
7.2.1
Full Analysis Set (FAS) ································································70
7.2.2
Per Protocol Set (PPS) ··································································70
7.2.3
Safety Analysis Set (SAF)······························································70
7.2.4
Pharmacogenomics Set (PGS) ·························································70
7.3
Demographics and Other Baseline Characteristics········································70
7.4
Analysis of Efficacy ··········································································70
7.4.1
Analysis of Primary Efficacy Endpoint···············································71
7.4.1.1
Primary Analysis···································································71
7.4.1.2
Secondary Analysis································································71
7.4.1.3
Subgroup Analysis·································································71
7.4.2
Analysis of Secondary Efficacy Endpoints···········································71
7.4.3
Analysis of Exploratory Endpoints····················································72
7.4.4
Immunogenicity Analysis ······························································73
7.5
Analysis of Pharmacogenomic Data ························································73
7.6
Analysis of Safety·············································································73
7.6.1
Adverse Events ··········································································73
7.6.2
Clinical Laboratory Evaluation ························································74
7.6.3
Vital Signs Evaluation ··································································75
7.6.4
Physical Examination···································································75
7.7
Protocol Deviations and Other Analyses···················································75
7.8
Interim Analysis (and Early Discontinuation of the Clinical Study)····················76
7.8.1
Safety ·····················································································76
7.8.2
Efficacy···················································································76
7.9
Handling of Missing Data, Outliers, Visit Windows, and Other Information ·········76
8
OPERATIONAL AND ADMINISTRATIVE CONSIDERATIONS ····················77
8.1
Procedure for Clinical Study Quality Control ·············································77


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL-
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 6 of 177
Version 3.0, Incorporating Substantial Amendment 2
8.1.1
Data Collection ··········································································77
8.1.1.1
Patient Reported Outcomes (pPRO)·············································78
8.1.2
Specification of Source Documents···················································78
8.1.3
Clinical Study Monitoring······························································78
8.1.4
Direct Access to Source Data/Documents············································78
8.1.5
Data Management ·······································································79
8.1.6
Protocol Deviations ·····································································79
8.1.7
End of Trial in All Participating Countries···········································80
8.2
Ethics and Protection of Subject Confidentiality··········································80
8.2.1
Institutional Review Board (IRB) / Independent Ethics Committee (IEC) / 
Competent Authorities (CA) ···························································80
8.2.2
Ethical Conduct of the Study···························································80
8.2.3
Informed Consent of Subjects ·························································81
8.2.3.1
Subject Information and Consent················································81
8.2.3.2
Supply of New and Important Information Influencing the Subject’s 
Consent and Revision of the Written Information ·····························81
8.2.4
Subject Confidentiality ·································································81
8.3
Administrative Matters ·······································································82
8.3.1
Arrangement for Use of Information and Publication of the Clinical Study ·····82
8.3.2
Documents and Records Related to the Clinical Study ·····························82
8.3.3
Protocol Amendment and/or Revision················································82
8.3.4
Insurance of Subjects and Others······················································83
8.3.5
Signatory Investigator for Clinical Study Report····································83
9
QUALITY ASSURANCE········································································83
10
STUDY ORGANIZATION······································································84
10.1
Data Monitoring Committee (DMC) ·······················································84
10.2
Other Study Organization ····································································84
10.2.1
Adjudication Committee (AC)·························································84
11
REFERENCES ····················································································85
12
APPENDICES ·····················································································87
12.1
Appendix 1:  List of Excluded Concomitant Medications ·······························87
12.2
Appendix 2:  Laboratory Tests ······························································88
12.3
Appendix 3:  4 Variable MDRD ····························································90
12.4
Appendix 4:  Grading of Local Reactogenicity············································91


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12.5
Appendix 5:  Grading of Signs of Systemic Reactogenicity·····························92
12.6
Appendix 6:  Grading of Acute Kidney Allograft Rejection·····························93
12.7
Appendix 7:  Definition of CMV Disease in Solid Organ Transplant Recipients·····95
12.8
Appendix 8:  Opportunistic Infections······················································97
12.9
Appendix 9:  Special Infections Related to Kidney Transplant··························99
12.10
Appendix 10:   Liver Safety Monitoring and Assessment······························ 100
12.11
Appendix 11:  Common Serious Adverse Events······································· 103
12.12
Appendix 12:  Categories of Post Transplant Lymphoproliferative Disorder 
(PTLD) ······················································································· 104
12.13
Appendix 13:  EQ-5D Questionnaire ····················································· 105
12.14
Appendix 14:  Kidney Transplant Questionnaire (KTQ-34)··························· 109
12.15
Appendix 15:  SF-12········································································ 112
12.16
Appendix 16:   Retrospective Pharmacogenomics (PGx) Sub-Study················· 113
12.17
Appendix 17:  Long-term Follow-up Questionnaire···································· 115
12.18
Appendix 18:  Health Economic Assessment (Inpatient and Outpatient 
Utilization)··················································································· 116
13
ATTACHMENT 1:  SUBSTANTIAL AMENDMENT 2 ································ 117
14
SPONSOR’S SIGNATURES·································································· 177


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I. SIGNATURES
1.  SPONSOR’S SIGNATURE
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the 
Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-
Seronegative Kidney Transplant Recipients Receiving an Organ from a CMV-
Seropositive Donor
ISN/Protocol 0113-CL-2001 / Version 3.0
Incorporating Substantial Amendment 2 / 06 January 2014
Required signatures (e.g., Protocol authors, Sponsor’s reviewers and contributors, etc.) are 
located in Section 14 Sponsor’s Signatures; e-signatures (when applicable) are located at the 
end of this document.


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2.  INVESTIGATOR’S SIGNATURE
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the 
Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-
seronegative Kidney Transplant Recipients Receiving an Organ from a CMV-
seropositive Donor
ISN/Protocol 0113-CL-2001 / Version 3.0
Incorporating Substantial Amendment 2 / 06 January 2014
I have read all pages of this clinical study protocol for which Astellas is the Sponsor. I agree 
to conduct the study as outlined in the protocol and to comply with all the terms and 
conditions set out therein. I confirm that I will conduct the study in accordance with ICH 
GCP guidelines and applicable local regulations. I will also ensure that sub-investigator(s) 
and other relevant members of my staff have access to copies of this protocol and the ICH 
GCP guidelines to enable them to work in accordance with the provisions of these 
documents.
Principal Investigator:
Signature:
Printed Name:
Date (DD MMM YYYY)
Address:




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III. LIST OF ABBREVIATIONS AND DEFINITION OF KEY TERMS
List of Abbreviations
Abbreviations
Description of Abbreviations
ABMR
Antibody Mediated Rejection
AC
Adjudication Committee
AE
Adverse Event
aGVHD
Acute Graft-versus-host Disease
ALP
Alkaline Phosphatase
ALT
Alanine Aminotransferase (GPT)
ANC
Absolute Neutrophil Count
ANOVA
Analysis of Variance
ANCOVA
Analysis of Covariance
AP
Alkaline Phosphatase
APEBV
Astellas Pharma Europe B.V.
APGD
Astellas Pharma Global Development, Inc.
AREC
Astellas ethical committee
AST
Aspartate Aminotransferase (GOT)
ASP0113
DNA vaccine encoding the two CMV plasmids gB and pp65 
AT
Aminotransferase
ATG
Anti-thymocyte Globulin
ATN
Acute Tubular Necrosis
AUST
Astellas US Technologies, Inc.
AVT
Antiviral Therapy
AVP
Antiviral Prophylaxis
BAK
Benzalkonium Chloride
BAL
Bronchoalveolar Lavage
BKVAN
BK Virus Associated Nephropathy
BPAR
Biopsy Proven Acute Rejection
BPP
Bayesian predictive probability 
BUN
Blood Urea Nitrogen
CA
Competent Authorities
cGVHD
Chronic Graft-Versus-Host-Disease
CI
Confidence Intervals
CIOMS
Council for International Organizations of Medical Sciences
CK
Creatinine Kinase
CMH
Cochran-Mantel-Haenszel
CMV
Cytomegalovirus
CNS
Central Nervous System
CPK
Creatine Phosphokinase
CRF
Case Report Form
CRO
Contract Research Organization
CSR
Clinical Study Report
CT
Computed Tomography
DDC
Deceased Donor Criteria
DILI
Drug-induced Liver Injury
dL
Deciliter
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic Acid


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Abbreviations
Description of Abbreviations
EBV
Epstein-Barr Virus
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
eCTD
Electronic Common Technical Document
EDC
Electronic Data Capture
eGFR
Estimated Glomerular Filtration Rate
ELISA
Enzyme-linked Immunosorbent Assay
ELISPOT
Enzyme-linked Immunosorbent Spot
EOD
End Organ Disease
EQ-5D
EuroQol – 5  dimensions 5 levels
ER
Emergency Room
EU
European Union
EudraCT
European Union Drug Regulatory Authorities Clinical Trials
FAS
Full Analysis Set
FDA
Food and Drug Administration
FSI
First Subject In
gB
Glycoprotein B
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
GPF
Global Protocol Format
GWAS
Genome-Wide Association Studies
hCG
Human Chorionic Gonadotropin
H0
Null Hypothesis
H1
Alternative Hypothesis
HBV
Hepatitis B Virus
HCT
Hematopoietic Cell Transplant
HCV
Hepatitis C Virus
HEA
Health Economics Assessment
HEOR
Health Economics and Outcomes Research
HHC
Home Healthcare
HHV
Human Herpes Virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HLA
Human Leukocyte Antigen
HSV
Herpes Simplex Virus
IB
Investigator’s Brochure
ICD-9
International Classification of Diseases
ICF
Informed Consent Form
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
ICU
Intensive Care Unit
IEC
Independent Ethics Committee
IFN-
Interferon Gamma
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IM
Intramuscular
IMPD
Investigational Medicinal Product Dossier
IND
Investigational New Drug


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Abbreviations
Description of Abbreviations
INR
International Normalized Ratio
IRB
Institutional Review Board
IRT
Interactive Response Technology
ISN
International Study Number
ITT
Intent-to-treat
IU
International Unit
IUD
Intra Uterine Device
IUS
Intra Uterine System
IV
Intravenous 
IVIG
Intravenous Immunoglobulin
KTQ
Kidney Transplant Questionnaire
L
Liter
LA CRF
Liver Abnormality Case Report Form
LDT
Laboratory Developed Test
LFT
Liver Function Tests
LLOQ
Lower Limit of Quantitation
LSO
Last Subject Out
MAA
Marketing Authorization Application 
MDRD
Modification of Diet in Renal Disease
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram
mL
Milliliter
m2
Millimeter squared
MMF
Mycophenolate mofetil
mmHg
Millimeters of Mercury
NASH
Non Alcoholic Steatohepatitis
NCI-CTCAE
National Institutes of Health Common Terminology Criteria for Adverse Events
NDA
New Drug Application
NK
Natural Killer
PBS
Phosphate-buffered Saline
PCR
Polymerase Chain Reaction
PCS
Potentially Clinically Significant
PE
Physical Examination
PGS
Pharmacogenomics Set
PGx
Pharmacogenomics
PHI
Protected Health Information
PK
Pharmacokinetic
PO
Per Os (oral)
PP
Per Protocol
pp65
Phosphoprotein 65
PPS
Per Protocol Set
pPRO
Paper Patient Reported Outcomes
PTLD
Post Transplant Lymphoproliferative Disorder
QOL
Quality of Life
RBC
Red Blood Cell
RNA
Ribonucleic Acid
SAE
Serious Adverse Event
SAF
Safety Analysis Set


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Abbreviations
Description of Abbreviations
SAP
Statistical Analysis Plan
SBP
Systolic Blood Pressure
SF-12
ShortForm-12 Health Survey
SOP
Standard Operating Procedure
SOT
Solid Organ Transplant
SUSAR
Suspected Unexpected Serious Adverse Reaction
TBL
Total Bilirubin
TCMR
T-Cell Mediated Rejection
TE
Treatment-emergent
TEAE
Treatment-emergent Adverse Event
TLFs
Tables, Listings and Forms
TMF
Trial Master File
ULN
Upper Limit of Normal
VZV
Varicella Zoster Virus
WBC
White Blood Cell
WHO
World Health Organization


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Definition of Key Study Terms
Terms
Definition of terms
Adverse Event
An adverse event is any untoward medical occurrence in a subject who was 
administered a Study Drug or has undergone study procedures that does not 
necessarily have a causal relationship with the treatment.
Adverse Reaction
An adverse reaction means any adverse event caused by a drug.
Baseline
Baseline is the time point prior to the first dose of randomized Study Drug. 
Visit 2 is considered the Baseline Visit in this study. The last measurement /
evaluation prior to the first dose of randomized therapy is considered the 
baseline measure/evaluation.
CMV Infection
Replication of CMV (isolation of the virus or detection of viral protein or 
nucleic acid in any body fluid or tissue).
CMV End Organ 
Disease (EOD)
As defined in Appendix 7.
CMV Syndrome
As defined in Appendix 7.
CMV Viremia
Presence of CMV in the blood.
End of Study
The point in time when the last protocol-defined assessment has been 
completed (end of the Long-term Follow-up Period). 
End of Treatment
The point in time when the subject receives the last dose of Study Drug. 
Enrollment
The point in time when the subject signs the informed consent.
Evaluable Subject
A subject who meets all inclusion criteria and does not meet any exclusion 
criteria and who has received at least one injection of Study Drug. 
Long-term Follow-
up Period
The period of time from the Day 395 Visit (Visit 13) through the completion 
of the 4½ year additional safety follow-up.
Long-term Follow-
up Withdrawal
A subject who completes the Primary Study Period but does not complete the 
Long-term Follow-up Period for any reason.
Preemptive 
Therapy
A therapeutic treatment regimen where treatment for an infection/disease is 
initiated only after it is detected/confirmed.
Primary Follow-up 
Period
The period of time from the end of the Study Drug treatment through the Day 
395 Visit (Visit 13).
Primary Study 
Period
The period of time from enrollment (i.e., signing of informed consent) 
through the Day 395 Visit (Visit 13).
Primary Study 
Withdrawal
A subject who is randomized but does not complete the Primary Study Period 
for any reason.
Principal 
Investigator
A physician or a Pharm D approved by Astellas responsible for the conduct of 
the clinical trial at a trial site. If a trial is conducted by a team of individuals at 
a trial site, the Principal Investigator is the responsible leader of the team.
Prophylactic 
Therapy
A therapeutic treatment regimen where treatment is administered prior to the 
detectable presence of infection or disease as a preventative measure.


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Terms
Definition of terms
Randomization
The action to allocate a subject to a treatment group. In this study, 
randomization occurs after the subject has met all inclusion and exclusion 
criteria between days -14/+30 relative to the transplant date.
Reactogenicity
Local or systemic inflammatory effects relating to the study drug injection.
Screening
The process for identifying a candidate for the study and evaluating their 
eligibility to participate.
Screen Failure
A subject who signs the informed consent and undergoes the protocol-specific 
screening procedures, but does not fulfill the protocol inclusion and/or 
exclusion criteria. This subject should not be randomized.
Serious Adverse 
Event
An adverse event is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: results in 
death, is life threatening, results in persistent or significant disability / 
incapacity or substantial disruption of the ability to conduct normal life 
functions, results in congenital anomaly or birth defect, requires inpatient 
hospitalization or leads to prolongation of hospitalization, or is a medically 
important event.
Source Data
All information in original records and certified copies of original records of 
clinical findings, observations, or other activities in a clinical trial necessary 
for the reconstruction and evaluation of the trial. Source data are contained in 
source documents.
Source Documents
Original documents, data and records including source data.
Subject
An individual who participates in a clinical trial.
Treatment Period
The period of time from the first dose of Study Drug through the last dose of 
Study Drug.


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IV. SYNOPSIS
Date and Version # of Protocol Synopsis:
06 January 2014 / Version 3.0
Sponsor:  
Astellas Pharma Global Development Inc (APGD)
Protocol Number:  
0113-CL-2001
Name of Study Drug: 
ASP0113
Phase of Development:  
Phase 2
Title of Study:  
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Efficacy and 
Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant 
Recipients Receiving an Organ from a CMV-Seropositive Donor
Planned Study Period: 
First subject in (FSI) 4Q2013; Last Subject Out (LSO) 2Q2017, (Primary Study Period)
Long-term Follow-up Period LSO 4Q2021
Study Objective(s): 
1.
To evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence of CMV 
viremia (defined as plasma viral load ≥1000 IU/mL by central laboratory assay) through one 
year post first Study Drug injection in CMV-seronegative subjects receiving a kidney from a 
CMV-seropositive donor.
2.
To evaluate the safety of ASP0113 in CMV-seronegative subjects receiving a kidney from a 
CMV-seropositive donor.
Planned Total Number of Study Centers and Location(s):  
Approximately 80 sites globally
Locations: Countries may include, but are not limited to: United States, Canada, Germany, Spain,  
France and Australia 
Study Population:  
CMV-seronegative subjects who have received a kidney from a living or deceased CMV-
seropositive donor.
Number of Subjects to be Enrolled / Randomized:  
140 (70 per Treatment Group)
Study Design Overview:  
This is a randomized, double-blind, placebo-controlled trial.
140 CMV-seronegative subjects who have received a kidney from a living or deceased 
CMV-seropositive donor will be randomized 30 days ± 3 days after transplantation (Day 0) in a 
1:1 ratio to ASP0113 or placebo.
Prior to Randomization, subjects will be stratified by use of anti-thymocyte globulin and by receipt 
of a kidney from a living or deceased donor.
Subjects will receive either 5 doses of ASP0113 or 5 doses of placebo on Days 30 ± 3, 60 ± 5, 
90 ± 5, 120 ± 5, and 180 ± 5 in relation to the day of transplant.
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir or 
ganciclovir (dose per package insert) through the day of Randomization to prevent CMV disease.  
(The subject can miss up to two doses of valganciclovir or ganciclovir during this time period for 
any reason).


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Subjects will then continue to receive CMV-specific anti-viral prophylaxis (AVP) with valgan-
ciclovir or ganciclovir until 100 days post transplant. Subjects can have valganciclovir or 
ganciclovir interrupted, dose adjusted or replaced by other CMV-specific AVP per standard of care 
after the day of Randomization if renal function is compromised, there are toxicities related to the
administration of the AVP, or for any other medically indicated reason.
In all subjects, plasma will be collected for central laboratory CMV viral load testing every two 
weeks from Day 100 through Day 200, then monthly through last study visit.
In cases where CMV disease (CMV syndrome or CMV tissue-invasive disease) is suspected from 
the first Study Drug injection through Day 395, a sample for CMV viral load will be collected at the 
time of the first CMV symptom recognition and sent to a local and the central laboratory.
CMV-specific anti-viral therapy (AVT) should be initiated for CMV disease and can be initiated for 
CMV viremia based on the central or local laboratory results and standard of care.
If CMV-specific AVT is initiated, a central CMV viral load will be obtained at a minimum of 
weekly from the time CMV-specific AVT is initiated until discontinuation.  
In addition, each time a local CMV viral load sample is collected, a plasma sample will also be 
collected and sent to the central laboratory for CMV viral load testing. 
Subjects will be followed for one year post first Study Drug injection (Study completion/Day 395)
for CMV viremia, CMV syndrome, CMV tissue-invasive disease, CMV-specific AVT, graft 
survival, and subject survival. 
Subjects will be followed for one year post first Study Drug injection for resistance to valganciclovir 
or ganciclovir. Viral resistance will be assessed by a Central lab when there is no reduction in viral 
load two weeks after initiating valganciclovir/ganciclovir, when there is no improvement in clinical 
signs and symptoms two weeks after initiating valganciclovir /ganciclovir or any time it is clinically 
indicated. 
Immunogenicity to pp65 and gB will be assessed prior to Dose 1, two weeks after Dose 2, prior to 
Dose 3, two weeks after Dose 4, prior to Dose 5 and at the last study visit.  
Subjects will be evaluated for local and systemic reactogenicity 15 minutes and one hour after each 
Study Drug injection and for 7 days by subject reporting via diary after each Study Drug injection. 
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing of the 
informed consent through one year post first Study Drug injection.  
Subjects will be contacted by telephone 6 months after Day 395, then annually for the next 4 years, 
to evaluate long-term safety related to the deoxyribonucleic acid (DNA) vaccine. Mortality, 
development of any new malignancies, development of infection requiring hospitalization or 
resulting in death, graft survival, creatinine and erythema and/or induration at 
the injection sites will be assessed by questionnaire and available patient records.  
An Independent Data Monitoring Committee (DMC) will be chartered to oversee the safety of 
subjects and review of the futility analysis.
An Adjudication Committee (AC) will be chartered to adjudicate all cases of CMV syndrome, CMV 
tissue-invasive disease and CMV-specific antiviral therapy.
Inclusion/Exclusion Criteria:  
Subjects will be selected based on Inclusion and Exclusion Criteria listed. Waivers to eligibility 
criteria will not be allowed.


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Inclusion:  
1.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written 
informed consent and privacy language as per national regulations (e.g., Health Insurance 
Portability and Accountability (HIPAA) Authorization for U.S. sites) must be obtained from the 
subject or legally authorized representative prior to any study-specific procedures (including 
withdrawal of prohibited medication, if applicable).
2.
Subject is willing to comply with the protocol.
3.
Subject is ≥18 years of age or the legal age of consent (whichever is greater). 
4.
Subject is CMV-seronegative at time of transplant and has received a kidney from a CMV-
seropositive living or deceased donor. CMV serostatus of the recipient can be determined from 
8 weeks prior to transplant, by local laboratory, through day of transplantation. If CMV 
serostatus is not available from this time period, CMV serostatus may be assessed at the 
Screening Visit, by local laboratory, with results available prior to Randomization. 
5.
Subject started valganciclovir or ganciclovir within 10 days of transplant and has received it 
through Randomization, per regulatory label (package insert).
6.
Female subject must be either: 
Of non- child-bearing potential:
o
post-menopausal (defined as at least 1 year without any menses) prior to Screening, or 
o
documented surgically sterile or status post hysterectomy (at least 1 month prior to 
Screening).  
Or, if of childbearing potential:
o
must have a negative urine pregnancy test at Screening, and 
o
if heterosexually active must use two forms of birth control* (at least one of which 
must be a barrier method) starting at Screening and during the Primary Study Period.  
7.
Female subject must not be breastfeeding at Screening and during the Primary Study Period.
8.
Female subject must not donate ova starting at Screening and during the Primary Study Period.
9.
Male subject and his female spouse/partners who are of childbearing potential must be using 
highly effective contraception consisting of two forms of birth control* (one of which must be a 
barrier method) starting at Screening and during the Primary Study Period. 
*Acceptable forms of birth control include: 
Established use of oral, injected or implanted hormonal methods of contraception. 
Placement of intrauterine device (IUD) or intrauterine system (IUS). 
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault 
caps) with spermicidal foam/gel/film/cream/suppository.
Partner male sterilization (i.e., vasectomy)
10. Male subject must not donate sperm starting at Screening and during the Primary Study Period.
11. Subject agrees not to participate in another interventional drug study while on treatment.
Exclusion:  
1.
Subject is planned to undergo a course of CMV-specific prophylactic therapy with antiviral 
drugs with a duration of greater than 100 days.
2.
Subject has received from one month prior to transplant or is planning to receive CMV 
immunoglobulin.
3.
Subject has had CMV viremia or CMV disease from time of transplant until time of 
Randomization.


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4.
Subject has received, at any time, an organ transplant other than a kidney. (Dual allocation of a 
kidney is acceptable).
5.
Subject requires dialysis on the day of Randomization.
6.
Recipient or donor is known to be positive for human immunodeficiency virus (HIV), hepatitis 
B surface antigen, or hepatitis B core IgM or IgG antibody.
7.
Subject is known to have latent or active tuberculosis which has not been adequately treated.
8.
Subject required desensitization for ABO blood type incompatibility or a positive T or B cell 
crossmatch.  
9.
Subject has received any of the following substances or treatments:
a. Investigational research products within 28 days or 5 half lives whichever is longer, prior 
to Transplantation, or subject is scheduled to receive investigational research products 
through one year after Randomization. 
b. Alemtuzumab within 90 days prior to Randomization or is scheduled to receive 
alemtuzumab any time through one year post Randomization.
c. Rituximab within 120 days prior to Randomization or is scheduled to receive rituximab 
any time through one year post Randomization.  
d. Eculizumab or bortezomib from the Day of Transplantation through the Day of 
Randomization or is scheduled to receive eculizumab or bortezomib any time through one 
year post Randomization. 
e. IVIG and/or plasmapheresis from Day of Transplant through Day of Randomization.
f. Live attenuated vaccines within one month (30 days) prior to the first dose of Study Drug 
or is scheduled to receive live attenuated vaccines within one month of any Study Drug 
injection. 
g. Subunit or killed vaccines within 14 days prior to the first dose of Study Drug or is 
scheduled to receive a subunit or killed vaccine within 14 days prior to any Study Drug 
injection.
h. Administration of a CMV vaccine, including any prior exposure to ASP0113.
i. Subject has received the following anti-viral therapies or it is planned for them to receive 
the AVT for prophylaxis of viral infections in excess of the following doses from time of 
transplant through Randomization:
Aciclovir: 1600 mg orally (total daily dose), or 500 mg/m2/dose Intravenous (IV) 
(total daily dose)
Valaciclovir: 1000 mg orally (total daily dose)
Famciclovir: 500 mg orally (total daily dose) 
10. Subject has received any anticoagulants including, but not limited to, vitamin K antagonists, 
heparin or its derivatives, low molecular weight heparin, factor X inhibitors, or thrombin 
inhibitors within 5 half-lives prior to Randomization or is expected to use anticoagulants within 
5 half-lives prior to any Study Drug injection. Low dose anticoagulants that are used for 
prevention of deep vein thrombosis and antiplatelet agents are allowed.
11. Subject has any contraindication to or cannot be dosed with valganciclovir or ganciclovir per 
package insert on the Day of Randomization for any reason.
12. Subject has, or is expected to have during the Primary Study Period, a contraindication to an 
intramuscular injection.
13. Subject, within 3 days prior to Randomization, has an Aspartate Aminotransferase (AST) or 
Alanine Aminotransferase (ALT) greater than 3 x Upper Limits of Normal (ULN) or total 
bilirubin greater than 2 x ULN unless secondary to suspected Gilbert’s disease.


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14. Subject has a current malignancy or a recent history of malignancy (within the past 5 years 
prior to Screening) except non-metastatic basal or squamous cell carcinoma of the skin that has 
been treated successfully or cancer in situ of the cervix uteri that has been successfully treated 
by local therapy.
15. Subject is being treated for an active infection at the time of Randomization.  
16. Subject has any condition or an unstable medical or psychiatric condition, including a history 
of illicit drug(s) or alcohol abuse that the Investigator believes will place the subject at 
unacceptable risk or interfere with compliance to protocol requirements.
17. Subject has any other condition which, in the opinion of the Investigator, precludes the 
subject’s participation in the trial.
18. Subject has known allergies or previous adverse reactions to ganciclovir or valganciclovir.  
19. Subject has had an allergic reaction to any component of the vaccine, or to aminoglycosides, as
kanamycin is used during the manufacturing process of the vaccine.
Investigational Product(s):  
ASP0113
Dose(s):  
1 mL of a 5mg/mL solution of ASP0113 will be administered intramuscularly (IM) in the deltoid 
muscle, alternating sides with each dose, if possible.
Subjects will receive five injections of ASP0113 over an approximately 5 month period.
Mode of Administration:  
Intramuscular (IM)
Comparator:  
The Placebo is phosphate-buffered saline (PBS) 
Dose(s):
1 mL administered IM in the deltoid muscle alternating sides with each dose, if possible. Subjects 
will receive five injections of Placebo over an approximately 5 month period.
Mode of Administration:  
Intramuscular (IM)
Concomitant Medication Restrictions or Requirements:   
Concomitant Medications and Therapies
CMV Prophylaxis
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir or 
ganciclovir (dose per package insert) through Randomization to prevent CMV disease. (The subject 
can miss up to two doses of valganciclovir or ganciclovir during this time period for any reason).
After Randomization, subjects will then receive CMV-specific AVP with valganciclovir or 
ganciclovir until 100 days post transplant. Subjects can have valganciclovir or ganciclovir 
interrupted, dose adjusted or replaced by other CMV-specific AVP per standard of care after the 
Day of Randomization if renal function is compromised, there are toxicities related to the 
administration of the AVP, or for any other medically indicated reason.
Viral Prophylaxis
Viral prophylaxis for infection other than CMV should be administered according to standard 
institutional protocols. Prophylactic use of aciclovir (acyclovir), valaciclovir (valacyclovir), or 


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famciclovir should not exceed the following doses following transplant (Day 0) through one year 
post first Study Drug injection (Day 395/Visit 13). 
Aciclovir: 1600 mg orally (total daily dose), or 500 mg/m2/dose IV (total daily dose)
Valaciclovir: 1000 mg orally (total daily dose)
Famciclovir: 500 mg orally (total daily dose) 
These doses may be exceeded if necessary to treat active infections.
Pneumocystis jiroveci Pneumonia Prophylaxis
Pneumocystis jiroveci pneumonia prophylaxis must be initiated for all study participants according to 
the site’s standard practice for kidney transplant recipients and applied uniformly to all enrolled 
subjects. Dose may be adjusted or therapy interrupted for renal dysfunction, adverse events related to 
the administration of the therapy or for other clinically indicated reasons. If there is no prophylactic 
Pneumocystis protocol, the investigator must decide on appropriate Pneumocystis jiroveci pneumonia 
prophylaxis.
Prohibited Concomitant Medications (Drugs and Therapies):
Investigational research products through completion of Day 395 visit (Visit 13).
Planned Alemtuzumab and, anti-CD20 antibodies (including rituximab), eculizumab or 
bortezomib are not allowed from the Day of Randomization through  the Primary Study Period
(Day 395).  These treatments may be given after the Day of Randomization if clinically indicated.
Prophylactic use of CMV immunoglobulin. 
Live attenuated vaccines within one month (30 days) prior to each dose of Study Drug.
Subunit or killed vaccines within 14 days before any Study Drug injection. 
Anticoagulants, within 5 half-lives of Study Drug administration, including but not limited to 
vitamin K antagonists, heparin or its derivatives, low molecular weight heparin, factor X 
inhibitors, or thrombin inhibitors. Low dose anticoagulants that are used for prevention of deep 
vein thrombosis and antiplatelet agents are allowed.  
Duration of Treatment:  
Subjects will receive either 5 doses of ASP0113 or 5 doses of placebo on Days 30 ±3, 60 ±5, 90 ±5, 
120 ±5, and 180 ±5 in relation to the day of transplant.  
Discontinuation Criteria:
Study and Treatment Discontinuation
Subjects will be withdrawn from investigational study treatment and all follow up assessments and 
will only be followed for mortality through public records if the following occurs: 

Withdrawal of consent by the subject.
Treatment Only Discontinuation
Subjects should continue to be followed according to the study Schedule of Assessments and Long 
Term Follow-up Schedule of Assessments, except post-dose Day 14 safety and laboratory and 
reactogenicity assessments/visits for those doses not given, but will be withdrawn from 
investigational study treatment if any of the following occur:  
Investigator’s decision that further treatment is not in the best interest of the subject.
Graft failure
Pregnancy (female subjects only).


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Local reactogenicity with a grade ≥ 3 based on the criteria defined in appendices and confirmed 
by a health care professional.
Systemic reactogenicity for any grade ≥3 fever or any other grade 4 systemic reaction within one 
week of vaccination and confirmed by a health care professional.
Anaphylaxis Grade ≥ 3 per NCI ver. 4.03 criteria.
Long Term Follow-up Period
Subjects will only be followed for mortality through public records in case of withdrawal of consent 
by the subject. 
Endpoints for Evaluation:  
Primary Efficacy
Incidence of CMV viremia (defined as plasma viral load of ≥ 1000 IU/mL by central assay) through 
one year post first Study Drug injection.
Secondary Efficacy
Incidence of:

Adjudicated CMV disease, including CMV syndrome and CMV tissue-invasive disease 
through one year post first Study Drug injection.

CMV viremia (defined as plasma viral load ≥the lower limit of quantification [LOQ]) by central 
assay through one year post first Study Drug injection. 

Adjudicated CMV-specific antiviral therapy for the treatment of CMV viremia or disease 
through one year post first Study Drug injection.

Graft survival through one year post first Study Drug injection.

Subject survival through one year post first Study Drug injection.
Exploratory Efficacy

Number of opportunistic infections other than CMV through one year post first Study Drug
injection.

Time to first CMV viremia (defined as plasma viral load of ≥1000 IU/mL by central assay) 
through one year post study first Study Drug injection.

Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-invasive 
disease, through one year post first Study Drug injection.

Number of episodes of CMV viral load of ≥1000 IU/mL by central assay through one year 
post first Study Drug injection.

Peak CMV viral load through one year post first Study Drug injection. 
•
Viral load area under the curve (AUC), as a measure of “cumulative viral load” through 
one year post first Study Drug injection.

Number of episodes of adjudicated CMV- associated disease, including CMV syndrome and 
CMV tissue-invasive disease, through one year post first Study Drug injection.

Number of episodes of viral resistance to ganciclovir or valganciclovir through one year post 
first Study Drug injection as determined by a central laboratory assay. 

Incidence of biopsy-proven (T or B cell) rejection (BPAR) (Banff 2007 Grade > 1) through 
one year post first Study Drug injection.

Estimated glomerular filtration rate (eGFR) at the last study visit, calculated using the 4 variable 
Modification of Diet in Renal Disease (MDRD) formula.


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
Incidence of clinically treated acute graft rejection through one year post first Study Drug 
injection.

Patient-reported outcomes through one year post first Study Drug injection:
o
EuroQol-5 dimensions 5 levels (EQ-5D)
o
Kidney Transplant Questionnaire (KTQ) 
o
Short Form Health Survey version 2 (SF-12v2) 

Healthcare resource utilization through one year post first Study Drug injection:
o
Resource use will be collected including the following: .hospitalizations recorded as 
number of days in the Intensive Care Unit, Step-down Unit, and general medical ward, 
(including emergency room visits greater than 24 hours), also non -protocol -related 
physician visits and emergency room visits of less than 24 hours.
Immunogenicity Variables

T-cell responses to pp65 through one year post first Study Drug injection. 

gB-specific antibody levels through one year post first Study Drug injection.
Safety Assessments

Vital signs

Adverse events using the National Institutes of Health Common Terminology Criteria for 
Adverse Events (NCI-CTCAE) v. 4.03 grading scale

Local reactogenicity signs and symptoms using both the NCI-CTCAE v. 4.03 grading scale and 
the protocol-specified reactogenicity scale 

Systemic reactogenicity signs and symptoms using both the NCI-CTCAE v. 4.03 grading scale 
and the protocol-specified reactogenicity scale

Clinical laboratory assessments as defined in Appendices

Physical examination
Statistical Methods: 
Sample Size Justification: 
In a recent study of prophylactic valganciclovir given at 900 mg/day for 100 days to donor CMV-
seropositive/recipient CMV seronegative (D+R-) kidney transplant recipients (Humar, 2006),
CMV viremia, defined as CMV viral load > 600 copies/mL, was seen through one year in 83 of 163 
subjects [50.9%, 95% CI = (43.0%, 58.8%)]. In another study (Couzi, 2012), CMV infection, 
defined as two consecutive positive Polymerase Chain Reaction (PCR) assay results, was seen in 
11 of 32 subjects [34.4%, 95% Confidence Interval (CI) = (18.6%, 63.2%)], respectively. Pooled 
from these two studies by weighted average, it is estimated that placebo rate is 46% (70% weight 
on Humar’s result). A sample size of 64 subjects per arm will allow the study to have 80% power 
to detect a reduction in CMV viremia to 25% due to ASP0113 at 52 weeks using a 1-sided test with 
a type 1 error rate of 5%. To allow for loss to follow-up, 70 subjects per arm will be enrolled for a 
total sample size of 140 subjects.
Efficacy:  
The Full Analysis Set (FAS) to be used for primary analysis of the primary efficacy variable will 
consist of all randomized subjects who receive at least one Study Drug injection and have at least 
one post dose viral load assessment by central laboratory. The FAS will be used for all efficacy 
analyses.
The primary analysis of the incidence of CMV viremia will consist of a Cochran-Mantel-Haenszel 
(CMH) test stratified by the factors used in the stratified randomization. Subjects who are lost to 
follow-up will be assumed to have met the primary endpoint. The secondary variables will each be 
similarly analyzed. 


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The event rates of the secondary variables will each be compared between treatments using the same 
CMH method as in the primary analysis. The survival endpoints (time to first event) will be 
analyzed using a Cox proportional hazards model. The Cox model will include the randomization 
factors. The common hazard ratio and confidence limits will be estimated. The 1-sided p-values for 
testing the hypothesis that the hazard ratio is equal to unity will be calculated. The Kaplan-Meier
survival curves for the treatment groups will be displayed.
Pharmacogenomics:
Subjects who consent to participate in the optional pharmacogenomics sub-study will have a whole 
blood sample collected during the Baseline visit, after Randomization but prior to the first Study 
Drug injection, for exploratory retrospective pharmacogenomics (PGx) analysis.
Safety:  
The safety analysis set will consist of all randomized subjects who have received at least one Study 
Drug injection. This analysis set will be used for all summaries of adverse events, reactogenicity, 
clinical lab data, physical exams, vital signs and subject survival through one year post first Study 
Drug injection. All recorded AEs will be listed, including duration, outcome, toxicity grade, and 
association with use of Study Drug.
Interim Analyses: 
Two interim safety and efficacy analyses are planned. The first one will occur when 50 subjects 
(approximately 25 in each group) have completed the month 6 visit assessment. The second interim 
analysis will occur when 90 subjects (approximately 45 per group) have completed the 6 month visit 
assessment. 
A Data Monitoring Committee (DMC), comprising individuals who are not on the study team and 
not investigators, will be established to review safety and efficacy data at each interim look. A 
detailed description of the DMC, its role in this clinical trial, and the timing of the scheduled 
reviews will be provided in the DMC Charter.
Data from all subjects who have been enrolled will be included in the safety reviews. All data 
submitted to the DMC will remain blinded to Astellas personnel involved in the study. A detailed 
safety data interim analysis plan will be included in the DMC Charter.
Interim efficacy analyses will be performed for the sole purpose of assessing futility. Interim 
efficacy analyses will include all available data from subjects who have completed the 6 month 
visit. At each interim, Bayesian predictive probability (BPP) that the observed rate of viremia in the 
ASP0113 treatment group being at least 25% less than the observed viremia rate in the placebo 
treatment group will be calculated.
If the BPP ≤ 0.20, it will be concluded that ASP0113 meets futility criterion. 
Extensive simulations were conducted to assess the operating characteristics of this futility criterion, 
and the results are satisfactory. The simulation algorithm, scenarios and results will be summarized 
in the SAP for this protocol.




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Table 1: Schedule of Assessments 
Screening1
Baseline
Randomiz
ation and 
Dose 1
Dose 2
Dose 3
Day 100
Dose 4
Dose 5
Study 
Completio
n/ Early 
Terminati
on23
Visit Number
1
2
3*
4
5
6
7*
8
9
10
11*
12
13
Day 
(From Transplant for dosing visits or 
prior dose)
-14 through +30
Day of Transplant 
= Day 02
30
14 days 
after
Dose 125
60
14 days 
after 
Dose 225
90
14 days 
after Dose 
325
120
14 days 
after 
Dose 425
180
14 days after 
Dose 525
270
395
Visit Window (days)
+/-3
+/- 3
+/- 5
+/- 3
+/- 5
+/- 3
+/- 5
+/- 3
+/-5
+/- 3
+/- 10
+14
Month
1
2
3
4
6
9
13
  Valganciclovir/Ganciclovir 3
By Day 10 Post Transplant
Informed Consent4
X
Subject Number Assignment5
X
Inclusion/Exclusion Assessment
X
XP
EQ-5D, KTQ, SF-126
XP
XP
XP
XP
XP
X
Medical History & Demographics7
X
Clinical Evaluation (Physical Exam & 
Vitals)8
X
XP
XP
XP
XP
XP
X
X
Concomitant Medication Review (including 
immunosuppressants) 9
X
XP
XP
X
XP
XP
X
XP
X
X
Health Economic Assessment (HEA)
X
XP
XP
XP
XP
XP
X
X
Clinical Laboratories10
X
XP
X
XP
X
XP
X
XP
X
XP
X
X
Urinalysis, with Microscopic Evaluation
X
XP
X
XP
X
XP
X
XP
X
XP
X
X
Urine:Protein Creatinine Ratio
X
XP
X
XP
X
XP
X
XP
X
XP
X
X
Pregnancy Test (females)11
X
XP
XP
XP
XP
XP
X
X
CMV Serologies12
X
Adverse Event and SAE Review13
X
XP
XP
X
XP
XP
X
XP
X
X
Transplant Information14, 15
X
Randomization1
XP
CMV Plasma Viral Load Testing 
(see Table 1a)16, 17, 24
Every 2 Weeks
Monthly
CMV Genotypic Resistance Testing, when 
applicable18, 24
Immunology Lab19, 24
XP
X
XP
X
XP
X
Pharmacogenomics (PGx) – (Optional)20, 24
XP
Study Drug injection21
X
X
X
X
X
Local & Systemic Reactogenicity 
Assessment22
X
X
X
X
X
Patient and Graft Survival
X
P = procedure should be completed prior to dosing     * = Visit procedures may be performed by Home Health Care (HHC)


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Table 1a: Plasma Viral Load Schedule
Every Other Week
Monthly
Day 
100*
Day 
114*
Day 
128*
Day 
142*
Day 
156*
Day 
170*
Day 184
Day 
198*
Day 
230*
Day 
260
Day 
290*
Day 
320*
Day 
350*
Day 
380*
Day 
395
CMV Visit Window (days)
+/-3
+/-3
+/-3
+/-3
+/-3
+/-3
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+14/-5
CMV Window 
Day
179-189
Day 
193-203
Day 
255-267
Overlap with Regular 
Visit†
Days 
179-185
Days 
191-197
Days 
260-267
Days 
395-
409
May draw with Visit:
Visit 7*
Visit 10
Visit 11*
Visit 12
Visit 13
CMV Plasma Viral Load 
Testing16, 17,  24
X
X
X
X
X
X
XP
X
X
X
X
X
X
X
X
* = Visit procedures may be performed by Home Health Care (HHC).  Viral load blood draws may be combined with Visits 10, 11 12 & 13 at the investigator 
site when they are scheduled to coincide within each visit’s windows .
† Days in Study Schedule when CMV and Regular Visit can be performed together per Protocol.  The overlap used assumes the visits are done exactly on the 
specified visit day from Transplant.  If +/- window is used for a dosing visit, the corresponding follow up visit should take place within the 14 days +/-3 from 
the date of the Study Drug dose.  Visits 10 & 11 must be at least 7 days apart.


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Tables 1 and 2 Footnotes:
1.
Screening may be done from Day -14 up to Randomization, Day 30. Screening and Randomization can take place on the same day as long as Clinical Labs 
are drawn and results are available on the day of Randomization. If Screening is done > 3 days prior to Randomization, Clinical Labs, urinalysis and urine 
protein: creatinine ratio must be repeated and available prior to Randomization. Subjects may be rescreened due to rescheduling of transplant surgery 
provided the screening procedures are repeated and fall within the -14 day to + 30-day window relative to the Day of Transplant. First study drug dosing 
must take place within 24 hours of Randomization.
2.
The date of transplant (day of skin closure) defines Day 0 and all visit days are relative to Day 0.  
3.
Subjects are to receive prophylactic valganciclovir or ganciclovir starting within 10 days post transplant through the Day of Randomization to prevent 
CMV disease. (The subject can miss up to two doses of valganciclovir or ganciclovir during this time period for any reason). Valganciclovir or ganciclovir 
dose is to be given per the package insert. The subject will then continue to receive CMV-specific AVP until 100 days post transplant. Subjects can have 
CMV-specific AVP interrupted, dose adjusted or replaced by other CMV-specific AVP per standard of care after the Day Randomization if renal function 
is compromised, there are toxicities related to the administration of the AVP, or for any other medically indicated reason.
4.
Informed consent must be obtained prior to the performance of any study-related procedure.
5.
Subjects will be assigned a subject number for use throughout the study at the Screening Visit via the Interactive Response Technology (IRT) system.
6.
The EQ-5D, Kidney Transplant Questionnaire (KTQ) and the SF-12 v2, should be completed by the subject prior to any other study assessments or visit 
procedures. Subjects should complete these assessments in the following order: EQ-5D first, KTQ second, SF-12 last. For all three patient-reported 
outcome measures, i.e. EQ-5D, KTQ, SF-12, the answers must come from the subject. If the subject is unable to fill out the questionnaire, the assessment 
should not be performed. If the subject is unable to answer an individual question, the rest of the questionnaire should still be completed.
7.
Medical history must include demographics, (age, gender, race), diagnosis for renal failure, length of time on dialysis, history of prior kidney transplant, 
and diabetes. 
8.
A complete physical examination (PE) will be conducted at the Screening, Baseline and the Study Completion/Day 395 Visit (V13). At all other visits 
where a PE is performed (Visits 4, 6, 8, 10 and 12); symptom-directed physical examinations may be done. The evaluations conducted at each visit are to 
be performed by the Investigator or qualified medical personnel who routinely perform these evaluations in this patient population. Vital signs will be 
collected immediately prior to Study Drug injection, at 15 minutes and 60 minutes post Study Drug injection. Vital signs include blood pressure, pulse rate, 
respiratory rate and temperature. Height will be collected at the Screening Visit only. Weight will be collected at V1, V2 and at Study Completion/Day 395 
(Visit 13). If Screening is done > 3 days prior to Randomization, the PE must be repeated at Randomization.
9.
All concomitant medications and therapies administered from 14 days prior to transplant through the Study Completion Visit (Day 395/Visit 13) will be 
collected on the eCRF. Medications used for anesthesia during the transplant surgery will not be recorded. 
10. Clinical laboratory samples will be drawn at Screening (Visit 1), before each Study Drug injection, at each follow-up time point for the injections, and at 
the last study visit. Clinical labs will be performed by a local laboratory and will include hematology, biochemistry, including a hepatic profile, urinalysis
with microscopic evaluation and urine protein: creatinine ratio. Screening clinical labs may be re drawn once if initial results would preclude 
Randomization and the Investigator feels out of range results were transient. Results will be entered into the eCRF. Safety labs (hematology, biochemistry, 
hepatic profile, urine protein: creatinine ratio and urinalysis) drawn by Home Health Care for Investigator sites utilizing this service will be analyzed by the 
Central Laboratory.


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11. For all females of childbearing potential, a urine pregnancy test will be performed at Screening, prior to each dose, at Visit 10, 12, and at the Study 
Completion/Day 395 Visit (Visit 13). All pregnancy tests will be done locally. For subjects who receive mycophenolate mofetil (MMF), additional 
pregnancy testing should be done in accordance with local requirements.
12. CMV serologies must have been performed within 8 weeks prior to transplant. If CMV serostatus is not available from this time period, CMV serostatus 
may be assessed at the Screening Visit with results available prior to Randomization.
13. AEs and SAEs will be collected from time of signing of informed consent through one year post Study Drug injection [Study Completion Day 395 Visit 
(Visit 13)]. AEs should be recorded as a change in medical status or medical history, from the time of signing of the informed consent until the first dose of 
study drug. SAEs from the time of signing the informed consent will be recorded on the SAE worksheet and reported per Section 5.5.6. AEs reported after 
the first dose will be reported on the AE eCRF. Note: The transplant surgery that occurs on Day 0 is not considered an AE or an SAE.
14. Transplant information includes type of transplant (Living Related Donor, Living Unrelated Donor, or Deceased Donor).
15. Donor information includes donor demographics (age, gender, race), viral serologies (CMV [required], HBV, HCV, EBV, [if available]; and HCV PCR 
RNA [if available]), ABO blood group and HLA typing. Recipient information includes ABO blood group, HLA typing, HLA cross match at time of 
transplant (as determined by the site’s standard method of determination), and viral serologies (CMV [required], HBV, HCV and EBV [if available], and 
HCV PCR RNA [if available]).
16. Plasma viral load by the central laboratory will be routinely monitored every other week (+/-3 days) from Day 100 through Day 200, then monthly (+/- 5 
days) until end of study. Plasma viral load by central and local laboratory will also be assessed for cause in case of suspect CMV disease and at least once a 
week by Central lab from initiation of CMV-specific AVT until the course is completed. For cause CMV viral loads should be performed at a local lab 
approved by Astellas as Central lab viral load results may not be available in a timely manner to guide treatment decisions.  
17. Plasma viral load assessment results performed by the local laboratory will be reported on the eCRF. Local CMV plasma viral load testing may be 
performed only at a local laboratory approved by the Sponsor.  
18. A plasma sample will be drawn and sent to the central lab and results will be reported for CMV genotypic resistance when there is viremia without a 
reduction in viral load after two weeks of treatment with valganciclovir and/or ganciclovir, or when clinical signs and symptoms have not improved two 
weeks after initiating or increasing valganciclovir and/or ganciclovir for CMV viremia or disease or any time resistance to any CMV-specific AVT is 
suspected by the Investigator.
19. Immunogenicity laboratories include collection of blood for the gB antibody and pp65 T-cell assays. Samples should be drawn at Visits 2, 5, 6, 9, 10 and 
13. Visits 2, 6 and 10 are Study Drug injection visits and blood sampling will be collected prior to the Study Drug injection. Samples for T-cell assays will 
not be collected if the Absolute Lymphocyte Count (ALC) is known to be < 500 mm3 by local or central laboratory measurement.   
20. Subjects who consent to participate in the PGx sub study will have a whole blood sample collected during the Baseline Visit (Visit 2), after Randomization
but prior to the first Study Drug injection.
21. A Study Drug injection should not be given if the subject 1) has been on an anticoagulant within 5 half-lives prior to the injection(Low dose anticoagulants 
that are used for prevention of deep vein thrombosis are allowed) or 2) has a Temperature ≥100.4◦F or 38◦C (per NCI Grade 1).
22. Local reactogenicity and symptoms of systemic reactogenicity will be evaluated one hour after each injection and then for seven days after each injection 
by subject reporting via diary. After injection in the clinic, the subject must be in direct view of the clinic staff for 15 minutes following each injection, then 
remain in the clinic area for an additional 45 minutes for evaluation of local and systemic reactogenicity. Vital signs, including temperature, pulse, 
respiration and blood pressure will be collected just prior to injection, 15 minutes post Study Drug injection and at one hour post Study Drug injection. 
Using the pre-injection vital signs as baseline, if a post Study Drug injection vital sign meets Grade 1-4 criteria per Appendix 5, they are to be repeated and 
confirmed within 5 minutes of the first assessment.


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23. The Study Completion/Day 395 Visit (Visit 13) must occur on Day 395 up through +14 days (between Day 395 to 379). For a subject who prematurely 
withdraws from the study (discontinues treatment with no continued follow-up), the Study Completion Visit should be completed within 14 days of study 
withdrawal.
24. Specimen drawn and sent to the Central Laboratory.
25. If a Study Drug dose is missed, the 14 day follow up clinical laboratory samples for hematology, biochemistry, urinalysis and urine protein: creatinine ratio
and hepatic profile should not be collected. Scheduled Immunogenicity Labs (Visit 5 & 9) must still be collected.


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Table 2:  Schedule of Assessments – Long-term Follow-up Period
Month
18
30
42
54
66
Year (relative to first Study Drug)
1.5
2.5
3.5
4.5
5.5
Window
(months)
± 1
± 1.5
± 1.5
± 1.5
± 1.5
Mortality, including primary cause of death and date
X
X
X
X
X
Development of any new malignancies
X
X
X
X
X
Development of infection requiring hospitalization or resulting in death
X
X
X
X
X
Erythema and/or induration at sites of immunizations
X
X
X
X
X
Graft Survival
X
X
X
X
X
Creatinine*
X
X
X
X
X
Subjects will be contacted by telephone at 6 months after Day 395, then annually, for the next 4 years for long-
term safety related to the DNA vaccine. Items are to be assessed by questionnaire and via retrospective chart 
review of available medical records.
During the long-term follow-up period, if an SAE is identified and deemed possibly or probably related to the 
study medication, an SAE report on the SAE worksheet must be sent to the sponsor per Section 5.5.6.
*Creatinine values will be recorded if they have been collected within 3 months prior to the follow-up telephone 
contact and are included in the subject’s available medical records.


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1
INTRODUCTION
1.1
Background  
CMV is a member of the Herpesviridae family, double-stranded DNA viruses which become 
latent in host cells after acute infection. CMV infection is ubiquitous and evidence of sero-
conversion has been found in all populations. CMV infection is usually harmless, except in 
the fetus and the immunocompromised host. In the immunocompromised host, primary 
infection, reinfection or reactivation of latent virus can cause significant morbidity and 
mortality. Persons undergoing a solid organ transplant (SOT) are particularly susceptible to 
both primary infection and reactivation of CMV as a result of the pharmacologic 
immunosuppression used to prevent graft rejection.
The morbidity and mortality associated with CMV infection is secondary to both the direct 
and the indirect effects of CMV. CMV infection can result in CMV disease, both CMV 
syndrome and CMV tissue-invasive disease. The highest risk of CMV disease occurs in 
CMV-seronegative recipients of an organ from a CMV seropositive donor.
The use of either prophylactic or preemptive anti-viral therapy (AVT) has led to a reduction 
of CMV disease, but late CMV disease, after therapy is discontinued remains a problem.
In addition to the direct effects of CMV infection (CMV disease) the indirect effects of CMV 
infection include allograft rejection, decreased graft and patient survival, and an increase in 
opportunistic infections [Fishman & Rubin, 2007]. The indirect effects may possibly result 
from alterations in the immune system after subclinical reactivation episodes or by expression 
of viral genes during latency [Boeckh & Geballe, 2011].
Vaccines designed to induce or enhance the adaptive immune response to CMV could reduce 
the risk of CMV disease, allograft rejection, graft and patient survival and opportunistic 
infections other than CMV. The control of CMV infection is associated with preserved CMV-
specific cellular immune responses, including CD4+, CD8+, and natural killer (NK) T cells 
[Sylwester et al, 2005]. In addition, humoral responses have also been shown to be important 
in preventing viral dissemination [Griffiths et al 2011].
ASP0113 is a first-in-class vaccine that is designed for the prevention of CMV infection in 
SOT recipients through stimulation of both humoral and cell-mediated immune responses. It 
contains 2 plasmids which encode CMV glycoprotein B (gB) and tegument phosphoprotein 
65 (pp65). gB is the major neutralizing target for antibodies stimulated by CMV in healthy 
humans [Britt et al, 1990]; pp65 is one of the proteins most frequently recognized by CD8 
cells after a CMV infection in healthy humans [Kern et al, 2002; Gyulai et al, 2000; Wills et 
al, 1996]. ASP0113 has been studied in subjects undergoing hematopoietic cell transplant 
and warrants further study in the SOT population.     
1.1.1
Non-clinical and Clinical Data
In mice, vaccination with ASP0113 leads to production of antibodies against gB and pp65 
and a robust T-cell response to pp65. Plasmid numbers of ASP0113 are barely detectable at 
the injection site and are not associated with genomic DNA 2 months after vaccination.  


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Administration of ASP0113 as a single dose is well-tolerated and results in no demonstrable 
clinical signs of toxicity due to injection of vaccine. Repeat dose administration of ASP0113 
in rabbits is well-tolerated, with no vaccine-related changes in clinical signs and symptoms. 
However, vaccination with ASP0113 did lead to a significant, but reversible, increase in 
creatine phosphokinase (CPK) and minimal to moderate inflammation of the muscle, skin and 
subcutis, that persisted to a slight degree in the recovery period. Based on these nonclinical 
animal studies, ASP0113 is not anticipated to present a toxicity risk in humans when 
delivered by intramuscular injection, and immunogenicity data suggest that vaccination can 
induce immune responses to human CMV. For a detailed summary of the preclinical studies 
please refer to the current Investigator’s Brochure (IB) .
1.1.2
Clinical Data  
To date, ASP0113 has been evaluated in a Phase 1 study in healthy volunteers and a Phase 2 
study of matched related donor/recipient pairs and related or unrelated recipients undergoing 
allogeneic HCT for hematologic disorders.
1.1.3
Phase 1 (VCL-CB01-101) Results
The first clinical study of ASP0113 was a multicenter, randomized, open-label Phase 1 clinical 
study (VCL-CB01-101) designed to evaluate the safety and immunogenicity of ASP0113 in 44 
healthy adult CMV-seropositive and CMV-seronegative volunteers at doses of either 1 mg or 
5 mg (IM) administered on weeks 0, 2, and 8 in a dose escalation format and at a dose of 5 mg 
(IM) administered on days 0, 3, 7 and 28 (accelerated schedule)[Wloch et al, 2008].
Volunteers receiving the higher dose or accelerated vaccine schedule tended to experience 
more local reactogenicity, but the severity of the treatment-emergent adverse events (TEAEs) 
did not increase with increasing dose and a more compressed schedule. The incidence of local 
reactogenicity, predominantly injection site pain, was 62.5% for the lowest weekly dose group, 
87.5% for the highest weekly dose group, and 100% for the accelerated schedule group. 
Several cutaneous TEAEs (4.2%) were considered related to ASP0113 by the Investigator and 
included erythema, rash and pruritus. One volunteer did experience a transient increase in CPK 
value greater than 5 x the upper limit of normal, but less than 10x normal. 
Immune responses to the 2 immunogens encoded in the vaccine, gB and pp65, were assessed 
by the use of an indirect gB binding enzyme-linked immunosorbent assay (ELISA) for 
antibody responses to gB and a pp65 direct ex-vivo interferon gamma (IFN-enzyme-linked 
immunosorbent spot (ELISPOT) assay for T-cell responses to pp65. At 16 weeks, antibody 
and cell responses were elicited in 38% and 50% of the CMV-seronegative volunteers 
administered 1 mg and 5 mg ASP0113, respectively. CMV-seropositive volunteers had 
increases in pp65 T-cell responses of 12.5% and 37.5% across all groups, but no increase in 
gB antibody levels were detected for CMV-seropositive volunteers.


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1.1.4
Phase 2 (CB01-202) Results  
The second clinical study of ASP0113 was a multicenter, randomized, double-blind Phase 2 
clinical study designed to evaluate the efficacy, immunogenicity and safety of ASP0113 in 
donors and CMV-seropositive recipients undergoing 5 of 6 or 6 of 6 HLA-allele-matched 
allogeneic HCT for the treatment of hematologic disorders [Kharfan-Dabaja et al, 2012]. A 
total of 108 subjects were enrolled in the study, including 14 donor/recipient pairs, and 
received at least one dose of Study Drug [5 mg/mL (1 mL dose)] or placebo. Recruitment of 
donor/ recipient pairs was found to be impractical early in the study so that arm was 
discontinued; the results are not discussed here. The intent-to-treat (ITT) and per protocol (PP) 
populations comprise 80 and 74 transplant recipients, respectively. Recipients received 
injections at approximately Days -5 to -3, 21 to 42 (one injection in this window, health 
permitting), on Day 84, and on Day 196 relative to transplantation. Results discussed below are 
for the PP population.
The primary efficacy endpoint of the study was the occurrence of clinically significant CMV 
viremia, defined as detection of CMV viremia that resulted in the initiation of CMV-specific 
antiviral therapy during the first year of transplant. The clinical decision to treat at the sites was 
based on the most current local or central CMV assay results. CMV-specific antiviral therapy 
was initiated for a lower percentage of recipient subjects in the ASP0113 group (47%) than in 
the placebo group (61.8%), but the difference was not statistically significant (p=0.145, 
Cochran-Mantel-Haenszel test stratified by site). The PP population was modified for this 
analysis to exclude two subjects who received CMV-specific AVT because of false positive 
results from the local viral load assay.  
When the occurrence of CMV viremia, as defined as > 500 copies/mL by a laboratory 
developed test (LDT) based upon the LightCycler® polymerase chain reaction (PCR), was 
evaluated in a central laboratory, the rate was lower in the ASP0113 group (33%) than in the 
placebo group (62%) and was statistically significant (p=0.008, Cochran-Mantel-Haenszel test 
stratified by site). Exploratory endpoints also demonstrated a delay in time to initial viremia 
(p=0.003), number of CMV infection episodes (p=0.017) and duration of viremia when 
normalized as percentage of time on study (p=0.042).


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Table 3: Viral Load Endpoints after 12-Month Follow-up in the CB01-202 Study 
– Per Protocol Population
ASP0113
(n=40)
Placebo 
(n=34)
P value
Occurrence of CMV infection (> 500 copies/mL)
13 (33%)
21 (62%)
0.008†
Time to initial viremia (days)
Median
> 365
109.5
0.003ǂ
Number of CMV infection episodes
0
27 (68%)
13 (38%)
0.017§
1
8 (20%)
14 (41%)
2
4 (10%)
3 (9%)
3
1 (3%)
3 (9%)
4
0
1 (3%)
Duration of viremia (days)
Mean
10.6 (0-68)
19.4 (0-181)
0.071§
Duration of viremia (normalized as % of time on 
study)
Mean
4.9 (0-63)
7.6 (0-49)
0.042§
Viral load area under the curve (copies mL*days)
Mean
66,238
127,875
0.069§
Median
0
37,000
Range
0-1 x 106
0-2 x 106
Peak viral load (copies/mL)
Mean
2838
8971
0.061§
Median
0
3250
Range
0-29,500
0-145,000
All results are based on LightCycler® PCR assay for CMV (Roche Molecular Systems) using analyte 
specific reagents performed at the 
.
P value was computed by: †Cochran-Mantel-Haenszel test stratified by site, ǂlog rank test stratified by site or 
§Wilcoxon rank sum.  
In a post hoc analysis, the rate of the following clinical endpoints were numerically reduced, 
but were not statistically significant. Acute Graft vs. Host Disease (aGVHD) (grade 3-4) 
occurred less frequently in the ASP0113 group (5.0%) than in the placebo group (14.7%) 
(p=0.2364); chronic Graft vs. Host Disease (cGVHD) (high risk) occurred less frequently in 
the ASP0113 group (10.0%) than in the placebo group (20.6%) (p=0.3259. In addition, the 
incidence rate of a composite endpoint of CMV EOD, mortality (overall), aGVHD (grade 3-
4), and cGVHD (high risk) was lower in the ASP0113 group (32.5% ) than in the placebo 
group (52.9% ), although the difference was not statistically significant (p=0.1719).
Immune responses to the two immunogens, gB and pp65, encoded in the vaccine were assessed 
by two immunoassays: 1) a gB-specific IgG-binding ELISA; and 2) an ex vivo pp65-specific 
IFN-gamma ELISPOT [Kharfan-Dabaja et al, 2012]. T-cell responses to CMV pp65 and gB as 
well as gB-specific serum antibody levels were similar in the ASP0113 and placebo recipients 
prior to conditioning therapy and transplant. The CMV pp65 T-cell responses were numerically 
enhanced in the ASP0113 group relative to the placebo group at all post-transplant times 
evaluated;  the differences in the responses were statistically significant at Day 84 (p=0.036
Wilcoxon rank sum test). Please refer to the Investigators' Brochure regarding other post-hoc 
analyses of the immunogenicity data.
The geometric mean gB-antibody levels in recipients in the ASP0113 group compared with 
recipients in the placebo group showed a trend towards significance at the fourth injection 


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(p=0.064, Wilcoxon rank sum test) and reached significance by day 365 (p=0.009, Wilcoxon 
rank sum test). Although the geometric mean gB antibody levels were higher for the ASP0113 
recipients at all time points evaluated, the repeated measurement ANOVA using log10
transformed data from days 56 to 365 did not show a significant difference between the 
longitudinal gB antibody responses (p=0.749).
The incidence of local reactogenicity was higher in the ASP0113 group than in the placebo 
group (22.9% and 10.9%, respectively), primarily due to injection site pain. Fatalities were 
reported for 20.8% recipients in the ASP0113 group and 32.6% recipients in the placebo group 
during the 1-year study follow-up. No recipient died due to Study Drug-related AEs. No 
subject experienced CPK elevation in this study. One subject in the ASP0113 arm discontinued 
the study due to a serious allergic reaction that was considered by the Investigator to be 
possibly related to ASP0113 (subject number
). 
 
 
 
1.2
Summary of Key Safety Information for Study Drugs
ASP0113 in nonclinical studies was in general well-tolerated. Nonclinical studies 
demonstrated that the risk of integration of injected DNA into the host’s genome is negligible 
per FDA regulatory guidance and induction of autoimmunity is unlikely. No systemic organ 
toxicity was noted. There was no local reactogenicity reported, but in the highest dose groups 
in a repeated-dose toxicity study in rabbits, there was histological evidence of inflammation 
in the muscles injected with vaccine and concurrent elevations in CPK.  
One healthy volunteer had a transient elevation in CPK (> 5x normal but < 10x normal). 
Local (injection site) reactions including pain, induration, erythema, pruritus, discomfort and 
swelling were reported more frequently in the higher dosing group and more accelerated 
schedule with ASP0113 in healthy volunteers and in the ASP0113 treated group when 
compared to the placebo group. The only discontinuation due to an SAE that was possibly 
related to ASP0113 was the transplant recipient who was previously discussed in section 1.1.4.   
1.3
Risk-Benefit Assessment  
Despite currently licensed CMV-specific antiviral therapies, CMV disease continues to cause 
significant morbidity and mortality in solid organ transplant recipients and CMV infection may 
be associated with multiple other clinical outcomes including allograft rejection, decreased 
graft and patient survival, and an increase in opportunistic infections [Fishman & Rubin, 2007]. 
In addition, the treatments and associated toxicities can incur significant healthcare costs. 
Prophylactic valganciclovir is approved for 200 days after transplant in the United States and 
100-200 days in Europe and Canada.  From 100-200 days, subjects will have a viral load 


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assessed by central laboratory and treated preemptively per the standard of care at the 
institution.
ASP0113 appeared to show efficacy in a single Phase 2 trial over multiple secondary 
endpoints [Kharfan-Dabaja et al, 2012]. The incidence of local reactogenicity may be greater 
with ASP0113 than placebo. In addition, while there were CPK elevations at the highest dose 
level in toxicity studies in rabbits, significant damage to the muscle, as determined by CPK 
elevations greater than 10 x upper limit of normal, has not been observed in humans. One 
SAE (hypersensitivity/allergic reaction) leading to discontinuation responded well to medical 
treatment and was deemed not life-threatening. False positive results in the assessment of 
CMV viral load can occur in subjects receiving ASP0113 with the use of PCR assays that 
utilize primers targeted at gB and pp65. Such false positive results, if unrecognized, can lead 
to misdiagnosis and unnecessary initiation of antiviral therapy. It is unknown if false positive 
results can occur with the pp65 antigenemia assay. 
Given the morbidity and mortality associated with CMV infection and treatment, signals of 
possible efficacy in a phase 2 trial in HCT recipients, ASP0113 warrants further investigation 
in the prevention of CMV infection in patients receiving a solid organ transplant.   
2
STUDY OBJECTIVE(S), DESIGN, AND ENDPOINTS
2.1
Study Objectives
The objectives of this study are:

To evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence of 
CMV viremia (defined as plasma viral load ≥ 1000 IU/mL by central laboratory assay) 
through one year post first Study Drug injection in CMV-seronegative subjects receiving 
a kidney from a CMV-seropositive donor.

To evaluate the safety of ASP0113 in CMV-seronegative subjects receiving a kidney 
from a CMV-seropositive donor.
2.2
Study Design and Dose Rationale
2.2.1
Study Design  
This is a randomized, double-blind, placebo-controlled trial which will enroll 140 CMV-
seronegative recipients of kidney transplant from a CMV-seropositive donor at 80 clinical 
sites. Subjects will be randomized at Day 30 ±3, in relation to the day of transplant, in a 1:1 
ratio to ASP0113 or placebo, and stratified by use of anti-thymocyte globulin (ATG) prior to 
Randomization and by receipt of a kidney from a living or deceased donor. The active 
compound will be a vaccine (ASP0113) which contains two plasmids encoding gB and pp65 
each at 2.5 mg/mL, formulated with CRL1005 poloxamer and benzalkonium chloride (BAK). 


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The placebo control will be phosphate-buffered saline (PBS). Subjects will receive either 5 
doses of ASP0113 or placebo on Days 30 ± 3, 60 ± 5, 90 ± 5, 120 ± 5  and 180 ± 5 in relation 
to the day of transplant (Day 0).  
Injections should be administered only when there is no medical contraindication to an 
intramuscular (IM) injection. Syringes will be masked prior to dosing to blind the subjects 
and all other personnel who need to remain blinded to the treatment assignment (i.e., site staff 
other than pharmacy personnel and staff designated to administer Study Drug injections). 
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir or 
ganciclovir (dose per package insert) through the day of Randomization to prevent CMV 
disease. (The subject can miss up to two valganciclovir or ganciclovir doses during this time 
period for any reason). Subjects will then continue to receive CMV specific CMV AVP with 
valganciclovir or ganciclovir (dose per package insert) to prevent CMV disease until 100 days 
post transplant.   Subjects can have valganciclovir or ganciclovir interrupted, dose adjusted or
replaced by other CMV-specific AVP per standard of care after the day of Randomization if 
renal function is compromised, there are toxicities related to the administration of the AVP or 
for any other medically indicated reason. In all subjects, plasma will be collected for central 
laboratory CMV viral load testing every two weeks from Day 100 through Day 200, then 
monthly through last Study visit Day 395.
In cases where CMV disease (CMV syndrome or CMV tissue-invasive disease) is suspected 
from the first Study Drug injection through Day 395, a local CMV viral load sample will be 
collected at the time of the first CMV symptom recognition.  
Through Day 395, CMV-specific AVT should be initiated for CMV disease and can be 
initiated for CMV viremia based on the central or local laboratory results and standard of care
at each institution. If CMV- specific AVT is initiated, a central CMV viral load will be 
obtained at a minimum of weekly from the time CMV- specific AVT is initiated until 
discontinuation. For cause CMV viral loads should be performed at a local lab approved by 
Astellas as Central lab viral load results will not be available in a timely manner to guide 
treatment decisions. 
In addition, every time a sample is collected for a local CMV viral load, a plasma sample 
should also be collected and sent to the central laboratory for CMV viral load testing. 
As one of the plasmids of the ASP0113 vaccine codes for the pp65 antigen, the theoretical 
possibility of interference with the pp65 antigenemia assay has been raised. At present, there 
are no data to suggest that such an interference occurs. However, to ensure subject safety and 
study integrity, sites that use pp65 antigen as their local methodology for the detection of 
CMV infection must adhere to the procedures defined below as a condition of participation in 
the trial:

The local pp65 antigenemia results must be entered into the eCRF database within 72 
hours (or next business day) of receipt to facilitate in-time monitoring of results.

The Medical Monitor must be called within 48 hours (or next business day) if the pp65 
antigenemia test is positive and the central laboratory PCR viral load result is negative.


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
Both the pp65 antigenemia and the central laboratory test must be repeated within 48 
hours of receipt of results, if the local pp65 antigenemia result is positive, the central 
laboratory PCR viral load result is negative and the subject is treated with CMV-specific 
AVT . Further treatment decisions are to be discussed with the Medical Monitor.
The plasmids in the Study Drug may interfere with certain PCR assays. If a PCR assay is 
used that amplifies the genes UL55/gB or UL83/pp65, this could result in either a false 
positive viral load or unblinding of the study subject.
Sites that are determined to have an unacceptable assay in their local lab but are able to 
determine a Sponsor- deemed acceptable work practice flow for utilizing another acceptable 
local assay or methodology will be allowed to participate in the trial. Note: Local CMV plasma 
viral load testing may be performed only at a local laboratory approved by the Sponsor.
Subjects will be followed for one year after first Study Drug injection (Primary Study 
completion/Day 395) for CMV viremia, CMV syndrome, CMV tissue-invasive disease, 
CMV-specific AVT, graft survival fand subject survival.
Subjects will be followed for one year after the first Study Drug injection for resistance to 
valganciclovir or ganciclovir. Viral resistance will be assessed by a Central lab when there is no 
reduction in viral load two weeks after initiating valganciclovir/ganciclovir, when there is no 
improvement in clinical signs and symptoms two weeks after initiating valganciclovir/ganciclovir or 
any time resistance to any CMV-specific AVT is suspected by the Investigator.
Immunogenicity to pp65 and gB will be assessed prior to Dose 1, two weeks after Dose 2, 
prior to Dose 3, two weeks after Dose 4, prior to Dose 5 and at the last study visit.  
Subjects will be evaluated for local and systemic reactogenicity 15 minutes and one hour after 
each Study Drug injection and for 7 days by subject reporting via diary after each Study Drug
injection.  
Subjects will be contacted by telephone at 6 months after Day 395, then annually for the next 
4 years to evaluate long-term safety related to the DNA vaccine. Items to be assessed by 
questionnaire and available patient records include mortality, development of any new 
malignancies, development of infection requiring hospitalization or resulting in death, graft 
survival, creatinine, and erythema and/or induration at the injection sites (see Appendix 17).  
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing of 
the informed consent through one year post Study Drug injection. AEs occurring from 
signing of informed consent until just prior to the first dose of Study Drug, should be reported 
as a change in medical status or medical history. SAEs from the time of signing the informed 
consent will be recorded on the SAE worksheet and reported per Section 5.5.6.AEs reported 
after the first dose will be reported on the AE eCRF.  The transplant surgery that occurs on 
Day 0 is not considered an AE or an SAE.
An independent Data Monitoring Committee (DMC) will be chartered to oversee the safety 
of subjects and review of the futility analysis. An Adjudication Committee (AC) will be 


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chartered to adjudicate all cases of CMV syndrome, CMV tissue-invasive disease and CMV-
specific antiviral therapy.
2.2.2
Dose Rationale  
Efficacy and safety data were collected from normal healthy subjects in a Phase 1 trial as well 
as HCT recipients in a Phase 2 clinical trial (VCL-CB01-101 and CB01-202, respectively). 
The dose used in the Phase 2 study was 1 mL of 5 mg/mL and 4 doses were given over 
approximately a 6 month time period. The dose and dose schedule appeared to be well 
tolerated. 
In the current study, five doses of 1 mL of 5 mg/mL of Study Drug or Placebo are planned.  
The first two doses will be given during the CMV-specific prophylactic therapy to prime the 
immune response. The third dose will be given at 90 days post transplant to boost the immune 
response at the time that CMV-specific prophylaxis is discontinued.  The last two doses will 
be given on Days 120 and 180 to coincide with late onset CMV disease.
2.3
Endpoints 
2.3.1
Primary Efficacy Endpoints
Incidence of CMV viremia (defined as plasma viral load of ≥1000 IU/mL by central assay)
through one year post first Study Drug injection.
2.3.2
Secondary Efficacy Endpoints 
Incidence of :

Adjudicated CMV-associated disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection.

CMV viremia (defined as plasma viral load ≥the lower limit of quantification [LLOQ]) 
by central assay through one year post first Study Drug injection. 

Adjudicated CMV-specific antiviral therapy for the treatment of CMV viremia or disease 
through one year post first Study Drug injection.

Graft survival through one year post first Study Drug injection.

Subject survival through one year post first Study Drug injection.
2.3.3
Exploratory Efficacy Endpoints

Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.

Time to first CMV viremia (defined as plasma viral load of ≥1000 IU/mL by central 
assay) through one year post study first Study Drug injection.

Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection.


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
Number of episodes of CMV viral load of ≥1000 IU/mL by central assay through one 
year post first Study Drug injection.

Peak CMV viral load and area under the curve (AUC) through one year post first Study 
Drug injection. 

Viral load area under the curve (AUC), as a measure of “cumulative viral load” through 
one year post first Study Drug injection.

Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.

Number of episodes of viral resistance to ganciclovir or valganciclovir through one year 
post first Study Drug injection as determined by a central laboratory assay. 

Incidence of biopsy-proven (T or B cell) rejection (BPAR)(Banff 2007 Grade > 1) 
through one year post first Study Drug injection.

Estimated glomerular filtration rate (eGFR) at the last study visit calculated using the 4
variable MDRD formula.

Incidence of clinically treated acute graft rejection through one year post first Study Drug
injection.

Patient-reported outcomes through one year post first Study Drug injection.
o
EuroQol-5 dimensions 5 levels (EQ-5D)
o
Kidney Transplant Questionnaire (KTQ)
o
Short Form Health Survey version 2 (SF-12v2)

Healthcare resource utilization through one year post first Study Drug injection.
o
Resource use will be collected including the following: hospitalizations recorded 
as number of days in the Intensive Care Unit, Step-down Unit, and general 
medical ward (including emergency room visits greater than 24 hours), also non -
protocol -related physician visits and emergency room visits of less than 24 hours.  
2.3.4
Immunogenicity Variables

T-cell responses to pp65 through one year post first Study Drug injection.

gB-specific antibody levels through one year post first Study Drug injection.
2.3.5
Safety Variables

Vital signs.

Adverse Events using the NCI-CTCAE v. 4.03 grading scale.

Local reactogenicity signs and symptoms using both the NCI-CTCAE v. 4.03 grading 
scale and the protocol-specified reactogenicity scale.

Systemic reactogenicity signs and symptoms using both the NCI-CTCAE v. 4.03 grading 
scale and the protocol-specified reactogenicity scale. 

Clinical laboratory assessments as defined in appendices.

Physical examination.


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3
STUDY POPULATION
3.1
Selection of Study Population 
This study will randomize kidney transplant recipients who are at least 18 years of age or of 
legal age of consent, whichever is greater, and are CMV-seronegative and have received a 
kidney from a CMV-seropositive donor.  
Subjects will be enrolled in the trial based on negative CMV serostatus as confirmed by a 
local laboratory from 8 weeks prior to transplant through day of transplantation. If CMV 
serostatus is not available from this time period, CMV serostatus may be assessed at the 
Screening Visit and results must be available at the time of Randomization.
3.2
Inclusion Criteria
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written 
informed consent and privacy language as per national regulations (e.g., Health Insurance 
Portability and Accountability (HIPAA) Authorization for U.S. sites) must be obtained 
from the subject or legally authorized representative prior to any study-specific 
procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is willing to comply with the protocol.
3. Subject is ≥18 years of age or the legal age of consent (whichever is greater). 
4. Subject is CMV-seronegative at time of transplant and has received a kidney allograft 
from a CMV-seropositive living or deceased donor. CMV serostatus of the recipient can 
be determined from 8 weeks prior to transplant, by local laboratory, through day of 
transplantation. If CMV serostatus is not available from this time period, CMV serostatus 
may be assessed at the Screening Visit, by local laboratory, with results available prior to 
Randomization.  
5. Subject started valganciclovir or ganciclovir within 10 days of transplant and has received 
it through Randomization per regulatory label (package insert).
6. Female subject must be either: 
•
Of non- child-bearing potential:
o
post-menopausal (defined as at least 1 year without any menses) prior to 
Screening, or 
o
documented surgically sterile or status post hysterectomy (at least 1 month 
prior to Screening).  
•
Or, if of childbearing potential:
o
must have a negative urine pregnancy test at Screening, and 
o
if heterosexually active, must use two forms of birth control* (at least one of 
which must be a barrier method) starting at Screening and during the Primary 
Study Period.   


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7. Female subject must not be breastfeeding at Screening and during the Primary Study 
Period. 
8. Female subject must not donate ova starting at Screening and during the Primary Study 
Period. 
9. Male subject and their female spouse/partners who are of childbearing potential must be 
using highly effective contraception consisting of two forms of birth control* (one of 
which must be a barrier method) starting at Screening and during the Primary Study 
Period.
* Acceptable forms include: 

Established use of oral, injected or implanted hormonal methods of contraception. 

Placement of an intrauterine device (IUD) or intrauterine system (IUS). 

Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) 
with spermicidal foam/gel/film/cream/suppository.

Partner male sterilization (i.e., vasectomy)
10. Male subject must not donate sperm starting at Screening and during the Primary Study 
Period.  
11. Subject agrees not to participate in another interventional drug study while on treatment.
Waivers to the inclusion criteria will NOT be allowed.
3.3
Exclusion Criteria
Subject will be excluded from participation if any of the following apply:
1. Subject is planned to undergo a course of CMV-specific prophylactic therapy with 
antiviral drugs with a duration of greater than 100 days.
2. Subject has received from one month prior to transplant or is planning to receive CMV 
immunoglobulin.
3. Subject has had CMV viremia or CMV disease from time of transplant until time of 
Randomization.
4. Subject has received, at any time, an organ transplant other than a kidney. (Dual 
allocation of a kidney is allowed).
5. Subject requires dialysis on the day of Randomization.
6. Recipient or donor is known to be positive for human immunodeficiency virus (HIV), 
hepatitis B surface antigen, or hepatitis B core IgM or IgG antibody.
7. Subject is known to have latent or active tuberculosis which has not been adequately 
treated.
8. Subject required desensitization for ABO blood type incompatibility or a positive T or B 
cell crossmatch.


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9. Subject has received any of the following substances or treatments:
a.
Investigational therapy within 28 days or 5 half lives whichever is longer, prior to
Transplantation, or subject is scheduled to receive investigational research products 
through one year after Randomization. 
b. Alemtuzumab within 90 days prior to Randomization or is scheduled to receive 
alemtuzumab any time through one year post Randomization.
c.
Rituximab within 120 days prior to Randomization or is scheduled to receive 
rituximab any time through one year post Randomization.  
d. Eculizumab or bortezomib from the Day of Transplantation through the Day of 
Randomization or is scheduled to receive eculizumab or bortezomib any time 
through one year post Randomization. 
e. IVIG and/or plasmapheresis from Day of Transplant through Day of Randomization.
f.
Live attenuated vaccines within one month (30 days) prior to the first dose of Study 
Drug or is scheduled to receive live attenuated vaccines within one month of any 
Study Drug injection.
g. Subunit or killed vaccines within 14 days prior to the first dose of Study Drug or is 
scheduled to receive subunit or killed vaccines within 14 days of any Study Drug 
injection.
h. Administration of a CMV vaccine, including any prior exposure to ASP0113.
i.
Subject has received the following anti-viral therapies or it is planned for them to 
receive the AVT for prophylaxis of viral infections in excess of the following doses 
from time of transplant through Randomization:

Aciclovir: 1600 mg orally (total daily dose), or 500 mg/m2/dose IV (total daily 
dose)

Valaciclovir: 1000 mg orally (total daily dose)

Famciclovir: 500 mg orally (total daily dose) 
10. Subject has received any anticoagulants including, but not limited to, vitamin K 
antagonists, heparin or its derivatives, low molecular weight heparin, factor X inhibitors, 
or thrombin inhibitors within 5 half-lives prior to randomization or is expected to use
anticoagulants within 5 half-lives prior to any Study Drug injection. Low dose 
anticoagulants that are used for prevention of deep vein thrombosis and antiplatelet agents
are allowed.  
11. Subject has any contraindication to or cannot be dosed with valganciclovir or ganciclovir 
per package insert on the Day of Randomization for any reason.
12. Subject has, or is expected to have during the Primary Study Period, a contraindication to an 
intramuscular injection.
13. Subject, within 3 days prior to Randomization, has an AST or ALT greater than 3 x ULN 
or total bilirubin greater than 2 x ULN unless secondary to suspected Gilbert’s disease. 


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14. Subject has a current malignancy or a recent history of malignancy (within the past 5 
years prior to Screening) except non-metastatic basal or squamous cell carcinoma of the 
skin that has been treated successfully or cancer in situ of the cervix uteri that has been 
successfully treated by local therapy.
15. Subject is being treated for an active infection at the time of Randomization.
16. Subject has any condition or an unstable medical or psychiatric condition, including a 
history of illicit drug(s) or alcohol abuse that the Investigator believes will place the 
subject at unacceptable risk or interfere with compliance to protocol requirements.
17. Subject has any other condition which, in the opinion of the Investigator, precludes the 
subject’s participation in the trial.
18. Subject has known allergies or previous adverse reactions to ganciclovir or
valganciclovir.
19. Subject has had an allergic reaction to any component of the vaccine, or to amino-glycosides,
as kanamycin is used during the manufacturing process of the vaccine.
Waivers to the exclusion criteria will NOT be allowed. 
4
TREATMENT(S)
4.1
Identification of Investigational Product(s)
4.1.1
Test Vaccine(s)
ASP0113 contains 2 closed circular plasmid macromolecules. The plasmids are purified from 
cellular components and formulated with CRL1005 poloxamer and benzalkonium chloride 
(BAK), a cationic surfactant, in phosphate-buffered saline (PBS). The combination of 
CRL1005 and BAK produces a thermodynamically stable self assembled particulate system 
with a defined particle size, surface charge and stability profile at room temperature. BAK is 
used to control and maintain the particle size distribution of the formulation.  
ASP0113 will be supplied by the Sponsor as a frozen solution in single dose 2-mL vials 
containing 1.3 mL of 5 mg/mL ASP0113. ASP0113 is packaged in a cardboard secondary 
container. 
ASP0113 is a milky white suspension at room temperature, and clear at temperatures below 
the cloud point of CRL1005 (4°C-7°C).
ASP0113 should be stored frozen at -25oC ± 10oC. 
Detailed instructions for the preparation and administration of ASP0113 will be provided in 
the Pharmacy Manual.


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4.1.2
Placebo 
Placebo will be supplied by the Sponsor in 2-mL vials containing phosphate-buffered saline. 
It is a clear colorless liquid. Placebo will be stored frozen at -25°C ± 10°C. Detailed 
instructions for the preparation and administration of placebo will be provided in the 
Pharmacy Manual.
4.2
Packaging and Labeling
All medication used in this study will be prepared, packaged, and labeled under the 
responsibility of qualified staff at APGD-AUST or Sponsor’s designee in accordance with 
APGD-AUST or Sponsor’s designee Standard Operating Procedures (SOPs), Good 
Manufacturing Practice (GMP) guidelines, ICH GCP guidelines, and applicable local 
laws/regulations.
Each carton and vial will bear a label conforming to regulatory guidelines, Good 
Manufacturing Practice and local laws and regulations which identifies the contents as 
investigational drug.
In the European Union, a qualified person of Astellas Pharma Europe B.V. (APEBV) or 
Sponsor’s designee will perform the final release of the medication according to Directive 
2003/94/EC annex 13.
The study centers will be provided cartons each containing 6 vials of ASP0113 or placebo 
(vehicle). ASP0113 and Placebo should be stored in the original carton. The vials should be 
stored at -25C ± 10C until the day of dosing.  
4.3
Study Drug Handling 
Current ICH GCP Guidelines require the investigator to ensure that Study Drug deliveries 
from the Sponsor are received by the investigator/or designee, and

that such deliveries are recorded,

that Study Drug is handled and stored according to labeled storage conditions,

that Study Drug with appropriate expiry/retest and is only dispensed to study subjects in 
accordance with the protocol, and

that any unused Study Drug is returned to the Sponsor.
Drug inventory and accountability records for the Study Drugs will be kept by the 
investigator/or designee. Study Drug accountability throughout the study must be 
documented and reconciled. The following guidelines are therefore pertinent:

The investigator agrees not to supply Study Drugs to any persons except the eligible 
subjects in this study in accordance with the protocol.


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
The investigator or designee will keep the Study Drugs in a pharmacy or other locked and 
secure storage facility under controlled storage conditions, accessible only to those 
authorized by the investigator to dispense these test drugs.

A Study Drug inventory will be maintained by the investigator or designee. The inventory 
will include details of material received and a clear record of when they were dispensed 
and to which subject.

At the conclusion or termination of this study, the investigator or designee agrees to 
conduct a final supply inventory and to record the results of this inventory on the Drug
Accountability Record. It must be possible to reconcile delivery records with those of 
used and/or returned medication. Any discrepancies must be accounted for and 
documented. Appropriate forms of deliveries and returns must be signed by the site staff 
delegated this responsibility.

The site must return Study Drug to the Sponsor or designee at the end of the study or 
upon expiration.

Used or unused Study Drug should be returned to the depot for destruction unless 
prohibited by local policy. In this instance, Study Drug may be destroyed at the study center 
according to standard institutional procedures after drug accountability has been conducted 
by the Sponsor or representative. Should this occur, a copy of the standard institutional 
procedure for destroying investigational drugs will be provided to the Sponsor. Upon 
destruction, a copy of the certificate of destruction must be provided for the Sponsor files 
and site drug accountability records.
4.4
Blinding
This is a double blind study. Subjects will be randomized to receive ASP0113 or placebo in a 
double-blind fashion such that the investigator, Sponsor’s study management team, clinical 
staff, nor the subject will know which agent is being administered. The randomization 
number will be assigned based on information obtained from the Interactive Response 
Technology (IRT).
4.4.1
Retention of the Assignment Schedule and Procedures for Treatment Code 
Breaking 
The randomization list and study medication blind will be maintained by the IRT system 
vendor.
The Data Monitoring Committee (DMC) will be provided with access to the dosing 
assignment for periodic review of the unblinded data as documented in the DMC Charter.  
4.4.2
Breaking the Treatment Code by the Sponsor 
The Sponsor may break the treatment code for subjects who experience a Suspected 
Unexpected Serious Adverse Reaction (SUSAR),  in order to determine if the individual case 
or a group of cases requires expedited regulatory reporting. Individual Emergency Codes will 


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be provided to the limited staff who are responsible to break the codes for all SUSAR cases 
for reporting purposes.
The treatment code for each randomized subject will be provided by the IRT in the event of a 
medical emergency requiring knowledge of the treatment assigned to the subject. The time, 
date, subject number and reason for obtaining any of these codes, and therefore breaking the 
blind, must be documented in the study file. They must only be requested by the investigator 
or other persons designated as sub-investigators. No subjects or other study personnel will be 
made aware of the treatment given to any subject unless a medical emergency necessitates 
such disclosure.  
Unblinding of the study medication should only be considered for subject safety or when 
critical therapeutic decisions are contingent upon knowing the blinded study drug assignment.  
Any unblinding by the investigational staff must be reported immediately to the Sponsor and 
must include an explanation of why the study medication was unblinded. If possible, the 
Sponsor should be contacted prior to unblinding of the study medication.
4.5
Assignment and Allocation
At the Screening Visit, after the Informed Consent Form (ICF) has been signed, site staff will 
access the IRT system, enter the subject’s required information, and the subject will receive a 
subject number assignment through the IRT for use throughout the study.
Randomization will be performed via Interactive Response Technology (IRT). Prior to the 
initiation of the study treatment, the site staff will contact/access the IRT system in order to 
determine the randomly assigned treatment. Specific procedures for randomization through 
the IRT system are contained in the study procedures manual.
Subjects who subsequently meet the inclusion/exclusion criteria will be randomly assigned to 
receive either ASP0113 or placebo. The randomization to treatment will be stratified by the 
use of anti-thymocyte globulin and by receipt of a kidney from a living or deceased donor.
The IRT vendor will generate the randomization schedule. To obtain the randomized 
treatment assignment for a subject, the pharmacist or designee will utilize an IRT system, 
which is available seven days a week, 24 hours a day.
Randomization is to be done after the completion of the Screening period, and at least 30 days ± 
3 days after transplant day (Day 0). After submitting required information about the eligible 
subject, the drug kit number assignment will be provided.
Study Drug assignment will remain blinded to all site staff except the pharmacist, designated 
staff and the unblinded administrator.  
If a subject is randomized but does not receive Study Drug, the kit number will not be used 
again. In this instance, the treatment assignment should only be known by the pharmacist and 
designated staff (i.e., the blind must be maintained as it is with all other subjects).   


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5
TREATMENTS AND EVALUATION
5.1
Dosing and Administration of Study Drug(s) and Other Medication(s)
One (1) mL of 5 mg/mL ASP0113 or placebo will be administered to the subjects at the 
clinical site via injection in the deltoid muscle, alternating sides with each dose, if possible. 
Preparation of Study Drug will be described in the Pharmacy Manual for the study. The 
syringes will be masked as described in the Pharmacy Manual to maintain the study blind.  
5.1.1
Dose/Dose Regimen and Administration Period
Doses will be given at the following time points:
●
Dose 1 at Day 30 ± 3 days, post transplant.
●
Dose 2 at Day 60 (± 5 days)
●
Dose 3 at Day 90 (± 5 days)
●
Dose 4 at Day 120 (± 5 days)
●
Dose 5 at Day 180 (± 5 days)
An injection should not be given if, 1) the subject has been on an anticoagulant within 5 half-
lives prior to the injection or there is any other contraindication to an intramuscular injection
or 2) has a Temperature ≥100.4◦F or 38◦C (per NCI Grade 1.)  Low dose anticoagulants that 
are used for prevention of deep vein thrombosis are allowed. Immunosuppressive agents used 
to prevent rejection should be given according to the standard of care at the center and taking 
note of the list of prohibited medication.
5.1.2
Increase or Reduction in Dose of the Study Drug
Dose increases or decreases are not allowed. If a dose is missed, the subject should continue 
on the same schedule of study drug injections and the same schedule of assessments except 
for the Day 14 follow up visit for the missed dose; clinical labs for hematology, biochemistry 
and hepatic profile should not be collected. Scheduled Immunogenicity Labs (Visit 5 & 9) 
must still be collected.  
5.1.3
CMV Prophylactic Therapy
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) through Randomization to prevent CMV disease. 
(The subject can miss up to two valganciclovir or ganciclovir doses during this time period 
for any reason). After Randomization, subjects will then receive CMV-specific AVP until 
100 days post transplant. Subjects can have CMV-specific AVP interrupted, dose adjusted or 
replaced by other CMV-specific AVP per standard of care after the day of Randomization, if 
renal function is compromised,there are toxicities related to the administration of the AVP or 
for any other medically indicated reason.Previous and Concomitant Treatment (Medication 
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5.1.3.1 Viral Prophylaxis
Viral prophylaxis for infection other than CMV should be administered according to standard 
institutional protocols. Prophylactic use of aciclovir (acyclovir), valaciclovir (valacyclovir), 
or famciclovir should not exceed the following doses following transplant (Day 0) through 
one year post Study Drug injection (Day 395/Visit 13) [Kumar & Humar, 2011; Tomblyn et 
al, 2009].
Aciclovir: 1600 mg orally (total daily dose), or 500 mg/ m2/dose IV (total daily dose).
Valaciclovir: 1000 mg PO (total daily dose).
Famciclovir: 500 mg PO (total daily dose). 
These doses may be exceeded if necessary to treat active infections post first Study Drug
injection.
5.1.3.2 Pneumocystis jiroveci Pneumonia Prophylaxis
Pneumocystis jiroveci pneumonia prophylaxis must be initiated for all study participants 
according to the site’s standard practice for kidney transplant recipients and applied uniformly 
to all enrolled subjects.  Dose may be adjusted or therapy interrupted for renal dysfunction, 
adverse events related to the administration of the therapy or for other clinically indicated 
reasons. If there is no prophylactic Pneumocystis protocol, the investigator must decide on 
appropriate Pneumocystis jiroveci pneumonia prophylaxis.
5.1.3.3 Prohibited Concomitant Medication
•
Investigational research products through completion of Day 395 visit (Visit 13).
• Planned alemtuzumab and, anti-CD20 antibodies (including rituximab) eculizumab or 
bortezomib are not allowed from the Day of Randomization through the Primary Study 
Period (Day 395).  These treatments may be given after the Day of Randomization if 
clinically indicated.
Prophylactic use of CMV immunoglobulin. 
•
Live attenuated vaccines within one month (30 days) prior to each Study Drug injection.
•
Subunit or killed vaccines within 14 days prior to any Study Drug injection. 
•
Anticoagulants, within 5 half-lives of Study Drug administration, including but not limited 
to vitamin K antagonists, heparin or its derivatives, low molecular weight heparin, factor 
X inhibitors, or thrombin inhibitors. Low dose anticoagulants that are used for prevention 
of deep vein thrombosis and antiplatelet agents are allowed.
5.1.3.4 Concomitant Medication (Drugs and Therapies)
All concomitant medications, immunosuppressive agents and therapies administered from 
14 days prior to transplant through the Primary Treatment Period (Visit 13/Day 395) will be 
recorded at each study visit on the eCRF. Subjects should be instructed not to take any new 


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medications or change the dose and frequency of their ongoing medications throughout the 
study period without consulting the investigator.
Medications used for anesthesia purposes during the transplant will not be recorded. 
5.1.4
Treatment Compliance
The dose and schedule of study product administered to each subject will be recorded on the 
appropriate form at every Study Drug administration visit. Reasons for partial administration 
(such as subject intolerance of injection or loss of Study Drug through human error) or 
omission of Study Drug will also be recorded. This information, plus vial accountability 
through the IRT system for Study Drug at every administration visit will be used to assess 
compliance with the treatment. 
Treatment compliance should be monitored closely and deviation in compliance should be 
reported to the Sponsor.
5.2
Demographics and Baseline Characteristics
5.2.1
Demographics
The subject’s age, gender, race and ethnicity will be recorded at the Screening Visit.
5.2.2
Medical History
A detailed medical history for each subject, including history of prior CMV, history of 
transfusion starting at one month prior to transplant, diagnosis for renal failure, length of time 
on dialysis, history of prior kidney transplant and diabetes, will be obtained at the Screening 
Visit. All relevant past and present conditions will be recorded for the main body systems, as 
well as prior surgical procedures. Typical events related to post operative recovery from the 
current transplant that occur prior to consent for this trial will be listed as medical history.
Any untoward medical events that occur during the Screening period (prior to Study Drug
administration) will be captured as medical history in the eCRF.
5.2.3
Transplant Information
Type of transplant 
Living Related Donor
Living Unrelated Donor
Deceased Donor
5.2.4
Donor Information
Demographics, (age, gender, race)
Viral Serologies; CMV (required), HBV, HCV, EBV (if available) and HCV PCR RNA, (if 
available)


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ABO blood group
HLA typing
5.2.5
Recipient Information
ABO blood group
HLA typing
HLA cross match at time of transplant (as determined by the site’s standard method of 
determination)
Viral Serologies CMV (required), HBV, HCV, EBV (if available), and HCV PCR RNA, (if 
available)
5.3
Efficacy and Immunogenicity Assessments
5.3.1
Primary Efficacy Assessment 
CMV Plasma Viral Load as assessed by a central assay.
Central viral load will be assessed according to Table 1a (Schedule of Assessments), any time 
a measurement of a viral load is clinically indicated, during CMV anti-viral therapy and any 
time a local CMV viral load is collected.
5.3.2
Secondary Efficacy Assessments
●
Adjudicated CMV disease:  CMV syndrome and CMV Tissue Invasive Disease as 
defined in Appendix 7
●
CMV Plasma Viral Load by Central Assay
●
Adjudicated CMV-specific AVT for CMV viremia or CMV disease
Initiation of AVT with activity against CMV will be adjudicated by an Adjudication 
Committee as set forth in the Adjudication Charter.
●
Graft Survival
Graft survival is defined as any subject that does not fit the definition of graft loss as follows: 
graft loss is defined as subject death; re-transplant; nephrectomy; or return to permanent 
dialysis (i.e., for > 30 days) at Study Month 13,/Day 395 and 6 months after Day 395 then, 
annually for the next 4 years.
●
Subject Survival 
Subject survival is any subject that is known to be alive at Study Month 13/Day 395. For the 
Long Term Follow Up period, patient survival is any subject that is known to be alive at the 
conclusion of the Long Term Follow-Up period.
5.3.3
Exploratory Efficacy Assessments
●
Opportunistic infections as defined in Appendix 8


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●
CMV Plasma Viral Load by central assay 
●
CMV disease: CMV syndrome and CMV Tissue Invasive Disease as defined in 
Appendix 7
●
Genotypic resistance to valganciclovir and ganciclovir
●
Biopsy Proven Acute Rejection (BPAR) as defined in Appendix 6
●
eGFR at the last study visit
●
Clinically treated acute graft rejection
5.3.3.1 Immunogenicity 
An indicator of immunogenicity elicited by the vaccine is predicted to be an increase in gB-
specific antibody levels and the T-cell response to pp65 protein over time compared with the 
placebo group.  
Two immunogenicity assessments will be performed:
1. T-cell response to viral protein pp65 using intracellular cytokine staining (ICS).
2. Antibody response to gB antigen using an ELISA-based platform.
Assessments will be done from peripheral blood mononuclear cells (T-cells) or serum samples 
(antibody) isolated over the course of the trial. Time points of the assessments are as follows:
On Visits V2, V5, V6, V9 and V10 and V13:
o Samples for T-cell assays will not be collected if the Absolute Lymphocyte Count 
(ALC) is known to be < 500 mm3 by local or central laboratory measurement. 
o If the visit coincides with a study drug administration, the sample will be drawn prior 
to injection.
Further details will be available in the Laboratory Manual.
5.3.4
Resource Utilization and Patient Reported Outcomes 
Additional assessments include the following patient reported outcome measures and 
resource utilization.    
●
EuroQol (EQ-5D)
●
Kidney Transplant Questionnaire (KTQ)
●
Short Form Health Survey version 2 (SF-12v2)
●
Health Economic Assessment (HEA)
The EQ-5D, Kidney Transplant Questionnaire (KTQ) and the SF-12 v2, should be completed 
by the subject prior to any other study assessments or visit procedures. Subjects should 
complete these assessments in the following order: EQ-5D first, KTQ second, SF-12 last. For 
all three patient-reported outcome measures, i.e., EQ-5D, KTQ, SF-12, the answers must 
come from the subject. If the subject is unable to fill out the questionnaire, the assessment 
should not be performed. If the subject is unable to answer an individual question, the rest of 
the questionnaire should still be completed. The questionnaires will be provided in the local 
language of the subject.


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Health economic information will be collected for subjects through the Primary Study Period 
Completion/Day 395 Visit (Visit 13) (See Section 5.3.4.4).
5.3.4.1 EQ-5D
The EQ-5D is an international standardized non-disease specific (i.e. generic) instrument for 
describing and evaluating health status. It is a measure of health-related quality of life (QOL), 
capable of being expressed as a single index value and specifically designed to complement 
other health status measures. The questionnaire will be provided in the local language of the 
subject. The EQ-5D has 5 domains: Mobility, Self-Care, Usual Activities, Pain/Discomfort, 
and Anxiety/Depression. Each domain has 3 response levels (e.g., 1=no problems, 2=some 
problems, 3=extreme problems). In addition, it has a visual analogue scale that elicits a self-
rating by the respondent of his/her health status (see Appendix 13).
5.3.4.2 Kidney Transplant Questionnaire
The KTQ is a 25-item questionnaire that includes five domains or subscales, i.e., physical 
symptoms (based on six items), fatigue (based on five items), uncertainty/fear (based on four 
items), appearance (based on four items), and emotional (based on six items). A mean score 
ranging from 1 to 7 is reported for each of the five subscales, with higher scores representing 
better functioning, well-being, or fewer problems [Laupacis et al, 1993] (Appendix 14).
5.3.4.3 SF-12 Health Survey Version 2
The SF-12v2 is a well validated generic health-related quality of life questionnaire. It is a 
shortened form of the SF-36 Health Survey (SF-36) that assesses functional status, well-
being, and health status perceptions across the following eight domains: physical functioning, 
role functioning-physical, bodily pain, general health, vitality, social functioning, role 
functioning-emotional, and mental health. The SF-12v2 has been used in the renal transplant 
literature and has been utilized to validate other disease-specific symptom and health status 
measures [Chisholm-Burns et al, 2012].
5.3.4.4 Health Economic Assessment (HEA)
Health Economic Assessments will include the following:hospitalizations recorded as number 
of days in the Intensive Care Unit, Step-down Unit, and general medical ward, (including 
emergency room visits greater than 24 hours) also non-protocol- related physician visits and
emergency room visits less than 24 hours. The information will be collected by the site via a 
retrospective review of the subject’s medical record. HEA data will include both data being 
routinely captured for the subject (e.g., concomitant medications) as well as data that will be 
used specifically for these analyses (e.g., information on hospitalizations) (Appendix 18).


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5.4
Safety Assessment
Safety assessments include the following:
●
Vital signs
●
Adverse events graded by NCI CTCAE v. 4.03 criteria
●
Local reactogenicity signs and symptoms using both the NCI-CTCAE v. 4.03 grading 
scale and the protocol-specified reactogenicity scale 
●
Systemic reactogenicity signs and symptoms using both the NCI-CTCAE v. 4.03 grading 
scale and the protocol-specified reactogenicity scale
●
Laboratory assessments
●
Urinalysis, including microscopic evaluation
●
Physical examination
5.4.1
Vital Signs
Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate and temperature) 
will be collected at all dosing visits, and at Screening (V1), and at V12 and 13. Height will be 
collected at Screening only. Weight will be collected at V1, V2 and Study Completion (V13).
Vital signs will be collected as follows:
●
Vital signs will be collected immediately prior to injection, at 15 and 60 minutes post
Study Drug injection at study visits accompanied by injection. 
●
Vital signs will be collected once at Screening (Visit 1), and at Visits 12 and 13.
5.4.2
Adverse Events
See Section 5.5 Adverse Events and Other Safety Aspects for information regarding adverse 
event collection and data handling. 
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing of 
the informed consent through one year post Study Drug injection. AEs from the time of 
signing of informed consent through first dose of Study Drug should be captured on the 
medical history eCRF. If the AE is deemed possibly or probably related to Study Procedures 
prior to the first Study Drug injection, it will be recorded on the AE eCRF page.  SAEs that 
occur from the signing of the informed consent form will be reported as per Section 5.5 and 
captured on the AE eCRF page.  AEs and SAEs after the first dose of Study Drug should be 
captured on the AE eCRF page.
Data to be recorded includes the adverse event, date of onset, date of resolution, intensity, 
action taken with respect to Study Drug, treatment required, relationship to Study Drug and 
outcome of the event.  
Adverse events ongoing at V13 will be followed up for as long as necessary to adequately 
evaluate the subject’s safety or until the event stabilizes. If the event resolves during the 
study, a resolution date will be documented on the case report form.


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5.4.2.1 Adverse Events of Possible Hepatic Origin 
See Appendix 10 Liver Safety Monitoring and Assessment for detailed information on liver 
abnormalities, monitoring and assessment, if the AE for a subject enrolled in a study and 
receiving Study Drug is accompanied by increases in liver function testing (LFT, e.g., AST, 
ALT, bilirubin, etc.) or is suspected to be due to hepatic dysfunction. 
5.4.3
Local Reactogenicity Assessments
Local reactogenicity will be evaluated one hour after each injection in the clinic. The subject 
must be in direct view of the clinic staff for 15 minutes following each injection, then remain 
in the clinic area for an additional 45 minutes for evaluation of local and systemic 
reactogenicity. Local reactogenicity will be evaluated via diary (once the subject is trained) 
for the 7 days following each injection.  
Grading of reactogenicity will be done using the protocol-specified reactogenicity scale and 
the NCI-CTCAE v. 4.03 grading scale (Appendix 4). The daily maximum measurement of 
local reactogenicity signs and symptoms will be recorded.
5.4.4
Systemic Reactogenicity Assessments
Specific signs of systemic reactogenicity will be evaluated one hour after each injection 
(Appendix 5). The subject must be in direct view of the clinic staff for 15 minutes following 
each injection, then remain in the clinic area for an additional 45 minutes for evaluation of 
systemic reactogenicity. Vital signs, including temperature, pulse, respiration and blood 
pressure will be collected just prior to injection, 15 minutes post-injection and at one hour 
post-injection. Using the pre-injection vital signs as baseline, if a post Study Drug injection 
vital sign meets Grade 1-4 criteria per Appendix 5, it is to be repeated and confirmed within 5 
minutes of first assessment.  Systemic measurements that will be followed for 7 days are 
fever, fatigue and myalgia.  
Grading of reactogenicity will be done using the protocol-specified reactogenicity scale 
(Appendix 4) and the NCI-CTCAE v. 4.03 grading scale. The daily maximum measurement 
of systemic reactogenicity signs and symptoms will be recorded.
5.4.5
Laboratory Assessments
Please refer to Appendix 2 for a list of laboratory tests to be performed during the study.
Blood and urine samples will be collected for the following laboratory assessments:

Urine pregnancy testing for females of child bearing potential will be performed at the 
Screening Visit, prior to Study Drug when administered and according to the Schedule of 
Assessments, Table 1. Results must be available prior to Study Drug dosing. All 
pregnancy tests will be done locally.

CMV IgG antibody will be assessed within 8 weeks prior to transplant or at Screening if 
no CMV IgG antibody assay has been performed within that time period by the local 
laboratory. CMV plasma viral load will be monitored as outlined in Table 1a. Central 


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laboratory measurements for routine surveillance of viremia will be performed at the 
following time points:
o
Every other week from Day 100 to Day 200 (± 3 days).
o
Monthly from Day 200 until Day 395 (±5 days).

Local laboratory values for CMV viral load should be collected and documented in the 
eCRF for subjects whenever CMV disease (CMV syndrome or CMV tissue-invasive 
disease) is suspected within the first 12 months post first Study Drug injection and when 
CMV-specific AVT is initiated.  

If CMV AVT is initiated, Central lab CMV viral loads will be collected at a minimum of 
weekly from the time CMV specific AVT is initiated until discontinuation.  Note:  Central 
Lab turnaround time is estimated to be at least 3 days from receipt at the Central lab, not 
including holidays. If treatment decisions need to be made a local CMV viral load should 
be collected and analyzed at an Astellas approved laboratory.  

When a local lab sample is collected for CMV viral load, an additional sample must be 
collected and sent to the central lab. Any time a local value for CMV viral load is 
obtained it should be recorded in the eCRF.  
As one of the plasmids of the ASP0113 vaccine codes for the pp65 antigen, the theoretical 
possibility of interference with the pp65 antigenemia assay has been raised. At present there 
are no data to suggest that such an interference occurs. However, to ensure subject safety and 
study integrity, sites that use pp65 antigen as their local methodology for the detection of 
CMV infection must adhere to the procedures defined below as a condition of participation in 
the trial.

The local pp65 antigenemia results must be entered into the eCRF database within 72 
hours (or next business day) of receipt to facilitate in-time monitoring of results.

The Medical Monitor must be called within 48 hours (or next business day) if the pp65 
antigenemia test is positive and the central laboratory PCR viral load result is negative.

Both the pp65 antigenemia and the central laboratory test must be repeated within 48 
hours if the local pp65 antigenemia result is positive, the central laboratory PCR viral 
load result is negative and the subject is treated with CMV-specific AVT. Further 
treatment decisions are to be discussed with the Medical Monitor.
The plasmids in the Study Drug may interfere with certain PCR assays. If a PCR assay is
used that amplifies the genes UL55/gB or UL83/pp65, this could result in either a false 
positive viral load or unblinding of the study subject.
Sites that are determined to have an unacceptable assay in their local lab but are able to 
determine a Sponsor- deemed acceptable work practice flow for utilizing another acceptable 
local assay or methodology will be allowed to participate in the trial. Note: Local CMV plasma 
viral load testing may be performed only at a local laboratory approved by the Sponsor.


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Local laboratory samples as follows per the Schedule of Assessments, Table 1:

Hematology: red blood cells (RBC), white blood cells [(WBC) – total leukocytes], 
hemoglobin, hematocrit, platelets (thrombocytes), neutrophils, eosinophils, basophils, 
lymphocytes, monocytes.

Biochemistry: sodium, potassium, calcium, chloride, phosphorus, glucose, blood urea 
nitrogen (BUN), creatinine, CPK/CK, total protein, albumin.

If creatinine phosphokinase (CPK) levels are 5 x the upper limit of normal (ULN), at any 
time during the Primary Study Period, a repeat laboratory draw should be performed. If 
repeat CPK is still 5x the ULN, the Medical Monitor should be notified within 2 business 
days for further instructions.

Hepatic profile (total bilirubin, direct bilirubin, aspartate aminotransferase [AST], alanine 
aminotransferase [ALT], alkaline phosphase [AP]. See Appendix 10 for follow-up of liver 
function tests beyond the Upper Limit of Normal.

Urinalysis (pH, specific gravity, protein, glucose, ketones, bilirubin, blood, microscopic 
evaluation)

Urine protein: creatinine ratio
Clinically significant laboratory results should be followed until resolution or until they are no 
longer clinically significant or are medically stable. Other Assessments by Central Laboratory:  

Immunogenicity: gB-specific antibody levels and T-cell responses to pp65.

Genotypic resistance testing:  Resistance to ganciclovir or valganciclovir should be 
assessed when there is no reduction in viral load or no change in clinical symptoms two 
weeks after starting valganciclovir or ganciclovir treatment for CMV viremia or disease.

A whole blood sample for optional pharmacogenomics will be collected at Visit 2 after 
Randomization but prior to the first dose of Study Drug for subjects who agree to 
participate in the optional pharmacogenomics substudy. 

Safety labs (hematology, biochemistry, hepatic profile, urine protein:creatinine ratio and 
urinalysis) drawn by Home Health Care for Investigator sites utilizing this service will be 
analyzed by the Central Laboratory.
5.4.6
Physical Examination
Complete physical examinations (PE) will be performed at the Screening and Baseline Visits 
(Visit 1 and Visit 2) and at the Primary Study Period Completion/Day 395 (Visit 13). The PE 
will include the following: an examination of the skin, general appearance, neck (including 
thyroid), eyes, ears, nose, throat, lymph nodes, chest (lungs), heart, abdomen, musculoskeletal 
system, neurological system and any additional assessments needed to establish baseline 
status or evaluate symptoms or adverse events. At all other visits where a PE is performed, 
symptom-directed physical examinations may be done. If Screening is done > 3 days prior to 
Randomization, the PE must be repeated on the day of Randomization.


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The Investigator or qualified medical personnel who routinely perform these evaluations in 
this patient population will conduct the examination, determine findings, and assess any 
abnormalities as to clinical significance.
5.4.7
Home Health Care Service 
An optional Home Health Care Service is available through the Sponsor in lieu of the subject 
coming in to the Investigative site for the following visits 

Post-Dosing Visits 3, 7 and 11 for clinical laboratory collection.

CMV Plasma Viral Load Testing Visits (Central Laboratory Testing) at Day 100, 114, 
128, 142, 156, 170, 198, 230, 290, 320, 350, and 380. (Days 100 and 198 CMV testing
must correspond appropriately with visit windows for Visits 3 and 11 in order to be 
combined). 
Home Health Care visits are not allowed at any visit where a physical assessment, adverse 
event assessment or Immunology blood collection is due. For sites that choose to use the 
service, the home health care nurse will report vital signs and subject complaints at this visit 
via Sponsor approved source documents. The nurse will collect blood samples, process and 
ship them appropriately to the Central or local laboratory. Local CMV viral load testing may 
only be performed at a local laboratory approved by the Sponsor.       
This service may not be available in all regions.
5.4.8
Long Term Follow-Up
Subjects will be contacted by telephone at 6 months after Day 395, then annually for the next 
4 years for long-term safety related to the DNA vaccine. Items to be assessed by 
questionnaire and available patient records include mortality, development of any new 
cancer, development of infection requiring hospitalization or resulting in death, graft survival, 
creatinine and erythema and/or induration at the sites of immunizations (see Appendix 17). 
Creatinine values will be recorded if they have been collected within 3 months prior to the
follow-up telephone contact and are in the subject’s available medical records.
During the long-term follow-up period, if an SAE is identified and deemed possibly or 
probably related to the study medication, an SAE report on the SAE worksheet must be sent 
to the sponsor per Section 5.5.6.
5.5
Adverse Events and Other Safety Aspects
5.5.1
Definition of Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a subject administered a Study Drug
or has undergone study procedures and which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 


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An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG 
data, physical exam) should be defined as an AE only if the abnormality meets one of the 
following criteria:

Induces clinical signs or symptoms

Requires active intervention

Requires interruption or discontinuation of study medication

The abnormality or investigational value is clinically significant in the opinion of the 
investigator.

The transplant surgery that occurs on Day 0 is not considered an AE or an SAE.
5.5.2
Adverse Events of Special Interest
The following definitions should be used to properly record and report adverse events for the 
study.
5.5.2.1 Adverse Events Commonly Associated with Vaccines
The following adverse events have been reported with other vaccines and will be subject to 
specific monitoring:

Acute local vaccines reactions including as local pain, redness, swelling or induration

Acute systemic vaccine reactions including as anaphylaxis and convulsions

Late vaccine reactions including demyelinating disorders (e.g., Guillain-Barré syndrome, 
neuritis, neuropathy).
5.5.2.2 Infection

Bacterial, fungal and viral infections and the following information will be collected:  
Treatment with a antimicrobial agent for a specific clinical syndrome (not prophylaxis)

Positive cultures, pathologic identification of microbial agents or significant serological
changes related to clinical symptoms

Typical clinical presentation documented by investigator or appropriate consultant.
In addition, the following information should be collected for potential BK viral infections: 

Renal biopsy results, if performed.
Definitions of opportunistic, EBV and BK infections are provided in Appendices 8 and 9, 
respectively.
5.5.2.3 Post-Transplant Lymphoproliferative Disorder (PTLD)
Diagnosis of PTLD should be made following review of tissue specimens. The anatomic 
staging of PTLD will be captured, specifically if the allograft or Central Nervous System 
(CNS) is involved. PTLD will be classified according to the criteria in Appendix 12. 
Additionally, if available, ancillary pathologic information related to cell phenotype, clonality, 
presence of EBV in the tissue specimen, and donor vs. recipient origin will be collected.


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Tissue samples should be interpreted by a hematopathologist or pathologist who is familiar 
with the histopathologic features of PTLD. If as a matter of the subject’s routine medical 
evaluation tissues are examined for the presence of EBV by in situ hybridization, the cell of 
origin (B, T, null, mixed) is determined or radiographic evaluation is performed to document 
the extent of disease (e.g., CT scans) this information will be captured on the CRF.
5.5.3
Definition of Serious Adverse Events (SAEs)
An adverse event is considered “serious” if, in the view of either the investigator or Sponsor, 
it results in any of the following outcomes:

Results in death.

Is life threatening (an adverse event is considered “life-threatening” if, in the view of 
either the investigator or Sponsor, its occurrence places the subject at immediate risk of 
death. It does not include an adverse event that, had it occurred in a more severe form, 
might have caused death).

Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions.

Results in congenital anomaly, or birth defect.

Requires inpatient hospitalization or leads to prolongation of hospitalization 
(hospitalization for treatment/observation/examination caused by AE is to be considered 
as serious).

Other medically important events.

The transplant surgery that occurs on Day 0 is not considered an AE or an SAE.
Medical and scientific judgment should be exercised in deciding whether expedited reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
subject or may require intervention to prevent one of the other outcomes listed in the 
definition above. These events, including those that may result in disability/incapacity, should 
also usually be considered serious. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that 
do not result in hospitalization; or development of drug dependency or drug abuse.
Safety events of interest on the medicinal products administered to the subject as part of the 
study (e.g., Study Drug, comparator, background therapy) that may require expedited 
reporting and/or safety evaluation include, but are not limited to:

Overdose of the medicinal product(s)

Suspected abuse/misuse of the medicinal product(s)

Inadvertent or accidental exposure to the medicinal product(s)

Medication error involving the medicinal product(s) (with or without subject/patient 
exposure to the Sponsor medicinal product, e.g., name confusion)
All of the events of interest noted above should be recorded on the (e)CRF. Any situation 
involving these events of interest that also meets the criteria for an SAE should be recorded 
on the AE page of the (e)CRF and marked ‘serious’ and the SAE worksheet. 


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The Sponsor has a list of events that they classify as “always serious” events.  If an adverse 
event is reported that is considered to be an event per this classification as  “always serious”, 
additional information on the event may be requested.  
5.5.4
Criteria for Causal Relationship to the Study Drug
Adverse events that fall under either "Possible" or "Probable" should be defined as "adverse 
events whose relationship to the Study Drugs could not be ruled out".
Causal relationship 
to the Study Drug
Criteria for causal relationship
Not Related
A clinical event, including laboratory test abnormality, with a 
temporal  relationship to drug administration which makes a causal 
relationship improbable, and/or in which other drugs, chemicals or 
underlying disease provide plausible explanations.
Possible
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the drug, but which 
could also be explained by concurrent disease or other drugs or 
chemicals. Information on or drug withdrawal may be lacking or
unclear.
Probable
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the drug, unlikely to 
be attributed to concurrent disease or other drugs or chemicals, and 
which follows a clinically reasonable response on re- administration 
(rechallenge) or withdrawal (dechallenge).
5.5.5
Criteria for Defining the Severity of an Adverse Event
AEs, including abnormal clinical laboratory values, will be graded using the National Cancer 
Institute (NCI)-Common Terminology Criteria for Adverse Event (CTCAE) guidelines 
(Version 4.03). The items that are not stipulated in the NCI-CTCAE Version 4.03 will be 
assessed according to the criteria below and entered into the eCRF:
Grade
Assessment Standard
1-Mild
Asymptomatic, or mild symptoms, clinical or diagnostic observations 
noted; intervention not indicated.
2-Moderate
Local or noninvasive intervention indicated.
3-Severe
Medically significant but not immediately life threatening, 
hospitalization or prolonged hospitalization.
4-Life Threatening
Life threatening consequences, urgent intervention indicated.
5-Death
Death related to AE.


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5.5.6
Reporting of Serious Adverse Events (SAEs)
In the case of a serious adverse event (SAE), the investigator must contact the Sponsor by fax 
immediately (within 24 hours of awareness).
The investigator should complete and submit an SAE Worksheet containing all information 
that is required by the Regulatory Authorities to the Sponsor by fax immediately (within 24 
hours of awareness). If the faxing of an SAE Worksheet is not possible or is not possible 
within 24 hours, the local drug safety contact should be informed by phone.
The Investigator should fax the SAE Worksheet to: 
Fax number 
International Fax: 
Email:
If there are any questions, or if clarification is needed regarding the SAE, please contact the 
Sponsor's Medical Monitor/Expert or his/her designee (see Section II Contact Details of Key 
Sponsor’s Personnel). 
Follow-up information for the event should be sent promptly (within 7 days of the initial 
notification).
Full details of the SAE should be recorded on the medical records and on the (e)CRF.
The following minimum information is required:

ISN/Study number, 

Subject number, sex and age,

The date of report,

A description of the SAE (event, seriousness of the event), and

Causal relationship to the Study Drug.
Spontaneously reported possibly or probably related SAEs that occur outside of the study-
defined SAE reporting period, i.e., the Long Term Follow-up, should also be sent to the 
sponsor in accordance with the protocol defined SAE reporting guidelines.  
The Sponsor or Sponsor's designee will submit expedited safety reports (e.g. IND Safety 
Reports) to the regulatory agencies (e.g. FDA) as necessary, and will inform the investigators 
of such regulatory reports. Investigators must submit safety reports as required by their 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) within timelines set 
by regional regulations (e.g. EU, (e)CTD, FDA). Documentation of the submission to and 
receipt by the IRB/IEC of expedited safety reports should be retained by the site.
The Sponsor/delegated CRO will notify all investigators responsible for ongoing clinical 
studies with the Study Drug of all SAEs which require submission per local IRB/IEC 
requirements.


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The investigators should provide written documentation of IRB/IEC notification for each 
report to the Sponsor.
You may contact the Sponsor's Medical Monitor/Expert for any other problem related to the 
safety, welfare, or rights of the subject.
For Suspected Unexpected Serious Adverse Reactions (SUSAR) from a blinded trial, 
unblinded CIOMS-I report will be submitted to the authorities and IRB/IEC where required.
5.5.7
Follow-up of Adverse Events
All AEs occurring during or after the subject has discontinued the study are to be followed up 
until resolved or judged to be no longer clinically significant, or until they become chronic to 
the extent that they can be fully characterized. 
If during AE follow-up, the adverse event progresses to an "SAE", or if a subject experiences 
a new SAE, the investigator must immediately report the information to the Sponsor. 
Please refer to Appendix 10 Liver Safety Monitoring and Assessment for detailed instructions 
on Drug Induced Liver Injury (DILI).
5.5.8
Monitoring of Common Serious Adverse Events
Common serious adverse events are SAEs commonly anticipated to occur in the study 
population independent of drug exposure. SAEs classified as “common” are provided in 
Appendix 11 Common Serious Adverse Events for your reference. The list does NOT change 
your reporting obligations or prevent the need to report an AE meeting the definition of an 
SAE as detailed above. The purpose of this list is to alert you that some events reported as 
SAEs may not require expedited reporting to the regulatory authorities based on the 
classification of “common serious adverse events” as specified in Appendix 11 Common 
Serious Adverse Events. The Sponsor will monitor these events throughout the course of the 
study for any change in frequency. Any changes to this list will be communicated to the 
participating investigational sites. Investigators must report individual occurrences of these 
events as stated in Section 5.5.6 Reporting of Serious Adverse Events.
5.5.9
Procedure in Case of Pregnancy
If a female subject or partner of a male subject becomes pregnant during the study dosing 
period or within one year post first Study Drug injection, the investigator should report the 
information to the Sponsor as if it is an SAE. The expected date of delivery or expected date 
of the end of the pregnancy, last menstruation, estimated conception date, pregnancy result 
and neonatal data etc., should be included in this information.
The investigator will follow the medical status of the mother, as well as the fetus, as if the 
pregnancy is an SAE and will report the outcome to the Sponsor.
When the outcome of the pregnancy falls under the criteria for SAEs [spontaneous abortion, 
induced abortion, stillbirth, death of newborn, congenital anomaly (including anomaly in a 
miscarried fetus)], the investigator should respond in accordance with the report procedure 


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for SAEs. Additional information regarding the outcome of a pregnancy (which is 
categorized as an SAE) is mentioned below.

"Spontaneous abortion" includes miscarriage, abortion and missed abortion.

Death of an infant within 1 month after birth should be reported as an SAE regardless of 
its relationship with the Study Drug.

If an infant dies more than 1 month after the birth, it should be reported if a relationship 
between the death and intrauterine exposure to the Study Drug is judged as "possible" by 
the investigator.

In the case of a delivery of a living newborn, the "normality" of the infant is evaluated at 
the birth.

Unless a congenital anomaly is identified prior to spontaneous abortion or miscarriage, 
the embryo or fetus should be assessed for congenital defects by visual examination.

If during the conduct of a clinical trial, a male subject makes his partner pregnant, the 
subject should report the pregnancy to the investigator. The investigator will report the 
pregnancy to the Sponsor as an SAE.
5.5.10
Emergency Procedures and Management of Overdose
In the event of suspected ASP0113 overdose, the subject should receive supportive care and 
monitoring. The Medical Monitor/Expert should be contacted.
5.5.11
Supply of New Information Affecting the Conduct of the Study
When new information becomes available necessary for conducting the clinical study 
properly, the Sponsor will inform all investigators involved in the clinical study as well as the 
regulatory authorities. Investigators should inform the IRB/IEC of such information when 
needed. 
5.6
Test Drug Concentration
Not Applicable
5.7
Other Measurements, Assessments or Methods
5.7.1
Blood Sample for Future PGx Analysis (Retrospective PGx Analysis) 
A PGx research study may be conducted in the future to analyze or determine genes of relevance 
to clinical response, pharmacokinetics, and toxicity/safety issues. After randomization, but prior 
to the first dose of Study Drug (see schedule of assessments), subjects who consent to participate 
in the retrospective pharmacogenomics assessment will have a 5 mL sample of whole blood 
collected for possible retrospective PGx analysis. This sample will be collected using a 
vacutainer tube containing EDTA. After collection, gently invert the blood sample 8 to 10 times. 
The blood collection tube may either be stored upright at 4°C for up to 5 days prior to shipment 


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or stored frozen at -20°C or below at the site for extended storage. Samples will be shipped to a 
Sponsor designated banking CRO.
Labels should uniquely identify each sample and contain at least:
●
Protocol number (0113-CL-2001),
●
Subject number, and
●
Purpose and biological matrix (i.e., “biobanking”, “whole blood”).
Details on sample collection, labeling, storage and shipment procedures will be provided in a 
separate laboratory manual.
See Appendix 16, Retrospective PGx Sub-study for further details on the banking procedures.
5.8
Total Amount of Blood
The total amount of blood to be collected for central and local laboratory assessments per 
subject should not exceed 61 mL at any study visit and is expected to be approximately 
504 mL total for the study. Central laboratory volume drawn is estimated not to exceed 
50 mL per visit. As local laboratory amounts vary between institutions, the total amount may 
vary.
This total blood volume does not include the volume for the CMV viremia assessments when 
assessments are not done per schedule, nor does it include pharmacogenomics or genotypic 
resistance testing, as this will be performed only as required.  
Refer to the Laboratory Manual for more details regarding blood collection.
6
DISCONTINUATION
6.1
Discontinuation of Individual Subject(s) 
A discontinuation is a subject who enrolled in the study and for whom study treatment is 
permanently discontinued prematurely for any reason.  
The subject is free to withdraw from the study treatment and/or study for any reason and at 
any time without giving reason for doing so and without penalty or prejudice. The 
investigator is also free to terminate a subject's involvement in the study at any time if the 
subject's clinical condition warrants it.
If a subject is discontinued from the study with an ongoing adverse event or an unresolved 
laboratory result that is significantly outside of the reference range, the investigator will 
attempt to provide follow-up until the condition stabilizes or no longer is clinically significant. 


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6.1.1
Study and Treatment Discontinuation
Study and Treatment Discontinuation:
Subjects will be withdrawn from investigational study treatment and all follow- up assessments 
and will only be followed for mortality through public records if the following occurs:  
•
Withdrawal of consent by the subject.
Treatment Only Discontinuation:
Subjects will be withdrawn from investigational study treatment if any of the following occur, 
however, they should continue to be followed according to the protocol Schedule of 
Assessments (Table 1) and Long Term Follow-up Schedule of Assessments, except post-dose 
Day 14 safety and laboratory and reactogenicity assessments/visits for those doses not given.
•
Investigator’s decision that further treatment is not in the best interest of the subject.
•
Graft failure.
•
Pregnancy (female subjects only).
•
Local reactogenicity with a grade ≥3 based on the criteria defined in Appendix 4 and is 
confirmed by a health care professional and reported as a Drug Related Adverse Event.
•
Systemic reactogenicity, for any grade ≥ 3 fever or any grade 4 systemic reaction within 
one week of vaccination and is confirmed by a health care professional and reported as a 
Drug Related Adverse Event (Appendix 5). 
•
Anaphylaxis Grade ≥ 3 per NCI ver. 4.03 criteria.
Subjects who discontinue investigational treatment for these or for other reason(s) but do not 
withdraw consent should remain in the study and continue to be followed according to the 
visit schedule through the Long-term Follow-up Period. All study procedures should be 
completed for these subjects, with the exception of the post-dose Day 14 safety laboratory 
and reactogenicity assessments/visits for those doses that are not given. Subjects not willing 
to participate in the study procedures should be asked if they would be willing to be followed 
annually for mortality through the Long-term Follow-up Period. 
  
6.2
Discontinuation of the Site
If an investigator intends to discontinue participation in the study, the investigator must 
immediately inform the Sponsor.
6.3
Discontinuation of the Study
The Sponsor may terminate this study prematurely, either in its entirety or at any study site, 
for reasonable cause provided that written notice is submitted in advance of the intended 
termination. Advance notice is not required if the study is stopped due to safety concerns. If 


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the Sponsor terminates the study for safety reasons, the Sponsor will immediately notify the 
investigator and subsequently provide written instructions for study termination.
7
STATISTICAL METHODOLOGY  
A Statistical Analysis Plan (SAP) will be written by the responsible biostatistician of APGD
to provide details of the analysis, along with specifications for tables, listings and figures to 
be produced. The SAP will be finalized before the database lock at the latest. Any changes 
from the analyses planned in SAP will be justified in the Clinical Study Report (CSR).
Prior to database lock, a final review of data and tables, listings and forms (TLFs) meeting 
will be held to allow a review of the clinical trial data and to verify the data that will be used 
for analysis set classification. If required, consequences for the statistical analysis will be 
discussed and documented. A meeting to determine analysis set classifications will also be 
held prior to database lock.
In general, all data will be summarized with descriptive statistics (number of subjects, mean, 
standard deviation, minimum, median and maximum) for continuous endpoints, and 
frequency and percentage for categorical endpoints.
Unless specifically stated otherwise, all efficacy comparisons will be tested at 1-sided 0.05 
level and safety comparisons will be tested at 2-sided 0.05 level. Confidence intervals for 
efficacy estimates, if provided, will be constructed at 90% level.  
7.1
Sample Size
In a recent study of prophylactic valganciclovir given at 900 mg/day for 100 days to donor 
CMV-seropositive/recipient CMV seronegative (D+R-) kidney transplant recipients [Humar, 
2006], CMV viremia, defined as CMV viral load > 600 copies/mL, was seen through one year 
in 83 of 163 subjects [50.9%, 95% CI = (43.0%, 58.8%)]. In another study [Couzi, 2012], 
CMV infection, defined as two consecutive positive Polymerase Chain Reaction (PCR) assay 
results, was seen in 11 of 32 subjects (34.4%, 95% Confidence Interval (CI) = (18.6%, 
63.2%)), respectively. Pooled from these two studies by weighted average, it is estimated that 
placebo rate is 46% (70% weight on Humar’s result). A sample size of 64 subjects per arm will 
allow the study to have 80% power to detect a reduction in CMV viremia to 25% due to 
ASP0113 at 52 weeks using a 1-sided test with a type 1 error rate of 5%. To allow for loss to 
follow-up, 70 subjects per arm will be enrolled for a total sample size of 140 subjects.
7.2
Analysis Sets
Detailed criteria for analysis sets will be laid out in classification specifications and the 
allocation of subjects to analysis sets will be determined prior to database hard-lock. 


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7.2.1
Full Analysis Set (FAS)
The Full Analysis Set will consist of all subjects who are randomized and receive at least one 
dose of Study Drug and have at least one post dose viral load assessment by central 
laboratory. This will be the primary analysis set for efficacy analyses and for summaries of 
demographic and baseline characteristics. 
7.2.2
Per Protocol Set (PPS)
The Per Protocol Set (PPS) will be specified in detail prior to locking and unblinding the final 
study database. The PPS will include all subjects in the FAS who had no major protocol 
violations or other conduct during the study that would make a subject non-evaluable.
Complete criteria will be defined in the SAP. The PPS will be used for secondary analyses of 
efficacy variables and for selected demographic and baseline characteristics.  
7.2.3
Safety Analysis Set (SAF)
The Safety Analysis Set consists of all randomized subjects who received at least one dose of 
randomized Study Drug and for whom any data is reported after first dose of Study Drug.
The SAF will be used for summaries of demographic, baseline characteristics, and all safety 
related variables.
7.2.4
Pharmacogenomics Set (PGS) 
The pharmacogenomics set consists of all randomized subjects who consent to participate in 
the optional pharmacogenomics sub-study and who have a blood sample collected during the 
Baseline Visit, after Randomization but prior to the first dose of Study Drug. The PGS will be 
used for all pharmacogenomic analyses.
7.3
Demographics and Other Baseline Characteristics 
Demographics and baseline characteristics will be summarized overall and by treatment 
group using the SAF, FAS and PPS.
Continuous variables will be summarized by descriptive statistics (e.g., n, mean, standard 
deviation, minimum, median, and maximum) and discrete variables will be summarized by 
the number and percentage of subjects in each category.
7.4
Analysis of Efficacy 
Primary efficacy analysis will be conducted on the FAS. The PPS will be used to assess the 
robustness of the selected efficacy analysis based on the FAS.


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7.4.1
Analysis of Primary Efficacy Endpoint 
7.4.1.1 Primary Analysis
The primary efficacy endpoint, the incidence of CMV viremia (defined as plasma viral load
≥1000 IU/mL by central assay) through one year post first Study Drug injection, in subjects 
receiving a kidney from a living or deceased donor, will be analyzed using the Cochran-
Mantel-Haenszel (CMH) test stratified by use of anti-thymocyte globulin (ATG) and by receipt 
of a kidney from a living or deceased donor. 
The null and alternative hypotheses for this comparison are:
H0: Common Odds Ratio = 1.
H1: Common Odds Ratio  < 1.
The 1-sided p-values will be calculated, together with the 90% 2-sided confidence interval for 
the odds ratio. The primary analysis will be conducted using the FAS.  Determination of the 
primary endpoint in subjects in the FAS with missing central laboratory CMV viral load 
values is described in Section 7.9.
7.4.1.2 Secondary Analysis
The same analysis of the primary efficacy endpoint as described in 7.4.1.1 will be conducted 
using the PPS.  
7.4.1.3 Subgroup Analysis
The Breslow-Day test will be used to assess the consistency of the odds ratio across the strata. 
In the event that the Breslow-Day test is significant at the 0.10 level, tabulations of the 
treatment effect will be provided for each strata to assess the strength of possible treatment-
by-strata interactions. 
7.4.2
Analysis of Secondary Efficacy Endpoints 
The secondary efficacy endpoints in this study include: 
•
Incidence of adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease through one year post first Study Drug injection.
•
Incidence of CMV viremia (defined as plasma viral load ≥the lower limit of 
quantification [LLOQ]) by central assay through one year post first Study Drug injection.
•
Incidence of adjudicated CMV-specific antiviral therapy.
•
Incidence of graft survival through one year post Study Drug injection.
•
Incidence of subject survival through one year post Study Drug injection.
The secondary efficacy endpoints will be each analyzed using the same CMH method 
described in 7.4.1.1.
All analyses of secondary endpoints will be performed using FAS and PPS.


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7.4.3
Analysis of Exploratory Endpoints 
The exploratory endpoints in this study include: 
•
Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.
•
Time to first CMV viremia (defined as plasma viral load of ≥1000 IU/mL by central 
assay) through one year post first Study Drug injection.
•
Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection.
•
Number of episodes of CMV viral load of ≥1000 IU/mL by central assay through one 
year post first Study Drug injection.
•
Peak CMV viral load through one year first Study Drug injection.
•
Viral load area under the curve (AUC), as a measure of “cumulative viral load” through 
one year post first Study Drug injection.
•
Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.
•
Incidence of viral resistance to ganciclovir or valganciclovir through one year post Study 
Drug injection as determined by a central laboratory assay. 
•
Incidence of biopsy-proven (T or B cell) rejection (BPAR)(Banff 2007 Grade > 1) 
through one year post Study Drug injection.
•
Estimated glomerular filtration rate (eGFR) at the last study visit calculated using the 4 
variable MDRD formula.
•
Incidence of clinically treated acute graft rejection rate through one year post Study Drug
injection.
•
Health economic and outcomes research (HEOR) scores.
•
Patient-reported outcomes:
o
EQ-5D (EuroQol-5 dimensions 5 levels) will be used as a preference-based utility 
measure of patients’ quality of life.
o
KTQ (Kidney Transplant Questionnaire) will be used to evaluate transplant-
specific patients’ quality of life. 
o
SF-12v2 (Short Form Health Survey version 2) will be used to evaluate the overall 
patients’ quality of life. 
•
Healthcare resource utilization:
o
Resource use will be collected including the following: hospitalizations recorded 
as number of days in the Intensive Care Unit, Step-down Unit, and general 
medical ward, (including emergency room visits greater than 24 hours);) also non-
protocol- related physician visits and emergency room visits less than 24 hours. 


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Number of episodes of CMV viral load of ≥ 1000 IU/mL and number of episodes of adjudicated 
CMV-associated disease will each be compared between treatments using Poisson regression 
controlling for follow-up period and stratification factors.
The incidence endpoints will be each analyzed using CMH method described in 7.4.1.1.
The survival endpoints (time to first event) will be each analyzed in a Cox proportional 
hazards model. The Cox model will include the randomization factors. The common hazard 
ratio and confidence limits will be estimated. The 1-sided p-values for testing the hypothesis 
that the hazard ratio is equal to unity will be calculated. The Kaplan-Meier estimates of
survival curves for the treatment groups will be displayed.  
Peak CMV viral load and AUC through one year post first Study Drug injection will be 
compared using Wilcoxon rank-sum tests.
The change from baseline to last visit in estimated glomerular filtration rate (eGFR) and the 
changes in Health Economic and Outcomes Research (HEOR) scores and patient reported 
quality of life scores will be each compared between treatment groups using an ANCOVA 
model with the change in score as the outcome and the treatment as the factor and baseline 
value as the covariate. 
All analyses of exploratory endpoints will be performed using the FAS.
7.4.4
Immunogenicity Analysis
T-Cell responses to pp65 and gB-specific antibody levels will be compared at each time point 
using the Wilcoxon rank-sum test. Graphic presentation of the mean of T-Cell responses to 
pp65 and gB-specific antibody levels over time by treatment group will also be provided.
Immunogenicity analysis will be performed using the FAS.
7.5
Analysis of Pharmacogenomic Data
Pharmacogenomic data will be displayed using descriptive statistics for each treatment group 
on PGS. 
7.6
Analysis of Safety
7.6.1
Adverse Events
Treatment emergent (TE) is defined as the study period of time from the first dose of Study 
Drug through one year post first Study Drug injection. A TE adverse event (AE) is defined as 
any AE that started or worsened during the TE period. Unless otherwise stated, all analyses 
described in this section will be performed on events and measures during this period.
For the purpose of safety assessments in this study, adverse events recorded during the period 
between the informed consent and the first dose of Study Drug will be classified as Medical 
History.


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The coding dictionary for this study will be the Medical Dictionary for Regulatory Activities 
(MedDRA). It will be used to summarize adverse events (AEs) by system organ class and/or 
preferred term. The version of MedDRA to be used will be determined prior to final database 
lock.
The following summaries of adverse events will be provided by system organ class and 
preferred term for TE adverse events:  

Number and percentage of subjects with AEs

Number and percentage of subjects with drug-related AEs

Number and percentage of subjects with serious AEs

Number and percentage of subjects with AEs leading to permanent discontinuation of 
Study Drug injection 

Number and percentage of subjects with serious drug related AEs

Number and percentage of subjects with drug related AEs leading to permanent 
discontinuation of Study Drug injection 

Number and percentage of subjects with AEs by severity (worst degree)

Number and percentage of subjects with drug related AEs by severity (worst degree)

Number and percentage of subjects with AEs by relationship to Study Drug
Drug-related AE is defined as any AE with at least possible relationship to study treatment as 
assessed by the investigator or with missing assessment of the causal relationship. 
All summaries of serious TEAEs described above will also be performed for serious AEs that 
were reported any time after the start of Study Drug administration.
The number of deaths and of subjects with AEs of special interest that occur during the TE 
period will also be summarized.
Subgroups analyses for age group (< 65, ≥65), race group (white, black, other), sex (male, 
female), and the use of anti-thymocyte globulin (ATG) (yes/no) will be performed for the 
following summaries:

TEAEs

Drug-related TEAEs

Serious TEAEs

TEAEs leading to permanent discontinuation of Study Drug

Serious AEs during the study

AEs of special interest during the study
All AEs will be listed.
7.6.2
Clinical Laboratory Evaluation
Analyses of clinical laboratory data will be performed on laboratory evaluations during the 
study.
Clinical laboratory tests (e.g., hematology, biochemistry) will be summarized using mean, 
standard deviation, minimum, maximum and median for each treatment group at each 


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scheduled visit. Additionally, the change from baseline will be summarized by treatment 
group and visit. 
The shift in select laboratory tests from baseline (or final visit for renal function tests) to 
select time points (worst value during study, Months 1, 2, 3, 6, 9, and 12) will be 
summarized.  
Potentially clinically significant (PCS) laboratory test results that are observed any time 
during the TE period will be tabulated and compared across all treatment groups using a chi-
square test. This analysis will be conducted only on subjects that did not meet the PCS 
criteria at baseline.
Subgroups analyses for age group (< 65, ≥65), race group (white, black, other), sex (male, 
female), and the use of anti-thymocyte globulin (ATG) (yes/no) will be performed for the 
following summaries:

Summary of clinical laboratory tests at each scheduled visit

Summary of change from baseline at each scheduled visit

Summary of PCS laboratory values
7.6.3
Vital Signs Evaluation
Vital signs (oral temperature, systolic and diastolic blood pressure, weight, respiration rate 
and pulse rate) will be summarized using mean, standard deviation, minimum, maximum and 
median for each treatment group at each scheduled visit. Additionally, the change from 
baseline in these parameters will be summarized by treatment group and visit.
The number and percent of subjects that had a systolic blood pressure ≥160 mmHg at any 
time will be tabulated by treatment group for subjects whose baseline value was < 160 
mmHg. Subjects that did not have a baseline measurement will be excluded from the 
analyses. The number and percent of subjects that had a diastolic blood pressure ≥100 mmHg 
at any time and whose baseline value was less than 100 mmHg will be summarized similarly.
The analysis of vital signs described above will also be performed by the following subgroups: 
age group (< 65, ≥65), race group (white, black, other), sex (male, female), deceased donor 
and the use of anti-thymocyte globulin (ATG) (yes/no).
7.6.4
Physical Examination 
Physical results will be listed by treatment group.
7.7
Protocol Deviations and Other Analyses  
Protocol deviations as defined in Section 8.1.6 Protocol Deviations will be summarized for all 
randomized subjects by treatment group and total as well as by site. A data listing will be 
provided by site and subject.   


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The protocol deviation criteria will be uniquely identified in the summary table and listing. 
The unique identifiers will be as follows:
PD1 - Entered into the study even though they did not satisfy entry criteria, 
PD2 - Developed withdrawal criteria during the study and was not withdrawn,
PD3 - Received wrong treatment or incorrect dose,
PD4 - Received excluded concomitant treatment. 
7.8
Interim Analysis (and Early Discontinuation of the Clinical Study)
Two interim safety and efficacy analyses are planned. The first one will occur when 50 
subjects (approximately 25 in each group) have completed the month 6 visit assessment. The 
second interim analysis will occur when 90 subjects (approximately 45 per group) have 
completed the 6 month visit assessment. 
A Data Monitoring Committee (DMC), external from the Sponsor, will be established to 
review safety and efficacy data at each interim look. A detailed description of the DMC, its 
role in this clinical trial, and the timing of the scheduled reviews will be provided in the DMC 
Charter.
7.8.1
Safety
Data from all subjects who have been enrolled will be included in the safety reviews. All data 
submitted to the DMC will remain blinded to Astellas personnel involved in the study. A 
detailed safety data interim analysis plan will be included in the DMC Charter.
7.8.2
Efficacy
Interim efficacy analyses will be performed for the sole purpose of assessing futility. Interim 
efficacy analyses will include all available data from subjects who have completed the 6 month 
visit. At each interim, Bayesian predictive probability (BPP) that the observed rate of viremia 
in the ASP0113 treatment group being at least 25% less than the observed viremia rate in the 
placebo treatment group will be calculated. If the BPP ≤ 0.20, it will be concluded that 
ASP0113 meets futility criterion. 
Extensive simulations were conducted to assess the operating characteristics of this futility 
criterion, and the results are satisfactory. The simulation algorithm, scenarios and results will 
be summarized in the SAP for this protocol.
7.9
Handling of Missing Data, Outliers, Visit Windows, and Other 
Information
The primary efficacy endpoint of CMV viremia is based on central laboratory assessments of 
CMV viral load which are taken every 2 weeks from Day 100 to Day 198, monthly from 


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Day 230 to Day 395 and all for cause (suspect CMV syndrome or CMV tissue-invasive 
disease) viral loads. In the primary efficacy analysis, subjects who are lost to follow-up will 
be imputed as having viremia. Otherwise, viremia will not be imputed in cases where central 
lab CMV viral load data are missing. Only observed viral loads meeting the definition of 
viremia will be counted. 
However, secondary analyses of the primary endpoint will explore the consequences of 
alternative imputations. These will be described in the Statistical Analysis Plan.
The start and stop dates of AEs and concomitant medication will be imputed where necessary 
prior to unblinding. The imputed dates will be used to determine whether an AE is/is not 
treatment emergent. Listings of the AEs and concomitant medications will present the actual 
partial dates; imputed dates will not be shown.
Subjects who do not receive the Study Drug to which they have been randomized will be 
analyzed as treated for safety analysis and as randomized for efficacy analysis.
See the SAP for details of the definitions for windows to be used for analyses by visit.
8
OPERATIONAL AND ADMINISTRATIVE CONSIDERATIONS
8.1
Procedure for Clinical Study Quality Control
8.1.1
Data Collection
The investigator or site designee will enter data collected using an Electronic Data Capture 
(EDC) system. In the interest of collecting data in the most efficient manner, the investigator 
or site designee should record data (including laboratory values, if applicable) in the eCRF 
within 5 days after the subject visit.
The investigator or site designee is responsible to ensure that all data in the eCRFs and 
queries are accurate and complete and that all entries are verifiable with source documents. 
These documents should be appropriately maintained by the site.
The monitor should verify the data in the eCRFs with source documents and confirm that 
there are no inconsistencies between them.
Laboratory tests are performed at both local and central laboratories. Central laboratory data 
will be transferred electronically to the Sponsor or designee at predefined intervals during the 
study. The laboratory will provide the Sponsor or designee with a complete and clean copy of 
the data. 
For Screen failures the informed consent, demographic data, reason for failing, inclusion and 
exclusion criteria and Adverse Events will be collected in the eCRF.
Subject Assessment of Reactogenicity: A diary will be used for the 7-day reactogenicity 
follow-up. The subject will enter the data directly into the diary that will be provided at each 
Study Drug injection visit. 


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8.1.1.1 Patient Reported Outcomes (pPRO)
Subject diaries and questionnaires will be completed by the subject on paper. The investigator 
or site designee should review the diaries and questionnaire data while the subject is at the 
site. The investigator or site designee will enter the subject diary and questionnaire data 
directly into the EDC system.   
8.1.2
Specification of Source Documents
Source data must be available at the site to document the existence of the study subjects and 
to substantiate the integrity of study data collected. Source data must include the original 
documents relating to the study, as well as the medical treatment and medical history of the 
subject.  
The following information should be included in the source medical records:

Demographic data (age, sex, race, ethnicity, height and body weight)

Inclusion and exclusion criteria details

Participation in study and original signed and dated informed consent forms 

Visit dates

Medical history and physical examination details

Key efficacy and safety data, if applicable (as specified in the protocol)

Adverse events and concomitant medication 

Results of relevant examinations (e.g., ECG charts, X-ray films etc.)

Laboratory printouts (if applicable)

Dispensing and return of Study Drug details

Reason for premature discontinuation (if applicable)

Randomization number 
8.1.3
Clinical Study Monitoring
The Sponsor or delegated CRO is responsible for monitoring the clinical study to ensure that 
subject's human rights, safety, and well-being are protected, that the study is properly 
conducted in adherence to the current protocol and GCP, and study data reported by the 
investigator/sub-investigator are accurate and complete and that they are verifiable with 
study-related records such as source documents. The Sponsor is responsible for assigning 
study monitor(s) to this study for proper monitoring. They will monitor the study in 
accordance with planned monitoring procedures.  
8.1.4
Direct Access to Source Data/Documents
The investigator and the study site must accept monitoring and auditing by the Sponsor or 
delegated CRO as well as inspections from the IRB/IEC and relevant regulatory authorities. 
In these instances, they must provide all study-related records, such as source documents 
(refer to Section 8.1.2 "Specification of Source Documents") when they are requested by the 
Sponsor monitors and auditors, the IRB/IEC, or regulatory authorities. The confidentiality of 


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the subject's identities shall be well protected consistent with local and national regulations 
when the source documents are subject to direct access.
8.1.5
Data Management
Data Management will be coordinated by the Global Data Science of the Sponsor in 
accordance with the standard operating procedures (SOPs) for data management. All study 
specific processes and definitions will be documented by Data Management. (e)CRF 
completion will be described in the (e)CRF instructions. Coding of medical terms and 
medications will be performed using MedDRA and World Health Organization (WHO) Drug 
Dictionary respectively.
8.1.6
Protocol Deviations 
A protocol deviation is generally an unplanned excursion from the protocol that is not 
implemented or intended as a systematic change. The investigator is responsible for ensuring 
the study is conducted in accordance with the procedures and evaluations described in this 
protocol and must protect the rights, safety, and welfare of subjects. The investigator should 
not implement any deviation from, or changes of, the protocol, unless it is necessary to 
eliminate an immediate hazard to trial subjects.  
A protocol waiver is a documented prospective approval of a request from an investigator to 
deviate from the protocol. Protocol waivers are strictly prohibited.
For the purposes of this protocol, deviations requiring notification to Sponsor are defined as 
any subject who: 

Entered into the study even though they did not satisfy entry criteria. 

Developed withdrawal criteria during the study and not withdrawn.

Received wrong treatment or incorrect dose. 

Received excluded concomitant treatment. 
When a deviation from the protocol is identified for an individual subject, the investigator or 
designee must ensure the Sponsor is notified. The Sponsor will follow-up with the 
investigator, as applicable, to assess the deviation and the possible impact to the safety and/or 
efficacy of the subject to determine subject continuation in the study. 
If a deviation impacts the safety of a subject, the investigator must contact the Sponsor 
immediately.    
The investigator will also assure that deviations meeting IRB/IEC and applicable regulatory 
authorities’ criteria are documented and communicated appropriately. All documentation and 
communications to the IRB/IEC and applicable regulatory authorities will be provided to the 
Sponsor and maintained within the Trial Master File (TMF).  
NOTE: Other deviations outside of the categories defined above that are required to be 
reported by the IRB/IEC in accordance with local requirements will be reported, as 
applicable. 


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8.1.7
End of Trial in All Participating Countries
The end of trial in all participating countries is defined as the Last Subject’s Last Visit at the 
end of the Primary Study Period (Day 395). The Long Term Follow Up will continue after 
the end of trials’ Primary Study Period.
8.2
Ethics and Protection of Subject Confidentiality
8.2.1
Institutional Review Board (IRB) / Independent Ethics Committee (IEC) / 
Competent Authorities (CA)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol amendments, 
the Investigator’s Brochure, the informed consent and all other forms of subject information 
related to the study (e.g., advertisements used to recruit subjects) and any other necessary 
documents be reviewed by an IEC/IRB.  The IEC/IRB will review the ethical, scientific and 
medical appropriateness of the study before it is conducted.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will be 
obtained prior to the authorization of Study Drug shipment to a study site.
Any substantial amendments to the protocol will require IEC/IRB approval prior to 
implementation of the changes made to the study design at the site.  The investigator will be 
required to submit, maintain and archive study essential documents according to ICH GCP.
Any serious adverse events that meet reporting criteria, as dictated by local regulations, will 
be reported to both responsible Ethics Committees and Regulatory Agencies, as required. 
During the conduct of the study, the investigator should promptly provide written reports 
(e.g., ICH Expedited Reports, and any additional reports required by local regulations) to the 
IEC/IRB of any changes that affect the conduct of the study and/or increase the risk to 
subjects. Written documentation of the submission to the IEC/IRB should also be provided to 
Sponsor.
If required by local regulations, the investigator shall make accurate and adequate written 
progress reports to the IEC/IRB at appropriate intervals, not exceeding one year. The 
investigator shall make an accurate and adequate final report to the IRB/IEC within 90 days 
after the close-out visit for APGD-sponsored studies, or for APEB/APEL-sponsored studies 
within one year after last subject out (LSO) or termination of the study.
8.2.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, ICH guidelines, applicable 
regulations and guidelines governing clinical study conduct and the ethical principles that 
have their origin in the Declaration of Helsinki. 


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8.2.3
Informed Consent of Subjects
8.2.3.1 Subject Information and Consent
The investigator or his/her representative will explain the nature of the study to the subject or 
his/her guardian or legal representative, and answer all questions regarding this study. Prior to 
any study-related screening procedures being performed on the subject, the informed consent 
statement will be reviewed and signed and dated by the subject or his/her guardian or legal 
representative, the person who administered the informed consent and any other signatories 
according to local requirements. A copy of the signed informed consent form will be given to 
the subject and the original will be placed in the subject’s medical record. An entry must also 
be made in the subject’s dated source documents to confirm that informed consent was 
obtained prior to any study-related procedures and that the subject received a signed copy.
The signed consent forms will be retained by the investigator and made available (for review 
only) to the study monitor and auditor regulatory authorities and other applicable individuals 
upon request.
8.2.3.2 Supply of New and Important Information Influencing the Subject’s Consent 
and Revision of the Written Information
The investigator or his/her representative will immediately inform the subject orally whenever 
new information becomes available that may be relevant to the subject’s consent or may 
influence the subject’s willingness to continue to participate in the study (e.g., report of serious 
drug adverse reaction). The communication must be documented in the subject’s medical 
records and must document whether the subject is willing to remain in the study or not.
The investigator must update their ICF and submit it for approval to the IRB/IEC. The 
investigator or his/her representative must obtain written informed consent from the subject 
on all updated ICFs throughout their participation in the study. The investigator or his/her 
designee must re-consent subjects with the updated ICF even if relevant information was 
provided orally. The investigator or his/her representative who obtained the written informed 
consent and the subject should sign and date the informed consent form. A copy of the signed 
informed consent form will be given to the subject and the original will be placed in the 
subject’s medical record. An entry must be made in the subject’s records documenting the re-
consent process.
8.2.4
Subject Confidentiality
Individual subject medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited. Such medical information may be 
given only after approval of the subject to the subject's physician or to other appropriate 
medical personnel responsible for the subject's well-being.
The Sponsor shall not disclose any confidential information on subjects obtained during the 
performance of their duties in the clinical study without justifiable reasons.


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The Sponsor affirms the subject's right to protection against invasion of privacy. Only a 
subject identification number and/or initials will identify subject data retrieved by the 
Sponsor. However, the Sponsor requires the investigator to permit the Sponsor, Sponsor's 
representative(s), the IRB/IEC and when necessary, representatives of the regulatory health 
authorities to review and/or to copy any medical records relevant to the study.
The Sponsor will ensure that the use and disclosure of protected health information (PHI) 
obtained during a research study complies with the federal and/or regional legislation related 
to the privacy and protection of personal information (i.e., HIPAA). 
8.3
Administrative Matters
8.3.1
Arrangement for Use of Information and Publication of the Clinical Study
Information concerning the Study Drug, patent applications, processes, unpublished scientific 
data, the Investigator's Brochure and other pertinent information is confidential and remains 
the property of the Sponsor. Details should be disclosed only to the persons involved in the 
approval or conduct of the study. The investigator may use this information for the purpose of 
the study only. It is understood by the investigator that the Sponsor will use the information 
obtained during the clinical study in connection with the development of the vaccine and 
therefore may disclose it as required to other clinical investigators or to regulatory agencies. 
In order to allow for the use of the information derived from this clinical study, the 
investigator understands that he/she has an obligation to provide the Sponsor with all data 
obtained during the study.
Publication of the study results is discussed in the Clinical Study Agreement.
8.3.2
Documents and Records Related to the Clinical Study
The investigator will archive all study data (e.g., Subject Identification Code List, source 
data, CRFs, and Investigator's File) and relevant correspondence.  These documents are to be 
kept on file for the appropriate term determined by local regulation (for US sites, two years 
after approval of the NDA or discontinuation of the IND). The Sponsor will notify the 
site/investigator if the NDA/MAA is approved or if the IND/IMPD is discontinued.  The 
investigator agrees to obtain the Sponsor's agreement prior to disposal, moving, or 
transferring of any study-related records. The Sponsor will archive and retain all documents 
pertaining to the study according to local regulations. 
Data generated by the methods described in the protocol will be recorded in the subjects' 
medical records and/or study progress notes. All data will be entered on the CRFs supplied 
for each subject. 
8.3.3
Protocol Amendment and/or Revision
Any changes to the study that arise after approval of the protocol must be documented as 
protocol amendments: substantial amendments and/or non-substantial amendments. 
Depending on the nature of the amendment, either IRB/IEC, Competent Authority approval 


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or notification may be required. The changes will become effective only after the approval of 
the Sponsor, the investigator, the regulatory authority, and the IRB/IEC.
Amendments to this protocol must be signed by the Sponsor and the investigator. Written 
verification of IRB/IEC approval will be obtained before any amendment is implemented 
which affects subject safety or the evaluation of safety, and/or efficacy. Modifications to the 
protocol that are administrative in nature do not require IRB/IEC approval, but will be 
submitted to the IRB/IEC for their information, if required by local regulations.
If there are changes to the Informed Consent, written verification of IRB/IEC approval must 
be forwarded to the Sponsor. An approved copy of the new Informed Consent must also be 
forwarded to the Sponsor.
8.3.4
Insurance of Subjects and Others 
The Sponsor has covered this study by means of an insurance of the study according to 
national requirements. The name and address of the relevant insurance company, the certificate 
of insurance, the policy number and the sum insured are provided in the Investigator's File. 
8.3.5
Signatory Investigator for Clinical Study Report
ICH E3 guidelines recommend and EU Directive 2001/83/EC requires that a final study 
report which forms part of a marketing authorization application be signed by the 
representative for the Coordinating Investigator(s) or the Principal Investigator(s). The 
representative for the Coordinating Investigator (s) or the Principal Investigator(s) will have 
the responsibility to review the final study results to confirm to the best of his/her knowledge 
it accurately describes the conduct and results of the study. The representative for
Coordinating Investigator(s) or the Principal Investigator(s) will be selected from the 
participating investigators by the Sponsor prior to database lock.
9
QUALITY ASSURANCE
The Sponsor is implementing and maintaining quality assurance and quality control systems 
with written SOPs to ensure that trials are conducted and data are generated, documented, 
recorded, and reported in compliance with the protocol, GCP, and applicable regulatory 
requirement(s).
The Sponsor or Sponsor's designee may arrange to audit the clinical study at any or all 
investigational sites and facilities. The audit may include on-site review of regulatory 
documents, case report forms, and source documents. Direct access to these documents will 
be required by the auditors.


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10
STUDY ORGANIZATION
10.1
Data Monitoring Committee (DMC) 
A DMC external from the Sponsor will be chartered to oversee the safety of subjects and 
review of the futility analysis. The DMC will consist of independent reviewers who are not 
directly involved in the conduct of the study. 
10.2
Other Study Organization
10.2.1
Adjudication Committee (AC)
An Adjudication Committee (AC) external from the Sponsor will be chartered to adjudicate 
all subjects for cases of CMV syndrome, CMV tissue-invasive disease and CMV-specific 
antiviral therapy. The AC will consist of a multidisciplinary group of independent clinician-
scientists who are not directly involved in the conduct of the study. 


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11
REFERENCES 
American Journal of Kidney Diseases. 2002;39 (Suppl 1):S76-S110.
AJT Infectious Disease Community. Epstein-Barr virus and lymphoproliferative disorders after 
transplantation. Am J Transplantation. 2004;4(Suppl. 10):59-65.
Boeckh M and Geballe AP.  Cytomegalovirus: pathogen, paradigm, and puzzle.  J Clin Invest. 2011;
121(5):1673-1680.
Britt WJ, Vugler L, Butfiloski EJ, Stephens EB.  Cell surface expression of human cytomegalovirus 
(HCMV) gp55-116 (gB): use of HCMV-recombinant vaccinia virus-infected cells in analysis of 
the human neutralizing antibody response. J Virol. 1990;64:1079-1085.
Chisholm-Burns MA, Erickson SR, Spivey CA, Kaplan B. Health-related quality of life and 
employment among renal transplant recipients. Clin Transplant. 2012:26:411–417.
Couzi L, Helou S. Bachelet T, Moreau K, Martin S, Morel D. High incidence of anticytomegalovirus 
drug resistance among D+R- kidney transplant recipients receiving preemptive therapy. Am J 
Transplant. 2012;12:202-209. 
Dubberke ER and Brennan DC  Core Concepts in Renal Transplantation  Chapter 9  Infectious 
Complications in Renal Transplant Recipients  (A. Chandraker et al. (eds).
Fishman JA and Rubin RH. Infection in organ-transplant recipients. The New England Journal of 
Medicine. 2007;357:2601-14.
Griffiths PD, Stanton A, McCarrell E, Smith C, Osman M, Harber M, et al.  Cytomegalovirus 
glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised 
placebo-controlled trial. Lancet. 2011;377:1256-63.
Guidance for Industry titled “Drug-Induced Liver Injury: Premarketing Clinical Evaluation” issued by 
FDA on July 2009.
Guidance for Industry titled “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials” issued by FDA on September 2007.  
Gyulai Z, Endresz V, Burian K, Pincus S, Toldy J, Cox WI, et al. Cytotoxic T lymphocyte (CTL) 
responses to human cytomegalovirus pp65, IE1-Exon4, gB, pp150, and pp28 in healthy 
individuals: reevaluation of prevalence of IE1-specific CTLs. J Infect Dis. 2000;181:1537-46.
Humar A and Michaels M. American society of Transplantation Recommendations for Screening, 
Monitoring and Reporting of Infectious Complications in Immunosuppression Trials in 
Recipients of Organ Transplantation. Am J Transplantation. 2006;6:262-274.
Kern F, Bunde T, Faulhaber N, Kiecker F, Khatamzas E, Rudawski IM, et al. Cytomegalovirus (CMV) 
phosphoprotein 65 makes a large contribution to shaping the T cell repertoire in CMV-exposed 
individuals. J Infect Dis. 2002;185:1709-16.
Kharfan-Dabaja MA, Boeckh M, Wilck MB, Langston AA, Chu AH, Wloch MK, Guterwill DF, Smith
LR, Rolland AP, Kenney RT. A novel cytomegalovirus DNA vaccine in allogeneic 
haemopoietic stem-cell transplantation: a randomized, double-blind, placebo-controlled phase 2 
trial. Lancet Infectious Diseases. 2012;12:290-99.  
Kumar D, Humar A. The AST handbook of transplant infections. 2011.
Laupacis A, Pus N, Muirhead N, Wong C, Fergusion B, Keown P. Disease-specific quetionnaire for 
patients with a renal transplant. Nephron. 1993;64 (2):226-31.


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National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 
CTEP, 2010.  http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf.
Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff ’07 classification of renal 
allograft pathology: updates and future directions.  Am J Transplant. 2008;8:753-60.
Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F, et al.  Broadly targeted human 
cytomegalovirus specific CD4+ and CD8+ T cells dominate the memory compartments of 
exposed subjects.  JEM. 2005;202(5):673-685.
Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing 
infectious complications among hematopoietic cell transplantation recipients: A global 
perspective. Biol Blood Marrow Transplant. 2009;15:1143-1238.
Wills MR, Carmichael AJ, Mynard K, Jin X, Weekes MP, Plachter B, et al. The human cytotoxic T-
lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65:  
frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J Virol. 1996;70:7569-79.
Wloch MK, Smith LR, Boutsaboualoy S, Reyes L, Han C, Kehler J, et al.  Safety and Immunogenicity of 
a Bivalent Cytomegalovirus DNA Vaccine in Healthy Adult Subjects.  JID. 2008;197:1634-42. 
Company Reports:
ASP0113 Investigator’s Brochure, Astellas Pharma Global Development, Inc..


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12
APPENDICES
12.1
Appendix 1:  List of Excluded Concomitant Medications
●
Investigational research products through completion of Day 395 visit (Visit 13)
●
Planned Alemtuzumab and, anti-CD20 antibodies (including rituximab), eculizumab or 
bortezomib  are not allowed from Day of Randomization through  the Primary Study 
Period (Day 395).  These treatments may be given after the Day of Randomization if 
clinically indicated.
●
Prophylactic use of CMV immunoglobulin. 
●
Live attenuated vaccines within one month (30 days) prior to each dose of Study Drug.
●
Subunit or killed vaccines within 14 days before any Study Drug injection. 
●
Anticoagulants, within 5 half-lives of Study Drug administration, including but not limited 
to vitamin K antagonists, heparin or its derivatives, low molecular weight heparin, factor 
X inhibitors, or thrombin inhibitors. Low dose anticoagulants that are used for prevention 
of deep vein thrombosis and antiplatelet agents are allowed.


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12.2
Appendix 2:  Laboratory Tests
Central Laboratory Testing
Laboratory Test
Visit
Parameters to be Analyzed
Central CMV Plasma 
Viral Load
Every other week from 
Day 100-200, then 
monthly through end of 
study Day 395, for cause 
(suspect CMV syndrome 
or CMV tissue-invasive
disease), at least once a 
week from initiation of 
CMV-specific AVT until 
it is completed, any time a 
local CMV viral load is 
obtained

CMV plasma viral load by central lab assay
Genotypic resistance 
testing
When viremia is present 
with no reduction in viral 
load or clinical improve-
ment after 2 weeks of 
treatment with
valganciclovir and 
ganciclovir

Resistance to valganciclovir and ganciclovir
Immunogenicity
V2, V5, V6, V9, V10 & 
V13

gB-specific antibody levels

Immunological assays measuring T-cell 
responses to pp65 
Pharmacogenomics (PGx) 
– optional –whole blood 
sample
V2

Genomic analyses
Local Laboratory Testing
Laboratory Test
Visit
Parameters to be Analyzed
CMV Screening
Up to 8 weeks prior to 
transplant through day of 
transplant or at Screening 
(V1)

CMV serostatus
Hematology
Screening (V1) and Visits 
2-11 & 13

Red blood cells

White blood cells (total leukocytes)

Hemoglobin

Hematocrit

Platelets (thrombocytes)

Neutrophils (ANC)

Eosinophils

Basophils

Lymphocytes

Monocytes
Biochemistry
Screening (V1) and Visits 
2-11 & 13

Sodium

Potassium

Calcium

Chloride

Phosphorus

Glucose

BUN


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
Creatinine

Creatine phosphokinase (CPK)/Creatine kinase 
(CK)

Total protein

Albumin
Hepatic Profile
Screening (V1) and Visits 
2-11 & 13

Total bilirubin

Direct bilirubin

Alkaline Phosphatase

AST

ALT
Urinalysis
Screening (V1) and Visits 
2-11 & 13

pH 

specific gravity,

protein, glucose,

ketones,

bilirubin

blood

microscopic evaluation
Urine protein: creatinine 
ratio
Screening (V1) and Visits 
2-11 & 13

Protein: creatinine ratio
Urine Pregnancy Test 
(females of childbearing 
potential only)
Screening (V1), V2, V4, 
V6, V8, V10, 12 & 13

Human Chorionic Gonadotropin (hCG)


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12.3
Appendix 3: 4 Variable MDRD
Estimated GFR (eGFR) using Modification of Diet in Renal Disease (MDRD) formula
For creatinine in mg/dL:
eGFR=186 X Serum Creatinine -1.154 X Age -0.203 X [1.212 if Black] X [0.742 if Female]
[American Journal of Kidney Diseases 2002; 39(Suppl 1): S76-S110.Vol 39, Issue 2, Supplement 1, Pages 
S76-S110, Feb 2002]






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12.6
Appendix 6:  Grading of Acute Kidney Allograft Rejection 
2007 Update to the Banff 97 Diagnostic Categories for Renal Allograft Biopsies
Category
Global Assessment
Histopathological Findings
1
Normal
2
Antibody-mediated 
changes 
(may coincide with 
categories 3, 4 and 5 
and 6)
Due to documentation of  circulating antidonor antibody, and C4d or 
allograft pathology 
C4d depletion without morphologic evidence of active rejection
C4d+, presence of circulating antidonor antibodies, no signs of acute or 
chronic TCMR or ABMR (i.e., g0, cg0, ptc0, no ptc lamination).  Cases 
with simultaneous borderline changes or ATN are considered indeterminate
Acute antibody-
mediated rejection1
C4d+, presence of circulating antidonor antibodies, morphologic evidence 
of acute tissue injury, such as (Type/Grade):
Grade I
ATN-like minimal inflammation
Grade II
Capillary and/or glomerular inflammation (pct/g > 0) and/or thromboses
Grade III
Arterial – v3
Chronic active 
antibody-mediated 
rejection1
C4d+, presence of circulating antidonor antibodies, morphologic evidence 
of chronic tissue injury, such as glomerular double contours and/or 
peritubular capillary basement membrane multilayering and/or interstitial 
fibrosis/tubular atrophy and/or fibrous intimal thickening in arteries
3
Borderline 
(may coincide with 
categories 2 and 5 and 
6)
“Suspicious” for acute T-cell-mediated rejection 
This category is used when no intimal arteritis is present, but there are foci 
of tubulitis (t1, t2, or t3) with minor interstitial infiltrate (i0 or i1) or 
interstitial infiltrate (i2, i3) with mild (t1) tubulitis 
4
T-cell mediated 
rejection (TCMR, may 
coincide with categories 
2 and 5 and 6)
Acute T-cell-mediated 
rejection (Type/Grade)
Grade IA
Cases with significant interstitial infiltration (> 25% of parenchyma 
affected, i2 or i3) and foci of moderate tubulitis (t2) 
Grade IB
Cases with significant interstitial infiltration (> 25% of parenchyma 
affected, i2 or i3) and foci of severe tubulitis (t3)
Grade IIA
Cases with mild-to-moderate intimal arteritis (v1)
Grade IIB
Cases with severe intimal arteritis comprising > 25% of the luminal area 
(v2)
Grade III
Cases with “transmural” arteritis and/or arterial fibrinoid change and 
necrosis of medial smooth muscle cells with accompanying lymphocytic 
inflammation (v3)
Chronic active T-cell-
mediated rejection
“Chronic allograft arteriopathy” (arterial intimal fibrosis with mononuclear 
cell infiltration in fibrosis, formation of neo-intima)
5
Interstitial fibrosis 
and tubular atrophy
No evidence of specific etiology (may include nonspecific vascular and 
glomerular sclerosis, but severity graded by tubulointersitial features)
Grade I
Mild interstitial fibrosis and tubular atrophy (< 25% cortical area)
Grade II
Moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area)
Grade III
Severe interstitial fibrosis and tubular atrophy/loss (> 50% of cortical area)
6
Other
Changes not considered to be due to rejection-acute and/or chronic (for 
diagnosis see full article Table 14; may include isolated g, cg or cv lesions 
and coincide with categories 2, 3, 4 and 5) 
1 Suspicious for antibody-mediated rejection if C4d (in the presence of antibody) or alloantibody (C4d+) 
not demonstrated in the presence of morphologic evidence of tissue injury.


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Reference:  Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel F, et al. Banff ’07 classification 
of renal allograft pathology: updates and future directions.  Am J Transplant. 2008;8:753-60.


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12.7
Appendix 7:  Definition of CMV Disease in Solid Organ Transplant 
Recipients 
Disease type
Probable
Definite
CMV syndrome
One or more of the following: 
1. Fever > 38°C for at least 2 
days 
2. New or increased malaise 
3. Leukopenia
4. ≥5% atypical lymphocytes 
5. Thrombocytopenia 
6. Elevation of hepatic 
transaminases (ALT or AST) 
to 2 x upper limit of normal 
(applicable to nonliver 
transplant recipients) plus 
evidence of CMV in blood by 
viral culture, antigenemia or a 
DNA/RNA-based assay
Clinical and laboratory findings 
as in ‘probable’ case and no other 
cause of symptoms/signs 
identified
Pneumonia1
Signs and/or symptoms of 
pulmonary disease in the absence 
of other documented cause plus 
evidence of CMV in blood 
and/or3 bronchoalveolar lavage 
(BAL) fluid by viral culture, 
antigenemia or a DNA/RNA-
based assay
Signs and/or symptoms of 
pulmonary disease plus detection 
of CMV in lung tissue by culture, 
immunohistochemical analysis or 
in situ hybridization4 with or 
without evidence of CMV in 
blood or BAL fluid by viral 
culture, antigenemia (BAL) or a 
DNA/RNA-based assay
Gastrointestinal disease
Symptoms of upper or lower 
gastrointestinal disease plus 
macroscopic mucosal lesions on 
endoscopy plus evidence of CMV 
in blood or biopsy tissue by viral 
culture, antigenemia or an 
RNA/DNA-based assay
Symptoms or signs of upper or 
lower gastrointestinal disease 
plus detection of CMV in 
gastrointestinal tissue by culture, 
immunohistochemical analysis or 
in situ hybridization4
Hepatitis
Elevation of bilirubin and/or 
hepatic enzymes in the absence 
of other documented cause of 
hepatitis2 plus evidence of
CMV in blood by antigenemia or 
a DNA/RNA-based assay
Elevation of bilirubin and/or 
hepatic enzymes plus detection of 
CMV in liver tissue by culture, 
immunohistochemical analysis or 
in situ hybridization4


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Appendix 7:  Definition of CMV Disease in Solid Organ Transplant Recipients 
(continued)
Disease type
Probable
Definite
CNS disease
CNS symptoms in the absence of 
other documented cause plus 
evidence for CMV in CSF 
samples by viral culture, or 
DNA/RNA-based assay
CNS symptoms plus detection of 
CMV in CNS tissue by culture, 
immunohistochemical analysis or 
in situ hybridization4
Retinitis
Not applicable
Lesions typical of CMV retinitis 
must be confirmed by an 
ophthalmologist or by detection 
of CMV by culture or PCR of 
vitreous fluid
Other tissue invasive disease 
(nephritis, cystitis, myocarditis, 
pancreatitis, etc.)
Evidence of organ dysfunction in 
the absence of other documented 
cause2 plus evidence of CMV in 
blood by viral culture, 
antigenemia or DNA/RNA-based 
assay
Symptoms/signs of organ 
dysfunction plus detection of 
CMV in affected tissue by 
culture, immunohistochemical 
analysis or in situ hybridization4
1Superinfection or co infection with other pathogens may occur and should be noted when present.
2If affected organ is the allograft, acute rejection must be excluded as a cause for the clinical symptoms.
3The detection of CMV in both BAL and peripheral blood strengthens the evidence for probable CMV 
pneumonitis.
4Although, immunohistochemistry and in situ hybridization techniques are more sensitive for the detection 
of CMV-infected cells than morphologic examination, the presence of typical cytomegalovirus inclusions 
should be considered evidence of definite disease.
Reference:  
Humar A and Michaels M. American society of Transplantation Recommendations for Screening, 
Monitoring and Reporting of Infectious Complications in Immunosuppression Trials in Recipients of 
Organ Transplantation. Am J Transplantation. 2006;6:262-274.


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12.8
Appendix 8:  Opportunistic Infections

Viral infections
o
HHV-1:  Herpes simplex 1 (HSV 1)

Herpes labialis
o
HHV-2:  Herpes simplex 2 (HSV 2)

Herpes genitalis
o
HHV-3:  Varicella zoster virus (VZV)

Chicken Pox

Shingles
o
HHV-4:  Epstein Barr virus

Mononucleosis

Burkitt’s lymphoma

Nasopharyngeal carcinoma

Post-transplant lymphoproliferative disorder (PTLD)

Oral hairy leukoplakia
o
HHV-6:  Human herpes virus 6

Roseola subitum
o
HHV-7:  Human herpes virus 7

Roseola subitum

Pityriasis rosea
o
HHV-8:  Human herpes virus 8

Kaposi’s sarcoma

Effusion lymphoma

Multifocal Castleman’s disease
o
Simian virus 40
o
Jacob-Creutzfeld
o
BK virus


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Appendix 8: Opportunistic Infections continued

Bacterial infections
o
Legionellosis pneumophilia
o
Nocardiosis
o
Listeriosis monocytogenes

Fungal infections
o
Aspergillus
o
Candida
o
Coccidioides
o
Cryptococcus
o
Histoplasma
o
Mucormycosis
Diagnosis of infection must be supported by appropriate laboratory tests, histopathology, 
serologies, radiologic findings or culture.
Dubberke ER and Brennan DC.  Core Concepts in Renal Transplantation.  Chapter 9  
Infectious Complications in Renal Transplant Recipients  (A. Chandraker et al. (eds)


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12.9
Appendix 9:  Special Infections Related to Kidney Transplant
Epstein Barr Virus (EBV) Infection:  
Active, asymptomatic EBV infection is defined by the presence of a detectable EBV viral 
load as measured by a nucleic acid amplification assay. Asymptomatic infection may also be 
identified in lymphoid rich histopathologic specimens.
EBV Disease:
EBV disease is defined by the presence of active EBV infection with symptoms or signs 
attributable to the virus. 
BK Virus Infection:
BK virus infection (replicative infection) defined as quantitative BK viral DNA load, in blood 
or urine above the detection threshold for the given laboratory's assay. BK infection is
classified as either BK viruria or BK viremia or both. While the presence of decoy cells in 
urine on cytology is suggestive of BK infection, confirmation with a specific test (e.g., PCR) is 
required.
BK Virus Associate Nephropathy (BKVAN):
Proven BK virus associated nephropathy is defined by evidence of BK virus infection and the 
presence of:
●
Renal biopsy associated with:
o
an acute tubular necrosis-like picture or
o
interstitial nephritis mimicking acute rejection or
o
chronic allograft nephropathy with confirmation of the presence of BK virus by 
electron microscopy, immunohistochemistry or in-situ hybridization for BK virus. 
Although intra-nuclear viral inclusions are usually seen, their presence is not 
mandatory for a diagnosis of BKVAN. 
For purposes of this study, subjects with  presumptive BKVAN diagnosed in the presence of 
renal allograft dysfunction and a positive BKV DNA PCR result from blood in a subject with 
no viral inclusions at light microscopy and negative immunohistochemistry/in-situ
hybridization should be classified as BK virus infection (i.e. BK viremia rather than BKVAN). 


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12.10 Appendix 10:   Liver Safety Monitoring and Assessment 
Any subject enrolled in a clinical study with active drug therapy who reveals an increase of 
serum aminotransferases (AT) to > 3 × baseline value and greater than 3X ULN , or bilirubin 
> 2 × baseline value and greater than 2X ULN, should undergo detailed testing for liver 
enzymes (including at least ALT, AST, ALP, and TBL). Testing should be repeated within 
48-72 hours of notification of the test results. For studies in which a central laboratory is used, 
alerts will be generated by the central lab regarding moderate and severe liver abnormality to 
inform the investigator, study monitor and study team. As local laboratories are utilized for 
this study, the investigator must report a repeat confirmation of moderate or severe liver 
abnormalities to the Medical Monitor within 48-72 hours of the test results.  Subjects should 
be asked if they have any symptoms suggestive of hepatobiliary dysfunction.
Definition of  Liver Abnormalities
Confirmed abnormalities will be characterized as moderate and severe where ULN:
ALT or AST
Total Bilirubin
Moderate
> 3× baseline 
value & > 3x
ULN 
or
> 2× baseline value
& > 3xULN
Severe*
> 3× baseline 
value & > 3x
ULN
and
> 2× baseline value
& > 3x ULN
In addition, the subject should be considered to have severe hepatic abnormalities for any of 
the following:
ALT or AST > 8× ULN
ALT or AST > 5× ULN for more than 2 weeks  
ALT or AST > 3× ULN and INR > 1.5 (If INR testing is applicable/evaluated).
ALT or AST > 3× ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (> 5%). 
The investigator may determine that abnormal liver function results, other than as described 
above, may qualify as moderate or severe abnormalities and require additional monitoring 
and follow-up.
Follow-up Procedures
Confirmed moderate and severe abnormalities in hepatic functions should be thoroughly 
characterized by obtaining appropriate expert consultations, detailed pertinent history, 
physical examination and laboratory tests. The site should complete the Liver Abnormality 
Case Report Form (LA-CRF) that will be activated for any study subject with severe 
abnormalities as determined by the medical monitor. Subjects with confirmed abnormal liver 
function testing should be followed as described below.


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Confirmed moderately abnormal LFTs should be repeated 2-3 times weekly then weekly or 
less if abnormalities stabilize or the Study Drug has been discontinued and the subject is 
asymptomatic.  
Severe hepatic liver function abnormalities as defined above, in the absence of another 
etiology, may be considered an important medical event and may be reported as a Serious 
Adverse Event (SAE).  The Sponsor should be contacted and informed of all subjects for 
whom severe hepatic liver function abnormalities possibly attributable to Study Drug are 
observed.
To further assess abnormal hepatic laboratory findings, the investigator is expected to:
Obtain a more detailed history of symptoms and prior or concurrent diseases.  Symptoms and 
new onset-diseases should be recorded as ‘adverse events’ on the AE page of the (e)CRF. 
Illnesses and conditions such as hypotensive events, and decompensated cardiac disease that 
may lead to secondary liver abnormalities should be noted. Non-alcoholic steatohepatitis 
(NASH) is seen in obese hyperlipoproteinemic, and/or diabetic patients and may be 
associated with fluctuating aminotransferase levels.   The investigator should ensure that the 
medical history form captures any illness that pre-dates study enrollment that may be relevant 
in assessing hepatic function. 
Obtain a history of concomitant drug use (including non-prescription medication, 
complementary and alternative medications), alcohol use, recreational drug use, and special 
diets.  Medications, including dose, should be entered on the concomitant medication page of 
the (e)CRF.  Information on alcohol, other substance use, and diet should be entered on the 
LA-CRF or an appropriate document.
Obtain a history of exposure to environmental chemical agents.
Based on the subject’s history, other testing may be appropriate including: 

acute viral hepatitis (A,B, C, D, E or other infectious agents) 

ultrasound or other imaging to assess biliary tract disease

other laboratory tests including INR, direct bilirubin
Consider gastroenterology or hepatology consultations.
Submit results for any additional testing and possible etiology on the LA-CRF or an 
appropriate document.
Study Discontinuation
In the absence of an explanation for increased LFT’s, such as viral hepatitis, pre-existing or 
acute liver disease or exposure to other agents associated with liver injury, the subject may be 
discontinued from the study. The investigator may determine that it is not in the subject’s best 
interest to continue study enrollment. Discontinuation of treatment should be considered if:
ALT or AST > 8 × ULN
ALT or AST > 5 × ULN for more than 2 weeks 
ALT or AST > 3 × ULN and TBL > 2 × ULN or INR > 1.5) (If INR testing is 
applicable/evaluated)


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ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia ( > 5%). 
In addition, if close monitoring for a subject with moderate or severe hepatic laboratory tests 
is not possible, drug should be discontinued.
*Hy’s Law Definition-Drug-induced jaundice caused by hepatocellular injury, without a 
significant obstructive component, has a high rate of bad outcomes, from 10–50% mortality 
(or transplant). The two “requirements” for Hy’s Law are: 1) Evidence that a drug can cause 
hepatocellular-type injury, generally shown by an increase in transaminase elevations higher 
3 times the upper limit of normal (“2 x ULN elevations are too common in treated and 
untreated patients to be discriminating”). 2) Cases of increased bilirubin (at least 2 x ULN) 
with concurrent transaminase elevations at least 3x ULN and no evidence of intra- or extra-
hepatic bilirubin obstruction (elevated alkaline phosphatase) or Gilbert’s syndrome. [Temple 
R. Hy's law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf 2006 
Apr;15(4):241-3.]
Reference
Guidance for Industry titled “Drug-Induced Liver Injury: Premarketing Clinical Evaluation” 
issued by FDA on July 2009.  


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12.11   Appendix 11:  Common Serious Adverse Events
The following is a list of serious adverse events that the Sponsor considers to be associated 
with the disease state being studied. The list does NOT change your reporting obligations 
or prevent the need to report an adverse event meeting the definition of an SAE as 
detailed in Section 5.5.3 Definition of Serious Adverse Event (SAE). The purpose of this 
list is to alert you that some events reported as SAEs may not require expedited reporting to 
the regulatory authorities based on the classification of “common serious adverse events”. You 
are required to follow the requirements detailed in Section 5.5.6 Reporting of Serious Adverse 
Events (SAE).
For IND safety reporting, single occurrences of the following events may be excluded from 
expedited reporting to the FDA. If aggregate analysis of these events indicates that they occur 
more frequently with Study Drug, an expedited IND safety report may be submitted to the 
FDA.  

Kidney transplant rejection

Kidney allograft loss

Blood creatinine increased

Diabetes mellitus

Hyperglycemia

Increase blood glucose


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12.12 Appendix 12:  Categories of Post Transplant Lymphoproliferative 
Disorder (PTLD)
Categories of PTLD are the following:

Early Lesions
o
Reactive plasmacytic hyperplasia
o
Infectious mononucleosis-like

Polymorphic PTLD

Monomorphic PTLD (classify according to lymphoma classifications)
o
B cell neoplasms

Diffuse large B cell lymphoma (immunoblastic, centroblastic, anaplastic)

Burkitt/Burkitt-like lymphoma

Plasma cell myeloma

Plasmacytoma-like lesions

Maltoma
o
T cell neoplasm

Peripheral T cell lymphoma, unspecified type

Anaplastic large cell lymphoma (T or null cell)

Hepatosplenic gamma-delta T cell lymphoma

Other (i.e., T-NK type)

Hodgkin lymphoma and Hodgkin lymphoma-like PTLD
Reference:
AJT Infectious Disease Community. Epstein-Barr virus and lymphoproliferative disorders after 
transplantation. Am J Transplantation 2004; 4(Suppl. 10): 59-65.


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12.13 Appendix 13:  EQ-5D Questionnaire
Note that the below is an example; subjects will be provided with forms to be completed.


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Appendix 13: EQ-5D Questionnaire continued


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12.14 Appendix 14: Kidney Transplant Questionnaire (KTQ-34)
INSTRUCTION: This questionnaire asks for your views about your health-related quality of 
life. Please read each question very carefully and mark the response that best reflects your 
experience. Please note that the different sections ask for different types of responses. Please 
choose only one answer for each item and do not skip any items.
Amount of Time In the Past Two Weeks 
All of 
the time 
Most of 
the time 
A Good 
Bit of 
the time 
Some of 
the time 
A little 
of the 
time 
Hardly 
Any of 
the time 
None of 
the time 
1. How often in the past two weeks have 
you felt weak? 
1 
2 
3 
4 
5 
6 
7 
2. How often in the past two weeks have 
you felt impatient? 
1 
2 
3 
4 
5 
6 
7 
3. How often in the past two weeks have 
you felt depressed? 
1 
2 
3 
4 
5 
6 
7 
4. How often in the past two weeks have 
you felt stubborn? 
1 
2 
3 
4 
5 
6 
7 
5. How often in the past two weeks have 
you felt sluggish? 
1 
2 
3 
4 
5 
6 
7 
6. How often in the past two weeks have 
you felt anxious? 
1 
2 
3 
4 
5 
6 
7 
7. How often in the past two weeks have 
you felt fear or panic related to graft 
rejection? 
1 
2 
3 
4 
5 
6 
7 
8. How often in the past two weeks have 
you felt uncertain about your future? 
1 
2 
3 
4 
5 
6 
7 
9. How often in the past two weeks have 
you felt worried? 
1 
2 
3 
4 
5 
6 
7 
10. How often in the past two weeks have 
you felt protective of your transplant? 
1 
2 
3 
4 
5 
6 
7 
11. How often in the past two weeks have 
you felt irritable, difficult to get along 
with? 
1 
2 
3 
4 
5 
6 
7 
12. How often in the past two weeks have 
you felt generally frustrated? 
1 
2 
3 
4 
5 
6 
7 
13. How often in the past two weeks have 
you felt low in energy? 
1 
2 
3 
4 
5 
6 
7 
14. How often in the past two weeks have 
you felt dizzy or lightheaded? 
1 
2 
3 
4 
5 
6 
7 




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Amount of Trouble or Distress 
A Very 
Great 
Deal 
A Great 
Deal 
A Good 
Deal 
A 
moderate 
Amount 
Some 
Very 
Little 
None 
27. In the past two weeks, how much 
trouble or distress have you had because 
of not seeing clearly? 
1 
2 
3 
4 
5 
6 
7 
28. In the past two weeks, how much 
trouble or distress have you had because 
of swollen or bleeding gums? 
1 
2 
3 
4 
5 
6 
7 
29. In the past two weeks, how much 
trouble or distress have you had because 
of swelling in your ankles or legs? 
1 
2 
3 
4 
5 
6 
7 
30. In the past two weeks, how much 
trouble or distress have you had because 
of abdominal bloating? 
1 
2 
3 
4 
5 
6 
7 
31. In the past two weeks, how much 
trouble or distress have you had because 
of shortness of breath? 
1 
2 
3 
4 
5 
6 
7 
32. In the past two weeks, how much 
trouble or distress have you had because 
of headaches? 
1 
2 
3 
4 
5 
6 
7 
33. In the past two weeks, how much 
trouble or distress have you had because 
of your medication dosing schedule or the 
number of pills you take? 
1 
2 
3 
4 
5 
6 
7 
34. In the past two weeks, how much 
trouble or distress have you had because 
of decreased sexual interest or sexual 
activities? 
1 
2 
3 
4 
5 
6 
7 
Appendix 14: Kidney Transplant Questionnaire (KTQ-34) continued:


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12.15 Appendix 15:  SF-12


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12.16 Appendix 16:   Retrospective Pharmacogenomics (PGx) Sub-Study 
INTRODUCTION
PGx research aims to provide information regarding how naturally occurring changes in a 
subject’s gene and/or expression based on genetic variation may impact what treatment 
options are best suited for the subject. Through investigation of PGx by technologies such as 
genotyping, gene sequencing, statistical genetics and Genome-Wide Association Studies 
(GWAS), the relationship between gene profiles and a drug’s kinetics, efficacy or toxicity 
may be better understood. PGx research may identify which genes are involved in 
determining the way a subject may or may not respond to a drug.
OBJECTIVES
The PGx research that may be conducted in the future with acquired blood samples is 
exploratory. The objective of this research will be to analyze or determine genes of relevance 
to clinical response, and toxicity/safety issues.
By analyzing genetic variations, it may be possible to predict an individual subject’s response 
to ASP0113 in terms of efficacy and/or toxicity.
SUBJECT PARTICIPATION
Subjects who have consented to participate in this study may participate in this PGx sub-
study. As part of this sub-study, subjects must provide separate written consent prior to 
providing any blood samples that may be used at a later time for genetic analysis.
SAMPLE COLLECTION AND STORAGE
Subjects who consent to participate in this sub-study will provide one 5 ml tube of whole 
blood per Astellas’ instructions. Each sample will be identified by the unique subject number 
(first code). Samples will be shipped frozen to a designated banking CRO either directly from 
site or via a central laboratory as directed by Astellas. Detailed collection, storage, and 
shipment procedures will be included in the Laboratory Manual for the study.
BANKING CRO STORAGE AND SAMPLE CODING 
Once received at the banking CRO, the samples will be assigned a unique sample code 
(second code) and stored frozen. A table linking the subject number (first code) with the 
newly-assigned sample code (second code) will be kept by the banking CRO. PGx analysis 
will be conducted using the second code only.
PGx ANALYSIS
Details on the potential PGx analysis cannot be established yet. Astellas may initiate the PGx 
analysis in case evidence suggests that genetic variants may be influencing the drug’s 
kinetics, efficacy and/or safety. Prior to initiating any analysis on the banked samples, the 
Astellas ethical committee (AREC) must approve the analysis plan.


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DISPOSAL OF PGx SAMPLES / DATA
All PGx samples collected will be stored for a period of up to 15 years following study 
database hardlock. If there is no requirement for analysis, the whole blood sample will be 
destroyed after the planned storage period. The subject has the right to withdraw consent at 
any time. When a subject’s withdraw notification is received, the PGx sample will be 
destroyed. The results of any PGx analysis conducted on a sample prior to its withdrawal will 
be retained at Astellas indefinitely.
INFORMATION DISCLOSURE TO THE SUBJECTS
Retrospective PGx analysis may be conducted following the conclusion of the clinical study, 
if applicable. The results of the genetic analysis will not be provided to any investigators or 
subjects, nor can the results be requested at a later date. Any information that is obtained from 
the PGx analysis will be the property of Astellas. 


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12.17
Appendix 17:  Long-term Follow-up Questionnaire
Subjects will be contacted by telephone annually for 4 years starting at 1.5 years after the first
injection of Study Drug to evaluate for long-term safety related to the DNA vaccine. Items to 
be assessed by questionnaire and available medical records include mortality, development of 
any new cancer, development of infection requiring hospitalization, graft survival, creatinine 
and local immune-mediated reactions.  
During the long-term follow-up period, if an SAE is identified and deemed possibly or 
probably related to the study medication, an SAE report on the SAE worksheet must be sent 
to the sponsor per Section 5.5.6.
The following information will be collected at each of the contact time points:
1. Subject mortality, including primary cause of death and date of death (if applicable).
2. Development of any new/recurrent cancer (name).  
3. Development of infection requiring hospitalization or resulting in death (name of 
infecting agent, or medications or laboratory data leading to diagnosis).  
o
The subject will be asked whether he/she has been diagnosed with any new medical 
conditions requiring hospitalization to solicit this information.
4. Creatinine values will be recorded if they have been collected within 3 months prior to the 
follow-up telephone contact and are in the subject’s available medical records.
5. Initiation of dialysis.
6. Subsequent kidney transplant.
7. Immune-mediated reactions.  
o
The subject will be asked if he/she has had any redness or swelling at the site of the 
injection.


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12.18
Appendix 18:  Health Economic Assessment (Inpatient and 
Outpatient Utilization)
Are there any Inpatient Care visits to report? Yes 
No
If Yes, please record the number of days the patient was admitted to:  
Admission Unit/Floor
ICU Days_____________
                  # of Days
Step-down Unit Days______________
                                    # of Days
    Hospital General Medical/Surgical Ward Days_____________
                                                              # of Days
Was there an Emergency Room visit greater than 24 hours (without admittance)?  Yes  No
If yes, please indicate the number of Emergency Room days____________
                     
  # of days
Primary Reason (Diagnosis) for Admission:___________________
If a US site, please insert the ICD-9 code for the diagnosis.
If more than one Inpatient Care visit to report, please record diagnosis/ICD-9 code for each 
admission, and the number of days as noted above.
Are there any Non- Protocol- related Physician visits to report?
Yes
No
If Yes, please indicate the number of of visits:
Physician Visits_____________
# of visits


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13
ATTACHMENT 1:  SUBSTANTIAL AMENDMENT 2
I.  The purpose of this amendment is:
Substantial Changes
1. Definition of Terms, Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Revise to reflect that the Screening Period may begin -14 days from transplant up to day of 
Randomization.
RATIONALE:
Subjects are discharged frequently within several days after transplant and since the first dose 
of vaccine is one month after transplant, increasing the screening period to start up to 14 days 
prior to transplant allows a site to screen a subject at their pre-transplant evaluation.
Some sites may adjust medications used for induction therapy and CMV prophylaxis based 
on whether or not the subject has agreed to participate in the trial. Some sites prefer to 
discuss study objectives, procedures and obtain Informed Consent  prior to the transplant 
procedure when the subject is in a stable condition.  
2. Change the definition of CMV viremia to plasma viral load ≥1000 IU/mL
DESCRIPTION OF CHANGE:
Revise CMV viremia definition from plasma viral load ≥250 IU/mL to plasma viral load 
≥1000 IU/mL.
RATIONALE:
There is no known threshold of CMV viremia which correlates with CMV disease because
assays have not been standardized across institutions at this time. However, in the Phase 2 
trial, in hematopoetic stem cell recipients, the plasma viral load threshold that was associated 
with a reduction in clinical outcomes was ≥1000 IU/mL.
3. Change the use of anti-thymocyte globulin (ATG) as induction therapy for 
stratification criteria.  
DESCRIPTION OF CHANGE:
Remove the wording “as induction therapy” and added “Prior to Randomization” when 
describing the use of anti-thymocyte globulin.  
RATIONALE:
The stratification criteria for ATG was expanded from use for induction therapy to day of 
Randomization because ATG is commonly used to treat delayed graft function and acute 
rejection immediately post transplantation. In order to assess the population of patients who 
will receive the vaccine post approval, ATG is being allowed up to day of Randomization.  


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4. Change in anti-viral prophylaxis (AVP) dose adjustment wording
DESCRIPTION OF CHANGE:
Revise the period of adjustment for the CMV anti-viral prophylaxis (AVP) to after the Day of 
Randomization.
RATIONALE:
Clarifies the time point when the CMV AVP can be adjusted.
5. Additional wording to define AVP  
DESCRIPTION OF CHANGE:
Add wording to clarify that Investigators may use their clinical judgment for interrupting/ 
adjusting dosage of AVP.
RATIONALE:
Provide clarity on guidance for interrupting/adjusting AVP dosage.
6. Additional wording regarding CMV resistance.
DESCRIPTION OF CHANGE:
Insert additional wording if resistance to CMV AVT is suspected.    
RATIONALE:
To allow for investigator discretion in regards to suspected resistance to CMV AVT.
7. Add vital signs and evaluation of subjects 15 minutes post-study drug injection.
DESCRIPTION OF CHANGE:
A 15 minute post study drug administration vital signs is added.  
RATIONALE:
To further monitor the safety of a subject post study drug administration.
8.
Revise Inclusion Criteria 
DESCRIPTION OF CHANGE:
Add “per regulatory label (package insert)” to Inclusion Criteria 5. 
RATIONALE:
To allow subjects to be dosed based on their renal function, as noted in the package insert for 
their region.
9. Add Exclusion Criteria 
DESCRIPTION OF CHANGE:


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Add Exclusion Criteria 5 to exclude subjects that may require dialysis on the day of 
Randomization.
RATIONALE:
Subjects cannot be receiving dialysis on the day of Randomization because it is a 
contraindication to the use of valganciclovir which is required therapy for the first 80 days of 
the trial.
10. Delete Exclusion Criteria 
DESCRIPTION OF CHANGE:
Delete Exclusion Criteria 8 which excluded subjects that had an episode of hyper acute or 
acute rejection prior to Randomization.
RATIONALE:
Hyperacute or acute rejection is not expected to affect the efficacy of the vaccine. It is the 
drugs used to treat the episodes of rejection which may interfere with the efficacy of the 
vaccine because of their suppressive effects on the immune system. Therefore, instead of 
excluding a subject with hyperacute and acute rejection, medications which significantly 
suppress the immune response are added to exclusion criteria.
11. Revise Exclusion Criteria 
DESCRIPTION OF CHANGE:
Add eculizumab, bortezomib, intravenous immunoglobulin (IVIG) and plasmapheresis as 
prohibited from Day of Transplantation through the Day of Randomization to Exclusion 
Criteria 9.
RATIONALE:
Eculizumab, bortezomib, IVIG and plasmapheresis, because they significantly suppress 
immune responses, and therefore, may interfere with effectiveness of the vaccine.  
12. Revise Exclusion Criteria 
DESCRIPTION OF CHANGE:
Add further clarification to Exclusion Criteria 11 regarding contraindications for prophylaxis 
of CMV viremia/disease with valganciclovir or ganciclovir. 
RATIONALE:
To ensure the criteria reflects any reason a subject would not be able to receive valganciclovir/
ganciclovir at Randomization.
13. Revise Exclusion Criteria
DESCRIPTION OF CHANGE:
Add clarification to the time frame to contraindications for intramuscular injections 
referenced in Exclusion Criteria 12. 


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RATIONALE:
To eliminate subjects that are likely to have a contraindication to IM injections at Baseline
and throughout the Primary Study Period. 
14. Revise Exclusion Criteria 
DESCRIPTION OF CHANGE:
Add further clarification to Exclusion Criteria 13 regarding timeframe for AST or ALT 
criteria.
RATIONALE:
Subjects may require time for AST/ALT to return to normal post operatively.
15. Concomitant Medication Restriction or Requirements, CMV Prophylaxis
DESCRIPTION OF CHANGE:
Clarify the number of doses the subject can miss prior to Randomization and dose adjustment 
criteria per the Investigators clinical judgment.
RATIONALE:
To provide parameters for clinically indicated dosage holds or subject missed doses that will 
still qualify the subject for the study.
16. Concomitant Medication Restriction or Requirements, Pneumocystis jiroveci 
Pneumonia Prophylaxis
DESCRIPTION OF CHANGE:
Add wording for dose adjustments and interruptions to Pneumocystis jiroveci Pneumonia 
Prophylaxis.
RATIONALE:
To provide further clarification to support dose adjustment for clinical indications.
17. Concomitant Medication Restriction or Requirements, Prohibited Concomitant 
Medications (Drugs and Therapies)
DESCRIPTION OF CHANGE:
Revise wording for Alemtuzumab and Rituximab as well as adding additional prohibited 
medications. Also clarify time periods for prohibited medications.  
RATIONALE:
Alemtuzumab (T cell depleting agent), ATG (T cell depleting agent) and anti-CD 20 
antibodies (B cell depleting agent) may interfere with effectiveness of the vaccine.  
Therefore, if a subject is planned to receive any one of these agents through the primary 
study period they are excluded. However, it is not ethical to prevent subjects from receiving 
these agents if they are clinically indicated, and, to prevent protocol violations and drop-outs, 


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subjects may receive these agents if clinically indicated after they have been Randomized 
into the trial.
18. Concomitant Medication (Drugs and Therapies)
DESCRIPTION OF CHANGE:
Clarify that the medications used for anesthesia during the transplant will not be recorded.  
RATIONALE:
To clarify procedures other than the transplant using anesthesia must have those anesthetic 
agents recorded. Medications used for anesthesia are difficult to record and are not expected 
to affect the outcome of the trial.
19. Concomitant Medication Restriction or Requirements, Prohibited Concomitant 
Medications (Drugs and Therapies)
DESCRIPTION OF CHANGE:
Insert wording to note that IVIG and plasmapheresis are not allowed from Day of Transplant 
through the Day of Randomization.
RATIONALE:
IVIG and plasmapheresis significantly suppress immune responses and, therefore, are likely 
to interfere with the efficacy of the vaccine.
20. Discontinuation Criteria
DESCRIPTION OF CHANGE:
Clarify wording to reflect that grading should be confirmed by a health care professional’s
(HCP). 
RATIONALE:
To specify that grading > 3 as assessed by the subject, must be confirmed by a HCP.
21. Discontinuation Criteria
DESCRIPTION OF CHANGE:
Add anaphylaxis as discontinuation criteria.  
RATIONALE:
Anaphylaxis of Grade > 3 per NCI Criteria warrants discontinuation from the study.
22. Endpoints for Evaluation; Exploratory Endpoints
DESCRIPTION OF CHANGE:
Simplify the language of Healthcare utilization to be recorded.
RATIONALE:


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Previous language and data to be collected were duplicate data and clarification given on 
how to record inpatient and outpatient days.
23. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Additional Home Health Care visits are added with criteria expanded to provide clarification 
to visit windows and allowed procedures. 
RATIONALE:
To provide more flexibility for sites using the service for subjects that live remotely.
24. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Moved the screening window from ‘Day 10 to Day 30’ to ‘Day -14 to Day of Randomization 
(Day 30)’. 
RATIONALE:
Screening window is moved to accommodate Screening prior to Transplant.
25. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Change to standardize collection of concomitant medications for all subjects to 14 days prior 
to Transplant.
RATIONALE:
As screening can now take place from 14 days prior to Transplant until 30 days post 
Transplant, all subjects will have concomitant medications collected during that time period.
26. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Add urine protein: creatinine ratio
RATIONALE:
Urine protein: creatinine ratio is an important indicator of renal disease post transplant
27. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Add the criteria for recording of AEs as medical history until first dose of study drug and 
SAEs from signing of the Informed Consent being reported per SAE criteria.
RATIONALE:


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As Screening will now occur prior to transplant, criteria related to the reporting and capturing 
of AEs and SAEs prior to the administration of the Study Drug are defined.
28. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Add HCV PCR RNA donor and recipient criteria to be recorded if available.
RATIONALE:
This additional information is important when available to further assess safety issues that 
might occur during the trial and possible relatedness to the underlying disease and not 
administration of the vaccine.  
DESCRIPTION OF CHANGE:
Add wording for stable subjects that have Home Health Care visits for blood draws will only 
draw Central Lab CMV samples.
RATIONALE:
To eliminate the possibility of the use of an unapproved local laboratory being used and a 
potential false positive result.
29. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Add wording to note that subject should not have a temperature of  ≥100.4 prior to a study 
drug injection.
RATIONALE:
To accurately assess subject safety post vaccination.  
30. Flow Chart and Schedule of Assessments
DESCRIPTION OF CHANGE:
Add criteria for the repeat of vital signs post injection.
RATIONALE:
If vital signs meet Grade 1-4 criteria per Appendix 5, they will be confirmed for appropriate 
subject treatment, if needed.
31. Revise Exploratory Efficacy Assessment
DESCRIPTION OF CHANGE:
Clarify time point for eGFR exploratory assessment.
RATIONALE:


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Clarified the time point is the last study visit for those subjects that do not go through the 
entire trial to Day 395/Month 13.
32. Add Laboratory Assessments
DESCRIPTION OF CHANGE:
Add phosphorus to local laboratory samples collected. 
RATIONALE:
Correction to missing information.
33. Revise Long Term Follow-up language
DESCRIPTION OF CHANGE:
Spontaneously reported SAEs during the Long Term Follow-up that are possibly or probably 
related to the study drug are to be reported using the SAE worksheet.
RATIONALE:
SAEs that are possibly or probably related to study drug and have been reported by the 
subject or are found on hospital record reviews are required to be reported on SAE 
worksheets, as the subjects are still enrolled in the trial.
34. Revise Dose/Dose Regimen and Administration Period
DESCRIPTION OF CHANGE:
Add that an injection should not be given if a subject has a temperature ≥100.4.  
RATIONALE:
To accurately assess subject safety post vaccination.
35. Clarify Definitions of Adverse Events and Serious Adverse Events
DESCRIPTION OF CHANGE:
Clarified that the transplant surgery that occurs on Day 0 is not considered an AE or SAE.  
RATIONALE:
This is a planned event not considered an AE or SAE.
36. Appendix 5: Grading of Signs of Systemic Reactogenicity
DESCRIPTION OF CHANGE:
Define predose vital signs to be collected
RATIONALE:
To define what vital signs are to be used as baseline.


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37. Appendix 10: Liver Safety Monitoring Assessment
DESCRIPTION OF CHANGE:
Change the AST/ALT and TV from the ULN to the subject’s baseline value and ULN.
RATIONALE:
Subjects are permitted to begin the study with higher than normal ALT/AST and TB levels.  
This takes into account their possible higher baseline values.
38. Appendix 10: Liver Safety Monitoring Assessment
DESCRIPTION OF CHANGE:
Criteria are added for when Investigator is to contact Medical Monitor based on local 
laboratory values.
RATIONALE:
Additional criteria are needed as local labs are being used for this study.
39. Appendix 16: Retrospective Pharmacogenomics (PGx) Sub-Study
DESCRIPTION OF CHANGE:
Delete text referencing genetic testing and rename “exploratory” to “Retrospective”.
RATIONALE:
Clarification needed for possible PGx analysis.
Non-Substantial Changes
1. Update List of Abbreviations
DESCRIPTION OF CHANGE:
Revise abbreviations for Deceased Donor Criteria and Herpes Simplex Virus. Also add 
abbreviation for Intravenous Immunoglobulin. 
RATIONALE: 
To correct list of abbreviations to match body of protocol.  
2. Clarify Key Study Terms
DESCRIPTION OF CHANGE:
Clarify definitions for Adverse Events and Randomization.
RATIONALE:
Add wording to further define an adverse event occurring due to study procedures and revise 
definition for Randomization to reflect change in screening period.


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3. Update Planned Study Period
DESCRIPTION OF CHANGE:
Revise First Subject in to Q42013
RATIONALE:
To update study timelines.
4. Update Planned Total Number of Study Centers and Locations
DESCRIPTION OF CHANGE:
Remove Brazil and United Kingdom
RATIONALE:
Additional countries are not necessary for enrollment.
5. Minor wording clarifications
DESCRIPTION OF CHANGE:
Minor wording changes in Study Design, Discontinuation Criteria and Section 2.2.1
RATIONALE:
To provide further clarity to Investigators.
6. Exclusion Criteria 13
DESCRIPTION OF CHANGE:
Add wording to define when this contraindication is valid.
RATIONALE:
To provide further clarity to Investigators.
7. Transplant Information
DESCRIPTION OF CHANGE:
Add HCV PCR RNA to footnote.
RATIONALE:
This additional information is necessary when available to assess safety issues that might 
occur during the trial, but are related to the patient having active hepatitis C and not 
administration of the vaccine.
8. Healthcare resource utilization
DESCRIPTION OF CHANGE:  


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The data to be collected is changed to hospital days, physician visits and emergency room 
visits without admission.
RATIONALE:
To clarify necessary data or collection and provide clarification to sites on data entry.
9. Laboratory Assessments
DESCRIPTION OF CHANGE:
Wording is added so that a local CMV laboratory sample will be drawn with a Central Lab 
sample.
RATIONALE:
To add clarification to when local CMV’s are drawn.
10. Laboratory Assessments
DESCRIPTION OF CHANGE:
Add wording to note that HHC safety labs will be analyzed by the Central Lab.
RATIONALE:
To allow for regional limitations for local lab samples to be drawn by the HHC and clarify 
that the Central lab will be the standard collection in all regions.
11. Statistical Methodology
DESCRIPTION OF CHANGE:
Remove mention of soft lock for the database lock.  
RATIONALE:
The term is not universally understood so it is removed.
12. Analysis of Safety, Adverse Events, Clinical Laboratory Evaluation & Vital Signs 
Evaluation
DESCRIPTION OF CHANGE:
Remove “deceased donor criteria” and revise the ATG for induction use for defining AEs, 
Clinical Laboratory Evaluations and Vital Signs used for the Analysis of Safety.
RATIONALE:
Deceased donor criteria are not being collected and ATG for induction is removed as criteria 
and changed to ATG (at any time).


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13. Appendix 7
DESCRIPTION OF CHANGE:
Add wording for definite retinitis.
RATIONALE:
To further clarify methods of detection.
14. Dosing and Administration of Study Drug(s) and other Medication(s)
DESCRIPTION OF CHANGE:
Add text indicating that information regarding syringes is located in the Pharmacy Manual.  
RATIONALE:
To provide clarification to sites for where they can locate instructions regarding study drug 
administration. 
15. Administrative Changes
DESCRIPTION OF CHANGE: 
Include minor administrative-type changes, e.g., typos, format, consistency throughout the 
protocol.  
RATIONALE:
To provide clarifications to the protocol, and to ensure complete understanding of study 
procedures.


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II  Amendment Summary of Changes:
III. LIST OF ABBREVIATIONS AND DEFINITION OF KEY TERMS
List of Abbreviations
Page 11
WAS:
DCD
Deceased Donor Criteria
IS AMENDED TO:
DCD DDC
Deceased Donor Criteria
Page 12
WAS:
HHV
Herpes Simplex Virus
IS AMENDED TO:
HHV
Human Herpes Simplex Virus
Page 13
ADDED:
IVIG
Intravenous Immunoglobulin
III. LIST OF ABBREVIATIONS AND DEFINITION OF KEY TERMS
Definition of Terms
Page 15; Adverse Event
WAS:
An adverse event is any untoward medical occurrence in a subject administered a Study 
Drug which does not necessarily have a causal relationship with the treatment.
IS AMENDED TO:
An adverse event is any untoward medical occurrence in a subject who was administered a 
Study Drug which or has undergone study procedures that does not necessarily have a 
causal relationship with the treatment.
Page 16; Randomization
WAS:
The action to allocate a subject to a treatment group. In this study, randomization occurs after 
the subject has met all inclusion and exclusion criteria between days 10-30 +/- 3 days after 
the transplant date.
IS AMENDED TO:
The action to allocate a subject to a treatment group. In this study, randomization occurs after 
the subject has met all inclusion and exclusion criteria between days -14/+10- 30 relative to 
+/ 3 days after the transplant date.


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IV. Synopsis
Page 17; Planned Study Period 
WAS:
First subject in (FSI) 3Q2013; Last Subject Out (LSO) 2Q2017
Long-term Follow-up Period LSO 4Q2021
IS AMENDED TO:
First subject in (FSI) 4Q20133Q2013; Last Subject Out (LSO) 2Q2017, (Primary Study Period)
Long-term Follow-up Period LSO 4Q2021
IV. Synopsis
2.1 Study Objectives
Page 17; Study Objectives, # 1
Page 37; 1st bullet point
WAS:
To evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence of CMV 
viremia (defined as plasma viral load ≥ 250 IU/mL by central laboratory assay) through one 
year post first Study Drug injection in CMV-seronegative subjects receiving a kidney from a 
CMV-seropositive donor.
IS AMENDED TO:
To evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence of CMV 
viremia (defined as plasma viral load ≥2501000 IU/mL by central laboratory assay) through 
one year post first Study Drug injection in CMV-seronegative subjects receiving a kidney 
from a CMV-seropositive donor.
IV. Synopsis 
Page 17; Planned Total Number of Study Centers and Location(s)  
WAS:
Locations: Countries may include, but are not limited to: United States, Canada, Germany, 
Spain, United Kingdom, France, Australia and Brazil
IS AMENDED TO:
Locations: Countries may include, but are not limited to: United States, Canada, Germany, 
Spain, United Kingdom, France, and Australia and Brazil
IV. Synopsis
Pages 17-18; Study Design Overview
WAS:
This is a randomized, double-blind, placebo-controlled trial.
140 CMV-seronegative subjects who have received a kidney from a living or deceased 
CMV-seropositive donor will be randomized 30 days ± 3 days after transplantation (Day 0) 


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in a 1:1 ratio to ASP0113 or placebo.
Randomization will be stratified by use of anti-thymocyte globulin as induction therapy and 
by receipt of a kidney from a living or deceased donor.
Subjects will receive either 5 doses of ASP0113 or 5 doses of placebo on Days 30 ± 3, 60 ± 
5, 90 ± 5, 120 ± 5, and 180 ± 5 in relation to the day of transplant.
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) continuously until the day of Randomization to 
prevent CMV disease. Subjects will then receive CMV-specific anti-viral prophylaxis (AVP) 
until 100 days post transplant.
Subjects can have CMV-specific AVP interrupted or dose adjusted per standard of care after 
initiation if renal function is compromised or there are toxicities related to the administration 
of the AVP. In all subjects plasma will be collected for central laboratory CMV viral load 
testing every two weeks from Day 100 through Day 200, then monthly through last study 
visit.
In cases where CMV disease (CMV syndrome or CMV tissue-invasive disease) is suspected 
from the first Study Drug injection through Day 395, an additional central and local 
laboratory CMV viral load will be collected at the time of the first CMV symptom 
recognition.
CMV-specific anti-viral therapy (AVT) should be initiated for CMV disease and can be 
initiated for CMV viremia based on the central or local laboratory results and standard of 
care.
If CMV-specific AVT is initiated, both a central and a local CMV viral load will be obtained 
at a minimum of weekly from the time CMV-specific AVT is initiated until discontinuation.  
In addition, each time a local CMV viral load sample is collected, a plasma sample will also 
be collected and sent to the central laboratory for CMV viral load testing. 
Subjects will be followed for one year post first Study Drug injection (Study completion/Day 
395) for CMV viremia, CMV syndrome, CMV tissue-invasive disease, and CMV-specific 
AVT, graft survival, creatinine and subject survival through the Study Completion/Day 395 
Visit. 
Subjects will be followed for one year post first Study Drug injection for resistance to 
valganciclovir or ganciclovir. Viral resistance will be measured if the viral load has not 
decreased 2 weeks after initiating CMV-specific AVT or when there is no improvement in 
clinical signs and symptoms two weeks after initiating valganciclovir or ganciclovir for 
CMV viremia and/or disease.
Immunogenicity to pp65 and gB will be assessed prior to Dose 1, two weeks after Dose 2, 
prior to Dose 3, two weeks after Dose 4, prior to Dose 5 and at the last study visit.  
Subjects will be evaluated for local and systemic reactogenicity one hour after each Study 
Drug injection and for 7 days by subject reporting via diary after each Study Drug injection. 
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing 
of the informed consent through one year post first Study Drug injection.  
Subjects will be contacted by telephone annually at 6 months after Day 395, then annually 
for the next 4 years, to evaluate long-term safety related to the deoxyribonucleic acid (DNA) 
vaccine. Mortality, development of any new malignancies, development of infection 


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requiring hospitalization or resulting in death, graft survival, creatinine and erythema and/or 
induration at the injection sites will be assessed by questionnaire and available patient 
records.  
IS AMENDED TO:
This is a randomized, double-blind, placebo-controlled trial.
140 CMV-seronegative subjects who have received a kidney from a living or deceased 
CMV-seropositive donor will be randomized 30 days ± 3 days after transplantation (Day 0) 
in a 1:1 ratio to ASP0113 or placebo.
Prior to Randomization, subjects will be stratified by use of anti-thymocyte globulin as 
induction therapy and by receipt of a kidney from a living or deceased donor.
Subjects will receive either 5 doses of ASP0113 or 5 doses of placebo on Days 30 ± 3 60 ± 5, 
90 ± 5, 120 ± 5, and 180 ± 5 in relation to the day of transplant.
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) through continuously until the day of 
Randomization to prevent CMV disease. (The subject can miss up to two doses of 
valganciclovir or ganciclovir during this time period for any reason).
Subjects will then continue to receive CMV-specific anti-viral prophylaxis (AVP) with 
valganciclovir or ganciclovir until 100 days post transplant. 
Subjects can have valganciclovir or ganciclovir CMV specific AVP interrupted, or dose 
adjusted or replaced by other CMV-specific AVP per standard of care after the day of 
Randomization initiation if renal function is compromised, or there are toxicities related to 
the administration of the AVP, or for any other medically indicated reason.
In all subjects, plasma will be collected for central laboratory CMV viral load testing every 
two weeks from Day 100 through Day 200, then monthly through last study visit.
In cases where CMV disease (CMV syndrome or CMV tissue-invasive disease) is suspected 
from the first Study Drug injection through Day 395, a sample for an additional central and 
local laboratory CMV viral load will be collected at the time of the first CMV symptom 
recognition and sent to a local and the central laboratory.
CMV-specific anti-viral therapy (AVT) should be initiated for CMV disease and can be 
initiated for CMV viremia based on the central or local laboratory results and standard of 
care.
If CMV-specific AVT is initiated, both a central and a local CMV viral load will be obtained 
at a minimum of weekly from the time CMV-specific AVT is initiated until discontinuation.  
In addition, each time a local CMV viral load sample is collected, a plasma sample will also 
be collected and sent to the central laboratory for CMV viral load testing. 
Subjects will be followed for one year post first Study Drug injection (Study completion/Day 
395) for CMV viremia, CMV syndrome, CMV tissue-invasive disease, and CMV-specific 
AVT, graft survival, creatinine and subject survival through the Study Completion/Day 395 
Visit. 
Subjects will be followed for one year post first Study Drug injection for resistance to 
valganciclovir or ganciclovir. 
Viral resistance will be assessed by a Central lab when there is no reduction in measured 


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if the viral load has not decreased
two weeks after initiating valganciclovir/ ganciclovir, CMV specific AVT or when there is 
no improvement in clinical signs and symptoms two weeks after initiating valganciclovir or 
ganciclovir for CMV viremia and/or disease or any time it is clinically indicated.
Immunogenicity to pp65 and gB will be assessed prior to Dose 1, two weeks after Dose 2, 
prior to Dose 3, two weeks after Dose 4, prior to Dose 5 and at the last study visit.  
Subjects will be evaluated for local and systemic reactogenicity 15 minutes and one hour 
after each Study Drug injection and for 7 days by subject reporting via diary after each Study 
Drug injection. All adverse events (AEs) and serious adverse events (SAEs) will be collected 
from signing of the informed consent through one year post first Study Drug injection.  
Subjects will be contacted by telephone annually at 6 months after Day 395, then annually 
for the next 4 years, to evaluate long-term safety related to the deoxyribonucleic acid (DNA) 
vaccine. Mortality, development of any new malignancies, development of infection 
requiring hospitalization or resulting in death, graft survival, creatinine and erythema and/or 
induration at the injection sites will be assessed by questionnaire and available patient 
records.  
IV. Synopsis, Inclusion Criteria 
Page 19
WAS: 
5. Subject started valganciclovir or ganciclovir within 10 days of transplant and has received 
it up to the time of Randomization.
IS AMENDED TO:
5. Subject started valganciclovir or ganciclovir within 10 days of transplant and has received 
it through up to the time of Randomization, per regulatory label (package insert).
IV. Synopsis, Exclusion Criteria
3.3 Exclusion Criteria
Page 19
Page 43 
ADDED:  
5. The subject requires dialysis on the day of Randomization.
IV. Synopsis, Exclusion Criteria
3.3 Exclusion Criteria
Page 20
Page 43
DELETED:  
8. Subject has had an episode of hyper acute or acute rejection prior to Randomization.


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IV. Synopsis, Exclusion Criteria
3.3 Exclusion Criteria
Page 20; Exclusion # 9 
Page 44 
WAS:
9. Subject has received any of the following substances or treatments:
a.
Investigational research products within 28 days or 5 half lives whichever is longer, 
prior to Transplantation, or subject is scheduled to receive investigational research 
products through one year after Randomization. 
b. Alemtuzumab within 90 days prior to Randomization or is scheduled to receive 
alemtuzumab any time through one year post Randomization.
c.
Rituximab within 120 days prior to Randomization or is scheduled to receive 
rituximab any time through one year post Randomization.  
d. Live attenuated vaccines within one month (30 days) prior to the first dose of Study 
Drug or is scheduled to receive live attenuated vaccines within one month of any 
Study Drug injection. 
e.
Subunit or killed vaccines within 14 days prior to the first dose of Study Drug or is 
scheduled to receive a subunit or killed vaccine within 14 days prior to any Study 
Drug injection.
f.
Administration of a CMV vaccine, including any prior exposure to ASP0113.
g. Subject has received the following anti-viral therapies or it is planned for them to 
receive the AVT for prophylaxis of viral infections in excess of the following doses 
from time of transplant through Randomization:
Aciclovir: 1600 mg orally (total daily dose), or 500 mg/m2/dose Intravenous 
(IV) (total daily dose)
Valaciclovir: 1000 mg orally (total daily dose)
Famciclovir: 500 mg orally (total daily dose) 
IS AMENDED TO:  
9. Subject has received any of the following substances or treatments:
a. Investigational research products within 28 days or 5 half lives whichever is longer, 
prior to Transplantation, or subject is scheduled to receive investigational research 
products through one year after Randomization. 
b. Alemtuzumab within 90 days prior to Randomization or is scheduled to receive 
alemtuzumab any time through one year post Randomization.
c. Rituximab within 120 days prior to Randomization or is scheduled to receive 
rituximab any time through one year post Randomization.  
d. Eculizumab or bortezomib from the Day of Transplantation through the Day of 
Randomization or is scheduled to receive eculizumab or bortezomib any time 
through one year post Randomization. 
e. IVIG and/or plasmapheresis from Day of Transplant through Day of 
Randomization.
f. Live attenuated vaccines within one month (30 days) prior to the first dose of Study 
Drug or is scheduled to receive live attenuated vaccines within one month of any 
Study Drug injection. 


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g. Subunit or killed vaccines within 14 days prior to the first dose of Study Drug or is 
scheduled to receive a subunit or killed vaccine within 14 days prior to any Study 
Drug injection.
h. Administration of a CMV vaccine, including any prior exposure to ASP0113.
i. Subject has received the following anti-viral therapies or it is planned for them to 
receive the AVT for prophylaxis of viral infections in excess of the following doses 
from time of transplant through Randomization:
Aciclovir: 1600 mg orally (total daily dose), or 500 mg/m2/dose Intravenous 
(IV) (total daily dose)
Valaciclovir: 1000 mg orally (total daily dose)
Famciclovir: 500 mg orally (total daily dose) 
IV. Synopsis, Exclusion Criteria 
3.3 Exclusion Criteria
Page 20
Page 44
WAS:  
11. Subject has any contraindication to valganciclovir or ganciclovir including, but not 
limited to, renal dysfunction or cytopenias on the Day of Randomization.
IS AMENDED TO:
11. Subject has any contraindication to or cannot be dosed with valganciclovir or 
ganciclovir per package insert including, but not limited to, renal dysfunction or 
cytopenias on the Day of Randomization for any reason.
IV. Synopsis, Exclusion Criteria 
3.3 Exclusion Criteria
Page 20
Page 44
WAS:  
12. Subject has any contraindication to an intramuscular injection.
IS AMENDED TO:
12. Subject has, or is expected to have during the Primary Study Period, a any
contraindication to an intramuscular injection.
IV. Synopsis, Exclusion Criteria 
Page 20
WAS:
13. Subject has an Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) 
greater than 3 x Upper Limits of Normal (ULN) or total bilirubin greater than 2 x ULN 
unless secondary to suspected Gilbert’s disease at Screening.


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IS AMENDED TO:
13. Subject within 3 days prior to Randomization, has an Aspartate Aminotransferase 
(AST) or Alanine Aminotransferase (ALT) greater than 3 x Upper Limits of Normal 
(ULN) or total bilirubin greater than 2 x ULN unless secondary to suspected Gilbert’s 
disease at Screening.
IV.  Synopsis; Concomitant Medication Restrictions or Requirements
Page 21; CMV Prophylaxis
WAS:
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) continuously until day of Randomization to prevent 
CMV disease. Subjects will then receive CMV-specific AVP until 100 days post transplant. 
Subjects can have CMV-specific AVP interrupted or dose adjusted per standard of care after 
initiation if renal function is compromised or there are toxicities related to the administration 
of the AVP.
IS AMENDED TO:
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) through continuously until day of Randomization to 
prevent CMV disease. (The subject can miss up to two doses of valganciclovir or 
ganciclovir during this time period for any reason). Subjects will then receive CMV-
specific AVP with valganciclovir or ganciclovir until 100 days post transplant. Subjects 
can have valganciclovir or ganciclovir CMV specific AVP interrupted, or dose adjusted or 
replaced by other CMV-specific AVP per standard of care after the Day of 
Randomization initiation if renal function is compromised, or there are toxicities related to 
the administration of the AVP, or for any other medically indicated reason.
IV.  Synopsis; Concomitant Medication Restrictions or Requirements
5.1.4.2 Pneumocystis jiroveci Pneumonia Prophylaxis
Page 21; Pneumocystis jiroveci Pneumonia Prophylaxis
Page 50 ; 1st paragraph
WAS:
Pneumocystis jiroveci pneumonia prophylaxis must be administered to all study participants 
according to the site’s standard of practise and applied uniformly to all enrolled subjects. If 
there is no prophylactic Pneumocystis protocol, the investigator must decide on appropriate 
Pneumocystis jiroveci pneumonia prophylaxis.
IS AMENDED TO:
Pneumocystis jiroveci pneumonia prophylaxis must be initiated for administered to all study 
participants according to the site’s standard practice for kidney transplant recipients of 
practice and applied uniformly to all enrolled subjects. Dose may be adjusted or therapy 
interrupted for renal dysfunction, adverse events related to the administration of the 
therapy or for other clinically indicated reasons.  If there is no prophylactic Pneumocystis 


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protocol, the investigator must decide on appropriate Pneumocystis jiroveci pneumonia 
prophylaxis.
IV.  Synopsis; Concomitant Medication Restrictions or Requirements
Page 22 ; Prohibited Concomitant Medications (Drugs or Therapies), bullet points 1- 3
WAS:

Investigational research products through completion of Day 395 visit (Visit 13).

Alemtuzumab through completion of the study (Day 395 visit/Visit 13).
Rituximab through completion of the study (Day 395 visit/Visit 13) except for Post-
Transplant Lymphoproliferative Disorder.
IS AMENDED TO:

Investigational research products through completion of Day 395 visit (Visit 13).

Alemtuzumab through completion of the study (Day 395 visit /Visit 13).

Rituximab through completion of the study (Day 395 visit /Visit 13) except for Post
Transplant Lymphoproliferative Disorder.  

Planned alemtuzumab and, anti-CD20 antibodies (including rituximab) eculizumab 
or bortezomib are not allowed from the Day of Randomization through the Primary 
Study Period (Day 395).  These treatments may be given after the Day of 
Randomization if clinically indicated.
IV Synopsis; Discontinuation Criteria 
Page 22; Study and Treatment Discontinuation
WAS: 
Subjects will be withdrawn from study treatment and will only be followed for mortality 
through public records if the following occurs: 
Withdrawal of consent by the subject.
IS AMENDED TO: 
Subjects will be withdrawn from investigational study treatment and all follow up 
assessments and will only be followed for mortality through public records if the following 
occurs: 
Withdrawal of consent by the subject.
IV Synopsis; Discontinuation Criteria 
Page 22; Treatment Only Discontinuation
WAS: 
Treatment Only Discontinuation
Subjects should continue to be followed according to the study Schedule of Assessments and 
Long Term Follow-up Schedule of Assessments, except post-dose Day 14 safety and 
laboratory and reactogenicity assessments/visits for those doses not given, but will be 


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withdrawn from study treatment if any of the following occur:  
Investigator’s decision that further treatment is not in the best interest of the subject.
Graft failure
Pregnancy (female subjects only).
Local reactogenicity with a grade ≥ 3 based on the criteria defined in appendices.
Systemic reactogenicity for any grade ≥ 3 fever or any other grade 4 systemic reaction 
within one week of vaccination.
IS AMENDED TO: 
Subjects should continue to be followed according to the study Schedule of Assessments and 
Long Term Follow-up Schedule of Assessments, except post-dose Day 14 safety and 
laboratory and reactogenicity assessments/visits for those doses not given, but will be 
withdrawn from investigational study treatment if any of the following occur:  
Investigator’s decision that further treatment is not in the best interest of the subject.
Graft failure
Pregnancy (female subjects only).
Local reactogenicity with a grade ≥ 3 based on the criteria defined in appendices and 
confirmed by a health care professional.
Systemic reactogenicity for any grade ≥ 3 fever or any other grade 4 systemic reaction 
within one week of vaccination and confirmed by a health care professional.
Anaphylaxis Grade ≥3 per NCI ver. 4.03 criteria.
IV.  Synopsis; Endpoints for Evaluation
Page 22; Primary Efficacy
WAS:
Incidence of CMV viremia (defined as plasma viral load of ≥ 250 IU/mL by central assay)
through one year post first Study Drug injection.
IS AMENDED TO:
Incidence of CMV viremia (defined as plasma viral load of ≥ 1000250 IU/mL by central 
assay) through one year post first Study Drug injection.
IV.  Synopsis; Endpoints for Evaluation
Page 23; Exploratory Efficacy
WAS:
•
Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.
•
Time to first CMV viremia (defined as plasma viral load of ≥ 250 IU/mL by central 
assay) through one year post study first Study Drug injection.
•
Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection.


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•
Number of episodes of CMV viral load of ≥ 250 IU/mL by central assay through one 
year 
post first Study Drug injection.
•
Peak CMV viral load through one year post first Study Drug injection. 
•
Total CMV viral load through one year post first Study Drug injection.
•
Number of episodes of adjudicated CMV- associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.
•
Number of episodes of viral resistance to ganciclovir or valganciclovir through one year 
post first Study Drug injection as determined by a central laboratory assay. 
•
Incidence of biopsy-proven acute rejection (BPAR) through one year post first Study 
Drug injection.
•
Estimated glomerular filtration rate (eGFR) at month 13 calculated using the 4 variable
Modification of Diet in Renal Disease (MDRD) formula.

Incidence of clinically treated acute graft rejection through one year post first Study Drug 
injection.

Health economic and outcomes research (HEOR).

Patient-reported outcomes through one year post first Study Drug injection:
o
EuroQol-5 dimensions 5 levels (EQ-5D)
o
Kidney Transplant Questionnaire (KTQ) 
o
Short Form Health Survey version 2 (SF-12v2) 

Healthcare resource utilization through one year post first Study Drug injection:
Resource use will be collected including the following: concomitant medications and 
procedures, hospitalizations, nonscheduled outpatient/clinic visits, emergency room visits, 
skilled nursing facility care, and hospice care.
IS AMENDED TO:

Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.

Time to first CMV viremia (defined as plasma viral load of ≥ 2501000 IU/mL by central 
assay) through one year post study first Study Drug injection.

Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection.

Number of episodes of CMV viral load of ≥ 2501000 IU/mL by central assay through 
one year 
post first Study Drug injection.

Peak CMV viral load through one year post first Study Drug injection. 
•
Total CMV Viral load area under the curve (AUC), as a measure of “cumulative
viral load” through one year post first Study Drug injection.

Number of episodes of adjudicated CMV- associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.

Number of episodes of viral resistance to ganciclovir or valganciclovir through one year 


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post first Study Drug injection as determined by a central laboratory assay. 

Incidence of biopsy-proven acute(T or B cell) rejection (BPAR) (Banff 2007 Grade > 1) 
through one year post first Study Drug injection.

Estimated glomerular filtration rate (eGFR) at month 13the last study visit, calculated 
using the 4 variable MDRD formula.

Incidence of clinically treated acute graft rejection through one year post first Study Drug 
injection.

Health economic and outcomes research (HEOR).

Patient-reported outcomes through one year post first Study Drug injection:
o
EuroQol-5 dimensions 5 levels (EQ-5D)
o
Kidney Transplant Questionnaire (KTQ) 
o
Short Form Health Survey version 2 (SF-12v2) 

Healthcare resource utilization through one year post first Study Drug injection:
Resource use will be collected including the following: concomitant medications and 
procedures, .hospitalizations, nonscheduled outpatient/clinic visits, recorded as number of 
days in the Intensive Care Unit, Step-down Unit, and general medical ward, (including 
emergency room visits, skilled nursing facility care, greater than 24 hours), also non -
protocol -related physician visits and hospice care emergency room visits of. less than 24 
hours.
V.  Flow Chart and Schedule of Assessments
Page 26; Flow Chart 
WAS:
Screening/Informed Consent through Visit 13/Day 395
IS AMENDED TO:
Screening/Informed Consent through Visit 13/Day 395


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Local & Systemic Reactogenicity 
Assessment22
X
X
X
X
X
Patient and Graft Survival
X


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V. Flow Chart and Schedule of Assessments, Table 1a: Plasma Viral Load Schedule
Page 28
WAS: 
Every Other Week
Monthly
Day 
100*
Day 
114
Day 
128
*
Day 
142*
Day 
156*
Day 
170*
Day 
184
Day 
198*
Day 
230*
Day 
260
Day 
290*
Day 
320*
Day 
350*
Day 
380*
Day 
395
CMV Visit Window 
(days)
+/-3
+/-3
+/-3
+/-3
+/-3
+/-3
+/-3
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
May draw with Visit:
Visit 
7*
Visit 
10
Visit 
11*
Visit 
12
Visit 
13
CMV Plasma Viral Load 
Testing16, 17,  24
X
X
X
X
X
X
XP
X
X
X
X
X
X
X
X
ISAMENDED TO:
Every Other Week
Monthly
Day 
100*
Day 
114*
Day 
128*
Day 
142*
Day 
156*
Day 
170*
Day 
184
Day 
198*
Day 
230*
Day 
260
Day 
290*
Day 
320*
Day 
350*
Day 
380*
Day 
395
CMV Visit Window (days)
+/-3
+/-3
+/-3
+/-3
+/-3
+/-3
+/-35
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+14/-5
CMV Window 
Day
179-
189
Day 
193-
203
Day 
255-
267
Overlap with Regular 
Visit†
Days 
179-
185
Days 
191-
197
Days 
260-
267
Days 
395-
409
May draw with Visit:
Visit 
7*
Visit 10
Visit 
11*
Visit 
12
Visit 
13
CMV Plasma Viral Load 
Testing16, 17,  24
X
X
X
X
X
X
XP
X
X
X
X
X
X
X
X
* = Visit procedures may be performed by Home Health Care (HHC)).  Viral load blood draws may be combined with Visits 10, 11 12 & 13 at the 
investigator site when they are scheduled to coincide within each visit’s windows .
† Days in Study Schedule when CMV and Regular Visit can be performed together per Protocol.  The overlap used assumes the visits are done 
exactly on the specified visit day from Transplant.  If +/- window is used for a dosing visit, the corresponding follow up visit should take place within 
the 14 days +/-3 from the date of the Study Drug dose.  Visits 10 & 11 must be at least 7 days apart.


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V. Flow Chart and Schedule of Assessments, Tables 1 and 2 Footnotes
Pages 29-30
WAS: 
1.
The date of transplant (day of skin closure) defines Day 0 and all visit days are relative to Day 0.  
2.
Subjects are to receive prophylactic valganciclovir or ganciclovir starting within 10 days post transplant through Randomization. Valganciclovir or 
ganciclovir dose is to be given per the package insert. The subject is to receive CMV-specific AVP until 100 days post transplant. Subjects can have 
CMV-specific AVP interrupted or dose adjusted per standard of care after first dose of Study Drug  if renal function is compromised or there are 
toxicities related to the administration of the AVP.
3.
Informed consent must be obtained prior to the performance of any study-related procedure and before Randomization.
4.
Subjects will be assigned a subject number for use throughout the study at the Screening Visit via the Interactive Response Technology (IRT) system.
5.
The EQ-5D, Kidney Transplant Questionnaire (KTQ) and the SF-12 v2, should be completed by the subject prior to any other study assessments or 
visit procedures. Subjects should complete these assessments in the following order: EQ-5D first, KTQ second, SF-12 last. For all three patient-
reported outcome measures, i.e. EQ-5D, KTQ, SF-12, the answers must come from the subject. If the subject is unable to fill out the questionnaire, the 
assessment should not be performed. If the subject is unable to answer an individual question, the rest of the questionnaire should still be completed.
6.
Medical history must include demographics, (age, gender, race),  diagnosis for renal failure, length of time on dialysis, history of prior kidney 
transplant, and diabetes. 
7.
A complete physical examination (PE) will be conducted at the Screening, Baseline and the Study Completion/Day 395 Visit (V13). At all other visits 
where a PE is performed (Visits 4, 6, 8, 10 and 12); symptom-directed physical examinations may be done. The evaluations conducted at each visit are 
to be performed by the Investigator or qualified medical personnel who routinely perform these evaluations in this patient population. Vital signs will 
be collected immediately prior to Study Drug injection, at 15 minutes and 60 minutes post Study Drug injection. Vital signs include blood pressure, 
pulse rate, respiratory rate and temperature. Height will be collected at the Screening Visit only. Weight will be collected at V1 and at Study 
Completion/Day 395 (Visit 13). If Screening is done > 3 days prior to Randomization, the PE must be repeated at Randomization.
8.
All concomitant medications and therapies administered from 10 days prior to transplant through the Study Completion Visit (Day 395/Visit 13) will 
be collected on the eCRF. Medications used for anesthesia will not be recorded. 
9.
Clinical laboratory samples will be drawn at Screening (Visit 1), before each Study Drug injection, at each follow-up time point for the injections, and 
at the last study visit. Clinical labs will be performed by a local laboratory and will include hematology, biochemistry, including a hepatic profile and 
urinalysis with microscopic evaluation. Screening clinical labs may be re drawn once if initial results would preclude Randomization and the 
Investigator feels out of range results were transient. Results will be entered into the eCRF.  
10. For all females of childbearing potential, a urine pregnancy test will be performed at Screening, prior to each dose, at Visit 10, 12, and at the Study 
Completion/Day 395 Visit (Visit 13). All pregnancy tests will be done locally. For subjects who receive mycophenolate mofetil (MMF), additional 
pregnancy testing should be done in accordance with local requirements.
11. CMV serologies must have been performed within 8 weeks prior to transplant.  If CMV serostatus is not available from this time period, CMV 
serostatus may be assessed at the Screening Visit with results available prior to Randomization.
12. AEs and SAEs will be collected from time of signing of informed consent through one year post Study Drug injection [Study Completion Day 395 


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Visit (Visit 13)].  
13. Transplant information includes type of transplant (Living Related Donor, Living Unrelated Donor, or Deceased Donor).
14. Donor information includes donor demographics, (age, gender, race), viral serologies (CMV (required), HBV, HCV) EBV, (if available)), ABO blood 
group and HLA typing. (Recipient information includes ABO blood group, HLA typing, HLA cross match at time of transplant (as determined by the 
site’s standard method of determination), and viral serologies (CMV (required), HBV, HCV and EBV, (if available)).
15. Screening and Randomization can take place on the same day as long as Clinical Labs  are drawn and results are available on the day of 
Randomization. If Screening is done > 3 days prior to Randomization, Clinical Labs must be repeated at Randomization.
16. Plasma viral load by both the central and local laboratory will be routinely monitored every other week (+/-3 days) from Day 100 through Day 200, 
then monthly (+/- 5 days) until end of study. Plasma viral load by central and local laboratory will also be assessed for cause in case of suspect CMV 
disease and at least once a week from initiation of CMV-specific AVT until the course is completed.   
17. Plasma viral load assessment results performed by the local laboratory will be reported on the eCRF. Local CMV plasma viral load testing may be 
performed only at a local laboratory approved by the Sponsor.  
18. A plasma sample will be drawn and results will be reported for CMV genotypic resistance when there is viremia without a reduction in viral load after 
two weeks of treatment with valganciclovir and/or ganciclovir, or when clinical signs and symptoms have not improved two weeks after initiating or 
increasing valganciclovir and/or ganciclovir for CMV viremia or disease.
19. Immunogenicity laboratories include collection of blood for the gB antibody and pp65 T-cell assays. Samples should be drawn at Visits 2, 5, 6, 9, 10  
and 13. Visits 2, 6 and 10 are Study Drug injection visits and blood sampling will be collected prior to the Study Drug injection. Samples for T-cell 
assays will not be collected if the Absolute Lymphocyte Count (ALC) is known to be  < 500 mm3 by local or central laboratory measurement.   
20. Subjects who consent to participate in the PGx sub study will have a whole blood sample collected during the Baseline Visit (Visit 2), after 
Randomization but prior to the first Study Drug injection.
21. A Study Drug injection should not be given if the subject has been on an anticoagulant within 5 half-lives prior to the injection. Low dose 
anticoagulants that are used for prevention of deep vein thrombosis are allowed.
22. Local reactogenicity and symptoms of systemic reactogenicity will be evaluated one hour after each injection  and then for seven days after each 
injection by subject reporting via diary. After injection in the clinic, the subject must be in direct view of the clinic staff for 15 minutes following each 
injection, then remain in the clinic area for an additional 45 minutes for evaluation of local and systemic reactogenicity. Vital signs, including 
temperature, pulse, respiration and blood pressure will be collected just prior to injection, 15 minutes post Study Drug injection and at one hour post 
Study Drug injection. 
23. The Study Completion/Day 395 Visit (Visit 13) must occur on Day 395 up through +14 days (between Day 395 to 379). For a subject who 
prematurely withdraws from the study (discontinues treatment with no continued follow-up), the Study Completion Visit should be completed within 
14 days of study withdrawal.
24. Specimen drawn and sent to the Central Laboratory.
25. If a Study Drug dose is missed, the 14 day follow up clinical laboratory samples for hematology, biochemistry and hepatic profile should not be 
collected. Scheduled Immunogenicity Labs (Visit 5 & 9) must still be collected.


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IS AMENDED TO: 
1.
Screening may be done from Day -14 up to Randomization, Day 30.  Screening and Randomization can take place on the same day as long as 
Clinical Labs are drawn and results are available on the day of Randomization.  If Screening is done > 3 days prior to Randomization, 
Clinical Labs, urinalysis and urine protein: creatinine ratio must be repeated and available prior to Randomization. Subjects may be 
rescreened due to rescheduling of transplant surgery provided the screening procedures are repeated and fall within the -14 day to + 30-day 
window relative to the Day of Transplant. First study drug dosing must take place within 24 hours of Randomization.
2.
The date of transplant (day of skin closure) defines Day 0 and all visit days are relative to Day 0.  
3.
Subjects are to receive prophylactic valganciclovir or ganciclovir starting within 10 days post transplant through the Day of Randomization to 
prevent CMV disease. (The subject can miss up to two doses of valganciclovir or ganciclovir during this time period for any reason).
Valganciclovir or ganciclovir dose is to be given per the package insert. The subject will then continue is to receive CMV-specific AVP until 100 
days post transplant. Subjects can have CMV-specific AVP interrupted,or dose adjusted or replaced by other CMV-specific AVP per standard of 
care after the Day Randomizationfirst dose of Study Drug if renal function is compromised, or there are toxicities related to the administration of the 
AVP, or for any other medically indicated reason.
4.
Informed consent must be obtained prior to the performance of any study-related procedure and before Randomization.
5.
Subjects will be assigned a subject number for use throughout the study at the Screening Visit via the Interactive Response Technology (IRT) system.
6.
The EQ-5D, Kidney Transplant Questionnaire (KTQ) and the SF-12 v2, should be completed by the subject prior to any other study assessments or 
visit procedures. Subjects should complete these assessments in the following order: EQ-5D first, KTQ second, SF-12 last. For all three patient-
reported outcome measures, i.e. EQ-5D, KTQ, SF-12, the answers must come from the subject. If the subject is unable to fill out the questionnaire, the 
assessment should not be performed. If the subject is unable to answer an individual question, the rest of the questionnaire should still be completed.
7.
Medical history must include demographics, (age, gender, race), diagnosis for renal failure, length of time on dialysis, history of prior kidney 
transplant, and diabetes. 
8.
A complete physical examination (PE) will be conducted at the Screening, Baseline and the Study Completion/Day 395 Visit (V13). At all other visits 
where a PE is performed (Visits 4, 6, 8, 10 and 12); symptom-directed physical examinations may be done. The evaluations conducted at each visit are 
to be performed by the Investigator or qualified medical personnel who routinely perform these evaluations in this patient population. Vital signs will 
be collected immediately prior to Study Drug injection, at 15 minutes and 60 minutes post Study Drug injection. Vital signs include blood pressure, 
pulse rate, respiratory rate and temperature. Height will be collected at the Screening Visit only. Weight will be collected at V1, V2 and at Study 
Completion/Day 395 (Visit 13). If Screening is done > 3 days prior to Randomization, the PE must be repeated at Randomization.
9.
All concomitant medications and therapies administered from 1410 days prior to transplant through the Study Completion Visit (Day 395/Visit 13) 
will be collected on the eCRF. Medications used for anesthesia during the transplant surgery will not be recorded. 
10. Clinical laboratory samples will be drawn at Screening (Visit 1), before each Study Drug injection, at each follow-up time point for the injections, and 
at the last study visit. Clinical labs will be performed by a local laboratory and will include hematology, biochemistry, including a hepatic profile, and
urinalysis with microscopic evaluation and urine protein: creatinine ratio. Screening clinical labs may be re drawn once if initial results would 
preclude Randomization and the Investigator feels out of range results were transient. Results will be entered into the eCRF.  Safety labs 
(hematology, biochemistry, hepatic profile, urine protein: creatinine ratio and urinalysis) drawn by Home Health Care for Investigator sites 
utilizing this service will be analyzed by the Central Laboratory.
11. For all females of childbearing potential, a urine pregnancy test will be performed at Screening, prior to each dose, at Visit 10, 12, and at the Study 
Completion/Day 395 Visit (Visit 13). All pregnancy tests will be done locally. For subjects who receive mycophenolate mofetil (MMF), additional 


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pregnancy testing should be done in accordance with local requirements.
12. CMV serologies must have been performed within 8 weeks prior to transplant.  If CMV serostatus is not available from this time period, CMV 
serostatus may be assessed at the Screening Visit with results available prior to Randomization.
13. AEs and SAEs will be collected from time of signing of informed consent through one year post Study Drug injection [Study Completion Day 395 
Visit (Visit 13)].  AEs should be recorded as a change in medical status or medical history, from the time of signing of the informed consent 
until the first dose of study drug.  SAEs from the time of signing the informed consent will be recorded on the SAE worksheet and reported 
per Section 5.5.6. AEs reported after the first dose will be reported on the AE eCRF.  Note:  The transplant surgery that occurs on Day 0 is 
not considered an AE or an SAE.
14. Transplant information includes type of transplant (Living Related Donor, Living Unrelated Donor, or Deceased Donor).
15. Donor information includes donor demographics, (age, gender, race), viral serologies (CMV [required],) HBV, HCV, EBV, [if available]; and HCV 
PCR RNA [if available]),) ABO blood group and HLA typing. Recipient information includes ABO blood group, HLA typing, HLA cross match at 
time of transplant (as determined by the site’s standard method of determination), and viral serologies (CMV [required],), HBV, HCV and EBV [if 
available], and HCV PCR RNA [if available]).
15. Screening and Randomization can take place on the same day as long as Clinical Labs are drawn and results are available on the day of 
Randomization. If Screening is done > 3 days prior to Randomization, Clinical Labs must be repeated at Randomization.
16. Plasma viral load by both the central and local laboratory will be routinely monitored every other week (+/-3 days) from Day 100 through Day 200, 
then monthly (+/- 5 days) until end of study. Plasma viral load by central and local laboratory will also be assessed for cause in case of suspect CMV 
disease and at least once a week by Central lab from initiation of CMV-specific AVT until the course is completed.   For cause CMV viral loads 
should be performed at a local lab approved by Astellas as Central lab viral load results may not be available in a timely manner to guide 
treatment decisions.  
17. Plasma viral load assessment results performed by the local laboratory will be reported on the eCRF. Local CMV plasma viral load testing may be 
performed only at a local laboratory approved by the Sponsor.  
18. A plasma sample will be drawn and sent to the central lab and results will be reported for CMV genotypic resistance when there is viremia without a 
reduction in viral load after two weeks of treatment with valganciclovir and/or ganciclovir, or when clinical signs and symptoms have not improved 
two weeks after initiating or increasing valganciclovir and/or ganciclovir for CMV viremia or disease or any time resistance to any CMV-specific 
ATV is suspected by the Investigator.
19. Immunogenicity laboratories include collection of blood for the gB antibody and pp65 T-cell assays. Samples should be drawn at Visits 2, 5, 6, 9, 10 
and 13. Visits 2, 6 and 10 are Study Drug injection visits and blood sampling will be collected prior to the Study Drug injection. Samples for T-cell 
assays will not be collected if the Absolute Lymphocyte Count (ALC) is known to be ≤ 500 mm3 by local or central laboratory measurement.   
20. Subjects who consent to participate in the PGx sub study will have a whole blood sample collected during the Baseline Visit (Visit 2), after 
Randomization but prior to the first Study Drug injection.
21. A Study Drug injection should not be given if the subject 1) has been on an anticoagulant within 5 half-lives prior to the injection. (Low dose 
anticoagulants that are used for prevention of deep vein thrombosis are allowed) or 2) has a Temperature ≥100.4◦F or 38◦C (per NCI Grade 1).
22. Local reactogenicity and symptoms of systemic reactogenicity will be evaluated one hour after each injection and then for seven days after each 
injection by subject reporting via diary. After injection in the clinic, the subject must be in direct view of the clinic staff for 15 minutes following each 
injection, then remain in the clinic area for an additional 45 minutes for evaluation of local and systemic reactogenicity.  Vital signs, including 


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temperature, pulse, respiration and blood pressure will be collected just prior to injection, 15 minutes post Study Drug injection and at one hour post 
Study Drug injection. Using the pre-injection vital signs as baseline, if a post Study Drug injection vital sign meets Grade 1-4 criteria per 
Appendix 5, they are to be repeated and confirmed within 5 minutes of the first assessment. 
23. The Study Completion/Day 395 Visit (Visit 13) must occur on Day 395 up through +14 days (between Day 395 to 379). For a subject who 
prematurely withdraws from the study (discontinues treatment with no continued follow-up), the Study Completion Visit should be completed within 
14 days of study withdrawal.
24. Specimen drawn and sent to the Central Laboratory.
25. If a Study Drug dose is missed, the 14 day follow up clinical laboratory samples for hematology, biochemistry, urinalysis and urine protein: 
creatinine ratio and hepatic profile should not be collected. Scheduled Immunogenicity Labs (Visit 5 & 9) must still be collected.


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V. Flow Chart and Schedule of Assessments, Table 2, Schedule of Assessments – Long-
term Follow-up Period
Page 31; footnotes
WAS:
Subjects will be contacted by telephone at 6 months after Day 395, then annually, for the 
next 4 years for long-term safety related to the DNA vaccine. Items to be assessed by 
questionnaire and via retrospective chart review of available medical records. 
*Creatinine values will be recorded if they have been collected within 3 months prior to the 
follow-up telephone contact and are included in the subject’s available medical records.
IS AMENDED TO:
Subjects will be contacted by telephone at 6 months after Day 395, then annually, for the 
next 4 years for long-term safety related to the DNA vaccine. Items are to be assessed by 
questionnaire and via retrospective chart review of available medical records.
During the long-term follow-up period, if an SAE is identified and deemed possibly or 
probably related to the study medication, an SAE report on the SAE worksheet must 
be sent to the sponsor per Section 5.5.6.
*Creatinine values will be recorded if they have been collected within 3 months prior to the 
follow-up telephone contact and are included in the subject’s available medical records.
2.2.1 Study Design
Page 37, 1st paragraph
WAS:
This is a randomized, double-blind, placebo-controlled trial which will enroll 140 CMV-
seronegative recipients of kidney transplant from a CMV-seropositive donor at 80 clinical 
sites. Subjects will be randomized at Day 30 ±3, in relation to the day of transplant, in a 1:1 
ratio to ASP0113 or placebo, and stratified by use of anti-thymocyte globulin (ATG) as 
induction therapy and by receipt of a kidney from a living or deceased donor. The active 
compound will be a vaccine (ASP0113) which contains two plasmids encoding gB and pp65 
each at 2.5 mg/mL, formulated with CRL1005 poloxamer and benzalkonium chloride 
(BAK). 
IS AMENDED TO:
This is a randomized, double-blind, placebo-controlled trial which will enroll 140 CMV-
seronegative recipients of kidney transplant from a CMV-seropositive donor at 80 clinical 
sites. Subjects will be randomized at Day 30 ±3, in relation to the day of transplant, in a 1:1 
ratio to ASP0113 or placebo, and stratified by use of anti-thymocyte globulin (ATG) as 
induction therapyprior to Randomization and by receipt of a kidney from a living or 
deceased donor. The active compound will be a vaccine (ASP0113) which contains two 
plasmids encoding gB and pp65 each at 2.5 mg/mL, formulated with CRL1005 poloxamer 
and benzalkonium chloride (BAK). 


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2.2.1 Study Design
Page 38,4th and 5th paragraphs
WAS:
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) continuously until the day of Randomization to 
prevent CMV disease. Subjects will then continue to receive prophylactic valganciclovir or 
ganciclovir (dose per package insert) to prevent CMV disease until 100 days post transplant.   
Subjects can have CMV-specific AVP  interrupted or dose adjusted per standard of care after 
initiation if renal function is compromised or there are toxicities related to the administration 
of the AVP.
In all subjects, plasma will be collected for central laboratory CMV viral load testing every 
two weeks from Day 100 through Day 200, then monthly through last Study visit Day 395.
In cases where CMV disease (CMV syndrome or CMV tissue-invasive disease) is suspected 
from the first Study Drug injection through Day 395, an additional central and local CMV 
viral load sample will be collected at the time of the first CMV symptom recognition. 
IS AMENDED TO:
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) continuously untilthrough the day of Randomization 
to prevent CMV disease. (The subject can miss up to two valganciclovir or ganciclovir 
doses during this time period for any reason). Subjects will then continue to receive 
prophylacticCMV specific CMV AVP with valganciclovir or ganciclovir (dose per package 
insert) to prevent CMV disease until 100 days post transplant.   Subjects can have CMV
specific AVP  valganciclovir or ganciclovir interrupted or ,dose adjusted or replaced by 
other CMV-specific AVP  per standard of care after initiationthe day of Randomization if 
renal function is compromisedor, there are toxicities related to the administration of the 
AVP. ,or for any other medically indicated reason. In all subjects, plasma will be 
collected for central laboratory CMV viral load testing every two weeks from Day 100 
through Day 200, then monthly through last Study visit Day 395.
In cases where CMV disease (CMV syndrome or CMV tissue-invasive disease) is suspected 
from the first Study Drug injection through Day 395, an additional central and a local CMV 
viral load sample will be collected at the time of the first CMV symptom recognition.  
2.2.1 Study Design
Page 38, 6th paragraph
WAS:
Through Day 395, CMV-specific AVT should be initiated for CMV disease and can be 
initiated for CMV viremia based on the central or local laboratory results and standard of 
care at each institution. If CMV- specific AVT is initiated, a central and local CMV viral 
load will be obtained at a minimum of weekly from the time CMV- specific AVT is initiated 
until discontinuation. 
IS AMENDED TO:


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Through Day 395, CMV-specific AVT should be initiated for CMV disease and can be 
initiated for CMV viremia based on the central or local laboratory results and standard of 
care at each institution. If CMV- specific AVT is initiated, a central and local CMV viral 
load will be obtained at a minimum of weekly from the time CMV- specific AVT is initiated 
until discontinuation. For cause CMV viral loads should be performed at a local lab 
approved by Astellas as Central lab viral load results will not be available in a timely 
manner to guide treatment decisions.
2.2.1 Study Design
Pages 39: 11th and 12th paragraphs
WAS:
Subjects will be followed for one year after first Study Drug injection (Primary Study 
completion/Day 395) for CMV viremia, CMV syndrome, CMV tissue-invasive disease, 
CMV-specific AVT, graft survival, creatinine and subject survival through the Study 
Completion/Day 395 (Visit 13). 
Subjects will be followed for one year after the first Study Drug injection for resistance to 
valganciclovir or ganciclovir. Viral resistance will be measured if the viral load has not 
decreased 2 weeks after initiating CMV-specific AVT or when there is no improvement in 
clinical signs and symptoms two weeks after initiating valganciclovir and/or ganciclovir for 
CMV viremia and/or disease.
IS AMENDED TO:
Subjects will be followed for one year after first Study Drug injection (Primary Study 
completion/Day 395) for CMV viremia, CMV syndrome, CMV tissue-invasive disease, 
CMV-specific AVT, graft survival, creatinine and subject survival through the Study 
Completion/Day 395 (Visit 13). 
Subjects will be followed for one year after the first Study Drug injection for resistance to 
valganciclovir or ganciclovir. Viral resistance will be measured if assessed by a Central lab 
when the viral load has not decreased 2 weeks after initiating CMV specific AVT
orvalganciclovir/ganciclovir, when there is no improvement in clinical signs and symptoms 
two weeks after initiating valganciclovir and/or /ganciclovir foror any time resistance to 
any CMV viremia and/or disease-specific AVT is suspected by the Investigator.
2.2.1 Study Design
Pages 39: 16th paragraph
WAS:
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing 
of the informed consent through one year post Study Drug injection. AEs and SAEs 
occurring from signing of informed consent until just prior to the first dose of Study Drug, 
should be reported as a change in medical status or medical history. 
IS AMENDED TO:
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing 


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of the informed consent through one year post Study Drug injection. AEsand SAEs occurring 
from signing of informed consent until just prior to the first dose of Study Drug, should be 
reported as a change in medical status or medical history. SAE’s from the time of signing 
the informed consent will be recorded on the SAE worksheet and reported per Section 
5.5.6.AE’s reported after the first dose will be reported on the AE eCRF. The 
transplant surgery that occurs on Day 0 is not considered an AE or an SAE.
2.3.1 Primary Efficacy Endpoints
Page 40
WAS:
Incidence of first CMV viremia (defined as plasma viral load of ≥ 250 IU/mL by central 
assay) through one year post first Study Drug injection.
IS AMENDED TO:
Incidence of first CMV viremia (defined as plasma viral load of ≥ 1000250 IU/mL by central 
assay) through one year post first Study Drug injection.
2.3.3 Exploratory Efficacy Endpoints
Page 40-41
WAS:

Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.

Time to first CMV viremia (defined as plasma viral load of ≥ 250 IU/mL by central 
assay) through one year post study first Study Drug injection.

Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection.

Number of episodes of CMV viral load of ≥ 250 IU/mL by central assay through one 
year post first Study Drug injection.

Peak CMV viral load through one year post first Study Drug injection. 

Total CMV viral load through one year post first Study Drug injection.

Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.

Number of episodes of viral resistance to ganciclovir or valganciclovir through one year 
post first Study Drug injection as determined by a central laboratory assay. 

Incidence of biopsy-proven acute rejection (BPAR) through one year post first Study 
Drug injection.

Estimated glomerular filtration rate (eGFR) at the last study visit calculated using the 4 
variable MDRD formula.

Incidence of clinically  treated acute graft rejection  through one year post first Study 
Drug injection.


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
Health economic and outcomes research (HEOR).

Patient-reported outcomes through one year post first Study Drug injection.
o
EuroQol-5 dimensions 5 levels (EQ-5D)
o
Kidney Transplant Questionnaire (KTQ)
o
Short Form Health Survey version 2 (SF-12v2)

Healthcare resource utilization through one year post first Study Drug injection.
Resource use will be collected including the following: concomitant medications and 
procedures, hospitalizations, nonscheduled outpatient/clinic visits, emergency room visits, 
skilled nursing facility care, and hospice care.
IS AMENDED TO:

Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.

Time to first CMV viremia (defined as plasma viral load of ≥ 2501000 IU/mL by central 
assay) through one year post study first Study Drug injection.

Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection.

Number of episodes of CMV viral load of ≥ 2501000 IU/mL by central assay through 
one year post first Study Drug injection.

Peak CMV viral load and area under the curve (AUC) through one year post first 
Study Drug injection. 

Viral load area under the curve (AUC), as a measure of “cumulative Total CMV
viral load” through one year post first Study Drug injection.

Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.

Number of episodes of viral resistance to ganciclovir or valganciclovir through one year 
post first Study Drug injection as determined by a central laboratory assay. 

Incidence of biopsy-proven acute(T or B cell) rejection (BPAR)(Banff 2007 Grade > 1) 
through one year post first Study Drug injection.

Estimated glomerular filtration rate (eGFR) at the last study visit month 13 calculated 
using the 4 variable MDRD formula.

Incidence of clinically treated acute graft rejection through one year post first Study Drug 
injection.

Health economic and outcomes research (HEOR).

Patient-reported outcomes through one year post first Study Drug injection.
o
EuroQol-5 dimensions 5 levels (EQ-5D)
o
Kidney Transplant Questionnaire (KTQ)
o
Short Form Health Survey version 2 (SF-12v2)

Healthcare resource utilization through one year post first Study Drug injection.
Resource use will be collected including the following: concomitant medications and 
procedures, hospitalizations, nonscheduled outpatient/clinic visits, recorded as number of 


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days in the Intensive Care Unit, Step-down Unit, and general medical ward (including
emergency room visits greater than 24 hours), also non -protocol -related physician 
visits and emergency room visits, skilled nursing facility care, and hospice care. of less 
than 24 hours.  
3.2 Inclusion Criteria
Page 42
WAS: 
5. Subject started valganciclovir or ganciclovir (dose per package insert) within 10 days of 
transplant and has received it up to the time of Randomization.
IS AMENDED TO:
5. Subject started valganciclovir or ganciclovir (dose per package insert) within 10 days of 
transplant and has received it through up to the time of Randomization, per regulatory 
label (package insert).
3.3 Exclusion Criteria 
Page 44
WAS:
13. Subject has an AST or ALT greater than 3 x ULN or total bilirubin greater than 2 x ULN 
unless secondary to suspected Gilbert’s disease at Screening.
IS AMENDED TO:
13. Subject, within 3 days prior to Randomization, has an AST or ALT greater than 3 x 
ULN or total bilirubin greater than 2 x ULN unless secondary to suspected Gilbert’s 
disease at Screening. 
5.1 Dosing and Administration of Study Drug(s) and Other Medication(s)
Page 48
WAS: 
One (1) mL of 5 mg/mL ASP0113 or placebo will be administered to the subjects at the 
clinical site via injection in the deltoid muscle, alternating sides with each dose,  if possible. 
Preparation of Study Drug will be described in the Pharmacy Manual for the study. The 
syringes will be masked to maintain the study blind.  
IS AMENDED TO: 
One (1) mL of 5 mg/mL ASP0113 or placebo will be administered to the subjects at the 
clinical site via injection in the deltoid muscle, alternating sides with each dose, if possible. 
Preparation of Study Drug will be described in the Pharmacy Manual for the study. The 
syringes will be masked as described in the Pharmacy Manual to maintain the study blind.  


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5.1.1 Dose/Dose Regimen and Administration Period
Page 49, last paragraph, 1st sentence 
WAS: 
An injection should not be given if the subject has been on an anticoagulant within 5 half-
lives prior to the injection or there is any other contraindication to an intramuscular injection.  
IS AMENDED TO: 
An injection should not be given if, 1) the subject has been on an anticoagulant within 5 half-
lives prior to the injection or there is any other contraindication to an intramuscular injection
or 2) has a Temperature ≥100.4◦F or 38◦C (per NCI Grade 1).  
5.1.3 CMV Prophylactic Therapy
Page 49
WAS:
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) continuously until day of Randomization to prevent 
CMV disease. Subjects will then receive CMV-specific AVP until 100 days post transplant. 
Subjects can have CMV-specific AVP interrupted per standard of care after initiation, if 
renal function is compromised or there are toxicities related to the AVP.
IS AMENDED TO:
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) throughcontinuously until day of Randomization to 
prevent CMV disease. (The subject can miss up to two valganciclovir or ganciclovir 
doses during this time period for any reason). After Randomization, subjects Subjects
will then receive CMV-specific AVP until 100 days post transplant. Subjects can have 
CMV-specific AVP interrupted, dose adjusted or replaced by other CMV-specific AVP 
per standard of care after the day of Randomization, initiation, if renal function is 
compromised, or there are toxicities related to the administration of the AVP or for any 
other medically indicated reason AVP.
5.1.4.3 Prohibited Concomitant Medication
Page 50, bullet points 1-3
WAS:

Investigational research products through completion of Day 395 visit (Visit 13).

Alemtuzumab through completion of the Day 395 visit (Visit 13).

Rituximab through completion of the Day 395 visit (Visit 13) except for Post-Transplant 
Lymphoproliferative Disorder (PTLD).  
IS AMENDED TO:

Investigational research products through completion of Day 395 visit (Visit 13).


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
Alemtuzumab through completion of the Day 395 visit (Visit 13).

Rituximab through completion of the Day 395 visit (Visit 13) except for Post Transplant 
Lymphoproliferative Disorder (PTLD).  

Planned alemtuzumab and, anti-CD20 antibodies (including rituximab) eculizumab 
or bortezomib are not allowed from the Day of Randomization through the Primary 
Study Period (Day 395).  These treatments may be given after the Day of 
Randomization if clinically indicated.
5.1.4.4 Concomitant Medication (Drugs and Therapies)
Page50
WAS:
All concomitant medications, immunosuppressive agents and therapies administered from 
10 days prior to transplant through the Primary Treatment Period (Visit 13/Day 395) will be 
recorded at each study visit on the eCRF. Subjects should be instructed not to take any new 
medications or change the dose and frequency of their ongoing medications throughout the 
study period without consulting the investigator.
Medications used for anesthesia purposes will not be recorded. 
IS AMENDED TO:
All concomitant medications, immunosuppressive agents and therapies administered from 
1410 days prior to transplant through  the Primary Treatment Period (Visit 13/Day 395) will 
be recorded at each study visit on the eCRF. Subjects should be instructed not to take any 
new medications or change the dose and frequency of their ongoing medications throughout 
the study period without consulting the investigator.
Medications used for anesthesia purposes during the transplant will not be recorded.
5.2.4 Donor Information
Page 51
WAS
Demographics, (age, gender, race)
Viral Serologies (CMV required, HBV, HCV, EBV, if available)
ABO blood group
HLA typing
IS AMENDED TO:
Demographics, (age, gender, race)
Viral Serologies; (CMV (required), HBV, HCV, EBV (if available) and HCV PCR RNA, 
(if available)
ABO blood group
HLA typing


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5.2.5 Recipient Information 
Page 51
WAS
ABO blood group
HLA typing
HLA cross match at time of transplant (as determined by the site’s standard method of  
determination)
Viral Serologies (CMV required, HBV, HCV, EBV, if available)
IS AMENDED TO:
ABO blood group
HLA typing
HLA cross match at time of transplant (as determined by the site’s standard method of  
determination)
Viral Serologies (CMV (required), HBV, HCV, EBV, (if available), and HCV PCR RNA, 
(if available)
5.3.3 Exploratory Efficacy Assessments 
Page 52; 6th bullet point
WAS
●
eGFR at Month 13/Day 395
IS AMENDED TO:
●
eGFR at Month 13/Day 395 the last study visit
5.3.4.4 Health Economic Assessment (HEA) 
Page 54
WAS
Health Economic Assessments will include the following: concomitant medications and 
procedures, hospitalizations, nonscheduled clinic visits, emergency room visits, skilled 
nursing facility care, and hospice care. The information will be collected by the site via a 
retrospective review of the subject’s medical record. HEA data will include both data being 
routinely captured for the subject (e.g., concomitant medications) as well as data that will be 
used specifically for these analyses (e.g., information on hospitalizations) (Appendix 18).
IS AMENDED TO:
Health Economic Assessments will include the following: concomitant medications and 
procedures, hospitalizations, nonscheduled clinic visits, recorded as number of days in the 
Intensive Care Unit, Step-down Unit, and general medical ward, (including emergency 
room visits, skilled nursing facility care, greater than 24 hours) also non-protocol- related 
physician visits and hospice care.emergency room visits less than 24 hours.  The 
information will be collected by the site via a retrospective review of the subject’s medical 
record. HEA data will include both data being routinely captured for the subject (e.g., 


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concomitant medications) as well as data that will be used specifically for these analyses 
(e.g., information on hospitalizations) (Appendix 18).
5.4.1 Vital Signs 
Page 54
WAS: 
Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate and temperature) 
will be collected at all dosing visits, and at Screening (V1), and at V12 and 13. Height will 
be collected at Screening only. Weight will be collected at V1 and Study Completion (V13).
IS AMENDED TO: 
Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate and temperature) 
will be collected at all dosing visits, and at Screening (V1), and at V12 and 13. Height will 
be collected at Screening only. Weight will be collected at V1, V2 and Study Completion 
(V13).
5.4.2 Adverse Events
Page 55, 2nd paragraph
WAS
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing 
of the informed consent through one year post Study Drug injection. AEs and SAEs should 
be reported as a change in medical status or medical history from time of signing of informed 
consent through first dose of Study Drug. 
IS AMENDED TO:
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing 
of the informed consent through one year post Study Drug injection. AEs from the time of
signing of informed consent through first dose of Study Drug should be captured on the 
medical history eCRF. If the AE is deemed possibly or probably related to Study 
Procedures prior to the first Study Drug injection, it will be recorded on the AE eCRF 
page.  SAEs that occur from the signing of the informed consent form will be reported 
as per Section 5.5 and captured on the AE eCRF page.  AEs and SAEs after the first 
dose of Study Drug should be captured on the AE eCRF page. AEs and SAEs should be 
reported as a change in medical status or medical history from time of signing of informed 
consent through first dose of Study Drug. 
5.4.4 Systemic Reactogenicity Assessments
Page 55-56
WAS: 
Specific signs of systemic reactogenicity will be evaluated one hour after each injection 
(Appendix 5). The subject must be in direct view of the clinic staff for 15 minutes following 
each injection, then remain in the clinic area for an additional 45 minutes for evaluation of 


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systemic reactogenicity.  Vital signs, including temperature, pulse, respiration and blood 
pressure will be collected just prior to injection, 15 minutes post-injection and at one hour 
post-injection. Systemic measurements that will be followed for 7 days are fever, fatigue and 
myalgia.  
WAS AMENDED TO: 
Specific signs of systemic reactogenicity will be evaluated one hour after each injection 
(Appendix 5). The subject must be in direct view of the clinic staff for 15 minutes following 
each injection, then remain in the clinic area for an additional 45 minutes for evaluation of 
systemic reactogenicity.  Vital signs, including temperature, pulse, respiration and blood 
pressure will be collected just prior to injection, 15 minutes post-injection and at one hour 
post-injection. Using the pre-injection vital signs as baseline, if a post Study Drug 
injection vital sign meets Grade 1-4 criteria per Appendix 5, it is to be repeated and 
confirmed within 5 minutes of first assessment.  Systemic measurements that will be 
followed for 7 days are fever, fatigue and myalgia.  
5.4.5 Laboratory Assessments
Page 56, 3rd bullet point
WAS

Local laboratory values for CMV viral load should be collected and documented in the 
eCRF for subjects whenever AVT for CMV disease (CMV syndrome or CMV tissue-
invasive disease) is suspected within the first 12 months post first Study Drug injection, 
when CMV-specific AVT is initiated and at a minimum of weekly from the time CMV 
specific AVT is initiated until discontinuation.
IS AMENDED TO:

Local laboratory values for CMV viral load should be collected and documented in the 
eCRF for subjects whenever AVT for CMV disease (CMV syndrome or CMV tissue-
invasive disease) is suspected within the first 12 months post first Study Drug injection 
and, when CMV-specific AVT is initiated and at a minimum of weekly from the time 
CMV specific AVT is initiated until discontinuation.
5.4.5 Laboratory Assessments
Page 56, 4th bullet point
ADDED:

If CMV AVT is initiated, Central lab CMV viral loads will be collected at a 
minimum of weekly from the time CMV specific AVT is initiated until 
discontinuation. Note:  Central Lab turnaround time is estimated to be at least 3 
days from receipt at the Central lab, not including holidays. If treatment decisions 
need to be made a local CMV viral load should be collected and analyzed at an 
Astellas approved laboratory.  
5.4.5 Laboratory Assessments


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Page 57; Local Laboratory Samples as follows per the Schedule of Assessments, Table 1:  
2nd bullet point
WAS: 

Biochemistry: sodium, potassium, calcium, chloride, glucose, blood urea nitrogen 
(BUN), creatinine, CPK/CK, total protein, albumin. 
IS AMENDED TO: 

Biochemistry: sodium, potassium, calcium, chloride, phosphorus, glucose, blood urea 
nitrogen (BUN), creatinine, CPK/CK, total protein, albumin. 
5.4.5 Laboratory Assessments
Page 57; Local Laboratory Samples as follows per the Schedule of Assessments, Table 1: 6th
bullet point
ADDED:

Urine protein: creatinine ratio
5.4.5 Laboratory Assessments
Page 58, last bullet point
ADDED:

Safety labs (hematology, biochemistry, hepatic profile, urine protein: creatinine 
ratio and urinalysis) drawn by Home Health Care for Investigator sites utilizing
this service will be analyzed by the Central Laboratory.
5.4.7 Home Health Care Service
Page 58; 2nd bullet point
WAS: 

CMV Plasma Viral Load Testing Visits (Central Laboratory Testing) at Day 100, 128, 
142, 170, 198, 230, 290, 320, 350 and 380. (Days 100 and 198 visit windows 
correspond with Visits 3 and 11.)
IS AMENDED TO:

CMV Plasma Viral Load Testing Visits (Central Laboratory Testing) at Day 100, 114,
128, 142, 156, 170, 198, 230, 290, 320, 350, and 380. (Days 100 and 198 visit windows
CMV testing must correspond appropriately with visit windows for Visits 3 and 11.)
in order to be combined).  
5.4.8 Long Term Follow-Up
Page 58
ADDED:
During the long-term follow-up period, if an SAE is identified and deemed possibly or 
probably related to the study medication, an SAE report on the SAE worksheet must 


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be sent to the sponsor per Section 5.5.6.
5.5.1 Definition of Adverse Events (AEs)
Page 59; 5th bullet point
ADDED:

The transplant surgery that occurs on Day 0 is not considered an AE or an SAE.
5.5.3 Definition of Serious Adverse Events (SAEs)
Page 60; 7th bullet point 
ADDED:

The transplant surgery that occurs on Day 0 is not considered an AE or an SAE.
5.5.6 Reporting of Serious Adverse Events (SAEs)
Page 62; 1st paragraph after bullet points
ADDED:
Spontaneously reported possibly or probably related SAEs that occur outside of the 
study-defined SAE reporting period, i.e., the Long Term Follow-up, should also be 
sent to the sponsor in accordance with the protocol defined SAE reporting guidelines.  
5.7.1 Blood Sample for Future PGx Analysis (Retrospective PGx Analysis)
Page 64-65
WAS: 
A PGx research may be conducted in the future to analyze or determine genes of relevance 
to clinical response, pharmacokinetics, and toxicity/safety issues. After randomization, but 
prior to the first dose of Study Drug (see schedule of assessments), subjects who consent to 
participate in the retrospective pharmacogenomics assessment will have a 5 mL sample of 
whole blood for possible retrospective PGx analysis will be collected using a vacutainer 
tube containing EDTA. After collection, gently invert the blood sample 8 to 10 times. The 
blood collection tube may either be stored upright at 4°C for up to 5 days prior to shipment 
or stored frozen at -20°C or below at the site for extended storage. Samples will be shipped 
to a Sponsor designated banking CRO.
IS AMENDED TO:
A PGx research study may be conducted in the future to analyze or determine genes of 
relevance to clinical response, pharmacokinetics, and toxicity/safety issues. After 
randomization, but prior to the first dose of Study Drug (see schedule of assessments), 
subjects who consent to participate in the retrospective pharmacogenomics assessment will 
have a 5 mL sample of whole blood collected for possible retrospective PGx analysis. This 
sample will be collected using a vacutainer tube containing EDTA. After collection, gently 
invert the blood sample 8 to 10 times. The blood collection tube may either be stored 
upright at 4°C for up to 5 days prior to shipment or stored frozen at -20°C or below at the 


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site for extended storage. Samples will be shipped to a Sponsor designated banking CRO.
6.1.1 Study and Treatment Discontinuation  
Page 66
WAS:
Treatment Only Discontinuation:
Subjects will be withdrawn from study treatment if any of the following occur, however, 
they should continue to be followed according to the protocol Schedule of Assessments 
(Table 1). 
•
Investigator’s decision that further treatment is not in the best interest of the subject.
•
Graft failure.
•
Pregnancy (female subjects only).
•
Local reactogenicity with a grade ≥ 3 based on the criteria defined in Appendix 4 and is 
confirmed by the investigator and reported as a Drug Related Adverse Event.
•
Systemic reactogenicity, for any grade ≥ 3 fever or any grade 4 systemic reaction within 
one week of vaccination and is confirmed by the investigator and reported as a Drug 
Related Adverse Event (Appendix 5). 
Subjects who discontinue treatment for these or for other reason(s) but did not withdraw 
consent should remain in the study and continue to be followed according to the visit 
schedule through the Long-term Follow-up Period. All study procedures should be 
completed for these subjects, with the exception of the post-dose Day 14 safety laboratory 
and reactogenicity assessments/visits for those doses that are not given. Subjects not willing 
to participate in the study procedures should be asked if they would be willing to be 
followed annually for mortality through the Long-term Follow-up Period. 
IS AMENDED TO: 
Study and Treatment Discontinuation:
Subjects will be withdrawn from investigational study treatment and all follow- up 
assessments and will only be followed for mortality through public records if the 
following occurs:  

Withdrawal of consent by the subject.
Treatment Only Discontinuation:
Subjects will be withdrawn from investigational study treatment if any of the following 
occur, however, they should continue to be followed according to the protocol Schedule of 
Assessments (Table 1) and Long Term Follow-up Schedule of Assessments, except post-
dose Day 14 safety and laboratory and reactogenicity assessments/visits for those doses 
not given. 
•
Investigator’s decision that further treatment is not in the best interest of the subject.
•
Graft failure.
•
Pregnancy (female subjects only).
•
Local reactogenicity with a grade ≥ 3 based on the criteria defined in Appendix 4 and is 
confirmed by a health care professional the investigator and reported as a Drug 


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Related Adverse Event.
•
Systemic reactogenicity, for any grade ≥ 3 fever or any grade 4 systemic reaction within 
one week of vaccination and is confirmed by a health care professional professional 
the investigator and reported as a Drug Related Adverse Event (Appendix 5). 
•
Anaphylaxis Grade > 3 per NCI ver. 4.03 criteria.
Subjects who discontinue investigational treatment for these or for other reason(s) but do
did not withdraw consent should remain in the study and continue to be followed according 
to the visit schedule through the Long-term Follow-up Period. All study procedures should 
be completed for these subjects, with the exception of the post-dose Day 14 safety 
laboratory and reactogenicity assessments/visits for those doses that are not given. Subjects 
not willing to participate in the study procedures should be asked if they would be willing to 
be followed annually for mortality through the Long-term Follow-up Period. 
7 STATISTICAL METHODOLOGY
Page 66
WAS: 
A Statistical Analysis Plan (SAP) will be written by the responsible biostatistician of APGD 
to provide details of the analysis, along with specifications for tables, listings and figures to 
be produced. The SAP will be finalized before the database soft lock at the latest.
IS AMENDED TO: 
A Statistical Analysis Plan (SAP) will be written by the responsible biostatistician of APGD 
to provide details of the analysis, along with specifications for tables, listings and figures to 
be produced. The SAP will be finalized before the database soft lock at the latest.
7.4.1.1 Primary Analysis
Page 68; 1st paragraph of section
WAS:
The primary efficacy endpoint, the incidence of CMV viremia (defined as plasma viral load
≥250 IU/mL by central assay) through one year post first Study Drug injection, in subjects 
receiving a kidney from a living or deceased donor, will be analyzed using the Cochran-
Mantel-Haenszel (CMH) test stratified by use of anti-thymocyte globulin (ATG) as 
induction therapy and by receipt of a kidney from a living or deceased donor.
IS AMENDED TO: 
The primary efficacy endpoint, the incidence of CMV viremia (defined as plasma viral load
≥1000250 IU/mL by central assay) through one year post first Study Drug injection, in 
subjects receiving a kidney from a living or deceased donor, will be analyzed using the
Cochran-Mantel-Haenszel (CMH) test stratified by use of anti-thymocyte globulin (ATG) as 
induction therapy and by receipt of a kidney from a living or deceased donor. 
7.4.3 Analysis of Exploratory Endpoints


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Page 69-70
WAS:
The exploratory endpoints in this study include: 
•
Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.
•
Time to first CMV viremia (defined as plasma viral load of ≥ 250 IU/mL by central 
assay) through one year post first Study Drug injection.
•
Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection. 
•
Number of episodes of CMV viral load of ≥ 250 IU/mL by central assay through one 
year post first Study Drug injection.
•
Peak CMV viral load through one year first Study Drug injection.
•
Total viral load through one year post first Study Drug injection.
•
Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.
•
Incidence of viral resistance to ganciclovir or valganciclovir through one year post 
Study Drug injection as determined by a central laboratory assay. 
•
Incidence of biopsy-proven acute rejection (BPAR) through one year post Study Drug 
injection.
•
Estimated glomerular filtration rate (eGFR) at month 13 calculated using the 4 variable 
MDRD formula.
•
Incidence of clinically treated acute graft rejection rate through one year post Study 
Drug injection.
•
Health economic and outcomes research (HEOR) scores.
•
Patient-reported outcomes:
o
EQ-5D (EuroQol-5 dimensions 5 levels) will be used as a preference-based 
utility measure of patients’ quality of life.
o
KTQ (Kidney Transplant Questionnaire) will be used to evaluate transplant-
specific patients’ quality of life. 
o
SF-12v2 (Short Form Health Survey version 2) will be used to evaluate the 
overall patients’ quality of life. 
•
Healthcare resource utilization:
o
Resource use will be collected including the following: concomitant medications 
and procedures, hospitalizations, nonscheduled clinic visits, emergency room 
visits, skilled nursing facility care, hospice care. 
Number of episodes of CMV viral load of ≥ 250 IU/mL and number of episodes of 
adjudicated CMV-associated disease will each be compared between treatments using 
Poisson regression controlling for follow-up period and stratification factors.
The incidence endpoints will be each analyzed using CMH method described in 7.4.1.1.
The survival endpoints (time to first event) will be each analyzed in a Cox proportional 
hazards model. The Cox model will include the randomization factors. The common hazard 
ratio and confidence limits will be estimated. The 1-sided p-values for testing the hypothesis 
that the hazard ratio is equal to unity will be calculated. The Kaplan-Meier estimates of 
survival curves for the treatment groups will be displayed.  
Peak CMV viral load and total CMV viral load through one year post first Study Drug 


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injection will be compared using Wilcoxon rank-sum tests.
IS AMENDED TO: 
The exploratory endpoints in this study include: 
•
Number of opportunistic infections other than CMV through one year post first Study 
Drug injection.
•
Time to first CMV viremia (defined as plasma viral load of ≥ 1000250 IU/mL by central 
assay) through one year post first Study Drug injection.
•
Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue-
invasive disease, through one year post first Study Drug injection. 
•
Number of episodes of CMV viral load of ≥ 1000250 IU/mL by central assay through 
one year post first Study Drug injection.
•
Peak CMV viral load through one year first Study Drug injection.
•
Viral load area under the curve (AUC), as a measure of “cumulative Total viral 
load” through one year post first Study Drug injection.
•
Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.
•
Incidence of viral resistance to ganciclovir or valganciclovir through one year post 
Study Drug injection as determined by a central laboratory assay. 
•
Incidence of biopsy-proven (T or B cell)acute rejection (BPAR)(Banff 2007 Grade >
1) through one year post Study Drug injection.
•
Estimated glomerular filtration rate (eGFR) at the last study visit calculatedmonth 13 
calculated using the 4 variable MDRD formula.
•
Incidence of clinically treated acute graft rejection rate through one year post Study 
Drug injection.
•
Health economic and outcomes research (HEOR) scores.
•
Patient-reported outcomes:
o
EQ-5D (EuroQol-5 dimensions 5 levels) will be used as a preference-based 
utility measure of patients’ quality of life.
o
KTQ (Kidney Transplant Questionnaire) will be used to evaluate transplant-
specific patients’ quality of life. 
o
SF-12v2 (Short Form Health Survey version 2) will be used to evaluate the 
overall patients’ quality of life. 
•
Healthcare resource utilization:
o
Resource use will be collected including the following: hospitalizations 
recorded as number of days in the Intensive Care Unit, Step-down Unit, and 
general medical ward, (including emergency room visits greater than 24 
hours);) also non-protocol- related physician visits and emergency room 
visits less than 24 hours concomitant medications and procedures, 
hospitalizations, nonscheduled clinic visits, emergency room visits, skilled 
nursing facility care, hospice care.


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Number of episodes of CMV viral load of ≥ 1000250 IU/mL and number of episodes of 
adjudicated CMV-associated disease will each be compared between treatments using 
Poisson regression controlling for follow-up period and stratification factors.
The incidence endpoints will be each analyzed using CMH method described in 7.4.1.1.
The survival endpoints (time to first event) will be each analyzed in a Cox proportional 
hazards model. The Cox model will include the randomization factors. The common hazard 
ratio and confidence limits will be estimated. The 1-sided p-values for testing the hypothesis 
that the hazard ratio is equal to unity will be calculated. The Kaplan-Meier estimates of 
survival curves for the treatment groups will be displayed.  
Peak CMV viral load and AUCtotal CMV viral load through one year post first Study Drug 
injection will be compared using Wilcoxon rank-sum tests.
7.6.1 Adverse Events
Page 72; 8th paragraph 
WAS: 
Subgroups analyses for age group (< 65, ≥ 65), race group (white, black, other), sex (male, 
female), deceased donor criteria (DCD, non-DCD), and the use of anti-thymocyte globulin 
(ATG) as induction therapy criteria (yes/no) will be performed for the following summaries:
IS AMENDED TO:  
Subgroups analyses for age group (< 65, ≥ 65), race group (white, black, other), sex (male, 
female), deceased donor criteria (DCD, non DCD), and the use of anti-thymocyte globulin 
(ATG) as induction therapy criteria (yes/no) will be performed for the following summaries:
7.6.2 Clinical Laboratory Evaluation
Page 73; 5th paragraph 
WAS: 
Subgroups analyses for age group (< 65, ≥ 65), race group (white, black, other), sex (male, 
female), deceased donor criteria (DCD, non-DCD), and the use of anti-thymocyte globulin 
(ATG) as induction therapy criteria (yes/no) will be performed for the following summaries:
IS AMENDED TO:  
Subgroups analyses for age group (< 65, ≥ 65), race group (white, black, other), sex (male, 
female), deceased donor criteria (DCD, non DCD), and the use of anti-thymocyte globulin 
(ATG) as induction therapy criteria (yes/no) will be performed for the following summaries:
7.6.3 Vital Signs Evaluation 
Page 73; 3rd paragraph 
WAS: 
The analysis of vital signs described above will also be performed by the following 
subgroups: age group (< 65, ≥ 65), race group (white, black, other), sex (male, female), 
deceased donor criteria (DCD, non-DCD), and the use of anti-thymocyte globulin (ATG) as 


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induction therapy criteria (yes/no).
IS AMENDED TO:  
The analysis of vital signs described above will also be performed by the following 
subgroups: age group (< 65, ≥ 65), race group (white, black, other), sex (male, female), 
deceased donor criteria (DCD, non DCD), and the use of anti-thymocyte globulin (ATG) as 
induction therapy criteria (yes/no).
12.1 Appendix 1: List of Excluded Concomitant Medications 
Page 85
WAS:  
●
Investigational research products through completion of Day 395 visit (Visit 13)
●
Alemtuzumab through completion of the Day 395 (Visit 13).
●
Rituximab through completion of the Day 395 visit (Visit 13), except for Post-Transplant 
Lymphoproliferative Disorder.
●
Prophylactic use of CMV immunoglobulin. 
●
Live attenuated vaccines within one month (30 days) prior to each dose of Study Drug.
●
Subunit or killed vaccines within 14 days before any Study Drug injection. 
●
Anticoagulants, within 5 half-lives of Study Drug administration, including but not 
limited to vitamin K antagonists, heparin or its derivatives, low molecular weight 
heparin, factor X inhibitors, or thrombin inhibitors. Low dose anticoagulants that are 
used for prevention of deep vein thrombosis and antiplatelet agents are allowed.
IS AMENDED TO:
●
Investigational research products through completion of Day 395 visit (Visit 13)
●
Alemtuzumab through completion of the Day 395 (Visit 13).
●
Rituximab through completion of the Day 395 visit (Visit 13), except for Post Transplant 
Lymphoproliferative Disorder.
●
Planned Alemtuzumab and, anti-CD20 antibodies (including rituximab), 
eculizumab or bortezomib  are not allowed from Day of Randomization through  
the Primary Study Period (Day 395).  These treatments may be given after the Day 
of Randomization if clinically indicated.
●
Prophylactic use of CMV immunoglobulin. 
●
Live attenuated vaccines within one month (30 days) prior to each dose of Study Drug.
●
Subunit or killed vaccines within 14 days before any Study Drug injection. 
●
Anticoagulants, within 5 half-lives of Study Drug administration, including but not 
limited to vitamin K antagonists, heparin or its derivatives, low molecular weight 
heparin, factor X inhibitors, or thrombin inhibitors. Low dose anticoagulants that are 
used for prevention of deep vein thrombosis and antiplatelet agents are allowed.
12.2 Appendix 2: Laboratory Tests 
Page 87




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12.10 Appendix 10: Liver Safety Monitoring and Assessment 
Page98, 1st paragraph
WAS: 
Any subject enrolled in a clinical study with active drug therapy and reveals an increase of 
serum aminotransferases (AT) to > 3 × ULN, or bilirubin > 2 × ULN, should undergo 
detailed testing for liver enzymes (including at least ALT, AST, ALP, and TBL). Testing 
should be repeated within 48-72 hours of notification of the test results. For studies for 
which a central laboratory is used, alerts will be generated by the central lab regarding 
moderate and severe liver abnormality to inform the investigator, study monitor and study 
team. Subjects should be asked if they have any symptoms suggestive of hepatobiliary 
dysfunction.
IS AMENDED TO: 
Any subject enrolled in a clinical study with active drug therapy who reveals an increase of 
serum aminotransferases (AT) to > 3 × baseline value and greater than 3X ULN, or 
bilirubin > 2 × baseline value and greater than 2X ULN, should undergo detailed testing 
for liver enzymes (including at least ALT, AST, ALP, and TBL). Testing should be repeated 
within 48-72 hours of notification of the test results. For studies inforin which a central 
laboratory is used, alerts will be generated by the central lab regarding moderate and severe 
liver abnormality to inform the investigator, study monitor and study team. As local 
laboratories are utilized for this study, the investigator must report a repeat 
confirmation of moderate or severe liver abnormalities to the Medical Monitor within 
48-72 hours of the test results. Subjects should be asked if they have any symptoms 
suggestive of hepatobiliary dysfunction.
12.10 Appendix 10: Liver Safety Monitoring and Assessment 
Page 98, Definition of Liver Abnormalities, 1st paragraph 
WAS: 
Confirmed abnormalities will be characterized as moderate and severe where ULN:
ALT or AST
Total Bilirubin
Moderate
> 3× ULN
or
> 2× ULN
Severe*
> 3× ULN
and
> 2× ULN
IS AMENDED TO:  
Confirmed abnormalities will be characterized as moderate and severe where ULN:
ALT or AST
Total Bilirubin
Moderate
> 3× baseline 
value & > 3 x
ULN 
or
> 2× baseline value 
& > 3 x ULN
Severe*
> 3× baseline 
value & > 3 x
ULN
and
> 2× baseline value 
& > 3 x ULN


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ISN/Protocol 0113-CL-2001
- CONFIDENTIAL -
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
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Version 3.0, Incorporating Substantial Amendment 2
12.16 Appendix 16: Retrospective Pharmacogenomics (PGx) Sub-Study
Page 110, 1st and 2nd paragraphs 
WAS: 
PGx research aims to provide information regarding how naturally occurring changes in a 
subject’s gene and/or expression based on genetic variation may impact what treatment 
options are best suited for the subject. Through investigation of PGx by technologies such 
as genotyping, gene sequencing, statistical genetics and Genome-Wide Association Studies 
(GWAS), the relationship between gene profiles and a drug’s kinetics, efficacy or toxicity 
may be better understood. As many diseases may be influenced by one or more genetic 
variations, PGx research may identify which genes are involved in determining the way a 
subject may or may not respond to a drug.
OBJECTIVES
The PGx research that may be conducted in the future with acquired blood samples is 
exploratory. The objective of this research will be to analyze or determine genes of 
relevance to clinical response, pharmacokinetics, and toxicity/safety issues.
IS AMENDED TO: 
PGx research aims to provide information regarding how naturally occurring changes in a 
subject’s gene and/or expression based on genetic variation may impact what treatment 
options are best suited for the subject. Through investigation of PGx by technologies such 
as genotyping, gene sequencing, statistical genetics and Genome-Wide Association Studies 
(GWAS), the relationship between gene profiles and a drug’s kinetics, efficacy or toxicity 
may be better understood. As many diseases may be influenced by one or more genetic 
variations, PGx research may identify which genes are involved in determining the way a 
subject may or may not respond to a drug.
OBJECTIVES
The PGx research that may be conducted in the future with acquired blood samples is 
exploratory. The objective of this research will be to analyze or determine genes of 
relevance to clinical response, pharmacokinetics, and toxicity/safety issues.
12.16 Appendix 16: Retrospective Pharmacogenomics (PGx) Sub-Study
Page 111, last paragraph 
WAS:
Exploratory PGx analysis may be conducted following the conclusion of the clinical study, 
if applicable. The results of the genetic analysis will not be provided to any investigators or 
subjects, nor can the results be requested at a later date. Any information that is obtained 
from the PGx analysis will be the property of Astellas. 
IS AMENDED TO: 
ExploratoryRetrospective PGx analysis may be conducted following the conclusion of the 
clinical study, if applicable. The results of the genetic analysis will not be provided to any 
investigators or subjects, nor can the results be requested at a later date. Any information 


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL -
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 173 of 177
Version 3.0, Incorporating Substantial Amendment 2
that is obtained from the PGx analysis will be the property of Astellas. 
12.17 Appendix 17: Long-term Follow-up Questionnaire 
Page112, 1st paragraph 
WAS: 
Subjects will be contacted by telephone annually for 5.5 years starting at 1.5 years after the 
first injection of Study Drug to evaluate for long-term safety related to the DNA vaccine. 
Items to be assessed by questionnaire and available medical records include mortality, 
development of any new cancer, development of infection requiring hospitalization, graft 
survival, creatinine and local immune-mediated reactions. 
IS AMENDED TO:
Subjects will be contacted by telephone annually for 5.54 years starting at 1.5 years after the 
first injection of Study Drug to evaluate for long-term safety related to the DNA vaccine. 
Items to be assessed by questionnaire and available medical records include mortality, 
development of any new cancer, development of infection requiring hospitalization, graft 
survival, creatinine and local immune-mediated reactions.  
During the long-term follow-up period, if an SAE is identified and deemed possibly or 
probably related to the study medication, an SAE report on the SAE worksheet must 
be sent to the sponsor per Section 5.5.6. 
12.18 Appendix 18: Health Economic Assessment (Inpatient and Outpatient 
Utilization)
Page113-114
WAS: 
Are there any Inpatient Care visits to report? Yes 
No
If Yes, Date of Admission
(dd/MMM/yyyy)
Admission Unit/Floor (Choose one only)
ICU
Hospital Ward
Nursing Home/Long Term Care Facility
Skilled Nursing Facility
Rehabilitation Center
Private Residence with Home Health Care
Home with Hospice
Home without any Services
Other: ______________(Please specify)


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ISN/Protocol 0113-CL-2001
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EudraCT number 2013-000464-29
06 Jan 2014
Astellas
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Version 3.0, Incorporating Substantial Amendment 2
Primary Reason (Diagnosis) for Admission or Transfer:_____________
ICD-9 (for US sites only):
Date of Discharge
dd/MMM/yyyy
Discharge Unit/Floor (Choose one only)
ICU
Hospital Ward
Nursing Home/Long Term Care Facility
Skilled Nursing Facility
Rehabilitation Center
Private Residence with Home Health Care
Home with Hospice
Home without any Services
Other: ______________(Please specify)
Are there any Outpatient Care visits to report? Yes 
No
If Yes, Date of Visit
(dd/MMM/yyyy)
Place of Service (Choose one only)
Emergency Room visits (without admittance)
Physician Visits
Outpatient Lab/Radiology visits
Outpatient (Physical/Speech, etc.) Therapy Center
Other: ______________(Please specify)
IS AMENDED TO:
Are there any Inpatient Care visits to report? Yes 
No
If Yes, Dateplease record the number of days the patient was admitted to: Admission
(dd/MMM/yyyy)  
Admission Unit/Floor (Choose one only)
ICU Days_____________
            # of Days
Step-down Unit Days______________
                              # of Days


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06 Jan 2014
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Version 3.0, Incorporating Substantial Amendment 2
     Hospital General Medical/Surgical Ward Days_____________
                                                              # of Days
Nursing Home/Long Term Care Facility
Skilled Nursing Facility
Rehabilitation Center
Private Residence with Home Health Care
Home with Hospice
                             Home without any Services
Other: ______________(Please specify)
Was there an Emergency Room visit greater than 24 hours (without admittance)?  
Yes  No
If yes, please indicate the number of Emergency Room days____________
                     
# of days
Primary Reason (Diagnosis) for Admission:___________________ or 
Transfer:_____________
                                    If a US site, please insert the ICD-9 (code for the diagnosis. US 
sites only):
Date of Discharge
dd/MMM/yyyy
Discharge Unit/Floor (Choose one only)
ICU
Hospital Ward
Nursing Home/Long Term Care Facility
Skilled Nursing Facility
Rehabilitation Center
Private Residence with Home Health Care
Home with Hospice
                             Home without any Services
Other: ______________(Please specify)
If more than one Inpatient Care visit to report, please record diagnosis/ICD-9 code for 
each admission, and the number of days as noted above.


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ISN/Protocol 0113-CL-2001
- CONFIDENTIAL -
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
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Version 3.0, Incorporating Substantial Amendment 2
Are there any Outpatient Care Non- Protocol- related Physician visits to report?
Yes 
No
If Yes please indicate the number of Visits: Date of Visit (dd/MMM/yyyy) 
Place of Service (Choose one only)
Emergency Room (without admittance)
Physician Visits_____________
                                                                                  # of visits
Outpatient Lab/Radiology visits
Outpatient (Physical/Speech, etc.) Therapy Center
Other: ______________(Please specify)


Sponsor: APGD
ISN/Protocol 0113-CL-2001
- CONFIDENTIAL -
EudraCT number 2013-000464-29
06 Jan 2014
Astellas
Page 177 of 177
Version 3.0, Incorporating Substantial Amendment 2
[GPF V4.0]
14
SPONSOR’S SIGNATURES                



SAP_001.pdf: 
Sponsor: APGD
SAP Final Version 2
ISN/Protocol ASP0113-CL-2001
Astellas
Page 1 of 42
STATISTICAL ANALYSIS PLAN
Final Version 1, 15 April 2014
Final Version 2, 28 July 2016
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial 
to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, 
in Cytomegalovirus (CMV)-Seronegative Kidney Transplant 
Recipients Receiving an Organ from a CMV-Seropositive Donor
ISN: ASP0113-CL-2001
IND number: 11381
EudraCT 2013‐000464‐29
Astellas Pharma Global Development, Inc. (APGD)
1 Astellas Way
Northbrook, IL 60062
This confidential document is the property of the sponsor.  No unpublished information 
contained in this document may be disclosed without prior written approval of the sponsor.


Sponsor: APGD
SAP Final Version 2
ISN/Protocol ASP0113-CL-2001
Astellas
Page 2 of 42
Table of Contents
I.
LIST OF ABBREVIATIONS AND KEY TERMS··········································· 4
1
INTRODUCTION·················································································· 7
2
FLOW CHART AND SCHEDULE OF ASSESSMENTS·································· 7
3
STUDY OBJECTIVE(S) AND DESIGN······················································13
3.1
Study Objective(s) ············································································13
3.2
Study Design···················································································13
3.3
Randomization·················································································15
4
SAMPLE SIZE ····················································································16
5
ANALYSIS SETS ·················································································16
5.1
Full Analysis Set (FAS) ······································································16
5.2
Safety Analysis Set (SAF) ···································································17
5.3
Immunogenicity Analysis Set (IAS)························································17
6
ANALYSIS VARIABLES ·······································································17
6.1
Efficacy Endpoints············································································17
6.1.1
Primary Efficacy Endpoint·····························································17
6.1.2
Secondary Efficacy Endpoints·························································17
6.1.3
Exploratory Efficacy Endpoints ·······················································17
6.1.4
Immunogenicity Variables ·····························································18
6.1.5
Resource Utilization and Patient Reported Outcomes ······························18
6.2
Safety Variables···············································································19
6.3
Pharmacokinetic Variables···································································19
6.4
Pharmacodynamic Variables ································································19
7
STATISTICAL METHODOLOGY ···························································19
7.1
General Considerations·······································································19
7.2
Study Population ··············································································20
7.2.1
Disposition of Subjects ·································································20
7.2.2
Protocol Deviations ·····································································20
7.2.3
Demographic and Medical History····················································20
7.2.4
Previous and Concomitant Medications ··············································21
7.2.5
Antiviral therapies·······································································21
7.2.6
Transplant Information ·································································21


Sponsor: APGD
SAP Final Version 2
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Astellas
Page 3 of 42
7.3
Study Drug·····················································································22
7.4
Analysis of Efficacy ··········································································22
7.4.1
Analysis of Primary Endpoint ·························································22
7.4.2
Analysis of Secondary Efficacy Endpoints···········································24
7.4.3
Analysis of Exploratory Endpoints····················································24
7.4.4
Analysis of Immunogenicity Variables···············································26
7.5
Analysis of Safety·············································································27
7.5.1
Treatment Emergent Adverse Events ·················································27
7.5.2
Adverse Events of Special Interest····················································28
7.5.3
Clinical Laboratory Evaluation ························································30
7.5.4
Vital Signs················································································31
7.5.5
Pregnancies···············································································31
7.5.6
Physical Examination···································································31
7.6
Analysis of PK·················································································31
7.7
Analysis of PD·················································································31
7.8
Interim Analysis (and Early Discontinuation of the Clinical Study)····················31
7.9
Handling of Missing Data, Outliers, Visit Windows, and Other Information ·········32
7.9.1
Missing Data ·············································································32
7.9.2
Outliers ···················································································33
7.9.3
Visit Windows ···········································································33
8
REFERENCES ····················································································34
9
APPENDICES ·····················································································35
9.1
Appendix 1: Handling of the Human Leukocyte Antigen (HLA) Mismatching·······35
9.2
Appendix 2: Futility Analysis ·······························································36
9.3
Appendix 3: Simulation Studies·····························································37
9.4
Appendix 4: List of the SAP Changes and Rationale·····································40
9.5
Appendix 5: Signatures·······································································42


Sponsor: APGD
SAP Final Version 2
ISN/Protocol ASP0113-CL-2001
Astellas
Page 4 of 42
I.
LIST OF ABBREVIATIONS AND KEY TERMS
List of Abbreviations
Abbreviations
Description of abbreviations
AC
Adjudication Committee
AE
Adverse Event
ALP
Alkaline Phosphatase
ALT
Alanine Transaminase
ANCOVA
Analysis of Covariance
APGD
Astellas Pharma Global Development
AST
Aspartate Transaminase
ATC
Anatomical Therapeutic Chemical
ATG
Anti-thymocyte globulin
AUC
Area under the concentration-time curve
AVT
Antiviral therapy
BMI
Body Mass Index
BPAR
Biopsy proven acute rejection
BPP
Bayesian predictive probability
CI
Confidence Intervals
CMH
Cochran–Mantel–Haenszel test
CMV
Cytomegalovirus
CRF
Case Report Form
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Event
DBP
Diastolic Blood Pressure
DMC
Data Monitoring Committee
D+R-
Donor CMV seropositive and recipient CMV seronegative
EBV
Epstein Barr virus
eGFR
Estimated glomerular filtration rate
FAS
Full Analysis Set
HEA
Health Economic Assessment
ICH
International Conference on Harmonization
KTQ
Kidney transplant questionnaire
MedDRA
Medical Dictionary for Regulatory Activities
MDRD
Modification of Diet in Renal Disease Study
NCI
National Cancer Institute
PCR
Polymerase chain reaction 
PGx
Pharmacogenomics 
PT
Preferred Term
SAE
Serious Adverse Event 
SAF
Safety Analysis Set
SAP
Statistical Analysis Plan
SAS 
Statistical Analysis Software
SBP
Systolic Blood Pressure
SF-12
Short Form health survey 12 item 
SOC
System Organ Class
TEAE
Treatment Emergent Adverse Event
TLF
Tables, Listings and Figures
ULN
Upper Limit of Normal
WHO-DD
World Health Organization Drug Dictionary


Sponsor: APGD
SAP Final Version 2
ISN/Protocol ASP0113-CL-2001
Astellas
Page 5 of 42
List of Key Terms
Terms
Definition of terms
Endpoint
A variable that pertains to the trial objectives
Variable
Any quantity that varies; any attribute, phenomenon or event that can have 
different qualitative or quantitative values.
Adverse Event
An adverse event is any untoward medical occurrence in a subject 
administered a study drug or undergone a study procedure which does not 
necessarily have a causal relationship with the treatment.
Adjudication 
Committee
A group of clinical experts who will create specific, standardised event 
definitions for each suspected events of interest including all cases of CMV 
syndrome, CMV tissue-invasive disease and CMV-specific antiviral 
therapy.
Baseline
Baseline is the time point prior to the first dose of randomized study drug. 
Visit 2 is considered the Baseline Visit in this study.  The last measurements 
/ evaluation prior to the first dose of randomized therapy is considered the 
baseline measure/evaluation.
CMV Viremia
Presence of CMV in the blood.
Double-Blind
Neither the subjects of the trial nor the persons administering the trial know 
the true treatments.
End of Study
The point in time when the last protocol-defined assessment has been 
completed (end of the Long-term Follow-up Period). 
End of Treatment
The point in time when the subject receives the last dose of study drug.
Enrollment
The point in time when the subject signs the informed consent.
Evaluable Subject
A subject who meets all inclusion criteria and does not meet any exclusion 
criteria and who has received at least one injection of study drug. 
Hard Lock
Hard lock of a study database occurs after all issues discovered in final data 
review have been resolved and it is expected that no more changes to the 
study database will occur. Only after hard lock are treatment assignments 
unblinded. 
Independent 
Statistician
The statistician who is not part of the study team 
Investigational Period
The time between the first dose of study drug (Visit 2) through one year 
post first dose of study drug (Visit 13).
Long-term Follow-up
Period
The period of time from the Day 395 Visit (Visit 13) through the completion 
of the 4½ year additional safety follow-up.
Long-term Follow-up 
Withdrawal
A subject who completes the Primary Study Period but does not complete 
the Long-term Follow-up Period for any reason.
Preemptive Therapy
A therapeutic treatment regimen where treatment for an infection/disease is 
initiated only after it is detected/confirmed.
Primary Study Period
From first study drug injection (Day 1) to the time of early termination or 1-
year post first study drug injection (Day 380), whichever is first.
Primary Study 
Withdrawal
A subject who is randomized but does not complete the Primary Study 
Period for any reason.
Protocol-defined CMV 
viremia 
CMV plasma viral load >1000 IU/mL as assessed by the central laboratory.


Sponsor: APGD
SAP Final Version 2
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Astellas
Page 6 of 42
Terms
Definition of terms
Prophylactic Therapy
A treatment administered prior to the detectable presence of infection or 
disease as a preventative measure.
Randomization
The action to allocate a subject to a treatment group. In this study, 
randomization occurs after the subject has met all inclusion and exclusion 
criteria at +30 post transplant .
Screening
The process for identifying a candidate for the study and evaluating their 
eligibility to participate. This occurs between days -14 prior to Transplant 
and +30 days post Transplant. 
Screen Failure
A subject who signs the informed consent and undergoes the protocol-
specific screening procedures, but does not fulfill the protocol inclusion 
and/or exclusion criteria. This subject should not be randomized.
Serious Adverse Event
An adverse event is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: results 
in death, is life threatening, results in persistent or significant disability / 
incapacity or substantial disruption of the ability to conduct normal life 
functions, results in congenital anomaly or birth defect, requires inpatient 
hospitalization or leads to prolongation of hospitalization, or is a medically 
important event.
Source Data
All information in original records and certified copies of original records of 
clinical findings, observations, or other activities in a clinical trial necessary 
for the reconstruction and evaluation of the trial. Source data are contained 
in source documents.
Source Documents
Original documents, data and records including source data.
Soft Lock
Soft lock of a study database occurs when all data have been entered and 
queried and the database is considered ready for final data review.
Treatment assignments remain blinded during soft lock and the final data 
review.
Subject
An individual who participates in a clinical trial.
Treatment Emergent 
Adverse Events
Adverse events occurring after the first dose of study drug and through one 
year post first dose of study drug. 
Treatment Period
The period of time from the first dose of study drug through the last dose of 
study drug.


Sponsor: APGD
SAP Final Version 2
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Astellas
Page 7 of 42
1
INTRODUCTION
The SAP is finalized and signed prior to database hard lock and unblinding of treatment 
groups.
The changes to the original SAP that affect the analyses are summarized in Appendix 4   Any 
changes from the planned analyses  in the final SAP will be explained in the Clinical Study 
Report (CSR).
2
FLOW CHART AND SCHEDULE OF ASSESSMENTS 
Flow Chart
Screening/Informed Consent through Visit 13/Day 395
Screening Period
1.
Baseline is date of first dose (Visit 2). The day of transplant is Day 0 and all visit days 
are relative to Day 0 with the exception of the injection safety follow up visits which are 
relative to each dose.  A visit window is allowed for each visit.
2.
Screening and baseline visits may take place on the same day if all clinical labs as 
measured by the local laboratory meet inclusion and exclusion criteria.
Long-term Follow-up Period: Primary Study Period Completion through Long-term
Follow-up Completion (Day 395/Visit 13 through 5.5 years post first Study Drug injection)
*
Subjects will be contacted by telephone at 6 months after Day 395, then annually for the 
next 4 years, to evaluate for long-term safety related to the DNA vaccine.  Items to be 
assessed by questionnaire and available patient records are mortality, development of any 
new malignancies, development of infection requiring hospitalization or resulting in 
death, graft survival, creatinine and erythema and induration at the injection site. Subjects 
that discontinue treatment early will be followed per the same schedule.


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Table 1
Schedule of Assessments 
Screening1
Baseline
Randomizat
ion and 
Dose 1
Dose 2
Dose 3
Day 100
Dose 4
Dose 5
Study 
Completion/ 
Early 
Terminatio
n23
Visit Number
1
2
3*
4
5
6
7*
8
9
10
11*
12
13
Day 
(From Transplant for dosing visits or prior 
dose)
-14 through +30
Day of Transplant
= Day 02
30
14 days 
after
Dose 125
60
14 days 
after 
Dose 225
90
14 days 
after 
Dose 325
120
14 days 
after 
Dose 425
180
14 days after 
Dose 525
270
395
Visit Window (days)
+/-3
+/- 3
+/- 5
+/- 3
+/- 5
+/- 3
+/- 5
+/- 3
+/-5
+/- 3
+/- 10
+14
Month
1
2
3
4
6
9
13
Valganciclovir/Ganciclovir 3
By Day 10 Post Transplant
Informed Consent4
X
Subject Number Assignment5
X
Inclusion/Exclusion Assessment
X
XP
EQ-5D, KTQ, SF-126
XP
XP
XP
XP
XP
X
Medical History & Demographics7
X
Clinical Evaluation (Physical Exam & Vitals)8
X
XP
XP
XP
XP
XP
X
X
Concomitant Medication Review (including 
immunosuppressants) 9
X
XP
XP
X
XP
XP
X
XP
X
X
Health Economic Assessment (HEA)
X
XP
XP
XP
XP
XP
X
X
Clinical Laboratories10
X
XP
X
XP
X
XP
X
XP
X
XP
X
X
Urinalysis, with Microscopic Evaluation
X
XP
X
XP
X
XP
X
XP
X
XP
X
X
Urine:Protein Creatinine Ratio
X
XP
X
XP
X
XP
X
XP
X
XP
X
X
Pregnancy Test (females)11
X
XP
XP
XP
XP
XP
X
X
CMV Serologies12
X
Adverse Event and SAE Review13
X
XP
XP
X
XP
XP
X
XP
X
X
Transplant Information14, 15
X
Randomization1
XP
CMV Plasma Viral Load Testing 
(see Table 1a)16, 17, 24
Every 2 Weeks
Monthly
CMV Genotypic Resistance Testing, when 
applicable18, 24
Immunology Lab19, 24
XP
X
XP
X
XP
X
Pharmacogenomics (PGx) – (Optional)20, 24
XP
Study Drug injection21
X
X
X
X
X
Local & Systemic Reactogenicity Assessment22
X
X
X
X
X
Patient and Graft Survival
X
P = procedure should be completed prior to dosing     * = Visit procedures may be performed by Home Health Care (HHC)


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Table 1a
Plasma Viral Load Schedule
Every Other Week
Monthly
Day 
100*
Day 
114*
Day 
128*
Day 
142*
Day 
156*
Day 
170*
Day
184
Day 
198*
Day 
230*
Day
260
Day 
290*
Day 
320*
Day 
350*
Day 
380*
Day 
395
CMV Visit Window (days)
+/-3
+/-3
+/-3
+/-3
+/-3
+/-3
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+/-5
+14/-5
CMV Window 
Day
179-189
Day 
193-203
Day 
255-267
Overlap with Regular 
Visit†
Days 179-
185
Days 
191-197
Days 
260-267
Days 
395-409
May draw with Visit:
Visit 7*
Visit 10
Visit
11*
Visit 12
Visit 13
CMV Plasma Viral Load 
Testing16, 17,  24
X
X
X
X
X
X
XP
X
X
X
X
X
X
X
X
* = Visit procedures may be performed by Home Health Care (HHC).  Viral load blood draws may be combined with Visits 10, 11 12 & 13 at the investigator site when they are 
scheduled to coincide within each visit’s windows .
† Days in Study Schedule when CMV and Regular Visit can be performed together per Protocol.  The overlap used assumes the visits are done exactly on the specified visit day from 
Transplant.  If +/- window is used for a dosing visit, the corresponding follow up visit should take place within the 14 days +/-3 from the date of the Study Drug dose.  Visits 10 & 11
must be at least 7 days apart.
Tables 1 and 2 Footnotes:
1.
Screening may be done from Day -14 up to Randomization, Day 30. Screening and Randomization can take place on the same day as long as Clinical Labs are drawn and results 
are available on the day of Randomization. If Screening is done > 3 days prior to Randomization, Clinical Labs, urinalysis and urine protein: creatinine ratio must be repeated and 
available prior to Randomization. Subjects may be rescreened due to rescheduling of transplant surgery provided the screening procedures are repeated and fall within the -14 day 
to + 30-day window relative to the Day of Transplant. First study drug dosing must take place within 24 hours of Randomization.
3.
The date of transplant (day of skin closure) defines Day 0 and all visit days are relative to Day 0.
4.
Subjects are to receive prophylactic valganciclovir or ganciclovir starting within 10 days post transplant through the Day of Randomization to prevent CMV disease. (The subject 
can miss up to two doses of valganciclovir or ganciclovir during this time period for any reason). Valganciclovir or ganciclovir dose is to be given per the package insert. The 
subject will then continue to receive CMV-specific AVP until 100 days post transplant. Subjects can have CMV-specific AVP interrupted, dose adjusted or replaced by other 
CMV-specific AVP per standard of care after the Day Randomization if renal function is compromised, there are toxicities related to the administration of the AVP, or for any 
other medically indicated reason.
5.
Informed consent must be obtained prior to the performance of any study-related procedure.
6.
Subjects will be assigned a subject number for use throughout the study at the Screening Visit via the Interactive Response Technology (IRT) system.
Footnotes continue on next page


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7.
The EQ-5D, Kidney Transplant Questionnaire (KTQ) and the SF-12 v2, should be completed by the subject prior to any other study assessments or visit procedures. Subjects 
should complete these assessments in the following order: EQ-5D first, KTQ second, SF-12 last. For all three patient-reported outcome measures, i.e. EQ-5D, KTQ, SF-12, the 
answers must come from the subject. If the subject is unable to fill out the questionnaire, the assessment should not be performed. If the subject is unable to answer an individual 
question, the rest of the questionnaire should still be completed.
8.
Medical history must include demographics, (age, gender, race), diagnosis for renal failure, length of time on dialysis, history of prior kidney transplant, and diabetes. 
9.
A complete physical examination (PE) will be conducted at the Screening, Baseline and the Study Completion/Day 395 Visit (V13). At all other visits where a PE is performed 
(Visits 4, 6, 8, 10 and 12); symptom-directed physical examinations may be done. The evaluations conducted at each visit are to be performed by the Investigator or qualified 
medical personnel who routinely perform these evaluations in this patient population. Vital signs will be collected immediately prior to Study Drug injection, at 15 minutes and 
60 minutes post Study Drug injection. Vital signs include blood pressure, pulse rate, respiratory rate and temperature. Height will be collected at the Screening Visit only. Weight 
will be collected at V1, V2 and at Study Completion/Day 395 (Visit 13). If Screening is done > 3 days prior to Randomization, the PE must be repeated at Randomization.
10.
All concomitant medications and therapies administered from 14 days prior to transplant through the Study Completion Visit (Day 395/Visit 13) will be collected on the eCRF. 
Medications used for anesthesia during the transplant surgery will not be recorded. 
11.
Clinical laboratory samples will be drawn at Screening (Visit 1), before each Study Drug injection, at each follow-up time point for the injections, and at the last study visit. 
Clinical labs will be performed by a local laboratory and will include hematology, biochemistry, including a hepatic profile, urinalysis with microscopic evaluation and urine 
protein: creatinine ratio. Screening clinical labs may be re drawn once if initial results would preclude Randomization and the Investigator feels out of range results were transient. 
Results will be entered into the eCRF. Safety labs (hematology, biochemistry, hepatic profile, urine protein: creatinine ratio and urinalysis) drawn by 
 for 
Investigator sites utilizing this service will be analyzed by the Central Laboratory.
12.
For all females of childbearing potential, a urine pregnancy test will be performed at Screening, prior to each dose, at Visit 10, 12, and at the Study Completion/Day 395 Visit 
(Visit 13). All pregnancy tests will be done locally. For subjects who receive mycophenolate mofetil (MMF), additional pregnancy testing should be done in accordance with 
local requirements.
13.
CMV serologies must have been performed within 8 weeks prior to transplant. If CMV serostatus is not available from this time period, CMV serostatus may be assessed at the 
Screening Visit with results available prior to Randomization.
14.
AEs and SAEs will be collected from time of signing of informed consent through one year post Study Drug injection [Study Completion Day 395 Visit (Visit 13)]. AEs should 
be recorded as a change in medical status or medical history, from the time of signing of the informed consent until the first dose of study drug. SAEs from the time of signing the 
informed consent will be recorded on the SAE worksheet and reported per Section 5.5.6. AEs reported after the first dose will be reported on the AE eCRF. Note: The transplant 
surgery that occurs on Day 0 is not considered an AE or an SAE.
15.
Transplant information includes type of transplant (Living Related Donor, Living Unrelated Donor, or Deceased Donor).
Footnotes continue on next page


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16.
Donor information includes donor demographics (age, gender, race), viral serologies (CMV [required], HBV, HCV, EBV, [if available]; and HCV PCR RNA [if available]), ABO 
blood group and HLA typing. Recipient information includes ABO blood group, HLA typing, HLA cross match at time of transplant (as determined by the site’s standard method 
of determination), and viral serologies (CMV [required], HBV, HCV and EBV [if available], and HCV PCR RNA [if available]).
17.
Plasma viral load by the central laboratory will be routinely monitored every other week (+/-3 days) from Day 100 through Day 200, then monthly (+/- 5 days) until end of study. 
Plasma viral load by central and local laboratory will also be assessed for cause in case of suspect CMV disease and at least once a week by Central lab from initiation of 
CMV-specific AVT until the course is completed. For cause CMV viral loads should be performed at a local lab approved by Astellas as Central lab viral load results may not be 
available in a timely manner to guide treatment decisions.  
18.
Plasma viral load assessment results performed by the local laboratory will be reported on the eCRF. Local CMV plasma viral load testing may be performed only at a local 
laboratory approved by the Sponsor.  
19.
A plasma sample will be drawn and sent to the central lab and results will be reported for CMV genotypic resistance when there is viremia without a reduction in viral load after 
two weeks of treatment with valganciclovir and/or ganciclovir, or when clinical signs and symptoms have not improved two weeks after initiating or increasing valganciclovir 
and/or ganciclovir for CMV viremia or disease or any time resistance to any CMV-specific AVT is suspected by the Investigator.
20.
Immunogenicity laboratories include collection of blood for the gB antibody and pp65 T-cell assays. Samples should be drawn at Visits 2, 5, 6, 9, 10 and 13. Visits 2, 6 and 10 are 
Study Drug injection visits and blood sampling will be collected prior to the Study Drug injection. Samples for T-cell assays will not be collected if the Absolute Lymphocyte 
Count (ALC) is known to be ≤500 mm3 by local or central laboratory measurement.   
21.
Subjects who consent to participate in the PGx sub study will have a whole blood sample collected during the Baseline Visit (Visit 2), after Randomization but prior to the first 
Study Drug injection.
22.
A Study Drug injection should not be given if the subject 1) has been on an anticoagulant within 5 half-lives prior to the injection(Low dose anticoagulants that are used for 
prevention of deep vein thrombosis are allowed) or 2) has a Temperature ≥ 100.4° F or 38° C (per NCI Grade 1).
23.
Local reactogenicity and symptoms of systemic reactogenicity will be evaluated one hour after each injection and then for seven days after each injection by subject reporting via 
diary. After injection in the clinic, the subject must be in direct view of the clinic staff for 15 minutes following each injection, then remain in the clinic area for an additional 
45 minutes for evaluation of local and systemic reactogenicity. Vital signs, including temperature, pulse, respiration and blood pressure will be collected just prior to injection, 
15 minutes post Study Drug injection and at one hour post Study Drug injection. Using the pre-injection vital signs as baseline, if a post Study Drug injection vital sign meets 
Grade 1-4 criteria per Appendix 5, they are to be repeated and confirmed within 5 minutes of the first assessment. 
24.
The Study Completion/Day 395 Visit (Visit 13) must occur on Day 395 up through +14 days (between Day 395 to 379). For a subject who prematurely withdraws from the study 
(discontinues treatment with no continued follow-up), the Study Completion Visit should be completed within 14 days of study withdrawal.
25.
Specimen drawn and sent to the Central Laboratory.
26.
If a Study Drug dose is missed, the 14 day follow up clinical laboratory samples for hematology, biochemistry, urinalysis and urine protein: creatinine ratio and hepatic profile 
should not be collected. Scheduled Immunogenicity Labs (Visit 5 & 9) must still be collected. 


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Table 2
Schedule of Assessments – Long-term Follow-up Period
Month
18
30
42
54
66
Year (relative to first Study Drug)
1.5
2.5
3.5
4.5
5.5
Window
(months)
± 1
± 1.5
± 1.5
± 1.5
± 1.5
Mortality, including primary cause of death and date
X
X
X
X
X
Development of any new malignancies
X
X
X
X
X
Development of infection requiring hospitalization or resulting in death
X
X
X
X
X
Erythema and/or induration at sites of immunizations
X
X
X
X
X
Graft Survival
X
X
X
X
X
Creatinine*
X
X
X
X
X
Subjects will be contacted by telephone at 6 months after Day 395, then annually, for the next 4 years for long-term safety related to the DNA vaccine. Items are to be assessed by 
questionnaire and via retrospective chart review of available medical records.
During the long-term follow-up period, if an SAE is identified and deemed possibly or probably related to the study medication, an SAE report on the SAE worksheet must be sent to 
the sponsor per Section 5.5.6. 
*Creatinine values will be recorded if they have been collected within 3 months prior to the follow-up telephone contact and are included in the subject’s available medical records.


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3
STUDY OBJECTIVE(S) AND DESIGN
3.1
Study Objective(s)
The objectives of this study are:
●
To evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence 
of CMV viremia (defined as plasma viral load ≥ 1000 IU/mL by central laboratory 
assay) through one year post first Study Drug injection in CMV-seronegative subjects 
receiving a kidney from a CMV-seropositive donor.
●
To evaluate the safety of ASP0113 in CMV-seronegative subjects receiving a kidney 
from a CMV-seropositive donor.
3.2
Study Design
This is a randomized, double-blind, placebo-controlled trial which will enroll 
140 CMV-seronegative recipients of kidney transplant from a CMV-seropositive donor at 
about 80 clinical sites. Subjects will be randomized at Day 30 ±3, in relation to the day of 
transplant, in a 1:1 ratio to ASP0113 or placebo, and stratified by use of anti-thymocyte 
globulin (ATG) prior to Randomization and by receipt of a kidney from a living or deceased 
donor. The active compound will be a vaccine (ASP0113) which contains two plasmids 
encoding gB and pp65 each at 2.5 mg/mL, formulated with CRL1005 poloxamer and 
benzalkonium chloride (BAK). 
The placebo control will be phosphate-buffered saline (PBS). Subjects will receive either 
5 doses of ASP0113 or placebo on Days  30 ± 3, 60 ± 5, 90 ± 5, 120 ± 5  and 180 ± 5 in 
relation to the day of transplant (Day 0).  
Injections should be administered only when there is no medical contraindication to an 
intramuscular (IM) injection. Syringes will be masked prior to dosing to blind the subjects 
and all other personnel who need to remain blinded to the treatment assignment (i.e., site 
staff other than pharmacy personnel and staff designated to administer Study Drug 
injections). 
Starting within 10 days of transplant, subjects will have received prophylactic valganciclovir 
or ganciclovir (dose per package insert) through the day of Randomization to prevent CMV 
disease. (The subject can miss up to two valganciclovir or ganciclovir doses during this time 
period for any reason). Subjects will then continue to receive CMV specific CMV AVP with 
valganciclovir or ganciclovir (dose per package insert) to prevent CMV disease until 100 days 
post transplant.  Subjects can have valganciclovir or ganciclovir interrupted, dose adjusted or 
replaced by other CMV-specific AVP per standard of care after the day of Randomization if 
renal function is compromised, there are toxicities related to the administration of the AVP or 
for any other medically indicated reason. In all subjects, plasma will be collected for central 
laboratory CMV viral load testing every two weeks from Day 100 through Day 200, then 
monthly through last Study visit Day 395.


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In cases where CMV disease (CMV syndrome or CMV tissue-invasive disease) is suspected 
from the first Study Drug injection through Day 395, a local CMV viral load sample will be 
collected at the time of the first CMV symptom recognition.  
Through Day 395, CMV-specific AVT should be initiated for CMV disease and can be 
initiated for CMV viremia based on the central or local laboratory results and standard of care 
at each institution. If CMV- specific AVT is initiated, a central CMV viral load will be 
obtained at a minimum of weekly from the time CMV- specific AVT is initiated until 
discontinuation. For cause CMV viral loads should be performed at a local lab approved by 
Astellas as Central lab viral load results will not be available in a timely manner to guide 
treatment decisions. 
In addition, every time a sample is collected for a local CMV viral load, a plasma sample 
should also be collected and sent to the central laboratory for CMV viral load testing. 
As one of the plasmids of the ASP0113 vaccine codes for the pp65 antigen, the theoretical 
possibility of interference with the pp65 antigenemia assay has been raised. At present, there 
are no data to suggest that such an interference occurs. However, to ensure subject safety and 
study integrity, sites that use pp65 antigen as their local methodology for the detection of 
CMV infection must adhere to the procedures defined below as a condition of participation in 
the trial:
●
The local pp65 antigenemia results must be entered into the eCRF database within 
72 hours (or next business day) of receipt to facilitate in-time monitoring of results.
●
The Medical Monitor must be called within 48 hours (or next business day) if the 
pp65 antigenemia test is positive and the central laboratory PCR viral load result is 
negative.
●
Both the pp65 antigenemia and the central laboratory test must be repeated within 
48 hours of receipt of results, if the local pp65 antigenemia result is positive, the central 
laboratory PCR viral load result is negative and the subject is treated with CMV-specific 
AVT . Further treatment decisions are to be discussed with the Medical Monitor.
The plasmids in the Study Drug may interfere with certain PCR assays. If a PCR assay is 
used that amplifies the genes UL55/gB or UL83/pp65, this could result in either a false 
positive viral load or unblinding of the study subject.
Sites that are determined to have an unacceptable assay in their local lab but are able to 
determine a Sponsor- deemed acceptable work practice flow for utilizing another acceptable 
local assay or methodology will be allowed to participate in the trial. Note: Local CMV 
plasma viral load testing may be performed only at a local laboratory approved by the Sponsor.
Subjects will be followed for one year after first Study Drug injection (Primary Study 
completion/Day 395) for CMV viremia, CMV syndrome, CMV tissue-invasive disease, 
CMV-specific AVT, graft survival fand subject survival.
Subjects will be followed for one year after the first Study Drug injection for resistance to 
valganciclovir or ganciclovir. Viral resistance will be assessed by a Central lab when there is 
no reduction in viral load two weeks after initiating valganciclovir/ganciclovir, when there is 


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no improvement in clinical signs and symptoms two weeks after initiating 
valganciclovir/ganciclovir or any time resistance to any CMV-specific AVT is suspected by 
the Investigator.
Immunogenicity to pp65 and gB will be assessed prior to Dose 1, two weeks after Dose 2, 
prior to Dose 3, two weeks after Dose 4, prior to Dose 5 and at the last study visit.
Subjects will be evaluated for local and systemic reactogenicity 15 minutes and one hour 
after each Study Drug injection and for 7 days by subject reporting via diary after each Study 
Drug injection.  
Subjects will be contacted by telephone at 6 months after Day 395, then annually for the next 
4 years to evaluate long-term safety related to the DNA vaccine. Items to be assessed by 
questionnaire and available patient records include mortality, development of any new 
malignancies, development of infection requiring hospitalization or resulting in death, graft 
survival, creatinine, and erythema and/or induration at the injection sites.
All adverse events (AEs) and serious adverse events (SAEs) will be collected from signing of 
the informed consent through one year post Study Drug injection. AEs occurring from 
signing of informed consent until just prior to the first dose of Study Drug, should be 
reported as a change in medical status or medical history. SAEs from the time of signing the 
informed consent will be recorded on the SAE worksheet and reported per Section 5.5.6. AEs 
reported after the first dose will be reported on the AE eCRF. 
An independent Data Monitoring Committee (DMC) will be chartered to oversee the safety 
of subjects and review of the futility analysis. An Adjudication Committee (AC) will be 
chartered to adjudicate all cases of CMV syndrome, CMV tissue-invasive disease and 
CMV-specific antiviral therapy.
Two interim safety and efficacy analyses are planned. The first one will occur when 
50 subjects (approximately 25 in each group) have completed the month 6 visit assessment. 
The second interim analysis will occur when 90 subjects (approximately 45 per group) have 
completed the 6 month visit assessment. 
3.3
Randomization
At the Screening Visit, after the Informed Consent Form (ICF) has been signed, site staff will 
access the IRT system, enter the subject’s required information, and the subject will receive a 
subject number assignment through the IRT for use throughout the study.
Subjects who subsequently meet the inclusion/exclusion criteria will be randomly assigned to 
receive either ASP0113 or placebo. The randomization to treatment will be equally allocated 
(i.e., 1:1) and stratified by the use of anti-thymocyte globulin and by receipt of a kidney from 
a living or deceased donor. The IRT vendor will generate the randomization schedule. To 
obtain the randomized treatment assignment for a subject, the pharmacist or designee will 
utilize an IRT system, which is available seven days a week, 24 hours a day.


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Randomization is to be done after the completion of the Screening period, and at least 
30 days ± 3 after transplant day (Day 0). After submitting required information about the 
eligible subject, the drug kit number assignment will be provided.
Study Drug assignment will remain blinded to all site staff except the pharmacist and
designated staff administering the Study Drug.  
If a subject is randomized but does not receive Study Drug, the kit number will not be used 
again. In this instance, the treatment assignment should only be known by the pharmacist and 
designated staff (i.e., the blind must be maintained as it is with all other subjects).
4
SAMPLE SIZE
In a recent study of prophylactic valganciclovir given at 900 mg/day for 100 days to donor 
CMV-seropositive/recipient CMV seronegative (D+R-) kidney transplant recipients [Humar, 
2006], CMV viremia, defined as CMV viral load ≥ 1000 IU/mL, was seen through one year 
in 83 of 163 subjects [50.9%, 95% CI = (43.0%, 58.8%)]. In another study [Couzi, 2012], 
CMV infection, defined as two consecutive positive Polymerase Chain Reaction (PCR) assay 
results, was seen in 11 of 32 subjects (34.4%, 95% Confidence Interval (CI) = (18.6%, 
63.2%)), respectively. Pooled from these two studies by weighted average, it is estimated that 
placebo rate is 46% (70% weight on Humar’s result). A sample size of 64 subjects per arm 
will allow the study to have 80% power to detect a reduction in CMV viremia to 25% due to 
ASP0113 at 52 weeks using a 1-sided Chi-square test with a type 1 error rate of 5%. To allow 
for drop-out (randomized but not evaluable), 70 subjects per arm will be enrolled for a total 
sample size of 140 subjects.
5
ANALYSIS SETS
In accordance with International Conference on Harmonization (ICH) recommendations in 
guidelines E3 and E9, the following analysis sets will be used for the analyses.
This SAP includes the data analysis for the primary study period which is defined as 1-year 
post first study drug injection. Certain data summary will consider analysis windows as 
specified in relevant sections. The long-term follow-up period is not covered by this SAP.
5.1
Full Analysis Set (FAS)
The Full Analysis Set (FAS) consists of all randomized subjects who received at least one 
dose of randomized study drug and who have at least one post dose viral load assessment
within 1-year post first injection by central laboratory. 
Specifically, the following will lead to a subject’s exclusion from the FAS:
●
Did not take study drug , or
●
Had no viral load assessment by central laboratory after first study drug injection 
The FAS will be the primary analysis set for efficacy analyses and for summaries of selected 
demographic and baseline characteristics. For this population, data will be analyzed by the 
treatment group that patients were randomized to.


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5.2
Safety Analysis Set (SAF)
The Safety Analysis Set consists of all randomized subjects who received at least one dose of 
study drug. For the SAF, data will be analyzed according to the study medication that 
subjects received as the first dose even if it differs from what they were randomized to.
5.3
Immunogenicity Analysis Set (IAS)
The Immunogenicity Analysis Set (IAS) will include subjects who received randomized 
study drug and for whom at least one post-transplant immunogenicity measurement is 
available.
The IAS will be used for analyses of the immunogenicity data.
6
ANALYSIS VARIABLES
6.1
Efficacy Endpoints
6.1.1
Primary Efficacy Endpoint
Incidence of CMV viremia (defined as plasma viral load of ≥1000 IU/mL by central 
laboratory assay) through one year post first Study Drug injection is the primary efficacy 
endpoint.
6.1.2
Secondary Efficacy Endpoints
Secondary efficacy endpoints are: :
●
Proportion of subjects with Adjudicated CMV-associated disease including CMV 
syndrome and CMV tissue-invasive disease.
●
Proportion of subjects with plasma viral load ≥ the lower limit of quantification [LLOQ]
assessed by central laboratory. 
●
Proportion of subjects who took Adjudicated CMV-specific antiviral therapy for the 
treatment of CMV viremia or disease.
●
Proportion of subjects with graft survival.
6.1.3
Exploratory Efficacy Endpoints
●
Number of patients with at least one opportunistic infections other than CMV 
●
Time to first CMV viremia (defined as plasma viral load of ≥ 1000 IU/mL by central 
assay) through one year post study first Study Drug injection.
●
Time to first adjudicated CMV disease, including CMV syndrome and CMV 
tissue-invasive disease, through one year post first Study Drug injection.
●
Number of episodes of CMV viral load of ≥ 1000 IU/mL by central assay through one 
year post first Study Drug injection.
●
Peak CMV viral load through one year post first Study Drug injection. 
●
Viral load area under the curve (AUC) adjusted for duration through one year post first 
Study Drug injection.
●
Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease, through one year post first Study Drug injection.


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●
Proportion of subjects with viral resistance to ganciclovir or valganciclovir through one 
year post first Study Drug injection as determined by central laboratory assay. 
●
Proportion of subjects with biopsy-proven (T or B cell) acute rejection (BPAR) (Banff 
2007 Grade > 1) through one year post first Study Drug injection.
●
Estimated glomerular filtration rate (eGFR) at the last study visit calculated using the 
4 variable MDRD formula.
●
Proportion of subjects with clinically treated acute graft rejection through one year post 
first Study Drug injection.
6.1.4
Immunogenicity Variables
An indicator of immunogenicity elicited by the vaccine is predicted to be an increase in 
gB-specific antibody levels and the T-cell response to pp65 protein over time compared with
the placebo group.  
Two immunogenicity assessments will be performed:
1. T-cell response to viral protein pp65 using cultured ELISpot .
2. Antibody response to gB antigen using an ELISA-based platform.
Assessments will be done from peripheral blood mononuclear cells (T-cells) or serum samples 
(antibody) isolated over the course of the trial. Time points of the assessments are as follows:
Dose 1, Post Dose 2, Dose 3, Post Dose 4, Dose 5, and End of Study Visit:
○Samples for T-cell assays will not be collected if the Absolute Lymphocyte Count 
(ALC) is known to be < 500 mm3 by local or central laboratory measurement. 
○If the visit coincides with a study drug administration, the sample will be drawn 
prior to injection.
Further details will be available in the Laboratory Manual.
6.1.5
Resource Utilization and Patient Reported Outcomes 
Additional assessments include the following patient reported outcome measures and 
resource utilization.
●
EuroQol (EQ-5D)
●
Kidney Transplant Questionnaire (KTQ)
●
Short Form Health Survey version 2 (SF-12v2)
●
Health Economic Assessment (HEA)
The EQ-5D, Kidney Transplant Questionnaire (KTQ) and the SF-12 v2, should be completed 
by the subject prior to any other study assessments or visit procedures. Subjects should 
complete these assessments in the following order: EQ-5D first, KTQ second, SF-12 last. For 
all three patient-reported outcome measures, i.e., EQ-5D, KTQ, SF-12, the answers must 
come from the subject. If the subject is unable to fill out the questionnaire, the assessment 
should not be performed. If the subject is unable to answer an individual question, the rest of 


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the questionnaire should still be completed. The questionnaires will be provided in the local 
language of the subject.
Health economic information will be collected for subjects through one year post first study 
drug injection.
6.2
Safety Variables
Safety will be assessed by evaluation of the following variables:
●
Treatment-emergent adverse events 
●
Clinical laboratory variables
●
Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, temperature, 
and weight)
●
Physical examination.
6.3
Pharmacokinetic Variables
Not applicable.
6.4
Pharmacodynamic Variables
Not applicable.
7
STATISTICAL METHODOLOGY
7.1
General Considerations
All statistical analyses and summary information will be generated according to this analysis 
plan and any deviations from this plan will be documented in the clinical study report. Any 
numerical rounding should be performed at the end of calculations. The p-values will be 
displayed with 3 decimal places. Statistical significance will be determined prior to rounding 
the p-value.
For continuous variables, descriptive statistics will include the number of subjects (n), mean, 
standard deviation, median, minimum and maximum. Frequencies and percentages will be 
displayed for categorical data. Percentages by categories will be based on the number of 
subjects with no missing datathus the percentages will add up to 100%. Baseline will be the 
last non-missing value on or prior to first stidy drug unless otherwise specified.
All efficacy comparisons will be tested at the 1-sided 0.05 significance level. Confidence 
intervals for efficacy estimates, if provided, will be constructed at 2-sided 90% level.
All data processing, summarization, and analyses will be performed using SAS® Version 
9.1.3 or higher on Unix.
This SAP includes the data analysis for the primary study period (ie, 1-year post first study 
drug injection) which is defined as data collected through day 380 (=365+14+1 day).  Certain 
data summary will consider analysis window as specified in each section. The long-term 
follow-up period is not covered by this SAP and will be managed in a separate SAP.


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7.2
Study Population
7.2.1
Disposition of Subjects
The following subject data will be presented:
●
Number of subjects with informed consent, discontinued before randomization, and 
randomized;
●
Number and percentage of subjects randomized in each analysis set, by treatment group;
●
Number and percentage of subjects completed and discontinued treatment, by reason for 
treatment discontinuation for randomized subjects, by treatment group; 
●
Number and percentage of subjects completed and discontinued the study, by reasons for 
study discontinuation for randomized subjects and by treatment group; 
7.2.2
Protocol Deviations
Protocol deviations as defined in the study protocol (Section 8.1.6 Protocol Deviations) will 
be assessed for all randomized subjects. The number and percentage of subjects meeting any 
criteria will be summarized for each criterion and overall, by treatment group and total as 
well as by study site. Subjects deviating from a criterion more than once will be counted once 
for the corresponding criterion. Any subjects who have more than one protocol deviation will 
be counted once in the overall summary. A data listing will be provided by site and subject. 
The protocol deviation criteria will be uniquely identified in the summary table and listing. 
The unique identifiers will be as follows:
PD1 - Entered into the study even though they did not satisfy entry criteria, 
PD2 - Developed withdrawal criteria during the study and was not withdrawn,
PD3 - Received wrong treatment or incorrect dose,
PD4 - Received excluded concomitant treatment. 
7.2.3
Demographic and Medical History
Demographic and other baseline characteristics will be summarized by descriptive statistics
for FAS and SAF populations.
Number and percentage of subjects randomized in each country and site will be presented by 
treatment group for the SAF.
Descriptive statistics for age, weight, body mass index (BMI), BMI categories (<25, 25 to 
<30, and ≥30 kg/m2), height at study entry, and the demographic categories defined below
will be presented.


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Demographics
Categories
Ethnicity
Not Hispanic or Latino
Hispanic or Latino
Race
White
Black
Other
Age group
< 65 years
≥65 years
Gender
Female
Male
Medical history is coded in MedDRA, and will be summarized by System Organ Class
(SOC) and Preferred Term (PT), by treatment group for the SAF.
7.2.4
Previous and Concomitant Medications
Previous medications are coded with WHO-DD, and will be summarized by therapeutic 
subgroup (ATC 2nd level) and chemical subgroup (ATC 4th level) and preferred WHO name 
by treatment group for the SAF. 
A drug stopped before or on the day of the first study drug injection will be defined as 
previous medication. And a drug started within the primary stusy period will be defined as 
concomitant medication. As with previous medication, concomitant medication will be 
summarized for each treatment group by therapeutic subgroup (ATC 2nd level) and chemical 
subgroup (ATC 4th level) and preferred WHO name. Subjects taking the same medication 
multiple times will be counted once per medication and investigational period. A medication 
which can be classified into several chemical and/or therapeutic subgroups is presented in all 
chemical and therapeutic subgroups.
7.2.5
Antiviral therapies
Antiviral therapies, including those used for reasons other than CMV infection  will be 
summarized by reason for use.
All subjects should receive 100 days of prophylactic valganciclovir or ganciclovir 
continuously starting within 10 days of transplant. The numbers of days on the prophylaxis 
will be summarized by treatment for the SAF.
7.2.6
Transplant Information
The following characteristics of the transplant procedure will be summarized by treatment for 
the SAF.
●
Use of anti-thymocyte globulin (ATG) (Yes/No)
●
Type of transplant (living donor & ATG=Yes/ living donor & ATG=No/ deceased donor 
& ATG=Yes/ deceased donor & ATG=No)
●
Recipient and donor relatedness (living related donor, living unrelated donor, deceased 
donor)


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●
Donor demographics (age, gender, race)
●
Recipient and donor HLA typing
●
HLA cross match at time of transplant (see Appendix 1 for how the cross match is 
determined)
●
Recipient and donor ABO types
●
Recipient and donor Hepatitis B virus, Hepatitis C virus, and Epstein-Barr Virus 
serostatus, if available, and HCV PCR RNA, (if available)
●
Organ preservation method
7.3
Study Drug
Descriptive statistics for total number of injections subject received and the time from first 
dose to final dose of study drug will be presented by treatment. Furthermore, the number and 
percentage of subjects receiving study drug injection at each scheduled dose will be 
presented by treatment. These summaries will be produced for the SAF. 
7.4
Analysis of Efficacy 
7.4.1
Analysis of Primary Endpoint
7.4.1.1 Primary Analysis of Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects with CMV viremia which is 
defined as plasma viral load ≥1000 IU/mL assessed by central assay through one year post 
first Study Drug injection. CMV viral load tests are scheduled once every 2 weeks for the 
first 8 tests starting 100 days from transplant and  subsequently once per month for 7 more 
tests. In addition, a subject may have unscheduled tests (suspect CMV syndrome or CMV 
tissue-invasive disease) by the local laboratory so that the subject can be treated promptly 
with antiviral therapy (AVT) if needed. Everytime a local laboratory is performed, the 
sample should also be sent to the central laboratory for assessment. The CMV viral load 
collected from the central laboratory after first injection (Day 1) through day 380 
(=365+14+1) that were collected as scheduled or unscheduled assessments will be utilized.
A patient who discontinue the study without a positive CMV viral load will be imputed as 
having a CMV viremia. A patient who has more than one time with viral load ≥1000 IU/mL 
by central assay will be counted once in this summary. Any unscheduled central laboratory 
values within the window will be included.
A Cochran-Mantel-Haenszel (CMH) test at the 1-sided 5% level stratified by use of anti-
thymocyte globulin (ATG) and by receipt of a kidney from a living or deceased donor will be 
used to analyze the primary endpoint of CMV incidence rate.
The null and alternative hypotheses for this comparison are:
H0: Common Odds Ratio = 1.
H1: Common Odds Ratio < 1.
The odds ratio is defined as the ratio of odds of viremia in the ASP0113 group to that in the 
placebo group. The 1-sided p-value with the 2-sided exact 90% confidence interval for the 


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common odds ratio will be calculated (in SAS specifying the comor option in the exact 
statement of proc freq).
The primary analysis will be conducted for the FAS population.
7.4.1.2 Sensitivity Analysis for Primary Efficacy Endpoint
Three sensitivity analyses for the primary efficacy endpoint will be conducted. 
An analysis identical to the primary analysis described in Section 7.4.1.1 will be repeated: 
●
A subject with two consecutive missing central laboratory CMV assessments
●
Composite endpoint of either CMV viral load >=1000 IU/mL by central labortorys 
OR use of AVT per adjudication 
The third sensitivity analysis will be conducted using the Kaplan-Meier method for the FAS 
population. Time to first occurrence of a patient’s CMV viremia will be included and 
treatment groups will be compared using a log-rank test.
Time to first event (in days) is calculated for each subject by taking the difference between 
the date of first study drug injection and the date of first event during the primary study
period plus 1. If a subject does not have the event of interest through Day 380 the subject will 
be censored at Day 380. If a subject discontinues the study (or lost to follow up) before Day 
380 then the subject will be considered as censored at last assessment. If the event occurs 
outside the primary study period it will not be counted for the analysis. 
7.4.1.3 Subgroup Analysis of Primary Efficacy Endpoint
Subgroup analysis on the primary efficacy endpoint will be performed with a logistic model 
including treatment, subgroup, and treatment by subgroup interaction as explanatory 
variables. A subgroup with a level that has fewer than 10 patients within any treatment group, 
the level will be excluded from the interaction test while descriptive statistics will be 
provided. If none or only one level of the subgroup meets the 10-subject criterion no 
subgroup analysis will be performed. The proportion, odds ratio per subgroup factor and its
2-sided 90% confidence intervals will be calculated. As this is a phase 2 study and the 
interaction test between the treatment group and the subgroup factors should be interpreted 
with a caution, the p-value from the interaction test will be compared to 0.15.
The subgroup analysis will be performed for the FAS according to:
●
levels of randomization strata
●
use of ATG, alemtuzumab, or rituximab after randomization
●
use of ATG after randomization
●
use of alemtuzumab after randomization 
●
use of rituximab after randomization
●
use of alemtuzumab or ATG after randomization 
●
kidney preservation method (cold, PUMP)
●
age group (<65, ≥65) 
●
race (white, balck, other)


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●
gender (male, female).
7.4.2
Analysis of Secondary Efficacy Endpoints 
The secondary endpoints defined below are binary with yes/no coutcomes. These secondary 
endpoints will be analyzed on FAS using the same method for the primary efficacy endpoint 
analysis described in Section 7.4.1.1
7.4.2.1 Adjudicated Endpoints
An independent panel of medical experts will adjudicate the events below through one year 
post first study drug injection based on blinded data:
●
CMV associated disease including CMV syndrome and tissue invasive disease, 
●
CMV specific antiviral therapy for the treatment of CMV viremia or disease
The proportion of subjects with any of the two adjudicated events will be analyzed separately 
7.4.2.2 CMV Viremia Defined as Plasma Viral Load ≥ the Lower Limit of 
Quantification [LLOQ]) by Central Assay
The central laboroatory will have the LLOQ for CMV viral load assessment. When the viral 
load is below the LLOQ the actual viral load reading is not possible and will be denoted as 
≤LLOQ. If a sunject has any CMV viral load assessment greater than the LLOQ by central 
laboratory the subject will be classified as viremic. The proportion of subjects with viremia 
will be analysed. For the purpose of this analysis, the same imputation method should be 
used as for the primary analysis.
7.4.2.3 Graft Survival
Calculation of graft survival: any subject that does not fit the definition of graft loss as 
follows during the primary study period will be defined as “yes”: subject death, re-transplant, 
nephrectomy, or return to permanent dialysis (i.e., for >30 days). The proportion of subjects 
with graft survival will be analyzed.
7.4.3
Analysis of Exploratory Endpoints
The analyses of all exploratory variables defined in Section 6.1.3 will be performed on the 
FAS. Each of these variables will be summarized by treatment. If the endpoint is measured at 
different visits, the variable will be summarized by treatment at each visit and at Final Visit
unless stated specifically otherwise.
Comparisons between treatment groups for the following binary variables will be tested 
using the exact CMH method as described in Section 7.4.1.1.
●
viral resistance to ganciclovir or valganciclovir 
●
biopsy-proven acute rejection (BPAR)
●
clinically treated acute graft rejection
Viral resistance to ganciclovir or valganciclovir is confirmed by central laboratory. Biopsy 
proven acute rejection (BPAR) is captured in the CRFs. For acute antibody mediated 


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rejection with Banff grade ≥1 or for T-cell mediated rejection with grade ≥1a BPAR will be 
“yes”. Clinicall treated acute graft rejection will be from the CRF. 
The time to the first adjudicated CMV disease, including CMV syndrome and CMV 
tissue-invasive disease will be analized using the the same method as described in the third 
sensitivity analysis in Section 7.4.1.2
The following count variables may be affected by duration of follow-up which is the time of 
last assessment from first injection plus 1. Therefore, each of the variable will be compared 
between treatments using Poisson regression with treatment and randomization stratum as 
factors offset by follow-up time. The risk ratio, 1-sided 5% p value and the 90% confidence 
interval for the risk ratio will be presented.
●
Number of opportunistic infections other than CMV 
●
Number of episodes of CMV viral load of ≥1000 IU/mL by central assay 
●
Number of episodes of adjudicated CMV-associated disease, including CMV syndrome 
and CMV tissue-invasive disease
Classifications of opportunistic infections other than CMV: Any TEAE with the following 
classifications will be considered and decided by the medical and safety officers of the study 
team before unblinding case by case if it is an opportunistic infection: (1) SOC: Renal and 
Urinary disorders and HLGT= Viral infectious disorders, Chlamydial Infections disorder, 
Mycobacterial infectious disorders, Fungal infectious disorders, Bacterial infectious 
disorders, Protozoal infectious disorders; (2) SOC: Renal and Urinary disorders and HLT= 
Genitourinary tract inflammation and infection NEC, Bladder infections and inflammations, 
Renal infections and inflammation, Urethral infections and inflammations.
Count episodes of the protocol defined CMV viremia:  
An episode starts with CMV viral load ≥ 1000 IU/mL by central assay and ends with two 
consecutive CMV viral load < 1000 IU/mL by central assay separated by at least one week in 
time. An episode will not be counted if it starts outside the primary study Period.
The ordinal variables below assessed by the central laboratory will be compared between 
treatments using the stratum-adjusted Wilcoxon rank-sum test. This test is implemented in 
SAS Proc Freq using the CMH2 option for tests based on row mean scores and 
SCORES=MODRIDIT option for use of modified standardized rank score within strata:
●
Peak CMV viral load 
●
Cumulative viral load 
Calculation of cumulative viral load:  
Using the linear trapezoidal rule to calculate the area under the viral load over time curve 
(AUC) divided by the length of time for each subject.
The eGFR and its change from baseline will be summarized by treatment at each visit and at 
final visit. The change from baseline to final visit will be compared using analysis of


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covariance (ANCOVA) with treatment and randomization stratum as factors and baseline 
value as a covariate.  
Calculation of eGFR:
186 × 	
 
		. × 	. × [1.212   ] × [0.742  %		] ,
where serum creatinine is in mg/dL and age in years. The value in either bracket is 1 if the 
stated condition is not met. If serum creatinine is in SI units (mmol/L) instead of the US units 
(mg/dL) then its value needs to be converted to the US units first by multiplying a factor of 
1/88.4.
Data from KTQ and SF-12 will be listed without any analysis.
The EQ-5D is an international standardized non-disease specific (i.e., generic) instrument for 
describing and evaluating health status. It is a measure of health-related quality of life 
(QOL), capable of being expressed as a single index value and specifically designed to 
complement other health status measures. The questionnaire will be provided in the local 
language of the subject. The EQ-5D has 5 domains: Mobility, Self-Care, Usual Activities, 
Pain/Discomfort, and Anxiety/Depression. Each domain has 5 response levels with higher 
score indicating worse outcome. In addition, it has a visual analogue scale that elicits a 
self-rating by the respondent of his/her health on a vertical, visual analogue scale where the 
endpoints are labeled ‘The best health you can imagine’ (=100) and ‘The worst health you 
can imagine’ (=0). (see Appendix 13 of the Protocol).
The EQ-5D score for each domain, the visual analog score and the corresponding changes
from baseline will be summarized by treatment at each visit and at final visit.
7.4.4
Analysis of Immunogenicity Variables
T-cell responses to pp65 and gB-specific antibody levels will be summarized by visit and 
treatment group on the original scale. A plot of each of the immune responses over time by 
treatment will be produced. The comparisons between treatments will be made at each 
measurement visit using Wilcoxon rank sum test without adjusting for the multiplicity on the 
original scale. In addition, each of the immune response variables post baseline on the 
10 based log scale will be analyzed using repeated measures model, where the randomization 
stratum, treatment, time, and treatment by time interaction will be the explainatory variables. 
The self-consistent sandwich correlation structure will be used. If the test for the time by 
treatment interaction is significant (p value<0.1) the overall treatment group comparison will 
not be displayed in the plots.
As an exploratory analysis, the relationship between immunogenicity variables and treatment 
outcome will be assessed using logistic regression method. The treatment outcome is if 
subject is free of CMV viremia through one year post-transplant. The optimal cutoff values 
of the respective immunogenicity variables that will define the treatment outcome will be 
explored in terms of maximizing the area under the receiver operating characteristic (ROC) 
curves.


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All analyses of immunogenicity variables will be based on the IAS. 
7.5
Analysis of Safety
All analysis of safety will be presented by treatment group for the SAF. 
7.5.1
Treatment Emergent Adverse Events
The coding dictionary for this study will be MedDRA Version 16. 
TEAE is defined as an adverse event observed after the first study drug injection (Day 1) 
through Day 380. If the adverse event occurs on Day 1 and the onset check box is marked 
“Onset after first dose of study drug” or the onset check box is left blank, then the adverse 
event will be considered treatment emergent. If the adverse event occurs on Day 1 and the 
onset check box is marked “Onset before first dose of study drug”, then the adverse event 
will not be considered treatment emergent. If a subject experiences an event before the first 
study drug injection and continues during the primary study period, the event will be 
considered as TEAE only if it has worsened in severity during the primary study period 
(i.e., it is reported with a new start date).
An overview summary table will include the following:
●
Number and percentage of subjects with TEAEs,
●
Number and percentage of subjects with drug related TEAEs,
●
Number and percentage of subjects with serious TEAEs,
●
Number and percentage of subjects with serious drug related TEAEs,
●
Number and percentage of subjects with TEAEs leading to permanent discontinuation of 
study drug injection, and
●
Number and percentage of subjects with drug related TEAEs leading to permanent 
discontinuation of study drug injection, and
●
Number of deaths.
The number and percentage of subjects with TEAEs, as classified by SOC and PT will be 
summarized for each treatment group. Summaries will be provided for:
●
TEAEs
●
drug related TEAEs, 
●
serious TEAEs, 
●
drug related serious TEAEs, 
●
TEAEs leading to permanent discontinuation of study drug, 
●
drug related TEAEs leading to permanent discontinuation of study drug, 
●
TEAEs excluding serious adverse events that equal to or exceed a threshold of 5.0% in 
any treatment group, and 
●
common TEAEs that equal to or exceed a threshold of 5.0% in any treatment group. 
Drug-related AE is defined as any AE with at least possible relationship to study treatment as 
assessed by the investigator or with missing assessment of the causal relationship. AEs will 
be graded using National Cancer Institute (NCI)-Commom Terminology Criteria for Adverse 


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Event (CTCAE) guidelines version 4.03. There are five grades: 1=mild, 2=moderate, 
3=severe, 4=life threatening, 5=death. Missing severity will not be imputed.
The number and percentage of subjects with TEAEs, as classified by PT only, will be 
summarized for each treatment group.
TEAEs and the number and percentage of subjects with TEAEs, as classified by SOC and PT 
will also be summarized by severity and by relationship to study drug. If an adverse event 
changes in severity or relationship, then the subject will be counted only once with the worst 
severity and highest degree of relationship. Drug related TEAEs will be presented in a similar 
way by severity.
7.5.2
Adverse Events of Special Interest
The number and percentage of subjects with each protocol defined grade will be summarized 
by treatment group for each injection visit and for worst grades across visits unless specified 
otherwise. There should be no imputations for missing values.
7.5.2.1 Acute Local Reactions Assessed by Investigator and Subject
The symptoms of local vaccine reactions and severity grading are defined below:
Local Reaction
To Injectable 
Product
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially
Life -Threatening
(Grade 4)
Pain 
Does not 
interfere
with activity
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or interferes with 
activity
Any use of 
narcotic pain 
reliever or 
prevents daily
activity
Emergency room
(ER) visit or
hospitalization
Tenderness 
Mild discomfort 
to touch
Discomfort with 
movement
Significant
discomfort at rest
ER visit or
hospitalization
Erythema/Redness * 
2.0 – 5 cm
5.1 – 10 cm
> 10 cm
Necrosis or
exfoliative dermatitis
Induration / 
Swelling ** 
2.0 – 5 cm 
and does not 
interfere
with activity
5.1 – 10 cm or
interferes with
activity
> 10 cm or
prevents daily
activity
Necrosis
Local reactions assessed by subjects:
Each subject will take 7 day diaries post each injection to recod the symptoms and the 
corresponding grades as shown above. For each symptom the maximum grade of the 7 day 
diary associated with each injection visit will be defined as the symptom grade for that visit. 
Local reactions assessed by investigators:
Symptoms are assessed one hour post each injection by investigators and the results are 
captured in the CRFs.


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7.5.2.2 Acute Systemic Reactions Assessed by Subjects
The symptoms and grading of systemic vaccine reactions assessed by subjects are defined 
below:
Systemic 
(General)*
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially
Life –Threatening
(Grade 4)
Fatigue
No interference 
with activity
Some interference 
with activity
Significant; 
prevents daily 
activity
ER visit or 
hospitalization
Myalgia
No interference 
with activity
Some interference 
with activity
Significant; 
prevents daily 
activity
ER visit or 
hospitalization
Fever (°C)***
          (°F)***
38.0-38.4
100.4-101.1
38.5-38.9
101.2-102.0
39.0-40
102.1-104
> 40
> 104
Each subject will take 7 day diaries post each injection to recod the grades associated with 
fatigue and myalgia and record the tempertures based on which the protocol defined grade 
will be derived according the above table. For each symptom the maximum grade of the 
7 day diary associated with each injection visit will be defined as the symptom grade for that 
visit.
7.5.2.3 Acute Systemic Reactions Assessed by Investigators
The symptoms and grading of systemic vaccine reactions assessed by investigators are 
defined below.
Vital signs are assessed pre- and 1 hour post- each injection. Changes will be used to 
determine the grades 1-3 according to the charter below. Grade 4 (except for fever related) 
comes from the SAEs. If any SAE that is considered related to systemic reactions post each 
injection by the investigators (captured in the CRF) and meets one of the two criteria below 
will be a grade 4 systemic reaction: (1) PT=Endotracheal Intubation, or (2) PT= Tachycardia, 
Bradycardia, Hypertension, or Hypotension with NCI- CTCAE v4.03 severity grade ≥4. 


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Systemic 
(General)*
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially
Life –Threatening
(Grade 4)
Fever (°C)***
          (°F)***
38.0-38.4
100.4-101.1
38.5-38.9
101.2-102.0
39.0-40
102.1-104
> 40
> 104
Tachycardia-beats 
per minute
Increase in heart 
rate 5-15 
beats/minute
Increase in heart 
rate 16-30 
beats/minute
Increase in heart  
rate > 30 
beats/minute 
ER visit or 
hospitalization for 
arrhythmia
Bradycardia-beats 
per minute  
Decrease in heart
rate 5-10 
beats/minute
Decrease in heart 
rate 11-15 
beats/minute
Decrease in heart 
rate > 15 
beats/minute
ER visit or 
hospitalization for 
arrhythmia
Hypertension 
(systolic)-mm Hg
Increase in systolic 
blood pressure 
(SBP) 20-30 mmHg
Increase in SBP 
31 mmHG - 40 
mmHg 
Increase in SBP 
> 40 mmHg
ER visit or 
hospitalization for 
malignant 
hypertension
Hypotension 
(systolic)-mm Hg
Decrease in SBP 
5 mmHg
Decrease in SBP 
5.1 mmHg to 10.0 
mmHg
Decrease in SBP to 
> 10.0 mmHg
ER visit or 
hospitalization for 
hypotensive shock
Respiratory Rate-
breaths per minute 
(at rest)
17-20
21-25
> 25
Intubation
7.5.2.4 Late Vaccine Reactions
All TEAEs will be reviewed by the Sponsor medical before databased hard lock to determed 
the terms for  late vaccine reactions.  
The number and percentage of subjects with each NCI- CTCAE v4.03 severity grade will be 
presented by treatment group. 
7.5.3
Clinical Laboratory Evaluation
The baseline value for clinical laboratory evaluations is the last measurement taken prior to
or on the day of the first injection of study drug.  
Quantitative clinical laboratory variables, i.e. hematology, biochemistry, urine protein, urine 
creatinine and calculated ratio of protein/creatinine will be summarized descriptively 
(n, mean, standard deviation, minimum, median, and maximum) by visit. Clinical laboratory
samples are drawn at screening, before each study drug injection, at each follow-up point for 
the injections, and at the last study visit (See Analysis visit window in Section 7.9.3).
Additionally, a within subject change will be calculated as the post-baseline measurement 
minus the baseline measurement and summarized descriptely. 
7.5.3.1 Liver function Tests
Patients’ liver safety evaluations will be summarized by the following categories:
●
ALT or AST > 3xULN, > 5xULN, > 10xULN, >20xULN
●
ALT > 3xULN, > 5xULN, > 10xULN, >20xULN
●
AST > 3xULN, > 5xULN, > 10xULN, >20xULN


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●
ALP > 1.5xULN, >3xULN
●
Total Bilirubin >2xULN
●
ALT or AST > 3xULN and Total Bilirubin > 1.5xULN
●
ALT or AST > 3xULN and Total Bilirubin > 2xULN
●
ALT or AST > 3xULN and ALP< 2xULN and Total Bilirubin > 2xULN
The post-baseline values that are collected through day 380 and meeting the above criteria 
will be included without regards to the baseline values.
7.5.4
Vital Signs
The baseline value for vital signs is the last measurement taken on or prior to the first
injection of study drug.
Vital signs (temperature, systolic blood pressure, diastolic blood pressure, respiratory rate, 
pulse rate,) and the change from baseline will be summarized using mean, standard deviation, 
minimum, median, and maximum by analysis visit (see Section 7.9.3).
7.5.5
Pregnancies
Data will be listed.
7.5.6
Physical Examination
Data will be listed.
7.6
Analysis of PK
Not applicable.
7.7
Analysis of PD
Not applicable.
7.8
Interim Analysis (and Early Discontinuation of the Clinical Study)
No interim analysis evaluating the efficacy results are planned. The safety data will be 
monitored by the DMC according to the DMC Charter. Futility analyses with first 
50 subjects and with 90 subjects were conducted (Appendix 2). The details will be described 
in the clinical study report.
At each futility analysis, Bayesian predictive probability of success (BPP) that the overall 
results of the trial will achieve the desired outcome, i.e., viremia rate on ASP0113 is at least 
25% less than that on placebo, will be calculated based on the accrued data. If BPP ≤ 0.20, 
then we conclude ASP0113 meets futility criterion. 
The 20% cut-off for BPP is determined by simulation studies. The simulation studies cover 
the following scenarios: for each placebo viremia rate of  0.40, 0.46, and 0.51 the reduction 
in viremia due to ASP0113 run from 0% (no effect), 10% (marginal reduction), 25% 
(meaningful reduction), and 45% (significant reduction). Under each scenario, BPP is 
calculated at each interim look. The 20% cutoff produces satisfactory overall operating


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characteristics of stopping the study early when there is little effect and preserving the power 
when ASP0113 shows the hypothized effect. 
A Data Monitoring Committee (DMC), external from the Sponsor, will be established to 
review safety and efficacy data at each interim look. A detailed description of the DMC, its 
role in this clinical trial, and the timing of the scheduled reviews will be provided in the 
DMC Charter.
Production of tables and listings will be performed by the independent statistician at 
Astellas / independent Data Analysis programmer at 
 No member of the clinical 
trial team will have access to the reporting data base or will review the final tables and 
listings created for the DMC.
The primary responsibility of the DMC will be to monitor the trial for safety and futility 
concerns. The DMC will not stop the trial based on efficacy advantages. Therefore, the 
significance level need not be adjusted for the interim looks. 
7.9
Handling of Missing Data, Outliers, Visit Windows, and Other
Information
7.9.1
Missing Data
In the analysis of the primary endpoint, subjects who are lost to follow-up will be imputed as 
having viremia. Otherwise, viremia will not be imputed. Only observed viral loads from central 
labs meeting the definition of viremia will be counted.
Time to event variables will be considered censored at the time of the last assessment. Time to 
the first protocol-defined CMV viremia will be considered censored at the time of  the last 
recorded central laboratory CMV measurement.
The start and stop dates of AEs and concomitant medication will be imputed to allocate the 
concomitant medication and AEs to a treatment group, in addition to determining whether an 
AE is/is not treatment emergent. Listings of the AEs and concomitant medications will present 
the actual partial dates; imputed dates will not be shown.
In case of missing partial start and stop dates for concomitant medications, the following 
rules will be used:
If start date is missing or partial:
●
if month is missing, use January 
●
if day is missing, use the first day of the month under consideration
●
if year is missing, use year of the informed consent date 
●
if entire date is missing, use informed consent date 
If stop date is missing or partial:
●
if month is missing, use December 
●
if day is missing, use the last day of the month under consideration
●
if year or the entire date is missing, set to December 31st, 2099


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If the imputed start date is after the stop date, then the imputed start date will be one day 
prior to the stop date.
For AEs, a missing or incomplete onset date will be imputed according to the following 
conventions for the purpose of defining TEAE. 
1)
Missing year, the AE will be count as TEAE
2)
Missing month, the AE will be counted as TEAE if the year is equal to the consent 
year or one year later.
3)
Missing date, using the last date of the month to determine TEAE.
No imputation of missing data for other variables will be done.
7.9.2
Outliers
All values will be included in the analyses.
7.9.3
Visit Windows
The screening visit, all dosing visits, post dosing visits, Month 8 and End of Study visits for 
analyses will be based on dates relative to date of first study drug injection (Day 1) according 
to the table below:
CRF Visit
Target day
Range
Analysis visit
1
-43 to 1
-43 to 1
Screening
2
1
1 to 1
Dose 1
3
15
12-18
Post Dose 1
4
31
26-36
Dose 2
5
45
42-48
Post Dose 2
6
61
56-66
Dose 3
7
75
72-78
Post Dose 3
8
91
86-96
Dose 4
9
105
102-108
Post Dose 4
10
151
146-156
Dose 5
11
165
162-168
Post Dose 5
12
241
231-251
Month 8
13
366
352-380
End of Study
If a dose is missed, the subject should continue on the same schedule of study drug injections 
and the same schedule of assessments except for the 14 days after dose visit for the missed
dose; clinical labs for hematology, biochemistry and hepatic profile should not be collected. 
Scheduled Immunogenicity Labs (Visit 5 & 9) must still be collected.
If there is ambiguity about numbering of a visit, then visit number will be assigned so that no 
two visits are assigned the same visit number, and (1) the value which assessment day is the 
closest to the defined target day within these windows is used; (2) if two values are equally 
close, the later is used in the analysis; (3) if the assessment should be performed before each 
dosing then the value collected last before dosing will be used; (4) if the assessment should 
be performed on the same day as a dosing day then the assessments closest to the day of the 
injection should be used. 
Analyses will not exclude subject data due to the subject’s failure to comply with the visit 
schedule.


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8
REFERENCES
ICH Harmonized Tripartite Guideline E 3. Structure and Content of Clinical Study Reports, 
November 1995. (www.ich.org; Guidelines; "Efficacy" Topics)
ICH Harmonized Tripartite Guideline E 9. Statistical Principles for Clinical Trials, February 1998. 
(www.ich.org; Guidelines; "Efficacy" Topics)
Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff ’07 classification of renal
allograft pathology: updates and future directions. Am J Transplant. 2008;8:753-60.
Humar A and Michaels M. American society of Transplantation Recommendations for Screening,
Monitoring and Reporting of Infectious Complications in Immunosuppression Trials in
Recipients of Organ Transplantation. Am J Transplantation. 2006;6:262-274. 
Couzi L, Helou S. Bachelet T, Moreau K, Martin S, Morel D. High incidence of anticytomegalovirus
drug resistance among D+R- kidney transplant recipients receiving preemptive therapy. Am J
Transplant. 2012;12:202-209.
Laupacis A, Pus N, Muirhead N, Wong C, Fergusion B, Keown P. Disease-specific quetionnaire for
patients with a renal transplant. Nephron. 1993;64 (2):226-31.
Chisholm-Burns MA, Erickson SR, Spivey CA, Kaplan B. Health-related quality of life and
employment among renal transplant recipients. Clin Transplant. 2012:26:411–417.


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9
APPENDICES
9.1
Appendix 1: Handling of the Human Leukocyte Antigen (HLA) 
Mismatching
For the comparison of the HLA types between the donor and the recipient, the following 
steps should be done to calculate the number of HLA mismatches:
1.  If the entry for a locus is a numeric code and a dash (or missing), then the dash for that 
locus is to be replaced (for calculation only) by the numeric code (homozygote).
2.  The following rules should be applied when calculating the number of mismatches within 
a HLA A, B, and DR locus:
●
If both codes are missing in either the donor or recipient, the number of mismatches is 
unknown (missing)
●
If the two codes are non-missing and identical for the recipient and the donor (without 
regard to the order) or the donor is homozygote and the donor code matches either 
one of the recipient’s codes then the number of mismatches is 0.
Examples:
Donor
Recipient
Mismatch
A1   A2
A2   A1
0
A2   A2
A2   A1
0
●
If one code from the donor exists in the recipient but the other code is different 
between the donor and recipient or the donor has identical codes (homozygote) but 
they don’t match either code in the recipient, then the number of mismatches is 1. 
Examples:
Donor
Recipient
Mismatch
A2   A3
A2   A1
1
A2   A3
A2    A2
1
A2   A2
A3   A4
1
A2   A2
A1   A1
1
●
If the donor is not homozygote and all codes are different between the donor and the 
recipient then the number of mismatches is 2.
Example:
Donor
Recipient
Mismatch
A1   A2
A3   A4
2
3.  If the number of mismatches from any of the three loci are missing, then total number of 
HLA mismatches is missing.  Otherwise the total number of HLA mismatches is the sum 
of the mismatches from the three loci.
An example following rules 1-4 above is provided below:
Donor:
(broad types)
HLA A
HLA B
HLA DR
A11
A10
B5
B5
DR5
DR6
Recipient:
(broad types)
HLA A
HLA B
HLA DR
A10
A19
B12
B5
DR5
DR7
Mismatch:
HLA A
HLA B
HLA DR
Total
1 
0 
1
2


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9.2
Appendix 2: Futility Analysis
The decision rule for stopping the trial based on efficacy is outlined below:
1.
At the interim look, suppose we have cumulative & ( = 0, 1) subjects from treatment 
i ( = 0 for placebo and  = 1 for vaccine). The cumulative number of subjects with 
viremia in treatment i will be denoted as & ( = 0, 1).  
2.
The additional number of subjects with viremia at the end of trial could be any integer 
between 0 and ) −& for treatment i, where N is the total number of subjects planned 
for each group. The probability that there are additional   subjects with viremia in 
the placebo group and   subjects with viremia in the vaccine group at the end of trial 
is 
+( ,  ) = .) − 
 
/ (0 +  +  , 2 + ) − − )
(0 + , 2 +  −)
× .) − 
 
/
3(4567587,95:6787)
3(4567,95;767)
(A)
where α and β are some arbitrary prior parameters and (, <) = ∫>?(1 −


>)@A> is a beta function. (For this study, we use 0 = 0.6, 2 = 0.4.) The reduction 
in relative risk is estimated as 


 = 1 −
67587
6B58B with probability (A) above.
3.
Sum up the probabilities with which 


 ≥25% over all possible values of   and  
to get the predictive probability FF:
FF = G G +( ,  )	+(


 ≥25%)
:;7
87H
:;B
8BH
where the 	+ I = 1 if 


 ≥25% and 0 otherwise. 
If FF ≤I then ending the study is indicated. Otherwise the study should be 
continued. Here the cutoff =20% is an empirical value determined by simulation studies.


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9.3
Appendix 3: Simulation Studies
The number of incidence x has the binomial distribution given the probability parameter :
+(>|L) = M
>N LO(1 −L);O,   x=0, 1, …, n
(1)
We assume the distribution for follows beta distribution with parameters α and β:
+(L) = 	(0, 2) =

3(4,9) L4(1 −L)9,  0<<1
(2)
where B(α, β) is a beta function
(0, 2) =
P(4)P(9)
P(459) .
Then the posterior distribution is a beta distribution as well
+(L|>) = +(>|L)+(L)
+(>)
~LO(1 −L);OL4(1 −L)9
~L(45O)(1 −L)(95;O) = 	(0R, 2S), (3)
where 0R = 0 + > and 2S = 2 +  −>. This conjugate feature of Beta distribution will be 
used in the simulations below.
We start with a hypothetical scenario where the viremia incidence rate L& is known ( = 0 for 
placebo and  = 1 for vaccine). Let  and  be the cumulative number of subjects each 
group has at the first and second interim look, respectively. And let N denote the number of 
subjects each group has at the end of trial.
1.
The data at the first interim look will be simulated by drawing  = 25 random 
samples from <I(, L&)  ( = 0, 1). The number of incidence will be denoted 
as & ( = 0, 1).
2.
Based on the conjugate feature of the beta prior, the distribution of the viremia 
incidence rate should be updated to 	(0 + &, 2 +  −&) ( = 0, 1) at the first 
interim look.  Draw J random samples for T& from the above beta distribution, where 
T& is a random sample of the viremia incidence rate for the ith group ( = 0, 1) at the 
first interim look.
3.
For each T& draw M random samples from <I() −, T&) to simulate the 
outcomes at the end of trial when all subjects are recruited and followed up for the 
endpoint ( = 0, 1). The number of additional (plus) incidence will be denoted as +&
( = 0, 1). Consequently, the reduction in relative risk is estimated as 


 = 1 −
6775U677
67B5U67B. 
4.
Compute the proportion P of 


 ≥25% over the V × W random samples. If F ≤
I, here the cutoff a threshold value (say 20%) to be determined the simulation 
studies, then stop the study. Otherwise proceed to the step below.


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5.
Draw additional  − = 20 random samples from <I( −, L&)  
( = 0, 1). Suppose the number of incidence is & ( = 0, 1). The distribution of the 
viremia incidence rate is now updated to 	(0 + & + &, 2 +  −& −&)
( = 0, 1) at the second interim look. Draw J random samples for T& from the above 
beta distribution, where T& is a random sample of the viremia incidence rate for the 
ith group ( = 0, 1) at the second interim look.
6.
For each T& draw M random samples from <I() −, T&) to simulate the 
outcomes at the end of trial when all subjects are recruited and followed up for the 
endpoint ( = 0, 1). The additional number of incidence will be denoted as +&
( = 0, 1). The reduction in relative risk is estimated as 


 = 1 −
67756X75U6X7
67B56XB5U6XB. 
7.
Compute the proportion P of 


 ≥25% over the V × W random samples. If
F ≤I then stop the study. Otherwise continue the study to the end when all N 
subjects are enrolled and followed up for the end point one year after the first 
injection of study drug.
8.
Repeat steps 1-7 R times to estimate the probability of stopping the study at first and 
second looks for a given hypothetical scenario as the proportion of stopping over the 
R repetitions. 
We repeat the process for various scenarios. Specifically, the scenarios considered are (1) no 
effect (incidence rates in the two groups are equal), (2) minor effect (10% reduction in 
incidence rate), (3) meaningful effect (25% reduction in incidence rate), and (4) significant 
effect (45% reduction in incidence rate). The incidence rates for placebo group considered 
are 46% and 51%. For each scenario, we run the simulations with R=1000, J=1000, and 
M=1000.
Simulation results are presented in the tables below.
Table 1: The cumulative probability of the Bayesian predictive probability (BPP) that the 
viremia incidence rate is at least 25% lower in ASP0113 than that in placebo is less than 25% 
(futility) at each interim look for different scenarios.
Viremia incidence rate
Cumulative probability of futility
Prob of success
Placebo
ASP0113
1st look
2nd look
End of study
End of study
0.51
0.51
0.680
0.921
0.976
0.024
0.46
0.528
0.827
0.908
0.092
0.38
0.285
0.520
0.636
0.364
0.28
0.083
0.155
0.175
0.825
0.46
0.46
0.656
0.882
0.961
0.039
0.41
0.511
0.766
0.868
0.132
0.34
0.275
0.510
0.609
0.391
0.25
0.079
0.172
0.185
0.815


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Table 2: The cumulative probability of the Bayesian predictive probability (BPP) that the 
viremia incidence rate is at least 25% lower in ASP0113 than that in placebo is less than 20% 
(futility) at each interim look for different scenarios.
Viremia incidence rate
Cumulative probability of futility
Prob of success
Placebo
ASP0113
1st look
2nd look
End of study
End of study
0.51
0.51
0.632
0.905
0.971
0.029
0.46
0.474
0.800
0.897
0.103
0.38
0.247
0.479
0.614
0.386
0.28
0.064
0.138
0.159
0.841
0.46
0.46
0.608
0.865
0.957
0.043
0.41
0.454
0.747
0.862
0.138
0.34
0.246
0.470
0.594
0.406
0.25
0.059
0.149
0.164
0.836
Table 3: The cumulative probability of the Bayesian predictive probability (BPP) that the 
viremia incidence rate is at least 25% lower in ASP0113 than that in placebo is less than 15% 
(futility) at each interim look for different scenarios.
Viremia incidence rate
Cumulative probability of futility
Prob of success
Placebo
ASP0113
1st look
2nd look
End of study
End of study
0.51
0.51
0.579
0.879
0.966
0.034
0.46
0.425
0.760
0.885
0.115
0.38
0.195
0.435
0.590
0.410
0.28
0.046
0.116
0.141
0.859
0.46
0.46
0.554
0.846
0.954
0.046
0.41
0.385
0.710
0.850
0.150
0.34
0.205
0.421
0.567
0.453
0.25
0.045
0.118
0.137
0.863
When there is no treatment effect (0.46 vs 0.46 or 0.51 vs. 0.51) the BPP ≤ 0.25 criterion 
results in >65% chance to terminate the study; BPP ≤ 0.2 criterion results in about 61% 
chance while BPP ≤ 0.1  offers less than 50% chance which is too low to serve our purpose 
since the goal of the interim analysis is to stop early when there is no treatment effect.
When there is a fair treatment effect (25% reduction in viremia rate) (0.46 vs 0.34 or 0.51 vs. 
0.38) the BPP ≤ 0.25 criterion results in 30% chance to terminate the study while 
BPP ≤ 0.2 criterion results in about 23% chance.
The chance of mistakenly terminating study at interim for the 0.46/0.25 and 0.51/0.28 
scenarios is about 7% to 9% for the 0.2 criterion and >10% for the 0.25 criterion. 
Overall, the 0.2 cutoff performs well in terms of stop early when there is no treatment effect 
and the chance not to kill the study when there is a fair treatment effect.


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9.4
Appendix 4: List of the SAP Changes and Rationale
The changes to the approved SAP (15April 2014) that affect the analyses are specified with the 
rationale in the table below.
SAP Sections
Description
Rationale
5.2 Per Protocol 
Set (PPS)
Removed.
For a Phase 2 study, this type of analysis 
where a sizable number of patients are 
excluded from the PPS classification criteria 
may provide uninterpretable results. 
6.1.2 Secondary 
Efficacy Endpoints
Removed one of the secondary efficacy 
endpoint of subject survival through one 
year.
In order to avoid redundancy as as the 
mortality is summarized as a part of adverse 
event summary.
7.1 General 
Consideration
Specified the analysis duration   of the 
primary study period as data collected 
through day 380 (=365+14+1) for this 
SAP.
This analysis duration is specified by taking 
the protocol allowed visit windows in order 
to clarify the data inclusion for this analysis 
plan.
7.2.2 Protocol 
Deviation
Removed the category of PD5-Other.
In order to capture the protocol deviations to 
specific categories utilizing PD1 thorugh 
PD4.
7.4.1.2  Sensitivity 
Analysis for 
Primary Efficacy 
Endpoint

Clarified the analysis to assume a 
patient with at least 2 consecutive 
missing central laboratory viral load as 
a CMV viremic, and 

Added an analysis to consider a 
patient who took AVT that is 
adjudicated as a CMV viremia 
treatment but no evidence of CMV 
viremia by central laboratory is 
assumed CMV viremic.
These sensitivity analyses are planned in 
order to evaluate the robustness of the 
primary analysis for the primary efficacy 
endpoint.
7.4.3 Analysis of 
Exploratory 
Endpoints
The assessments of kidney transplantation 
and SF-12 questionnares to be only listed 
without a formal analysis within this 
analysis plan. 
A proper analysis for these questionnaires to 
be conducted by the HEOR expert.
7.5.2 Adverse 
Events of Special 
Interest
Removed the following AEs of special 
interest:

Opportunistic infections

Special infections related to 
kidney transplant

Post-transplant 
lymphoproliferative disorder
The opportunistic infection is a prespecified 
exploratory efficacy endpoint thus removed 
from this section in order to avoid 
redundency.
The second and third bullet items are 
removed because these events are not 
expected to occur under vaccine treatment.
7.5.3 Clinical 
Laboratory 
Evaluation
Removed the shift summary for laboratory 
parameters using low, normal and high 
normal ranges.  
The laboratory values are summarized for 
the change from baseline using the 
descriptive statististics.


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7.5.3 Clinical 
Laboratory 
Evaluation
Removed the following:

Potentially clinically significant 
(PCS) laboratories 

Shift tables for SGOT, SGPT, 
Platelets, Hematocrit, Hemoglobin, 
Serum creatinine, and Total 
bilirubin at granular categories 
This type of analysis is  considered 
medically not meaningful.
7.5.3.1 Liver 
Function Test
The criteria are updated to the following:

ALT or AST > 3xULN, > 5xULN, 
> 10xULN, >20xULN

ALT > 3xULN, > 5xULN, 
> 10xULN, >20xULN

AST > 3xULN, > 5xULN, 
> 10xULN, >20xULN

ALP > 1.5xULN, >3xULN

Total Bilirubin >2xULN

ALT or AST > 3xULN and Total 
Bilirubin > 1.5xULN

ALT or AST > 3xULN and Total 
Bilirubin > 2xULN

ALT or AST > 3xULN and 
ALP< 2xULN and Total Bilirubin 
> 2xULN
These new criteria are the sponsor’s 
standard categories.
7.5.4 Vital Signs
Removed the summary of  potentially 
significant vital signs based on special 
criteria.
The vital sign is summarized for the mean 
change from baseline using the descriptive 
statistics.  
7.8 Subgroups of 
Interest
Removed the subgroup analysis on 
adverse events of special interest for the
various subgroup factors. 
This type of subgroup analysis on 
potentially small number of patients with 
AEs of special interest may yield 
uninterpretable results.