A Phase 1/2, Randomized, Single Ascending Dose Study in Adults (Stage 1) and Randomized, Single Ascending Dose-Finding Study (Stage 2) in Elderly Subjects With ASP3772, a Pneumococcal Vaccine
Phase: PHASE1
Conditions: Pneumonia, Bacterial, Healthy Volunteers, Pneumococcal Disease
Sponsor: GlaxoSmithKline

Protocol Amendment 2
Study ID:  219659
Official Title of Study: A Phase 1/2, Randomized, Single Ascending Dose 
Study in Adults (Stage 1) and Randomized, Single Ascending Dose-Finding 
Study (Stage 2) in Elderly Subjects with ASP3772, a Pneumococcal Vaccine
NCT number: NCT03803202
Other Identifier: 3772-CL-1001
Date of Document: 04-DEC-2019

Sponsor: APGD
ISN/Protocol 3772-CL-1001
- CONFIDENTIAL -
02 Dec 2019
Astellas
Page 1 of 111
Version 2.1 Nonsubstantial Amendment 2
A Phase 1/2, Randomized, Single Ascending Dose Study in 
Adults (Stage 1) and Randomized, Single Ascending Dose-Finding 
Study (Stage 2) in Elderly Subjects with ASP3772, 
a Pneumococcal Vaccine 
ISN/Protocol 3772-CL-1001
Version 2.1
Incorporating Nonsubstantial Amendment 2 [see Section 13]
02 Dec 2019
IND 18657
Sponsor:
Astellas Pharma Global Development, Inc. (APGD)
1 Astellas Way
Northbrook, IL 60062
Protocol History:
Version 1.0 [Original, 07Aug2018]
Version 1.1 [Nonsubstantial amendment 1, 16Nov2018]
Version 2.0 [Substantial amendment 1, 28Feb2019]
The information contained in this document is supplied as a background for clinical investigations. This document contains 
confidential information, which is the intellectual property of Astellas. By accepting or reviewing this document, you agree 
to hold this information in confidence and not copy or disclose it to others or use it for unauthorized purposes except (1) as 
otherwise agreed to in writing; (2) where required by applicable law; (3) where disclosure is directly related to the care and 
safety of the research participant; and (4) where disclosure of such information is made to a member of the investigator’s 
team who agrees to hold this information in confidence. 

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Table of Contents
I.
SIGNATURES ······················································································ 7
II.
CONTACT DETAILS OF KEY SPONSOR’S PERSONNEL····························10
III.
LIST OF ABBREVIATIONS AND DEFINITION OF KEY TERMS ··················12
IV.
SYNOPSIS··························································································15
V.
FLOW CHART AND SCHEDULE OF ASSESSMENTS·································27
1
INTRODUCTION·················································································36
Background ····················································································37
Nonclinical and Clinical Data ·······························································38
Summary of Key Safety Information for Study Drugs ···································38
Risk Benefit Assessment ·····································································39
2
STUDY OBJECTIVE(S), DESIGN AND ENDPOINTS···································40
Study Objective(s) ············································································40
Study Design and Dose Rationale···························································40
2.2.1
Study Design·············································································40
2.2.2
Dose Rationale···········································································43
Endpoints·······················································································44
3
STUDY POPULATION··········································································45
Selection of Study Population ·······························································45
Inclusion Criteria··············································································46
Exclusion Criteria ·············································································47
4
IMMUNIZATION(S)·············································································48
Identification of Investigational Products ··················································48
4.1.1
Study Vaccine (ASP3772) ·····························································48
4.1.2
Comparative Vaccine(s) ································································49
4.1.2.1
Prevnar 13 ··········································································49
4.1.2.2
Pneumovax 23······································································49
Packaging and Labeling ······································································49
Study Vaccine Handling······································································49
Blinding ························································································50
4.4.1
Blinding Method·········································································50
4.4.2
Confirmation of the Indistinguishability of the Study Vaccines···················51

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4.4.3
Retention of the Assignment Schedule and Procedures for Study Vaccine 
Assignment Code Breaking ····························································51
4.4.4
Breaking the Study Vaccine Assignment Code for Emergency ···················51
4.4.5
Breaking the Study Vaccine Assignment Code by the Sponsor ···················51
Assignment and Allocation ··································································52
5
IMMUNIZATIONS AND EVALUATION···················································52
Dosing and Administration of Study Vaccine and Other Medications ·················52
5.1.1
Dose/Dose Regimen and Administration Period ····································52
5.1.2
Increase or Reduction in Dose of the Study Vaccine(s) ····························53
5.1.3
Previous and Concomitant Treatment (Medication and NonMedication 
Therapy) ··················································································54
5.1.4
Immunization Compliance ·····························································55
5.1.5
Criteria for Continuation of Immunization···········································55
5.1.6
Restrictions During the Study··························································55
Demographics and Baseline Characteristics ···············································56
5.2.1
Demographics············································································56
5.2.2
Medical History··········································································56
Immunogenicity Assessments ·······························································56
5.3.1
Immunological Response·······························································56
Safety Assessment ············································································56
5.4.1
Adverse Events ··········································································56
5.4.2
Vital Signs················································································57
5.4.3
Reactogenicity ···········································································57
5.4.4
Laboratory Assessments································································58
5.4.5
Anti-biotin Antibodies ··································································58
5.4.6
Physical Examination ···································································58
5.4.7
Electrocardiogram·······································································58
Adverse Events and Other Safety Aspects ·················································59
5.5.1
Definition of Adverse Events ··························································59
5.5.1.1
Abnormal Laboratory Findings ··················································60
5.5.1.2
Potential Cases of Drug-Induced Liver Injury ·································60
5.5.2
Definition of Serious Adverse Events (SAEs) ·······································60
5.5.2.1
Always Serious Adverse Events ·················································61
5.5.3
Criteria for Causal Relationship to Study Vaccine ··································61
5.5.4
Criteria for Defining the Severity of an Adverse Event ····························62

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5.5.5
Reporting of Serious Adverse Events (SAEs) ·······································62
5.5.6
Follow-up of Adverse Events··························································63
5.5.7
Monitoring of Common Serious Adverse Events ···································64
5.5.8
Special Situations········································································64
5.5.8.1
Pregnancy···········································································64
5.5.8.2
Medication Error, Overdose and “Off-Label Use” ····························65
5.5.8.3
Misuse···············································································65
5.5.8.4
Occupational Exposure ···························································65
5.5.8.5
(Suspicion of) Transmission of infectious agent·······························66
5.5.8.6
Suspected Drug-Drug Interaction················································66
5.5.9
Supply of New Information Affecting the Conduct of the Study··················66
5.5.10
Urgent Safety Measures ································································66
5.5.11
Reporting Urgent Safety Measures····················································66
Test Drug Concentration ·····································································67
Other Measurements, Assessments or Methods ···········································67
67
Total Amount of Blood·······································································67
6
DISCONTINUATION············································································68
Discontinuation of Individual Subject(s) From Study ····································68
6.1.1
Lost to Follow Up ·······································································68
Discontinuation of the Site···································································68
Discontinuation of the Study·································································69
7
STATISTICAL METHODOLOGY ···························································69
Sample Size····················································································69
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
Demographics and Baseline Characteristics ···············································70
7.3.1
Subject Disposition······································································70
7.3.2
Previous and Concomitant Medications ··············································70
7.3.3
Medical History··········································································71
Analysis of Immunogenicity·································································71
Analysis of Safety·············································································72
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7.5.1
Adverse Events ··········································································73
7.5.2
Laboratory Assessments································································73
7.5.3
Vital Signs················································································73
7.5.4
Physical Examination ···································································73
7.5.5
Routine 12-lead Electrocardiograms ··················································73
Analysis of Pharmacokinetics ·······························································73
Analysis of Pharmacodynamics ·····························································73
Major Protocol Deviations and Other Analyses ···········································74
Interim Analysis (and Early Discontinuation of the Clinical Study)····················74
Handling of Missing Data, Outliers, Visit Windows and Other Information ··········74
8
OPERATIONAL CONSIDERATIONS·······················································74
Data Collection················································································74
Screen Failures ················································································76
Major Protocol Deviations ···································································76
9
END OF TRIAL ···················································································77
10
STUDY ORGANIZATION······································································77
Dose Escalation Committee (DEC) ·························································77
11
REFERENCES ····················································································78
12
APPENDICES ·····················································································79
Ethical, Regulatory and Study Oversight Considerations ································79
12.1.1
Ethical Conduct of the Study···························································79
12.1.2
Institutional Review Board (IRB) ·····················································79
12.1.3
Protocol Amendment and/or Revision················································79
12.1.4
Financial Disclosure ····································································79
12.1.5
Informed Consent of Subjects ·························································80
12.1.5.1
Subject Information and Consent················································80
12.1.5.2
Supply of New and Important Information Influencing the Subject’s 
Consent and Revision of the Written Information ·····························80
12.1.6
Source Documents ······································································80
12.1.7
Record Retention ········································································81
12.1.8
Subject Confidentiality and Privacy···················································81
12.1.9
Arrangement for Use of Information and Publication of the Clinical Study ·····82
12.1.10
Signatory Investigator for Clinical Study Report····································82

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Procedure for Clinical Study Quality Control ·············································83
12.2.1
Clinical Study Monitoring······························································83
12.2.2
Direct Access to Source Data/Documents············································83
12.2.3
Data Management ·······································································83
12.2.4
Quality Assurance·······································································83
Contraception Requirements·································································84
List of Excluded Concomitant Medications················································86
Laboratory Assessment·······································································87
Grading of Local Reactogenicity····························································89
Grading of Signs of Systemic Reactogenicity ·············································90
Grading of Laboratory Abnormalities ······················································92
Liver Safety Monitoring and Assessment ··················································93
Common Serious Adverse Events···························································96
··97
13
ATTACHMENT 1:  NONSUBSTANTIAL AMENDMENT 2····························99
14
COORDINATING INVESTIGATOR’S SIGNATURE·································· 110
15
SPONSOR SIGNATURES ···································································· 111
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I.
SIGNATURES
1.  SPONSOR’S SIGNATURES
Required signatures (e.g., Protocol authors and contributors, etc.) are located in [Section 15
Sponsor Signature].

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2.  COORDINATING INVESTIGATOR’S SIGNATURE 
The Coordinating Investigator’s signature can be found in Section 14 Coordinating 
Investigator’s Signature, located at the end of this document.

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3.  INVESTIGATOR’S SIGNATURE
A Phase 1/2, Randomized, Single Ascending Dose Study in Adults (Stage 1) and 
Randomized, Single Ascending Dose-Finding Study (Stage 2) in Elderly Subjects 
with ASP3772, a Pneumococcal Vaccine 
ISN/Protocol 3772-CL-1001
Version 2.1
Incorporating Nonsubstantial Amendment 2
02 Dec 2019
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 International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical 
Practice (GCP) guidelines and applicable local regulations. I will also ensure that subinvestigator(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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II.
CONTACT DETAILS OF KEY SPONSOR’S PERSONNEL
24h-Contact for Serious 
Adverse Events (SAEs)
See [Section 5.5.5 Reporting of 
Serious Adverse Events] for 
SAE Fax Number and Email
Please fax or email the SAE Worksheet to:
Astellas Pharma Global Development, Inc. 
Pharmacovigilance
North America Fax number: 888-396-3750
North America Alternate Fax number: 847-317-1241
International Fax Number : +44-800-471-5263
Email: safety-us@astellas.com
Medical Monitor/ 
Study Physician:
, MD, PhD
, Medical Specialties
Astellas Pharma Global Development, Inc.
Cell/Mobile: 
Fax:
Email:
, MD
, Medical Affairs
ICON Clinical Research
2100 Pennbrook Parkway, North Wales, PA 19454
Tel:
Cell/Mobile: 
 (preferred)
Email:
Clinical Research Contacts:
Senior Clinical Study Manager 
Astellas Pharma Global Development, Inc.
1 Astellas Way, Northbrook, IL 60062
Tel: 
Cell/Mobile: 
Email: 
, MBA
Astellas Pharma Global Development, Inc.
1 Astellas Way, Northbrook, IL 60062
Tel: 
Cell/Mobile:
Email: 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

Sponsor: APGD
ISN/Protocol 3772-CL-1001
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Clinical Research Contacts:
(continued)
Project Manager
ICON Clinical Research
2100 Pennbrook Parkway, North Wales, PA 19454
Tel: 
Cell/Mobile:
Email:
, Project Management
ICON Clinical Research
320 Seven Springs Way #500, Brentwood, TN 37027 
Tel: 
Email:
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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III.
LIST OF ABBREVIATIONS AND DEFINITION OF KEY TERMS
Abbreviations
Description of abbreviations
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
anti-HCV
hepatitis C virus antibodies
APGD
Astellas Pharma Global Development Inc.
AST
aspartate aminotransferase 
AT
aminotransferase
CA
Competent Authorities
cEC
concerned Ethics Committee
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CP1
carrier protein
CRF
case report form
CRO
contract research organization
DEC
dose escalation committee
ECG
electrocardiogram
eCRF
electronic case report form
EEA
European Economic Area
ESV
end-of-study visit
FAS
full analysis set
FIH
first-in-human
FSH
follicle stimulating hormone
GCP
good clinical practice
GMC
geometric mean concentration
GMFR
geometric mean fold rise
GMP
good manufacturing practices
GMT
geometric mean titer
GSD
geometric standard deviation
HBsAg
hepatitis B surface antigen
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
ICF
informed consent form
ICH 
International Council for Harmonisation of technical requirements for registration 
of pharmaceuticals for human use
IEC
independent ethics committee
IgG
immunoglobulin G
IL
interleukin
IND
investigational new drug

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Abbreviations
Description of abbreviations
INR
international normalized ratio
IPD
invasive pneumococcal disease
IRB
institutional review board
IRT
interactive response technology
LA-CRF
liver abnormality case report form
MAAE
medically attended adverse event
MAPS
multiple antigen-presenting system
MedDRA
Medical Dictionary for Regulatory Activities
NOCD
new-onset chronic disease
NSAID
nonsteroidal anti-inflammatory drug
OPA
opsonophagocytic activity
PBMC
peripheral blood mononuclear cells
PCV13
Prevnar 13®
PIMMC
potentially immune mediated medical condition
PPS
per protocol set
PPSV23
Pneumovax®23
PS
polysaccharide
RBC
red blood cell
(S)AE
serious adverse event or adverse event
SAE
serious adverse event
SAF
safety analysis set
SAP
statistical analysis plan
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reactions
TBD
to be decided
TEAE
treatment-emergent adverse event
TBL
total bilirubin
Th17
T helper 17 cells
ULN
upper limit of normal
USM
urgent safety measure
WBC
white blood cell
WOCBP
woman of childbearing potential
CCI
CCI

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Definition of Key Study Terms
Terms
Definition of terms
Baseline 
Assessments of subjects as they enter a study before they receive any 
treatment. 
Endpoint 
Variable that pertains to the efficacy or safety evaluations of a study.
Enroll
To register or enter a subject into a clinical study. Note: Once a subject has 
received the study drug or placebo, the clinical study protocol applies to the 
subject. 
Intervention
The drug, device, therapy or process under investigation in a clinical study that 
is believed to have an effect on outcomes of interest in a study (e.g., health-
related quality of life, efficacy, safety and pharmacoeconomics). 
Investigational 
period
Period of time where major interests of protocol objectives are observed, and 
where the test drug or comparative drug (sometimes without randomization) is 
usually given to a subject, and continues until the last assessment after 
completing administration of the test drug or comparative drug.
Post investigational 
period
Period of time after the last assessment of the protocol. Follow-up observations 
for sustained adverse events and/or survival are done in this period.
Randomization
The process of assigning study subjects to treatment or control groups using an 
element of chance to determine assignments in order to reduce bias.
Screening
A process of active consideration of potential subjects for enrollment in a 
study.
Screen failure
Potential subject who did not meet 1 or more criteria required for participation 
in a study.
Screening period
Period of time before entering the investigational period, usually from the time 
when a subject signs the consent until just before the test drug or comparative 
drug (sometimes without randomization) is given to a subject. 
Study period
Period of time from the first site initiation date to the last site completing the 
study.
Variable
Any entity that varies; any attribute, phenomenon or event that can have 
different qualitative or quantitative values.

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IV.
SYNOPSIS
Date and Version No of Protocol Synopsis:
02 Dec 2019, Version 2.1
Sponsor:  
Astellas Pharma Global Development Inc. (APGD)
Protocol Number: 
3772-CL-1001
Name of Study Drug: 
ASP3772
Phase of Development:  
Phase 1/2
Title of Study:
A Phase 1/2, Randomized, Single Ascending Dose Study in Adults (Stage 1) and Randomized, Single 
Ascending Dose-Finding Study (Stage 2) in Elderly Subjects with ASP3772, a Pneumococcal Vaccine  
Planned Study Period: 
Stage 1:  1Q2019 – 2Q2019 
Stage 2:  3Q2019 – 3Q2020
Study Objective(s): 
Stage 1: 
Primary Objective:  To evaluate the safety and tolerability of 3 different dose levels of ASP3772 in 
comparison to the active comparator Prevnar 13® (PCV13) in adults 18 to 64 years of age. 
Secondary Objective:  To evaluate the immunogenicity of 3 different dose levels of ASP3772 in 
comparison to the active comparator PCV13 in adults 18 to 64 years of age. 
Stage 2: 
Primary Objective:  To evaluate the safety and tolerability of 3 different dose levels of ASP3772 in 
comparison to the active comparator PCV13 in elderly 65 to 85 years of age.
Secondary Objectives:  
To evaluate the immunogenicity of 3 different dose levels of ASP3772 in comparison to the active 
comparator PCV13 in elderly 65 to 85 years of age.
To evaluate the immunogenicity of 3 different dose levels of ASP3772 relative to the response seen 
following administration of Pneumovax®23 (PPSV23) for the serotypes not included in PCV13.
Planned Total Number of Study Centers and Location(s):  
Stage 1: Approximately 10 sites in United States
Stage 2: Approximately 25 sites (includes sites from Stage 1) in United States
Study Population:  
Stage 1:  Adults:18 to 64 years of age 
Stage 2:  Elderly: 65 to 85 years of age
Number of Subjects to be Enrolled/Randomized:  
Stage 1: A total of approximately 120 evaluable adults 18 to 64 years of age  
Number of Subjects per Cohort by Immunization
Cohort 
Stage 1 (Group 1)
ASP3772
Number of 
Subjects 
Comparator
Number of 
Subjects
1
1 g
30
PCV13
10
2
2 g
30
10
3
5 g
30
10
PCV13: Prevnar 13

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Stage 2:  A total of approximately 495 evaluable adult subjects from 65 to 85 years of age.
Number of Subjects per Cohort by Immunization
Cohort 
Stage 2 ( Group 2)
ASP3772
Number of Subjects 
Comparator 
Number of Subjects
4
1 µg
99
PCV13
33
5
2 µg
99
33
6
5 µg
99
33
PCV13: Prevnar 13
Study Immunization
Group
Stage 2 (Group 3)
Number of Subjects
PPSV23
99
PPSV23: Pneumovax 23
Study Design Overview:  
This is a combined phase 1, first-in-human (FIH), dose-escalation (Stage 1) and phase 2, dose-finding 
(Stage 2), observer-blinded study to evaluate the safety, tolerability and immunogenicity of ASP3772 
in adult and elderly subjects. 
The objectives of this study are to evaluate safety, tolerability including reactogenicity and 
immunogenicity in adult subjects 18 to 64 years of age in Stage 1 and in elderly subjects 65 to 
85 years of age in Stage 2, who are naïve to licensed or investigational pneumococcal vaccine.  
The study population will consist of 3 different groups: Group 1 - Stage 1 PCV13 naïve subjects 
randomized within 3 sequential cohorts to ASP3772 or PCV13; Group 2 - Stage 2 PCV13 naïve 
subjects randomized within 3 sequential cohorts to ASP3772 or PCV13; and Group 3 - Stage 2 
subjects previously vaccinated with PCV13 that will receive PPSV23.  
To minimize the risk to subjects, a sentinel group of subjects (n = 2; 1 ASP3772:1 PCV13) will be 
vaccinated in each cohort prior to initiating enrollment of the full cohort.  Safety data through day 7 
from sentinel subjects will be evaluated by the Dose Escalation Committee (DEC) prior to enrolling 
the remainder of the cohort.  Safety data through day 7 from all subjects within a dose cohort will be 
evaluated by the Dose Escalation Committee (DEC) prior to escalating to the next dose cohort within 
the adult and within elderly subjects. Based on the safety data through 30 days after immunization 
from the first 3 cohorts, the DEC will determine if Stage 2 can commence, and if sentinel dosing is 
required for Stage 2. All subjects within each cohort will remain under observation for approximately 
1 hour postimmunization, provided no reactions have occurred that require additional observation in 
the opinion of the investigator.  The DEC membership may include representatives from Astellas
Medical Science, Pharmacovigilance and Statistics personnel, as well as external independent safety 
physician(s).  The external safety physician will be selected based on expertise in vaccine clinical 
studies and other considerations such as the disease area. A DEC charter will detail the roles, 
responsibilities and procedures for decision-making.
See the Schedule of Assessments for details on procedures performed at each study visit for each 
group.
Stage 1 Group 1:
Stage 1 of the phase 1/2 design is a randomized, active-controlled, observer-blinded, dose-escalation 
study of the safety, tolerability and immunogenicity of the ASP3772 pneumococcal vaccine in adult 
subjects (18 to 64 years of age) compared with PCV13 with a 3:1 randomization (ASP3772:PCV13).  
After screening, subjects will be enrolled sequentially into 3 cohorts designated by escalating 
ASP3772 dose levels.  A single dose of ASP3772 will be administered as a 0.5 mL intramuscular 

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Study Design Overview (continued):  
injection into the deltoid muscle of the right or left arm on day 1 at 1 of 3 dose levels: 1, 2 or 5 g of 
ASP3772 for cohorts 1, 2 and 3 respectively.  The subjects randomized to PCV13 will receive a single 
injection of the standard dose of PCV13 on day 1.
After all subjects complete dosing in Cohort 1 (low dose, 1 g of ASP3772 or PCV13), safety 
(including reactogenicity) and tolerability through 7 days postimmunization will be assessed by the 
DEC.  Assessments of safety and tolerability by the DEC will occur prior to initiating the next dose 
group, Cohort 2 (2 μg of ASP3772 or PCV13) and then Cohort 3 (5 μg of ASP3772 or PCV13), based 
on safety and tolerability data through 7 days postimmunization.  
Safety and tolerability assessments will continue through 30 days postimmunization.  Safety 
assessments for serious adverse events (SAEs) and medically attended adverse events (MAAEs) 
including potential immune-mediated medical conditions (PIMMCs), and new-onset chronic disease 
(NOCDs) will continue through day 180 postimmunization.  Data will be collected in an observer-
blinded manner (vaccine recipients and those responsible for evaluation of any study endpoint will be 
unaware of which vaccine the subject received).  
Serum samples to measure immunoglobulin G (IgG) and opsonophagocytic activity (OPA) will be 
collected prior to the first study immunization on day 1 and on day 30 postimmunization.  
Stage 2 Group 2:
Stage 2 of the study is a dose-finding (sequentially higher doses), active-controlled, observer-blinded 
study with 3:1 randomization (ASP3772:PCV13) in elderly subjects 65 to 85 years of age.
After screening, PCV13 naïve subjects will be randomized within each cohort to receive ASP3772 or 
PCV13.  Subjects randomized to ASP3772 will receive a single dose of ASP3772 administered as a 
0.5 mL intramuscular injection into the deltoid muscle of the right or left arm on day 1, at 1 of 3 dose 
levels: 1, 2 or 5 g of ASP3772 for Cohorts 4, 5 and 6, respectively.  The subjects randomized to 
PCV13 will receive a single injection of the standard dose of PCV13. 
Approximately 396 subjects will be enrolled in Stage 2 of the study; 132 subjects per cohort 
(ASP3772 n = 99 and PCV13 n = 33).
Stage 2 will commence after the DEC has evaluated safety (including reactogenicity) data through 
30 days from all cohorts in Stage 1.  Dose escalation to Cohort 5 (intermediate dose, 2 g) in Stage 2 
will commence once the DEC has evaluated Stage 2 Cohort 4 (1 g) safety (including reactogenicity) 
and tolerability through 7 days postimmunization.  Dose escalation into Cohort 6 (high dose, 5 g) in 
Stage 2 will commence once the DEC has evaluated Stage 2 Cohort 5.  Randomization for Stage 2 
subjects will be stratified by age (65 to 74 years of age and 75 to 85 years of age) to ensure there is a 
balanced number of subjects immunized with PCV13 and ASP3772 with immunogenicity data across 
the elderly population.
Safety and tolerability assessments including adverse events (AEs) will continue through 30 days 
postimmunization.  Safety assessments for SAEs and MAAEs including PIMMCs and NOCDs will 
continue through day 180 postimmunization.
Data will be collected in an observer-blinded manner (vaccine recipients and those responsible for 
evaluation of any study endpoint will be unaware of which vaccine the subject received).  
Serum samples to measure IgG and OPA will be collected prior to study immunization on day 1 and 
postimmunization on day 30. 
Primary immunogenicity evaluation for dose finding is 30 days following the initial immunization.  
Stage 2 Group 3:
A separate group of elderly subjects previously immunized with PCV13 will be enrolled and receive 
the recommended booster immunization with PPSV23 only (n = 99) (Group 3).  

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Study Design Overview (continued):  
Prior immunization (PCV13) should have taken place no less than 10 months and no more than 
2 years prior to study vaccine administration.  Immunogenicity to the 11 non-PCV13 serotypes in
PPSV23 will be evaluated. Safety assessments will continue through 30 days postimmunization. 
Serum samples to measure IgG and OPA levels will be collected prior to study immunization on 
day 1 and postimmunization on day 30.
Inclusion/Exclusion Criteria:  
Inclusion:  
A 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 Act [HIPAA] Authorization for US sites) must be obtained from 
the subject prior to any study-related procedures (including withdrawal of prohibited medications, 
if applicable).
2. Stage 1: Subject is healthy male or female between 18 and 64 year of age inclusive, at screening. 
3. Stage 2: Subject is a male or female between 65 and 85 years of age, inclusive, at screening who
is healthy or has chronic controlled, stable disease with no change in disease severity, medical 
therapy and no hospitalization records in last 12 weeks as determined by medical history, physical 
examination and laboratory data and the clinical judgment of the investigator. 
4. A female subject is eligible to participate if she is not pregnant (see [Appendix 12.3 Contraception 
Requirements]) and at least 1of the following conditions applies:
a.
Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3
Contraception Requirements]
OR
b.
WOCBP who agrees to follow the contraceptive guidance as defined in [Appendix 12.3
Contraception Requirements] at screening and for at least 28 days after the study vaccine 
administration.
5. Female subject must agree not to breastfeed starting at screening and for 28 days after the study 
vaccine administration.  
6. Female subject must not donate ova starting at screening and for 28 days after the study vaccine 
administration. 
7. A male subject with female partner(s) of childbearing potential must agree to use contraception as 
detailed in [Appendix 12.3 Contraception Requirements] at screening and for at least 28 days after 
the study vaccine administration.
8. Male subject must not donate sperm starting at screening and for 90 days after the study vaccine 
administration. 
9. Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a 
condom for the duration of the pregnancy or time partner is breastfeeding at screening and for 
28 days after the study vaccine administration.  
10. Subject agrees not to participate in another interventional study while participating in the present 
study. 
Waivers to the inclusion criteria will NOT be allowed.

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Exclusion:  
A subject will be excluded from participation if any of the following apply:
1. Subject has a known or suspected hypersensitivity to ASP3772, its comparators or any 
components of the formulations used. 
2. Subject has had previous exposure with ASP3772.
3. Subject has had known previous exposure with PPSV23.  
4. Subject has received PCV13 or any other licensed or investigational pneumococcal vaccine 
at any time.  (Note: This exclusion criterion is not applicable to Group 3; those subjects 65 to 
85 years of age who previously received immunization with PCV13.  Prior PCV13 immunization 
should have taken place no less than 10 months and no more than 2 years prior to study 
immunization. These subjects are eligible to be enrolled in the nonrandomized arm of Stage 2, 
Group 3).
5. Subject has a history of microbiologically-proven invasive disease caused by Streptococcus 
pneumoniae.
6. Subject has an immune disorder(s) (including autoimmune disease) and/or clinical conditions 
requiring immunosuppressive drugs. 
7. Subject has any evidence of any unstable or active clinically significant cardiovascular, 
gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, 
neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy, as judged 
by the investigator, e.g., uncontrolled hypertension, uncontrolled diabetes, heart failure, 
uncontrolled chronic obstructive pulmonary disease, end-stage renal disease. 
8. Subject has history of illicit drug(s) or alcohol abuse that the investigator believes will interfere 
with the protocol requirements and/or a positive urine drug test (for Stage 1 subjects only) 
at screening. 
9. Subject has any clinically significant history of allergic conditions including drug allergies, asthma 
or anaphylactic reactions, but excluding untreated asymptomatic seasonal allergies prior to vaccine 
administration. 
10.Subject has a coagulation disorder contraindicating intramuscular immunization.
11.Subject has a positive serology test for hepatitis B surface antigen (HBsAg),  hepatitis A virus 
antibodies (immunoglobulin M), hepatitis C virus antibodies (anti-HCV) confirmed by reflex 
testing (HCV-RNA) or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 
at screening.
12.Subject has/had febrile illness (> 100.4°F oral equivalent) or symptomatic, viral, bacterial 
(including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to 
day 1.
13.Subject has any clinically significant abnormality following the investigator’s review of the 
physical examination, electrocardiogram (ECG) and protocol defined clinical laboratory tests 
during screening.
14. Subject is unlikely to adhere to study procedures, keep appointments, is planning to relocate 
during the study or cannot be adequately followed for safety according to the protocol.
15. Subject has any other condition, which, in the opinion of the investigator, precludes the subject’s 
participation in the study.

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16. Subject has received any vaccines within 30 days prior of receipt of the study vaccine (exception: 
Inactivated influenza virus vaccine given according to recommended guidelines must have been 
given at least 7 days prior to receiving study vaccine). 
17. Subject has had significant blood loss, donated 1 unit (450 mL or more) or received transfusion 
of any blood or blood products within 60 days or donated plasma within 7 days prior to day 1.
18. Subject has received any systemically absorbed antibiotics during the 7-day period prior to day 1.
Waivers to the exclusion criteria will NOT be allowed.
Investigational Product(s):
Study Vaccine: 
ASP3772 is a suspension containing multiple pneumococcal capsular polysaccharide (PS) serotypes
Dose(s):   
A single injection of 0.5 mL ASP3772 at either 1, 2 or 5 μg of each capsular PS serotype
Mode of Administration:
Intramuscular injection into the deltoid muscle of the right or left arm.
Comparative Vaccine(s):
Prevnar 13 (PCV13):
PCV13 pneumococcal capsular PS serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F in 
each 0.5 mL dose.
Dose(s):
A single injection of 0.5 mL suspension of PCV13 supplied in a single-dose prefilled syringe.
Mode of Administration:
Intramuscular injection into the deltoid muscle of the right or left arm.
Pneumovax 23 (PPSV23):
Pneumovax 23 (pneumococcal vaccine polyvalent) capsular PS from S. pneumoniae types 1, 2, 3, 4, 
5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20A, 22F, 23F, 33F in each 
0.5 mL dose.
Dose(s): 
A single injection of 0.5 mL solution of PPSV23 supplied in a single-dose prefilled syringe.
Mode of Administration: 
Intramuscular injection into the deltoid muscle of the right or left arm.
Concomitant Medication Restrictions or Requirements:
Subjects will not be allowed to take immunizations, blood product, immunosuppressants including 
systemic steroids (topical steroids will be allowed) from first study vaccine administration until 
30 days postimmunization. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are 
allowed during the study, but not within 24 hours prior to immunization and collection of serum 
samples for immunogenicity.  Subjects who are taking concomitant medications (3 months prior to 
study enrollment) to treat pre-existing conditions (e.g., hypertension) must remain on stable doses of 
these medications throughout the study.  The doses of all concomitant medications should remain 
stable throughout the study, but may be changed for medical reasons as determined by the clinical 
investigator.

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If during the study, a subject’s health condition necessitates the use of any medication from those 
listed above, the investigator and medical monitor or designee(s), will discuss the case and determine 
if the subject should be withdrawn from the study.  The excluded concomitant medication will be 
recorded as a protocol deviation.  All concomitant medication including prescription and 
nonprescription, vitamins and natural and herbal remedies (e.g., St. John’s Wort) will be documented.
Use of systemically absorbed antibiotics during the 30-day period prior to collection of the 
immunogenicity samples should be restricted unless clinically warranted (e.g., avoid prophylaxis) to 
avoid interference with the immunoassay. If a subject has been treated with any systemically absorbed 
antibiotics between day 1 and day 30, the day 30 follow-up visit should take place at least 7 days after 
the last dose of the antibiotics.
Subjects may receive other routine immunizations at the 30-day follow-up visit after the completion 
of all study procedures at each site’s discretion; however, routine vaccines should not be given in less 
than 30 days poststudy immunization.
Duration of Study:  
Stage 1:
Adults 18 to 64 years of age - PCV13 Naïve Subjects (Group 1): 
Subjects will receive 1 immunization of ASP3772 or PCV13 administered on day 1.  Follow-up study 
visits will be conducted at 7, 30 and 180 days postimmunization.  The final study visit at day 180 may 
be conducted via telephone call.  
Stage 2:
Elderly 65 to 85 years of age - PCV13 Naïve Subjects (Group 2): 
Subjects will receive 1 immunization of ASP3772 or PCV13 administered on day 1.  
Follow-up study visits will be conducted at 7, 30 and 180 days postimmunization.  The final study 
visit at day 180 may be conducted via telephone call.  
Elderly 65 to 85 years of age - Previous PCV13 Exposed Subjects (Group 3): 
A third group of nonrandomized subjects previously vaccinated with PCV13 will be enrolled and 
receive a booster immunization with PPSV23 only on day 1.  A follow-up visit will be conducted at 
30 days postimmunization and this visit will also serve as the final study visit.  
Formal Stopping Rules:  
Early Termination of Subjects:
Individual subjects will be discontinued from the study if:

Subject is lost-to-follow-up despite reasonable efforts by the investigator to locate the subject.

Subject voluntarily withdraws from the study at any time for any reason.
Formal Stopping Rules for Cohorts:
No additional subjects will be randomized or dosed in the study until the events below occurring in a 
subject who received ASP3772 are reviewed by the DEC and the DEC recommends that it is 
acceptable to resume cohort immunization. 

Unexplained death of a subject.

Acute hypersensitivity reaction in a subject.

One of the sentinel subjects experiences an AE of severe intensity related to ASP3772, when 
sentinel subjects are required.

An SAE of the same character occurs in at least 2 subjects or 1 subject experiences a 
vaccine-related SAE.  

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
Grade 3 or higher lab abnormality considered related to the immunization occurs in 2 or more 
subjects [FDA Guidance for Industry, 2007].

The same type of reactogenicity event assessed as grade 3 or higher occurs in 2 or more subjects, 
or 1 of the sentinel subjects experiences a reactogenicity event assessed as grade 3 or higher, 
using the FDA toxicity grading scale for preventative vaccines [FDA Guidance for Industry, 
2007].

An imbalance of unsolicited AEs between ASP3772 and PCV13 is observed.
Decision Process for Dose Escalation:
After both sentinel subjects in a cohort have completed study procedures on day 7, the decision to 
open enrollment for the full cohort will be determined by DEC based on review of the Day 7 
reactogenicity and safety data of those 2 sentinel subjects. 
After all vaccinated subjects in a cohort have completed study procedures on day 7, the decision to 
dose escalate to next cohort within both stages will be determined by DEC based on the review of the 
following:

Day 7 reactogenicity and safety data (AEs, ECG, clinical laboratory tests, vital signs) from the 
current cohort. 

Day 7 reactogenicity and safety data from all subjects of the preceding cohort(s).
To evaluate safety by DEC, day 7 data is needed from a minimum of 38 subjects in each cohort for 
Stage 1.
Stage 2 will commence based on DEC review of the following: 

Day 7 reactogenicity and safety data (AEs, ECG, clinical laboratory tests, vital signs) from all 
subjects in Stage 1. 

Day 30 safety data (AEs, ECG, clinical laboratory tests, vital signs) from all subjects in Stage 1.
To evaluate safety by DEC, day 7 data is needed from a minimum of 129 subjects in each cohort for 
Stage 2.   Further details around the dose escalation process are included in the DEC charter. 
Dose Escalation Criteria:
Depending on the nature, frequency and severity of the safety profile observed in the study, and the 
study vaccine received, the DEC will decide whether to:

Proceed with dose escalation.

Proceed from Stage 1 to Stage 2.

Determine need of sentinel dosing in Stage 2 cohorts. 

Stop dose escalation.
Dose escalation may proceed unless 1 (or more) of the following apply in subject(s) receiving 
ASP3772:

Two or more subjects experience an AE of severe intensity related to ASP3772 or 2 or more 
subject(s) experience a reactogenicity event of grade 3 or higher intensity related to ASP3772.

One or more subject(s) experience a SAE related to ASP3772. 

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Endpoints for Evaluation:  
Stage 1:
Primary Endpoints
Safety and tolerability of ASP3772 will be assessed by:

Treatment-emergent adverse events (TEAEs) including MAAEs, PIMMCs, NOCDs

Vital signs (body temperature, blood pressure and pulse rate)

Reactogenicity assessed using solicited adverse reactions recorded daily by the subject through 
day 7 postimmunization.  These include local and systemic reactions with a predefined grading 
scale.  Local reactions are pain, tenderness, redness/erythema and swelling/induration.  Systemic 
reactions are nausea/vomiting, diarrhea, headache, fever, fatigue, and muscle discomfort or 
pain/myalgia. Joint pain/arthralgia through day 7 postimmunization will be assessed once by 
subject recall at the day 7 visit. 
Additional safety assessments include laboratory values, ECGs and physical examinations.
Secondary Endpoints
Endpoints used to assess the immunological response on day 30:

Functional OPA activity for each serotype characterized by an OPA titer-1 response expressed as 
the reciprocal of the serum dilution that causes a 50% reduction in the colony-forming units 

Pneumococcal serotype-specific anticapsular PS IgG for each serotype
Endpoints used to assess the immunological response on day 30 for the 11 serotypes unique to 
ASP3772:

Geometric mean fold rise (GMFR) in anticapsular PS IgG at 30 days relative to pre-
immunization

Proportion of subjects with a 4-fold increase in anticapsular PS IgG 

Functional OPA activity expressed as an OPA titer-1. 
Stage 2 Group 2:
Primary Endpoints 
Safety and tolerability of ASP3772 will be assessed by:

TEAEs including MAAEs, PIMMCs, NOCDs

Vital signs (body temperature, blood pressure and pulse rate)

Reactogenicity assessed using solicited adverse reactions recorded daily by the subject through 
day 7 postimmunization.  These include local and systemic reactions with a predefined grading 
scale.  Local reactions are pain, tenderness, redness/erythema and swelling/induration.  Systemic 
reactions are nausea/vomiting, diarrhea, headache, fever, fatigue, joint pain/arthralgia, and muscle 
discomfort or pain/myalgia.
Additional safety assessments include laboratory values, ECGs and physical examinations.
Secondary Endpoints 
Endpoints used to assess the immunological response on day 30:

Functional OPA activity for each serotype characterized by an OPA titer-1 response 

Pneumococcal serotype-specific anticapsular PS IgG for each serotype

For each of the serotypes unique to ASP3772, the GMFR in anticapsular PS IgG at 30 days 
relative to pre-immunization

For each of the serotypes unique to ASP3772, the proportion of subjects with a 4-fold increase 
relative to baseline in anticapsular PS IgG for ASP3772 and PCV13-treated subjects

Dose response in the OPA titer-1 for ASP3772

Dose response in the IgG antibodies for ASP3772

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Stage 2 Group 3: 
For the 11 serotypes contained in PPSV23 and not in PCV13, immunological response will be 
evaluated by the following endpoints 30 days after administration of PPSV23: 

Functional OPA activity characterized by an OPA titer-1

Pneumococcal serotype-specific anticapsular PS IgG 
Statistical Methods: 
Sample Size Justification 
The sample size in Stage 1 is considered sufficient to obtain preliminary estimates in a phase 1 study 
of safety and reactogenicity in the adult population, ages 18 to 64. 
In Stage 2, approximately 495 evaluable adult subjects from 65 to 85 years of age are planned to be 
enrolled. For each PCV13 serotype, the OPA titer-1 responses (geometric mean titer [GMT] and 
geometric standard deviation [GSD]) in subjects 60 to 64 years of age administered PCV13 (Source 
Prevnar13® label) were assumed to be representative of the response following immunization with 
ASP3772. The width of 95% confidence intervals for each serotype with 30, 100 and 150 subjects 
were calculated. A sample size of 100 subjects treated with ASP3772 under these assumptions was 
considered sufficient to provide good estimates of OPA titer-1 responses.
Analysis of Safety and Tolerability
Stage 1 and Stage 2 (Group 2):
Safety analyses will be performed on the safety population; all subjects who receive study 
immunization. Data from PCV13 subjects in each cohort will be pooled for comparison with the 
ASP3772 groups.  For each immunization arm, the frequencies and percentages will be displayed for 
the following TEAEs (coded using the Medical Dictionary for Regulatory Activities [MedDRA]) by 
system organ class and preferred term:

Overall

Serious

Related (yes or no) to study vaccine
Descriptive statistics for each laboratory test (e.g., hematology, biochemistry and urinalysis) and vital 
signs will be tabulated by immunization group, dose level for ASP3772 and scheduled time point.  
MAAEs, if any, will be summarized. 
For each local and systemic solicited reaction the percentage of subjects who reported each symptom 
by grade (None, Grade 1, 2, 3 or 4) will be summarized (n, %) by immunization group (PCV13 vs 
ASP3772) and dose level (ASP3772: 1, 2, 5 µg) and the percentage of subjects who reported any 
symptom.

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Analysis of Immunogenicity
Stage 1:
The following measures in adults 18 to 64 years of age will be used to characterize the immunological 
response 30 days following administration of either ASP3772 or PCV13. The following measures will 
be provided for each immunization group (PCV13 vs ASP3772) and dose level (ASP3772: 1, 2, 5 μg). 
∀
The GMT, GSD and 95% confidence interval (CI) for functional OPA for each serotype will be 
calculated. 
∀
The ratio of the OPA GMT (each ASP3772 dose level/PCV13) and 95% CI will be provided.  
∀
The geometric mean concentration (GMC), GSD and 95% CI for serotype-specific IgG for each 
of the serotypes will be calculated.
∀
The ratio of the IgG GMC (each ASP3772 dose level/PCV13) and 95% CI will be provided.  
∀
The GMFR, GSD and 95% CI will be calculated for each of the serotypes unique to ASP3772.  
∀
The proportion of subjects with a # 4-fold increase in anticapsular PS IgG and OPA relative to 
baseline will be calculated.
Stage 2; Group 2:
∀
The GMT, GSD and 95% CI for functional OPA activity for each serotype will be calculated. 
∀
The ratio of the GMT for functional OPA (each ASP3772 dose level/PCV13) for each serotype 
and the 95% CI will be provided.
∀
The GMC, GSD and 95% CI for serotype-specific IgG for each of the serotypes will be 
calculated. 
∀
The ratio of the GMC (each ASP3772 dose level/PCV13) and 95% CI will be provided for each 
serotype. 
∀
The GMFR, GSD and 95% CI will be calculated for each of the serotypes unique to ASP3772.  
∀
The proportion of subjects with a # 4-fold increase in anticapsular PS IgG and OPA relative to 
baseline will be calculated. 
∀
To assess the impact of ASP3772 dose, an analysis of covariance (ANCOVA) model with age 
(65 - 74, 75 - 85) as the covariate and immunization (ASP3772 1, 2, 5 μg or PCV13) as the factor 
of interest will be conducted on the natural logarithm (log) of pneumococcal OPA titers. 
∀
To assess the impact of ASP3772 dose, an ANCOVA model with age (65 - 74, 75 - 85) as the 
covariate and immunization (ASP3772 1, 2, 5 μg or PCV13) as the factor of interest will be 
conducted on the natural logarithm (log) of the IgG concentrations.
In addition, for both Stage 1 Group 1 and Stage 2 Group 2, SP1500+0785 levels (ng/mL) will be 
collected for those subjects given either ASP3772 or PCV13. Levels of the following cytokines will 
be collected for subjects given ASP3772 or PCV13: Th17, IL-17, 
 IL-22, 
 
The units for all are pg/mL. Non-parametric methods will be used for 
these analyses. A Kruskal-Wallis test will be used to test for overall differences between the 3 dose 
levels and PCV13. All treatment groups in Stage 1 will be compared, followed by paired comparisons 
between each of the ASP3772 dose levels and PCV13 using a Wilcoxon Test. The same set of 
comparisons will be made for subjects in Stage 2, Group 2.
Stage 2; Group 3: 
For the 11 serotypes contained in PPSV23 and not in PCV13, immunological response will be 
evaluated by the following endpoints at 30 days after administration of PPSV23:
∀
The GMFR, GSD and 95% CI
∀
The proportion of subjects with a # 4-fold increase in anticapsular PS IgG and OPA relative to 
baseline
∀
The GMT, GSD and 95% CI for the OPA titers 
The GMC, GSD and 95% CI for serotype-specific IgG levels.
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Pharmacokinetics:  
Not applicable.
Pharmacodynamics:  
Not applicable.
Interim analyses: 
No formal interim analysis for efficacy is planned. Safety data will be provided for DEC review after 
each dose cohort for the adult and elderly populations for dose escalation decisions. Prior to initiating 
the enrollment of the elderly subjects, the DEC will review the available data through 30 days post 
immunization in adult subjects. Details will be provided in the DEC Charter.

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V.
FLOW CHART AND SCHEDULE OF ASSESSMENTS
Flow Chart A
Stage 1
DEC: Dose Escalation Committee; ESV: end-of-study visit; ET: early termination; PCV13: Prevnar 13; PE: physical examination.
† DEC will review day 7 data for sentinel subjects before opening full cohort.
Days -28 to -3
Informed consent, PE 
and screening labs 
and
inclusion and 
exclusion criteria
Week 1
Day 7
Reactogenicity/safety/
immune response 
Week 4
Day 30/ ET
Immune response, 
safety 
DEC Review†
(Reactogenicity/safety 
data day 7)
Proceed with Cohort 
or sentinel subjects of 
Next Cohort
Week 1
Day 1
Randomization, 
vaccine dose 
ASP3772 or PCV13, 
safety, immune 
response 
Week 26
Day 180/ESV
Safety follow-up 
(Visit conducted as 
a phone call unless 
anti-biotin 
antibodies were 
elevated at day 30 
visit)
DEC Review
All reactogenicity and 
safety data through 
Day 30
Stage 2
Proceed with 
enrollment in Stage 2 
Stage 1
All subjects complete 
Week 4 Day 30 visit

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Flow Chart B
Stage 2
DEC: Dose Escalation Committee; ESV: end-of-study visit; ET: early termination; PCV13: Prevnar 13; PE: physical examination; PPSV23: Pneumovax 23
† DEC will review day 7 data for sentinel subjects before opening full cohort
PCV13 Naïve 
(Group 2)  
Days -40 to -3
Informed 
consent. PE and 
screening labs 
and inclusion 
and exclusion 
criteria
Week 1
Day 7
Reactogenicity/ 
safety/immune 
response
Week 4
Day 30/ ET
Immune 
response, safety 
DEC 
Review†
(Reactogen
icity/safety 
data day 7)
Proceed with  
Cohort or 
sentinel 
subjects of 
Next Cohort
Week 1
Day 1
Randomization, 
vaccine dose
ASP3772 or 
PCV13, safety, 
immune 
response
PCV13 > 10 months
< 2 years (Group 3)
Days -40 to -3
Informed consent, PE 
and screening labs 
and inclusion and 
exclusion criteria
Week 4
Day 30/ESV
Immune response, 
safety 
Week 1
Day 1
Vaccine – PPSV23, 
immune response 
Week 26
Day 180/ESV
Safety follow-up
(Visit conducted as 
a phone call unless 
anti-biotin 
antibodies were 
elevated at day 30 
visit)

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Table 1
Schedule of Assessments - Stage 1: Subjects 18 to 64 Years of Age (Group 1)
Assessments
Screeninga
Dosing
Follow-up
Visit Number
1
2
3
4
5
Visit Days (Window)
-28 to -3
1
7 (+1)
30 (±2)*
180 (±14)§
Informed Consentb
X
Inclusion/Exclusion Criteria 
X
X†
Randomizationc
X†
Demographics
X
Medical Historyd
X
X†
Physical Examinatione
X
X†
X
Routine 12-lead ECG
X
X†
X
X
Virologyf      
X
Urine Drug Screeng
X
X†
Pregnancy Testh
X
X†
X
Height, Body Weight
X
Study Immunization
X
Vital Signs (blood pressure, pulse rate, body temperature)i
X
X†
X
X
Clinical Laboratory Tests (hematology biochemistry, coagulation profile, 
hepatic profile, urinalysis)j
X
X†‡
X
X
Serum sample for Immunogenicity 
X†
X
Serum sample for Anti-biotin Antibodies
X†
X
Xl
Whole-blood sample for T-cell Immune Response Measurement
X†
X
X
Prior/Concomitant Medicationn
Reactogenicityo
AEsp
SAEsp
MAAEs including PIMMCs and NOCDsp
AE: adverse event; ECG: electrocardiogram; MAAE: medically attended adverse event; NOCD: new-onset chronic disease;
PIMMC: potential immune-mediated medical conditions; SAE: serious adverse event; WBC: white blood cell.
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†  To be performed prior to administration of study vaccine.  Note: Vital signs will also be performed after the administration of the study vaccine.
‡  Not required if collected at a screening visit, which is ≤ 7days from dosing visit. 
§  Visit conducted as a phone call unless anti-biotin antibodies were elevated at day 30 visit.
*  If a subject has received any systemically absorbed antibiotics between day 1 and day 30, the visit should take place at least 7 days after the last dose of the antibiotics.
a. Screening will be completed up to 28 days prior to study immunization. Subjects will be assigned a subject number for use throughout the study at the screening visit via the 
Interactive Response Technology (IRT) system
b. Informed consent must be obtained prior to the performance of any study-related procedure and before Randomization.
c. Subjects will be randomized via the IRT at the dosing visit.
d. Medical history will be collected at screening in order to assess Inclusion/Exclusion criteria and will be reconfirmed prior to study immunization.
e. A physical examination will be performed at the screening visit (days -28 thru -3), prior to study immunization (day 1) and day 30 visits.
f. Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody, hepatitis A virus antibodies (immunoglobulin M), HCV antibody (anti-HCV) confirmed by reflex 
testing (HCV-RNA) and HIV antigen/antibody (type 1 and/or type 2) at screening.
g. Perform screening test for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates at screening visit. Repeat urine drug screening before study 
immunization.  
h. Serum pregnancy test will be done at the screening visit. Urine pregnancy test will be done at study immunization (day 1) and day 30 visits. Not necessary for female subjects who 
are not of childbearing potential (e.g., post-menopausal [defined as at least 1 year without any menses] or documented surgically sterile) at screening and dosing visit.
i.
Body temperature, blood pressure and pulse rate will be assessed in a sitting position. At the dosing visit, body temperature, blood pressure, pulse rate and respiratory rate will be 
assessed  predose and approximately 30 min and 1 hour postdose.  Predose vital signs should be collected close to the vaccination and should not be more than 30 minutes prior to 
the dose administration. Body temperature will be collected by the subject daily through day 7 following the study immunization.
j.
Perform test for hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, differential WBC, platelets), biochemistry (sodium, potassium, calcium, chloride, glucose, total 
cholesterol, triglycerides, blood urea nitrogen, creatinine, total protein, albumin, c-reactive protein), coagulation profile (prothrombin time, activated partial thromboplastin time, 
fibrinogen), hepatic profile (alkaline phosphatase, aspartate transaminase, alanine transaminase, γ-glutamyltransferase, total bilirubin, lactate dehydrogenase), urinalysis (using 
dipstick - protein, glucose, pH, blood, leukocytes, urobilinogen, bilirubin, ketones, nitrite, urine microscopy [optional]).
k.
 
l.
Sample collection to test for serum anti-biotin antibodies should be repeated at the day 180 visit if tested positive on day 30. Biotin levels will be measured in the same sample if 
the sample is positive for anti-biotin.
m.
 Please see Laboratory Manual for more details.
n. All concomitant medications or therapies administered from the time the informed consent form (ICF) is signed through day 30 follow up visit will be collected.
Footnotes continued on next page
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o. Subject must remain at site for the first 60 minutes following the injection. Local reactogenicity will be evaluated at 1 hour by site staff and entered into an electronic diary by the 
subject while on site. The subject will evaluate local and systemic reactogenicity symptoms except for joint pain/arthralgia as per Appendix 12.7 daily and record the results in the 
electronic diary daily through day 7 following study immunization. On day 7, subject will be questioned if he/she experienced any joint pain/arthralgia or other illness, which is not 
incorporated into the reactogenicity assessment, in the electronic diary. 
p. All observed or spontaneously reported AEs, inclusive of MAAEs, PIMMCs and NOCDs will be documented,. AEs will be assessed at the study immunization visit, before and 
approximately 60 minutes after immunization. MAAEs will be reported through day 180. The investigator will avoid leading questions to influence reporting of AEs.

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Table 2
Schedule of Assessments - Stage 2: Subjects 65 to 85 Years of Age, PCV13 Naïve (Group 2)
Assessments
Screeninga
Dosing
Follow-up
Visit Number
1
2
3
4
5
Visit Day (Window)
-40 to -3
1
7 (+1)
30 (±2)*
180 (±14)§
Informed Consentb
X
Inclusion/Exclusion Criteria 
X
X†
Randomizationc
X†
Demographics
X
Medical Historyd
X
X†
Physical Examinatione
X
X†
X
Routine 12-lead ECG
X
X†
X
X
Virologyf
X
Height, Body Weight
X
Study Immunization
X
Vital Signs (blood pressure, pulse rate, body temperature)g
X
X†
X
X
Clinical Laboratory Tests (hematology, biochemistry, coagulation profile, 
hepatic profile, urinalysis)h
X
X†‡
X
X
Serum sample for Immunogenicityj
X†
X
Serum sample for Anti-biotin Antibodies
X†
X
Xk
Whole-blood sample for T-cell Immune Response Measurement
X†
X
X
Prior/Concomitant Medicationl
Reactogenicitym
AEsn
SAEsn
MAAEs including PIMMCs and NOCDsn
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AE: adverse event; ECG: electrocardiogram; MAAE: medically attended adverse event; NOCD: new-onset chronic disease; PCV13: Prevnar 13; 
; 
PIMMC: potential immune-mediated medical conditions; SAE: serious adverse event; WBC: white blood cell.
†  To be performed prior to administration of study vaccine.  Note: Vital signs will also be performed after the administration of the study vaccine.
‡  Not required if collected at a screening visit, which is ≤7days from dosing visit. 
§  Visit conducted as a phone call unless anti-biotin antibodies were elevated at day 30 visit.
*  If a subject has received any systemically absorbed antibiotics between day 1 and day 30, the visit should take place at least 7 days after the last dose of the antibiotics.
a. Screening will be completed up to 40 days prior to study immunization. Subjects will be assigned a subject number for use throughout the study at the screening visit via the 
Interactive Response Technology (IRT) system.
b. Informed consent must be obtained prior to the performance of any study-related procedure and before randomization.
c. Subjects will be randomized via the IRT system at the dosing visit.
d. Medical history will be collected at screening in order to assess Inclusion/Exclusion criteria and will be reconfirmed prior to study immunization.
e. A physical examination will be performed at the screening visit (days -40 thru -3), prior to study immunization (day 1) and day 30 visits.
f. Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M), HCV antibody (anti-HCV) confirmed by reflex testing (HCV-RNA) and 
HIV antigen/antibody (type 1 and/or type 2) at screening.
g. Body temperature, blood pressure and pulse rate will be assessed in a sitting position.  At the dosing visit, body temperature, blood pressure, pulse rate and respiratory rate will 
assessed predose at approximately 30 min and 1 hour postdose.  Predose vitals should be collected close to the immunization and should not be more than 30 minutes prior to the 
dose administration.  Body temperature will be collected by the subject daily through day 7 following the study immunization.
h. Perform test for hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, differential WBC, platelets), biochemistry (sodium, potassium, calcium, chloride, glucose, total 
cholesterol, triglycerides, blood urea nitrogen, creatinine, total protein, albumin, c-reactive protein), coagulation profile (prothrombin time, activated partial thromboplastin time, 
fibrinogen), hepatic profile (alkaline phosphatase, aspartate transaminase, alanine transaminase, γ-glutamyltransferase, total bilirubin, lactate dehydrogenase), urinalysis (using 
dipstick - protein, glucose, pH, blood, leukocytes, urobilinogen, bilirubin, ketones, nitrite, urine microscopy [optional]).
i.
 
j.
Immunogenicity data will be provided to the investigative site when available to support decision-making for the standard of care.
k. Sample collection to test for serum anti-biotin antibodies should be repeated at the day 180 visit if tested positive on day 30. Biotin levels will be measured in the same sample if the 
sample is positive for anti-biotin.
l.
All concomitant medications or therapies administered from the time the informed consent form (ICF) is signed through day 30 follow-up visit will be collected.
m. Subject must be under direct supervision for the first 60 minutes following the injection.  Local reactogenicity will be evaluated at 1 hour by site staff and entered into the electronic 
diary by the subject while on site. The subject will evaluate local and systemic reactogenicity symptoms except for joint pain/arthralgia as per Appendix 12.7 daily and record the 
results on an electronic diary daily through day 7 following the study immunization. On day 7, subject will be questioned if he/she experienced any other illness, which is not
incorporated into the reactogenicity assessment, in the electronic diary.
n. All observed or spontaneously reported AEs, inclusive of MAAEs, PIMMCs and NOCDs will be documented. AEs will be assessed at the study immunization visit, before and 
approximately 60 minutes after immunization. MAAEs will be reported through day 180. The investigator will avoid leading questions to influence reporting of AEs.
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Table 3
Schedule of Assessments - Stage 2: Subjects 65 to 85 Years of Age and Received PCV13 Within a Year of Randomization (Group 3)
Assessments
Screeninga
Dosing
Follow-up
Visit Number
1
2
3
Visit Day (Window)
-40 to -3
1
30 (±2)
Informed Consentb
X
Inclusion/Exclusion Criteria 
X
X†
Vaccine assignmentc
X†
Demographics
X
Medical Historyd
X
X†
Physical Examinatione
X
X†
X
Routine 12-lead ECG
X
X†
X
Virologyf
X
Height, Body Weight
X
Study Immunization 
X
Vital Signs (blood pressure, pulse rate, body temperature)g
X
X†
X
Clinical Laboratory Tests (hematology, biochemistry, coagulation profile, hepatic profile, 
urinalysis)h
X
X†‡
X
Serum sample for Immunogenicity 
X†
X
Prior/Concomitant Medicationj
AEsk
SAEsk
MAAEs including PIMMCs and NOCDsk
AE: adverse event; ECG: electrocardiogram; MAAE: medically attended adverse event; NOCD: new-onset chronic disease; PCV13: Prevnar 13; 
; 
PIMMC: potential immune-mediated medical conditions; SAE: serious adverse event; WBC: white blood cell.
†  To be performed prior to administration of study vaccine.  Note: Vital signs will also be performed after the administration of the study vaccine.
‡  Not required if collected at a screening visit, which is ≤7days from dosing visit. 
Footnotes continued on next page
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a. Screening will be completed up to 40 days prior to study immunization. Subjects will be assigned a subject number for use throughout the study at the screening visit via the 
Interactive Response Technology (IRT) system.
b. Informed consent must be obtained prior to the performance of any study-related procedure and before assigning vaccine via the IRT system.
c. Subjects will be assigned a vaccine via the IRT system at the dosing visit.
d. Medical history will be collected at screening in order to assess Inclusion/Exclusion criteria and will be reconfirmed prior to study immunization.
e. A physical examination will be performed at screening visit, prior to study immunization (day 1) and day 30 visits.
f. Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M), HCV antibody (anti-HCV) and HIV antigen/antibody (type 1 and/or type 
2) at screening.
g. Body temperature, blood pressure and pulse rate will be assessed in a sitting position.  
h. Perform test for hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, differential WBC, platelets), biochemistry (sodium, potassium, calcium, chloride, glucose, total 
cholesterol, triglycerides, blood urea nitrogen, creatinine, total protein, albumin, c-reactive protein), coagulation profile (prothrombin time, activated partial thromboplastin time, 
fibrinogen), hepatic profile (alkaline phosphatase, aspartate transaminase, alanine transaminase, γ-glutamyltransferase, total bilirubin, lactate dehydrogenase), urinalysis (using 
dipstick - protein, glucose, pH, blood, leukocytes, urobilinogen, bilirubin, ketones, nitrite, urine microscopy [optional]).
i.
 
j.
All concomitant medications or therapies administered from the time the informed consent form (ICF) is signed through day 30 follow-up visit will be collected.
k. All observed or spontaneously reported AEs, inclusive of MAAEs, PIMMCs and NOCDs will be documented.  AEs will be assessed at the study immunization visit, before 
immunization and through day 30.  The investigator will avoid leading questions to influence reporting of AEs.
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1
INTRODUCTION
Streptococcus (S.) pneumoniae is a significant cause of morbidity and mortality among infants, 
young children, the elderly and individuals who have certain underlying medical conditions.  
S. pneumoniae remains a leading cause of serious illness, including bacteremia, meningitis and 
pneumonia among children and adults worldwide.  It is also the most frequent cause of sinusitis 
and acute otitis media [CDC, 2010].  Pneumococcal disease can cause both invasive and 
noninvasive disease.  The most common form of noninvasive disease, nonbacteremic 
pneumococcal pneumonia, remains one of the most frequent disease manifestation accounting for 
pneumonia hospitalizations.  Invasive pneumococcal disease (IPD) is defined as S. pneumoniae
isolated from a normally sterile site (e.g., cerebrospinal fluid, blood, joint fluid, pleural fluid or 
peritoneal fluid).  The highest incidence of IPD is found at the extremes of age – in elderly adults 
and in young children < 2 years of age.  S. pneumoniae causes approximately 17000 cases of 
invasive disease each year among children younger than 5 years of age, including 700 cases of 
meningitis and 200 deaths [CDC, 2000].  The highest morbidity and mortality rates have been 
reported in developing countries, but the disease burden is also considerable in industrialized 
countries.
Two different vaccines for S. pneumoniae are currently available in the US.  PCV13, a 13-valent 
conjugate vaccine, has been approved for the prevention of IPD caused by the 13 serotypes 
contained in the vaccine in children and for the prevention of pneumonia and IPD in adults. In 
this vaccine, conjugation of pneumococcal saccharides to the CRM197 protein creates a 
saccharide-protein complex, which is capable of inducing a T-dependent immune response; thus, 
T helper cells are stimulated, leading to a substantial primary response and a strong booster 
response at re-exposure [PREVNAR 13 prescribing information, 2017].  However, there are 
> 90 serotypes of S. pneumoniae, and PCV13 provides protection only against those 13 serotypes 
contained in the vaccine.  While infections with S. pneumoniae of multidrug-resistant serotypes, 
which are contained in PCV13 decreased after availability of this vaccine, an increase of 
infections with multidrug-resistant serotypes 35B, 23A, 23B and 15B, which are not included in 
PCV13, was noted.  Also, PCV13 appeared to have marginal activity against serotype 3, as its 
prevalence persists in the population [Richter et al, 2014].
The second vaccine, Pneumovax®23 (PPSV23), is a 23-valent polysaccharide (PS) vaccine and is 
indicated for the prevention of pneumococcal disease in adults ≥ 50 years of age or in persons 
≥2 years of age at increased risk of pneumococcal disease.  It is composed of purified capsular
PS from 23 pneumococcal serotypes.  While this vaccine protects against more serotypes when 
compared to PCV13, it does not provide protection against the emerging serotypes 35B, 23A and 
23B.  In addition, PPSV23 elicits a T-independent PS immune response that stimulates mature B-
lymphocytes, but not T-lymphocytes, and induces an immune response that is neither long-lasting 
nor anamnestic upon subsequent challenge.  In addition, PS-type vaccines are not used in infants 
and children < 2 years of age, because these children respond poorly to T-independent antigens 
[Pneumovax 23 prescribing information, 2017; CDC, 2010].  Data suggest that PPSV23 protects 
adults and the elderly against IPD; however, no consistent effect has been observed in the 
prevention of pneumonia [Gruber et al, 2008].

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Thus, there is a medical need for a vaccine that provides T-cell dependent immunity against a 
broad range of serotypes of S. pneumoniae.  
Background
ASP3772 is an investigational vaccine that contains 24 serotypes of S. pneumoniae and a unique 
carrier protein (CP1) created by the fusion of 2 pneumococcal proteins (SP1500 and SP0785), 
which has the potential to induce a T- and B-cell response providing extended protection (refer 
to details in the [ASP3772 Investigator’s Brochure]). This novel pneumococcal vaccine is based 
on multivalent multiple antigen-presenting system (MAPS) platform containing each of the 13 
pneumococcal capsular PS contained in PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 
19A, 19F and 23F) and 11 additional pneumococcal capsular PS (serotypes 2, 8, 9N, 10A, 11A, 
12F, 15B, 17F, 20B, 22F and 33F), individually biotinylated and complexed with a CP1 carrier 
protein.  In nonclinical studies, MAPS vaccines have also been shown to induce antigen-
specific Th1/Th17 responses, which efficiently protect against pneumococcal disease [Zhang et 
al, 2013].
The MAPS platform takes advantage of the high affinity (dissociation constant 
[KD] ≈10-15M) noncovalent binding between biotin and rhizavidin, a biotin-binding protein, 
which has no significant predicted homology with human proteins.  Rhizavidin, a naturally 
occurring dimeric protein in the avidin protein family, was first discovered in Rhizobium etli, 
a symbiotic bacterium of the common bean.  Rhizavidin has only a 22% amino acid identity 
with chicken avidin, a protein commonly found in eggs, but with high conservation of amino 
acid residues involved in biotin binding.  No cross-reactivity to rhizavidin was observed in 
human serum samples obtained from subjects exposed to avidin [Helppolainen et al, 2007], 
suggesting that rhizavidin antibodies may not cross-react with chicken avidin.  Biotin 
conjugates have been used in several clinical applications without any reported adverse 
events (AEs) [Buller et al, 2014; Paty et al, 2010; Lazzeri et al, 2004].  The biotinylation of 
the PS and MAPS complexing process in ASP3772 has been optimized to consistently show 
no free biotin, thus reducing the potential for generating anti-biotin antibodies.
The total amount of aluminum per dose in ASP3772 vaccine formulation is expected to be 
0.625 mg, which is below the FDA/WHO maximum recommended dose of 0.85 mg to 1.25 mg.
CCI

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Nonclinical and Clinical Data
The nonclinical pharmacology data demonstrated that ASP3772 is highly immunogenic in 
New Zealand White rabbits.  The literature reported for conjugated pneumococcal vaccines 
suggests that an immunogenic response elicited in nonclinical programs is translatable to an 
immunogenic response in humans.  The successful translation between the rabbit 
immunogenicity studies and human efficacy observed for conjugated pneumococcal vaccines
supports the position that ASP3772 has the potential to be clinically effective. There were no 
treatment-related effects on survival, clinical signs, skin reaction, body weight/food 
consumption, ophthalmology, hematology parameters, serum biotin, anti-biotin antibodies or 
organ weights.  With the exception of the injection sites, there were no treatment-related 
macroscopic post-mortem or histopathological findings in the tissues/organs examined.  
Analysis of post-dose sera confirmed that animals treated with ASP3772 had robust serum 
immunoglobulin G (IgG) antibody responses to all pneumococcal polysaccharides included 
in the ASP3772.
In the pharmacology studies, intramuscular administration of ASP3772 in rabbits resulted in 
a higher immune response (antibody production) in the ASP3772 group in comparison to the 
PCV13 group not only for a majority of the PCV13 serotypes, but also for non-PCV13 
serotypes contained in ASP3772.  Antibody responses to the pneumococcal proteins were 
also robust in the ASP3772 group compared to the levels seen in the PCV13 group in rabbits.
Intranasal administration with either purified pneumococcal proteins (components of carrier 
protein) in mice induced a strong antigen-specific Th17 response and a significant reduction in 
pneumococci colony-forming units recovered from the nasopharyngeal wash following 
challenge with type 6B pneumococci (603 strain).  Similar responses were observed in 
subcutaneous immunization of 12-valent and 6-valent MAPS with CP1 carrier protein in mice. 
These data suggest that ASP3772 has the potential to be clinically effective at protecting against 
pneumococcal infection following immunization.  
Please refer to the current Investigator’s Brochure (IB) for the most recent data.
Summary of Key Safety Information for Study Drugs
No clinical studies of ASP3772 have been conducted to date.
In the 5-cycle intramuscular dose toxicity study in rabbits (3772-TX-0001), a total of 
5 intramuscular injections of ASP3772 at dose level of 5 µg of each PS per animal given once 
every 2 weeks to male and female New Zealand White rabbits over a period of 57 days was 
well-tolerated.  There were no treatment-related effects on survival, clinical signs, skin reaction, 
body weight/food consumption, ophthalmology, hematology parameters, serum biotin, anti-
biotin antibodies or organ weights.  With the exception of the injection sites, there were no 
treatment-related macroscopic post-mortem or histopathological findings in the tissues/organs 
examined.  Analysis of postdose sera confirmed that animals treated with ASP3772 had robust 
serum IgG antibody responses to all pneumococcal PS included in the ASP3772.

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In animals treated with ASP3772, slightly elevated body temperature, changes in clinical 
pathology and histopathological findings at the injection sites were observed.  The elevated 
body temperature and changes in clinical pathology such as reductions in prothrombin time 
and/or activated partial thromboplastin time, as well as increased fibrinogen concentrations, 
and decreased albumin and albumin/globulin ratio, and increased globulin, creatine kinase 
and C-reactive protein levels were considered to be consistent with the immune and/or 
inflammatory reactions induced by ASP3772 administration, which are expected responses in 
intramuscular immunization.  
Microscopic findings at the intramuscular injection sites included ASP3772-related findings 
consisting of minimal to moderate myofiber degeneration/necrosis, minimal to mild histiocytic 
inflammation (muscle) and minimal histiocytic inflammation (subcutis), as well as ASP3772-
related exacerbation of local injection site findings that included minimal to moderate mixed 
cell inflammation (subcutis), minimal to marked mixed cell inflammation (muscle), minimal to 
mild mixed cell inflammation (dermis), minimal to moderate hemorrhage (subcutis), minimal to 
mild hemorrhage (muscle) and minimal serocellular crusts (epidermis).  These changes 
recovered or tended to recover after a 4-week recovery period suggesting that the ASP3772-
related findings were reversible.  
In clinical studies, measurement of body temperature, monitoring of subjective symptoms 
such as pain and soreness, observation of injection sites, evaluation of clinical pathology 
parameters including coagulation, clinical chemistry and C-reactive protein will be monitored 
[Table 4].
Table 4
Summary of Potential Safety Concerns from Nonclinical Studies
Potential Safety Concern 
Relevance to Human Usage
Elevation of body temperature
Monitoring of body temperature 
Changes in clinical pathology (coagulation parameters, 
creatine kinase and C-reactive protein)
Monitoring of clinical laboratory measures
Changes at the injection sites
Observation of local injection reactions
Please refer to the current IB for key safety information.
Risk Benefit Assessment
Subjects participating in this clinical study may not benefit from administration of ASP3772. 
In contrast, subjects might experience AEs related to study vaccines (e.g., allergic reactions) 
or procedural complications (e.g., blood draws or slight skin irritation from the adhesive on 
the electrocardiogram [ECG] electrodes).  
A summary of the nonclinical safety findings and risk minimization and characterization 
actions are given in Table 4. Overall, the toxicological target organs and AEs that were 
identified in the nonclinical toxicology studies will be carefully monitored so that subjects 
will not be exposed to undue risks. However, since this is the first study of this vaccine in 
humans, the risk profile in humans is unknown. 

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2
STUDY OBJECTIVE(S), DESIGN AND ENDPOINTS
Study Objective(s)
Stage 1: 
Primary Objective:  To evaluate the safety and tolerability of 3 different dose levels of 
ASP3772 in comparison to the active comparator Prevnar 13® (PCV13) in adults 
18 to 64 years of age. 
Secondary Objective:  To evaluate the immunogenicity of 3 different dose levels of 
ASP3772 in comparison to the active comparator PCV13 in adults 18 to 64 years of age. 
Stage 2: 
Primary Objective:  To evaluate the safety and tolerability of 3 different dose levels of 
ASP3772 in comparison to the active comparator PCV13 in elderly 65 to 85 years of age.
Secondary Objectives:  
To evaluate the immunogenicity of 3 different dose levels of ASP3772 in comparison to the 
active comparator PCV13 in elderly 65 to 85 years of age.
To evaluate the immunogenicity of 3 different dose levels of ASP3772 relative to the 
response seen following administration of PPSV23 for the serotypes not included in PCV13.
Study Design and Dose Rationale
2.2.1
Study Design
Study Design Overview: 
This is a combined phase 1, first-in-human (FIH), dose-escalation (Stage 1) and phase 2, 
dose-finding (Stage 2), observer-blinded study to evaluate the safety, tolerability and 
immunogenicity of ASP3772 in adult subjects and in elderly subjects. 
The objectives of this study are to evaluate safety, tolerability including reactogenicity and 
immunogenicity in adult subjects 18 to 64 years of age in Stage 1 and in elderly subjects 
65 to 85 years of age in Stage 2, who are naïve to licensed or investigational pneumococcal 
vaccine.  
The study population will consist of 3 different groups: Group 1 - Stage 1 PCV13 naïve 
subjects randomized within 3 sequential cohorts to ASP3772 or PCV13; Group 2 - Stage 2 
PCV13 naïve subjects randomized within 3 sequential cohorts to ASP3772 or PCV13; and 
Group 3 - Stage 2 subjects previously vaccinated with PCV13 that will receive PPSV23.  

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Number of Subjects per Cohort by Immunization
Cohort 
Stage 1 (Group 1)
ASP3772
Number of 
Subjects 
Comparator
Number of 
Subjects
1
1 µg
30
PCV13
10
2
2 µg
30
10
3
5 µg
30
10
PCV13: Prevnar 13
Stage 2:  A total of approximately 495 adult subjects from 65 to 85 years of age.
Number of Subjects per Cohort by Immunization
Cohort 
Stage 2 ( Group 2)
ASP3772
Number of 
Subjects 
Comparator 
Number of 
Subjects
4
1 µg
99
PCV13
33
5
2 µg
99
33
6
5 µg
99
33
PCV13: Prevnar 13
Study Immunization 
Group
Stage 2 (Group 3)
Number of Subjects
PPSV23
99
PPSV23: Pneumovax 23
To minimize the risk to subjects, a sentinel group of subjects (n = 2; 1 ASP3772:1 PCV13) will 
be vaccinated in each cohort prior to initiating enrollment of the full cohort.  Safety data 
through day 7 from sentinel subjects will be evaluated by the Dose Escalation Committee 
(DEC) prior to enrolling the remainder of the cohort.  Safety data through day 7 from all 
subjects within a dose cohort will be evaluated by the DEC prior to escalating to the next dose 
cohort within the adult and within elderly subjects. Based on the safety data through 30 days 
after immunization from the first 3 cohorts, the DEC will determine if Stage 2 can commence, 
and if sentinel dosing is required for Stage 2.  All subjects within each cohort will remain under 
observation for approximately 1 hour post immunization, provided no reactions have occurred 
that require additional observation in the opinion of the investigator.  The DEC membership 
will include Astellas Medical Science, Pharmacovigilance and Statistics personnel, as well as 
external independent safety physician(s).  The external safety physician will be selected based 
on expertise in vaccine clinical studies and other considerations such as the disease area. A DEC 
charter will detail the roles, responsibilities and procedures for decision-making.
See the Schedule of Assessments [Table 1, Table 2 and Table 3] for details on procedures 
performed at each study visit for Group 1, Group 2 and Group 3, respectively. 
Stage 1 Group 1:
Stage 1 of the phase 1/2 design is a randomized, active-controlled, observer-blinded, 
dose-escalation study of the safety, tolerability and immunogenicity of the ASP3772 
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3:1 randomization (ASP3772:PCV13).  After screening, subjects will be enrolled sequentially 
into 3 cohorts designated by escalating ASP3772 dose levels.  A single dose of ASP3772 will 
be administered as a 0.5 mL intramuscular injection into the deltoid muscle of the right or left 
arm on day 1 at 1 of 3 dose levels: 1, 2 or 5 g of ASP3772 for cohorts 1, 2 and 3 respectively.  
The subjects randomized to PCV13 will receive a single injection of the standard dose of 
PCV13 on day 1.
Approximately 120 subjects will be enrolled in Stage 1 of the study; 40 subjects per cohort 
(ASP3772 n = 30 and PCV13 n = 10).
After all subjects complete dosing in Cohort 1 (low dose, 1 g of ASP3772 or PCV13), safety 
(including reactogenicity) and tolerability through 7 days postimmunization will be assessed by 
the DEC.  Assessments of safety and tolerability by the DEC will occur prior to initiating the 
next dose group, Cohort 2 (2 μg of ASP3772 or PCV13) and then Cohort 3 (5 μg of ASP3772 
or PCV13), based on safety and tolerability data through 7 days postimmunization.  
Safety and tolerability assessments will continue through 30 days postimmunization.  Safety 
assessments for serious adverse events (SAEs) and medically attended adverse events (MAAEs) 
including potential immune-mediated medical conditions (PIMMCs) and NOCDs will continue 
through day 180 postimmunization.  Data will be collected in an observer-blinded manner 
(vaccine recipients and any site staff who is responsible for evaluation of any study endpoint 
will be unaware of which vaccine the subject received).  
Serum samples to measure IgG and opsonophagocytic activity (OPA) will be collected prior 
to the first study immunization on day 1 and on day 30 postimmunization.  
Stage 2 Group 2: 
Stage 2 of the study is a dose-finding (sequentially higher doses), active-controlled, 
observer-blinded study with 3:1 randomization (ASP3772:PCV13) in elderly subjects 65 
to 85 years of age.
After screening, PCV13 naïve subjects will be randomized within each cohort to receive 
ASP3772 or PCV13.  Subjects randomized to ASP3772 will receive a single dose of 
ASP3772 administered as a 0.5 mL intramuscular injection into the deltoid muscle of the 
right or left arm on day 1, at 1 of 3 dose levels: 1, 2 or 5 g of ASP3772 for Cohorts 4, 5 and 
6, respectively.  The subjects randomized to PCV13 will receive a single injection of the 
standard dose of PCV13.  
Approximately 396 subjects will be enrolled in Stage 2 of the study; 132 subjects per cohort 
(ASP3772 n = 99 and PCV13 n = 33).
Stage 2 will commence after the DEC has evaluated safety (including reactogenicity) data 
through 30 days from all cohorts in Stage 1.  Dose escalation to Cohort 5 (intermediate dose, 
2 g) in Stage 2 will commence once the DEC has evaluated Stage 2 Cohort 4 (1 g) safety 
(including reactogenicity) and tolerability through 7 days postimmunization.  Dose escalation 
into Cohort 6 (high dose, 5 g) in Stage 2 will commence once the DEC has evaluated 
Stage 2 Cohort 5.  Randomization for Stage 2 subjects will be stratified by age (65 to 74 years 

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of age and 75 to 85 years of age) to ensure there is a balanced number of subjects immunized 
with ASP3772 or PCV13 with immunogenicity data across the elderly population. 
Safety and tolerability assessments including AEs will continue through 30 days 
postimmunization.  Safety assessments for SAEs and MAAEs including PIMMCs and NOCDs 
will continue through day 180 postimmunization.  Data will be collected in an observer-blinded 
manner (vaccine recipients and the site staff who is responsible for evaluation of any study 
endpoint will be unaware of which vaccine the subject received).  
Serum samples to measure IgG and OPA will be collected prior to study immunization on 
day 1 and postimmunization on day 30. 
Primary immunogenicity evaluation for dose finding is 30 days following the initial 
immunization.   
Stage 2 Group 3: 
A separate group of elderly subjects previously immunized with PCV13 will be enrolled and 
receive the recommended booster immunization with PPSV23 only (n = 99).  Prior immunization 
(PCV13) should have taken place no less than 10 months and no more than 2 years prior to study 
vaccine administration.  Immunogenicity to the 11 non-PCV13 serotypes contained in PPSV23 
will be evaluated.
Safety assessments will continue through 30 days postimmunization. 
Serum samples to measure IgG and OPA levels will be collected prior to study immunization
on day 1 and postimmunization on day 30.  
2.2.2
Dose Rationale
The proposed initial doses of 1, 2 and 5 g for this FIH clinical study were chosen based on 
the PS levels contained in marketed PS conjugate vaccines and the ASP3772 nonclinical 
pharmacology and toxicology studies.
The 3 currently licensed pneumococcal conjugated vaccines vary in the number of serotypes 
they contain, the carrier proteins used and the methods of conjugation employed.  The 
7-valent formulation (Pfizer’s Prevnar 7/Prevnar 7) with all serotypes conjugated to 
diphtheria toxoid mutant (CRM197), using a reductive animation conjugation method, was 
first licensed in the year 2000.  The 10-valent formulation (GlaxoSmithKline Biologicals’ 
Synflorix), with 8 serotypes conjugated to Protein D, a recombinant non-lipidated form of a 
highly conserved 40 kDa cell-surface lipoprotein of non-typeable Haemophilus influenzae, 
serotype 18C conjugated to tetanus toxoid and serotype 19F conjugated to diphtheria toxoid 
via bifunctional spacer, was licensed in Europe in 2009.  The 13-valent formulation (Pfizer’s 
PCV13/PCV13), with all serotypes conjugated to CRM197 using reductive animation, was 
licensed in 2010.  In addition, Merck initiated the development of a 15-valent formulation 
(V114), using the PS dose ranges used previously by the commercially available 
pneumococcal conjugated vaccines.  In all of these cases, the PS doses ranged from 1 µg to 
4.4 µg for each of the serotypes.  A nonclinical immunogenicity study with ASP3772 and 
PCV13 at one-tenth of the human PCV13 dose for each PS showed that ASP3772 

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serotype-specific responses to ASP3772 were comparable to those elicited by PCV13 for the 
13 serotypes in common between the vaccines. For the 11 noncommon serotypes, there was a 
robust response elicited in rabbit for ASP3772 and no response for PCV13. In the toxicology 
study in New Zealand White rabbits, ASP3772 was administered at 5 μg of each of the 24 PS 
every 2 weeks, for a total of 5 intramuscular injections (5 cycles). The findings were mild in 
nature, and monitorable and reversible.
The above information, coupled with the literature showing successful translation between 
the rabbit immunogenicity studies and human efficacy for pneumococcal vaccines, support 
the position that ASP3772 has the potential to be clinically effective at the proposed doses 
(1 μg, 2 μg and 5 μg).
Endpoints 
Stage 1:
Primary Endpoints
Safety and tolerability of ASP3772 will be assessed by:
●
Treatment-emergent adverse events (TEAEs) including MAAEs, PIMMCs and NOCDs
●
Vital signs (body temperature, blood pressure and pulse rate)
●
Reactogenicity assessed using solicited adverse reactions recorded daily by the subject 
through day 7 postimmunization.  These include local and systemic reactions with a 
predefined grading scale.  Local reactions are pain, tenderness, redness/erythema and 
swelling/induration.  Systemic reactions are nausea/vomiting, diarrhea, headache, fever, 
fatigue, and muscle discomfort or pain/myalgia.  Joint pain/arthralgia through day 7 
postimmunization will be assessed once by subject recall at the day 7 visit.
Additional safety assessments include laboratory values, ECGs and physical examinations.
Secondary Endpoints
Endpoints used to assess the immunological response on day 30 for the 13 serotypes 
contained in PCV13:
●
Functional OPA activity for each serotype characterized by an OPA titer-1 response 
expressed as the reciprocal of the serum dilution that causes a 50% reduction in the 
colony-forming units 
●
Pneumococcal serotype-specific anticapsular PS IgG for each serotype
Endpoints used to assess the immunological response on day 30 for the 11 serotypes unique 
to ASP3772:
●
Geometric mean fold rise (GMFR) in anticapsular PS IgG at 30 days relative to 
pre-immunization
●
Proportion of subjects with a 4-fold increase in anticapsular PS IgG 
●
Functional OPA activity expressed as an OPA titer-1

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Stage 2 Group 2:
Primary Endpoints 
Safety and tolerability of ASP3772 will be assessed by:
●
TEAEs including MAAEs, PIMMCs, and NOCDs
●
Vital signs (body temperature, blood pressure and pulse rate)
●
Reactogenicity assessed using solicited adverse reactions recorded daily by the subject 
through day 7 postimmunization.  These include local and systemic reactions with a 
predefined grading scale.  Local reactions are pain, tenderness, redness/erythema and 
swelling/induration.  Systemic reactions are nausea/vomiting, diarrhea, headache, fever, 
fatigue, joint pain/arthralgia and muscle discomfort or pain/myalgia.
Additional safety assessments include laboratory values, ECGs and physical examinations.
Secondary Endpoints 
Endpoints used to assess the immunological response on day 30:
●
Functional OPA activity for each serotype characterized by an OPA titer-1 response 
●
Pneumococcal serotype-specific anticapsular PS IgG for each serotype 
●
For each of the serotypes unique to ASP3772, the GMFR in anticapsular PS IgG at 
30 days relative to pre-immunization
●
For each of the serotypes unique to ASP3772, the proportion of subjects with a 4-fold 
increase relative to baseline in anticapsular PS IgG for ASP3772 and PCV13-treated 
subjects
●
Dose response in the OPA titer-1 for ASP3772
●
Dose response in the IgG antibodies for ASP3772
Stage 2 Group 3:
For the 11 serotypes contained in PPSV23 and not in PCV13, immunological response will 
be evaluated by the following endpoints at 30 days after administration of PPSV23: 
●
Functional OPA activity characterized by an OPA titer-1
●
Pneumococcal serotype-specific anticapsular PS IgG
3
STUDY POPULATION
Selection of Study Population 
The study population will consist of adult subjects 18 to 64 years of age in Stage 1 and 
elderly subjects 65 to 85 years in Stage 2. 
The study population will consist of 3 different groups: 
●
Group 1 (approximately 120 evaluable subjects) - Stage 1 PCV13 naïve subjects 
randomized within 3 sequential cohorts to ASP3772 or PCV13; 

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●
Group 2 (approximately 396 evaluable subjects) - Stage 2 PCV13 naïve subjects 
randomized within 3 sequential cohorts to ASP3772 or PCV13; and 
●
Group 3 (approximately 99 evaluable subjects) - Stage 2 subjects previously vaccinated 
with PCV13 that will receive PPSV23.  
The verification of inclusion and exclusion criteria for a subject’s participation in this study is 
to be determined by the investigator or a subinvestigator.
Inclusion Criteria
A 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 Act [HIPAA] Authorization for US sites) must 
be obtained from the subject prior to any study-related procedures (including withdrawal 
of prohibited medications, if applicable). 
2.
Stage 1: Subject is healthy male or female between 18 and 64 year of age inclusive, at 
screening. 
3.
Stage 2: Subject is a male or female between 65 and 85 years of age, inclusive, at 
screening who is healthy or has chronic controlled, stable disease with no change in 
disease severity, medical therapy and no hospitalization records in last 12 weeks as 
determined by medical history, physical examination and laboratory data and the clinical 
judgment of the Investigator. 
4.
A female subject is eligible to participate if she is not pregnant (see [Appendix 12.3
Contraception Requirements]) and at least 1 of the following conditions applies:
a.
Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3
Contraception Requirements]
OR
b. WOCBP who agrees to follow the contraceptive guidance as defined in 
[Appendix 12.3 Contraception Requirements] at screening and for at least 28 days 
after the study vaccine administration.
5.
Female subject must agree not to breastfeed starting at screening and for 28 days after 
the study vaccine administration.  
6.
Female subject must not donate ova starting at screening and for 28 days after the study 
vaccine administration. 
7.
A male subject with female partner(s) of childbearing potential must agree to use 
contraception as detailed in [Appendix 12.3 Contraception Requirements] at screening 
and for at least 28 days after the study vaccine administration.
8.
Male subject must not donate sperm starting at screening and for 90 days after the study 
vaccine administration. 

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9.
Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent 
or use a condom for the duration of the pregnancy or time partner is breastfeeding at 
screening and for 28 after the study vaccine administration.  
10. Subject agrees not to participate in another interventional study while participating in the 
present study. 
Waivers to the inclusion criteria will NOT be allowed.
Exclusion Criteria
A subject will be excluded from participation if any of the following apply:
1.
Subject has a known or suspected hypersensitivity to ASP3772 its comparators or any 
components of the formulations used. 
2.
Subject has had previous exposure with ASP3772.
3.
Subject has had known previous exposure with PPSV23.  
4.
Subject has received PCV13 or any other licensed or investigational pneumococcal 
vaccine at any time. (Note: This exclusion criterion is not applicable to Group 3; those 
subjects 65 to 85 years of age who previously received immunization with PCV13.  Prior 
PCV13 immunization should have taken place no less than 10 months and no more than 
2 years prior to study vaccine administration. These subjects are eligible to be enrolled in 
the nonrandomized arm of Stage 2, Group 3.
5.
Subject has a history of microbiologically-proven invasive disease caused by S. pneumoniae.
6.
Subject has an immune disorder(s) (including autoimmune disease) and/or clinical 
conditions requiring immunosuppressive drugs. 
7.
Subject has any evidence of any unstable or active clinically significant cardiovascular, 
gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, 
pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or 
malignancy, as judged by the investigator, e.g., uncontrolled hypertension, uncontrolled 
diabetes, heart failure, uncontrolled chronic obstructive pulmonary disease, end-stage 
renal disease. 
8.
Subject has history of illicit drug(s) or alcohol abuse that the investigator believes will 
interfere with the protocol requirements and/or a positive urine drug test (for Stage 1 
subjects only) at screening. 
9.
Subject has any clinically significant history of allergic conditions including drug 
allergies, asthma or anaphylactic reactions, but excluding untreated asymptomatic 
seasonal allergies prior to study vaccine administration.  
10. Subject has a coagulation disorder contraindicating intramuscular immunization.
11. Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A 
virus antibodies (immunoglobulin M), hepatitis C virus antibodies (anti-HCV) confirmed 

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by reflex testing (HCV-RNA) or antibodies to human immunodeficiency virus (HIV) 
type 1 and/or type 2 at screening.
12. Subject has/had febrile illness (> 100.4°F oral equivalent) or symptomatic, viral, 
bacterial (including upper respiratory infection) or fungal (noncutaneous) infection 
within 1 week prior to day 1.
13. Subject has any clinically significant abnormality following the investigator’s review of the 
physical examination, ECG and protocol defined clinical laboratory tests during screening. 
14. Subject is unlikely to adhere to study procedures, keep appointments, is planning to 
relocate during the study or cannot be adequately followed for safety according to the 
protocol.
15. Subject has any other condition, which, in the opinion of the investigator, precludes the 
subject’s participation in the study.
16. Subject has received any vaccines within 30 days prior of receipt of the study vaccine 
(exception: Influenza virus vaccine given according to recommended guidelines must be 
given at least 7 days prior to receiving study vaccine). 
17. Subject has had significant blood loss, donated 1 unit (450 mL or more) or received 
transfusion of any blood or blood products within 60 days or donated plasma within 
7 days prior to day 1.
18. Subject has received any systemically absorbed antibiotics during the 7-day period prior 
to day 1.
Waivers to the exclusion criteria will NOT be allowed.
4
IMMUNIZATION(S)
Identification of Investigational Products
4.1.1
Study Vaccine (ASP3772) 
ASP3772 is a suspension containing 24 pneumococcal capsular PS serotypes. It consists of 
biotinylated PS complexed with a carrier protein. ASP3772 is supplied as a sterile suspension 
in single-dose vials and appears as grey/white suspension. It is administered as a single 
intramuscular injection via needle and syringe into the deltoid muscle of the right or left arm. 
Each 0.5 mL dose of ASP3772 drug product is formulated to contain 1, 2 or 5 µg of each 
S. pneumoniae serotype 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 
18C, 19A, 19F, 20B, 22F, 23F and 33F PS as MAPS complexes. ASP3772 will be supplied 
by Astellas as single-use vials with respective dose. ASP3772 should be stored in refrigerator 
at 2°C to 8°C protected from exposure to light. Aseptic technique must be used for the 
preparation of ASP3772. 
Detailed instructions for the storage, handling, preparation and administration of the 
ASP3772 injectable solution along with instructions for storage, handling and use of syringe 
and needle are provided in the pharmacy manual. 

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4.1.2
Comparative Vaccine(s) 
4.1.2.1
Prevnar 13
Prevnar 13 (PCV13) is a suspension of pneumococcal capsular antigens of S. pneumoniae PS 
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F individually linked to a 
non-toxic diphtheria CRM197 protein.  It is administered as a single intramuscular injection 
of 0.5 mL into the deltoid muscle of the right or left arm.  PCV13 is supplied in a single-dose 
prefilled syringe by Astellas. 
Detailed instructions for the storage, handling, preparation and administration of the Prevnar 
13 prefilled syringe along with instructions for storage, handling and use of preferred syringe 
and needle are provided in the pharmacy manual or in the package insert. 
4.1.2.2
Pneumovax 23
PPSV23 (pneumococcal vaccine polyvalent) is a capsular PS from S. pneumoniae serotypes 
1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20A, 22F, 23F,
33F in each 0.5 mL dose.  It is administered as a single intramuscular injection of 0.5 mL 
solution into the deltoid muscle of the right or left arm.  PPSV23 is supplied in a single-dose 
prefilled syringe by Astellas. 
Detailed instructions for the storage, handling, preparation and administration of the PPSV23 
prefilled syringe along with instructions for storage, handling and use of preferred syringe 
and needle are provided in the pharmacy manual or in the package insert. 
Packaging and Labeling
All study vaccine(s) (ASP3772, PCV13 and PPSV23) used in this study will be prepared, 
packaged and labeled under the responsibility of qualified staff at Astellas Pharma Global 
Development Inc. (APGD) or sponsor’s designee in accordance with APGD or sponsor’s 
designee Standard Operating Procedures (SOPs), Good Manufacturing Practice (GMP) 
guidelines, ICH Good Clinical Practice (GCP) guidelines and applicable local laws/regulations.
Each vial will bear a label conforming to regulatory guidelines, GMP and local laws and 
regulations that identifies the contents as investigational vaccine. The study centers should 
store ASP3772, PCV13 and PPSV23 in original provided carton or packing, protected from 
sunlight and at a temperature indicated in pharmacy manual.
Study Vaccine Handling 
Current ICH GCP Guidelines require the investigator to ensure that study vaccine deliveries 
from the sponsor are received by the investigator/or designee and that:
●
Such deliveries are recorded,
●
Study vaccine is handled and stored according to labeled storage conditions,
●
Study vaccine with appropriate expiry/retest and is only dispensed to study subjects in 
accordance with the protocol, and
●
Any unused study vaccine is returned to the sponsor.

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Study vaccine inventory and accountability records will be kept by the study pharmacist. 
Study vaccine accountability throughout the study must be documented and reconciled. The 
following guidelines are therefore pertinent:
●
The investigator, study pharmacist agrees not to supply study vaccines to any persons 
except the eligible subjects in this study in accordance with the protocol.
●
The study pharmacist or designee will keep the study vaccines 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 study vaccines.
●
A study vaccine inventory will be maintained by the study pharmacist 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, study pharmacist or designee agrees to 
conduct a final vaccine supply inventory and to record the results of this inventory on the 
Vaccine Accountability Record or equivalent form in Interactive Response Technology 
(IRT) system. It must be possible to reconcile delivery records with those of used and/or 
returned study vaccine. 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 staff must return study vaccine to the sponsor or designee at the end of the study 
or upon expiration unless otherwise approved by the sponsor.
Blinding
4.4.1
Blinding Method
This is an observer-blind study since the comparator has a unique syringe that the sponsor 
cannot duplicate.  Subjects will be randomized at a 3:1 ratio (ASP3772:comparator vaccine 
PCV13) in a blinded fashion such that the investigator, clinical staff, nor the subject will 
know which agent is being administered.  Only the pharmacist and designated staff, including 
the person(s) injecting the vaccine will be unblinded to study vaccine.  The syringes will be 
masked prior to dosing to maintain the blind for subjects and all other personnel.  The details 
regarding study blinding will be described in the pharmacy manual.  The randomization 
number will be assigned based on information obtained from the IRT.  The study will be 
unblinded to the investigator after the database lock.
The safety and tolerability data for dose escalation by the DEC will be reviewed under 
blinded conditions.  If there are AEs that meet the criteria that could prohibit dose escalation, 
(i.e., a SAE, an AE of severe intensity, or 2 or more subjects experience a reactogenicity 
event of grade 3 or higher intensity), the study vaccine assignment for these subjects will be 
revealed to determine if these events are related to ASP3772.  If 10% or more of the subjects 
within a cohort experience the same or related AE, the study vaccine assignment for those 
subjects will be revealed to determine if there is an imbalance in unsolicited AEs between 
ASP3772 and PCV13.  The DEC can request the study vaccine assignment for 1 or more 
subjects.   

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4.4.2
Confirmation of the Indistinguishability of the Study Vaccines
Not applicable, as the comparator vaccines (PCV13 and PPSV23) are available in the form of 
pre-filled syringes and it is not possible to make the study vaccines indistinguishable.  The 
investigational product and comparator will be sent to the site in an unblinded fashion for the 
unblinded staff at the site to handle.
4.4.3
Retention of the Assignment Schedule and Procedures for Study Vaccine 
Assignment Code Breaking 
The randomization list and study medication blind will be maintained by the IRT system.  
The study pharmacist (or investigator’s designee) will be unblinded to prepare vaccine for 
administration according to randomization code.
4.4.4
Breaking the Study Vaccine Assignment Code for Emergency 
The study vaccine assignment code for each randomized subject will be provided by the IRT 
in the event of a medical emergency requiring knowledge of the study vaccine assigned to the 
subject.  The IRT will be programmed with blind-breaking instructions that may only be 
requested by the investigator or subinvestigators designated to have access to perform 
blind-break.  In case of a medical emergency, the investigator has the sole responsibility for 
determining if unblinding of subject’s vaccine assignment is warranted.  Subject safety must 
always be the first consideration in making such determination.  If the investigator decides 
that unblinding is warranted, the investigator should make every effort to contact the sponsor 
prior to unblinding a subject’s vaccine assignment unless this could delay emergency 
treatment for the subject. 
The investigator must have confirmed functionality to access code-break through the IRT 
system and must have a designated back up (e.g., redundant processes) to support emergency 
unblinding requirements. 
Prior to randomization, subjects should be provided with information that includes the site 
emergency contact number and back-up contact number in case of a medical emergency.  
Any unblinding by the investigational staff must be reported immediately to the sponsor and 
include an explanation of why the study vaccine was unblinded.  If unblinding is associated 
with a SAE the investigator is to follow the instructions in [Section 5.5.5 Reporting of SAE]. 
Care should be taken to limit knowledge of the randomization arm, in case this could affect 
the blinding of other subjects or future trial assessment for the subject. 
4.4.5
Breaking the Study Vaccine Assignment Code by the Sponsor 
The sponsor and DEC may break the study vaccine assignment 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 be provided to the limited staff who are responsible to 
break the codes for all SUSAR cases for reporting purposes.

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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. 
Each cohort will be initiated with randomization of 1 sentinel subject each assigned to either 
ASP3772 or PCV13. Sentinel subjects need to be replaced if discontinued or unable to follow 
up for at least 7 days. The safety data from sentinel subjects will be reviewed by the DEC to 
make a decision to proceed with enrollment of the rest of the cohort. Subjects in the full 
cohort who meet the inclusion/exclusion criteria will be randomized in a 3:1 ratio 
(ASP3772:PCV13) according to the randomization schedules through IRT.  In Stage 2, the 
randomization to study vaccine assignment will be stratified by age.  Prior to study 
immunization, the site staff will access the IRT system in order to determine the randomly 
assigned study vaccine.  The site personnel will dispense the study vaccine according to the 
IRT system’s assignment.  Specific procedures for randomization through the IRT are 
contained in the study procedures manual.
Subjects who subsequently meet the inclusion/exclusion criteria will be randomly assigned to 
receive either ASP3772 or PCV13. The randomization to study vaccine will be stratified by age.
The IRT vendor will generate the randomization schedule. To obtain the randomized study 
vaccine assignment for a subject, the pharmacist or designee will utilize an IRT system, 
which is available 7 days a week, 24 hours a day. After submitting required information 
about the eligible subject, the vaccine kit number assignment will be provided.
Study vaccine 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 vaccine, the kit number will not be used 
again. In this instance, the study vaccine 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).
5
IMMUNIZATIONS AND EVALUATION
Dosing and Administration of Study Vaccine and Other Medications
5.1.1
Dose/Dose Regimen and Administration Period
Stage 1:
Adults 18 to 64 years of age - PCV13 Naïve Subjects (Group 1): 
Subjects randomized to ASP3772 will receive a single immunization of ASP3772 as a 
0.5 mL intramuscular injection on day 1 at 1 of 3 dose levels: 1, 2 or 5 µg of ASP3772 for 
Cohorts 1, 2 and 3, respectively.  The subjects randomized to PCV13 will receive a single 
injection of the standard dose of PCV13 on day 1.  Follow-up study visits will be conducted 
at 7 and 30 days postimmunization.  The final study visit at day 180 may be conducted via 
telephone call.

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Stage 2:
Elderly 65 to 85 years of age - PCV13 Naïve Subjects (Group 2): 
Subjects randomized to ASP3772 will receive a single immunization of ASP3772 
administered as a 0.5 mL intramuscular injection on day 1, at 1 of 3 dose levels: 1, 2 or 5 µg 
of ASP3772 for Cohorts 4, 5 and 6, respectively.  The subjects randomized to PCV13 will 
receive a single 0.5 mL intramuscular injection of the standard dose of PCV13.  Follow-up 
study visits will be conducted at 7 and 30 days postimmunization.  The final study visit at 
day 180 may be conducted via telephone call.
Elderly 65 to 85 years of age - Previous PCV13 Exposed Subjects (Group 3): 
A third group of nonrandomized subjects previously vaccinated with PCV13 will be enrolled 
and receive a booster immunization (single 0.5 mL intramuscular injection) with PPSV23 on 
day 1.  A follow-up visit will be conducted at 30 days postimmunization and this visit will 
also serve as the final study visit. 
5.1.2
Increase or Reduction in Dose of the Study Vaccine(s)
Decision Process for Dose Escalation:
After both sentinel subjects in a cohort have completed study procedures on day 7, the 
decision to open enrollment for the full cohort will be determined by DEC based on review of 
the Day 7 reactogenicity and safety data of those 2 sentinel subjects. 
After all vaccinated subjects in a cohort have completed study procedures on day 7, the 
decision to dose escalate to next cohort within both stages will be determined by DEC based 
on the review of the following:
●
Day 7 reactogenicity and safety data (AEs, ECG, clinical laboratory tests and vital signs) 
from the current cohort. 
●
Day 7 reactogenicity and safety data from all subjects of the preceding cohort(s).
To evaluate safety by DEC, day 7 data is needed from a minimum of 38 subjects in each 
cohort for Stage 1.   
Stage 2 will commence based on DEC review of the following: 
●
Day 7 reactogenicity and safety data (AEs, ECG, clinical laboratory tests and vital signs) 
from all subjects in Stage 1. 
●
Day 30 safety data (AEs, ECG, clinical laboratory tests and vital signs) from all subjects 
in Stage 1.
To evaluate safety by DEC, day 7 data is needed from a minimum of 129 subjects in each 
cohort for Stage 2.  Further details around the dose escalation process are located in the DEC 
charter.

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Dose Escalation Criteria:
Depending on the nature, frequency and severity of the safety profile observed in the study, 
and the study vaccine received, the DEC will decide whether to:
●
Proceed with dose escalation. 
●
Proceed from Stage 1 to Stage 2.
●
Determine need of sentinel dosing in Stage 2 cohorts.
●
Stop dose escalation.
Dose escalation may proceed unless 1 (or more) of the following apply in subject(s) receiving 
ASP3772:
●
Two or more subjects experience an AE of severe intensity related to ASP3772 or 2 or 
more subject(s) experience a reactogenicity event of grade 3 or higher intensity.
●
One or more subject(s) experience a SAE related to ASP3772. 
Stopping criteria for study immunization are described in detail in [Section 5.1.5 Criteria for 
Continuation of Immunization].
5.1.3
Previous and Concomitant Treatment (Medication and NonMedication 
Therapy)
Subjects will not be allowed to take immunizations, blood product, immunosuppressants 
including systemic steroids (topical steroids will be allowed) from first study vaccine 
administration until 30 days postimmunization. Acetaminophen and nonsteroidal 
anti-inflammatory drugs (NSAIDs) are allowed during the study, but not within 24 hours 
prior to immunization and collection of serum samples for immunogenicity.  Subjects who 
are taking concomitant medications (3 months prior to study enrollment) to treat pre-existing 
conditions (e.g., hypertension) must remain on stable doses of these medications throughout 
the study.  The doses of all concomitant medications should remain stable throughout the 
study, but may be changed for medical reasons as determined by the clinical investigator.
If during the study, a subject’s health condition necessitates the use of any medication from 
those listed above, the investigator and medical monitor or designee(s), will discuss the case 
and determine if the subject should be withdrawn from the study.  The excluded concomitant 
medication will be recorded as a protocol deviation.  All concomitant medication including 
prescription and nonprescription, vitamins and natural and herbal remedies (e.g., St. John’s 
Wort) will be documented.
Use of systemically absorbed antibiotics during the 30-day period prior to collection of the 
immunogenicity samples should be restricted unless clinically warranted (e.g., avoid 
prophylaxis) to avoid interference with the immunoassay. If a subject has been treated with 
any systemically absorbed antibiotics between day 1 and day 30, the day 30 follow-up visit 
should take place at least 7 days after the last dose of the antibiotics.
Subjects may receive other routine immunization at the 30-day follow-up visit after the 
completion of all study procedures at each site’s discretion; however, routine vaccines should 
not be given in less than 30 days after study immunization. 

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A list of excluded concomitant medications is provided in [Appendix 12.4 List of Excluded 
Concomitant Medications]. 
5.1.4
Immunization Compliance
Immunization compliance will be recorded at the time of study immunization on day 1 at 
visit 2. Study immunization will take place in the clinical unit. The exact day and time of 
study vaccine administration will be documented.
Observation Period: Subjects will remain under observation for 1 hour postimmunization, 
(provided no reactions have occurred). If a subject experiences significant clinical symptoms, 
in the opinion of the investigator, then additional direct supervision may be required as 
needed for management of the symptoms. 
5.1.5
Criteria for Continuation of Immunization 
Formal Stopping Rules for Individual Subjects:
Individual subjects will be discontinued from the study if:
●
Subject is lost-to-follow-up despite reasonable efforts by the investigator to locate the 
subject.
●
Subject voluntarily withdraws from the study at any time for any reason. 
Formal Stopping Rules for Cohorts:
No additional subjects will be randomized or dosed in the study until the events below 
occurring in a subject who received ASP3772 are reviewed by the DEC and it is acceptable 
to resume cohort immunization. 
●
Unexplained death of a subject.
●
Serious acute hypersensitivity reaction in a subject.
●
One of the sentinel subjects experiences an AE of severe intensity related to ASP3772, 
when sentinel subjects are required.  
●
An SAE of the same character occurs in at least 2 subjects or 1 subject experiences a 
vaccine-related SAE. 
●
Grade 3 or higher lab abnormality considered related to the immunization occurs in 2 or 
more subjects [FDA Guidance for Industry, 2007].
●
The same type of reactogenicity event assessed as Grade 3 or higher occurs in 2 or more 
subjects, or 1 of the sentinel subjects experiences a reactogenicity event assessed as 
Grade 3 or higher, using the FDA toxicity grading scale for preventative vaccines [FDA 
Guidance for Industry, 2007].
●
An imbalance of unsolicited AEs between ASP3772 and PCV13 is observed.
5.1.6
Restrictions During the Study 
See [Section 5.1.3 Previous and Concomitant Treatment] for prohibited medications.

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Demographics and Baseline Characteristics
5.2.1
Demographics
Demographic information will be collected for all subjects (where permitted) at the screening 
visit and will include age, date of birth, sex, race and ethnicity.
5.2.2
Medical History
Medical history will be collected at the screening visit in order to assess Inclusion/Exclusion 
criteria and will be reconfirmed prior to study immunization (if screening was performed 
> 7 days from study immunization [day 1]). 
Immunogenicity Assessments
The immunogenicity assessments described below are accepted surrogates for efficacy in 
pneumococcal vaccine studies.
5.3.1
Immunological Response
Considering its mechanism of action, ASP3772 is expected to induce the immune response to 
pneumococcal PS and carrier proteins, the antigens present in ASP3772.  Blood samples to 
assess immunogenicity will be collected as indicated in the Schedule of Assessments 
[Table 1, Table 2 and Table 3]. Immunogenicity assessments will be performed from blood 
samples collected at the dosing visit (day 1) prior to study immunization and at the 7-day and
30-day follow-up visits.  Immunogenicity data will be provided to the investigative site when 
available.
Immunogenicity of ASP3772 will be evaluated by measuring serotype-specific anticapsular 
IgG antibody concentrations by multiplex direct Luminex immunoassays and OPA titers 
against the 24 vaccine serotypes in serum samples. OPA measures the functional killing 
activity of antibodies against the pneumococcal serotypes. In addition, pneumococcal carrier 
protein (SP1500+0785)-specific immune response will be assessed by measuring specific 
IgG in serum and activity against non-vaccine serotypes.  T helper 17 cells (Th17) response 
to SP1500+0785 will be evaluated by measuring interleukin (IL)-17,
 IL-22, 
induction in peripheral 
blood mononuclear cells (PBMCs) as exploratory assessments. 
Details on sampling, processing and storage will be described in the laboratory manual.  
Samples will be shipped on dry ice to a designated contract research organization (CRO) for 
the analyses.
Safety Assessment
5.4.1
Adverse Events
All observed or spontaneously reported AEs will be documented. TEAEs and MAAEs 
(including PIMMCs and NOCDs) will be assessed throughout the study, from the time of 
dosing (day 1) up to the last follow-up visit (day 30 for Group 3; day 180 for Groups 1 and 
CCI
CCI

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2).  Details of definitions and reporting of AEs (including TEAEs, MAAEs, PIMMCs and 
NOCDs) and SAEs are provided in [Section 5.5 Adverse Events and Other Safety Aspects].
5.4.2
Vital Signs
Vital signs (body temperature, blood pressure and pulse rate) will be measured at screening, 
the dosing visit (day 1) and at each subsequent visit (day 7 and day 30 [all groups]). On day 1, 
vital signs (body temperature, blood pressure, pulse rate and respiration rate) will be collected 
pre-dose and 30 min and 1 hour post-dose. Vital signs will be collected after the subject has 
been in seated position for at least 5 minutes. When vital signs are scheduled for the same 
time as blood sample or study vaccine administration, then vital signs will be taken first. 
Blood pressure should be obtained using the same cuff size and the same arm. Abnormal 
findings will be documented as clinical events through day 7 and AEs post day 7. 
Subjects will be instructed to measure and record in the electronic diary their body 
temperature daily through day 7.  Subjects will also be instructed to measure and record their 
body temperature in case of illness and contact the site if elevated.  
5.4.3
Reactogenicity
Subjects will remain at the study site 60 minutes after the injection for safety evaluation. 
Subjects may be discharged after 60 minutes at the discretion of the investigator.  Local and 
systemic reactogenicity will also be reported for each of 7 consecutive days following the 
study injection. 
Reactogenicity will be assessed using solicited adverse reactions from the time of 
immunization (day 1) up to 7 days postimmunization.  These include local and systemic 
reactions with a protocol-specified predefined grading scale (see [Appendix 12.6 Grading of 
Local Reactogenicity; Appendix 12.7 Grading of Signs of Systemic Reactogenicity; and 
Appendix 12.8 Grading of Laboratory Abnormalities]).  Local reactions are pain, tenderness, 
redness/erythema and swelling/induration.  Systemic reactions are nausea/vomiting, diarrhea, 
headache, fever, fatigue, joint pain or arthralgia and muscle discomfort or pain/myalgia.  The 
daily maximum measurement of local and systemic reactogenicity signs will be recorded by 
the subject during the 7-day period using an electronic subject electronic diary.  For Stage 1, 
subjects will be questioned at the day 7 visit if they experienced any joint pain/arthralgia 
through their day 7 visit postimmunization.  If their response is yes, they will be asked to 
provide the degree of severity using a 4-category grading scale from 1 (no interference with 
activity) to 4 (ER visit or hospitalization) as per Appendix 12.7.  For Stage 2, assessments of 
joint pain/arthralgia will be collected daily through day 7 using the electronic diary. All 
subjects will be questioned if they experienced any other illness through day 7 
postimmunization on their day 7 visit. Reactogenicity reactions will be reported as Clinical 
Events.  If the reactogenicity reaction extends beyond 7-day period or if serious, it will be 
recorded as an AE, and followed until resolution or deemed medically stable.  Subjects will 
be instructed to contact the site during the 7 consecutive days following an injection to report 
any reaction ≥ grade 2.  All local and systemic reactions ≥grade 3 require confirmation by a 
health care professional.  

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5.4.4
Laboratory Assessments
Laboratory assessments will be performed at the screening visit and at study immunization (if 
screening was performed > 7 days from study immunization [day 1]). Assessments will be 
repeated at follow-up visits on day 7 and day 30. See [Appendix 12.5 Laboratory Assessments] 
for details of laboratory tests.
Clinical significance of out-of-range laboratory findings is to be determined and documented 
by the investigator/subinvestigator who is a qualified physician.
5.4.5
Anti-biotin Antibodies
Anti-biotin antibodies will be measured from serum samples on day 1 prior to study 
immunization and at day 30 follow-up visit for Group 1 and Group 2 subjects. Serum anti-biotin 
antibodies will be repeated on day 180 if tested positive on day 30.  In subjects with positive 
serum anti-biotin antibodies, serum biotin levels will be measured in the same sample. 
5.4.6
Physical Examination
A physical examination consisting of an examination of general appearance, eyes, nose 
throat, neck (including thyroid), lymph nodes, chest, lungs, cardiovascular, abdomen, skin, 
extremities, musculoskeletal and neurological system including mental status will be 
conducted at the screening visit, prior to study immunization (day 1) and at the day 30 
follow-up visit. A symptom-directed physical exam may be performed at any other time, if 
necessary.  The screening physical examination also includes evaluation of significant, 
ongoing medical conditions. Any changes between screening and randomization will be 
captured in the medical/surgical history.
Any abnormal finding(s) at screening must not be exclusionary per the eligibility criteria and 
must be assessed and documented as not clinically significant if a subject is to be enrolled in 
the study. After receiving the study vaccine, new abnormal findings or a worsening of an 
ongoing abnormal condition will be recorded as an SAE or AE ([S]AE).
5.4.7
Electrocardiogram 
Standard 12-lead ECG recordings will be used for the purposes of safety assessment and 
subject management by the Investigator.
A 12-lead, resting ECG is to be recorded at each timepoint as indicated in Table 1, Table 2
and Table 3 (Schedule of Assessments). Subjects should remain supine for at least 5 minutes 
prior to all ECGs. Dates and times may be generated by the machine’s internal clock and are 
considered source data. The results are to be interpreted by qualified personnel in real time 
for the management of the subjects’ clinical condition. The principal investigator/designee 
will initial and date, and provide his/her clinical interpretation on each report. The results 
(normal, abnormal not clinically significant, abnormal clinically significant) are to be 
recorded in the electronic case report forms (eCRFs).
The ECG recorded during screening will be used to determine eligibility for study 
participation. Subjects who have a clinically significant abnormal ECG will not be eligible 

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for the study. The interpretation of the ECG from screening will be the baseline to which 
post-study vaccine dosing ECGs will be compared.
Unscheduled ECGs will be performed if clinically indicated.
If a machine-read corrected QT interval exceeds 500 msec after repeat measurement, this 
should be reported as an AE.
The original print-out and an electronic copy of all scheduled and unscheduled ECG tracings 
should be maintained on site as source data.
Adverse Events and Other Safety Aspects
5.5.1
Definition of Adverse Events 
An AE is any untoward medical occurrence in a subject administered a study vaccine, and 
which does not necessarily have to have a causal relationship with this immunization.  An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 
medicinal product whether or not considered related to the medicinal product.
In order to identify any events that may be associated with study procedures and could lead to 
a change in the conduct of the study, Astellas collects AEs even if the subject has not 
received study product. AE collection begins after the signing of the ICF and will be 
collected until 30 days after study vaccine administration or the subject is determined to be a 
screen failure.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences.
An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG 
data, physical exam) should be identified as an AE only if the abnormality meets 1 of the 
following criteria:
●
Induces clinical sign 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.
MAAEs are AEs for which the subject has received medical attention by medical personnel, 
or in an emergency room, or which led to hospitalization. For each reported AE, the 
investigator will ask the subject if such medical attention has been received. In addition, the 
investigator will assess each MAAE if it constitutes a new-onset chronic disease (NOCD), 
defined as a MAAE which a) was absent at baseline, b) is not resolved at the follow-up 
telephone call, c) requires continuous medical care or attention. The investigator will also 
assess if any MAAE constitutes a PIMMC. PIMMCs are defined as any AEs of autoimmune 

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or auto inflammatory nature. The investigator will record MAAEs, NOCDs and PIMMCs in 
the AE eCRF. 
5.5.1.1 Abnormal Laboratory Findings
Any abnormal laboratory test result (e.g., hematology, clinical chemistry, or urinalysis) or 
other safety assessment (e.g., ECGs, radiographic scans, vital signs measurements, physical 
examination), including those that worsen from baseline, that is considered to be clinically 
significant in the medical and scientific judgment of the investigator and not related to 
underlying disease, is to be reported as an unsolicited (S)AE.
Any clinically significant abnormal laboratory finding or other abnormal safety assessment, 
which is associated with the underlying disease does not require reporting as an (S)AE, 
unless judged by the investigator to be more severe than expected for the subject’s condition.
Repeating an abnormal laboratory test or other safety assessment, in the absence of any of the 
above criteria, does not constitute an AE.  Any abnormal test result that is determined to be 
an error does not require reporting as an AE.
5.5.1.2 Potential Cases of Drug-Induced Liver Injury
Refer to [Appendix 12.5 Liver Safety Monitoring and Assessment] for detailed instructions 
on drug-induced liver injury. Abnormal values in aspartate transaminase (AST) and/or 
alanine transaminase (ALT) concurrent or with abnormal elevations in total bilirubin that 
meet the criteria outlined in [Appendix 12.5 Liver Safety Monitoring and Assessment], in the 
absence of other causes of liver injury, are considered potential cases of drug-induced liver 
injury (potential Hy’s Law cases) and are always to be considered important medical events 
and reported per [Section 5.5.5 Reporting of Serious Adverse Events].
5.5.2
Definition of Serious Adverse Events (SAEs)
An AE 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 AE 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 AE 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 (except for planned procedures as allowed per study) 
or leads to prolongation of hospitalization (except if prolongation of planned 
hospitalization is not caused by an AE). Hospitalization for 
treatment/observation/examination caused by AE is to be considered as serious.) 
●
Other medically important events (defined in paragraph below)

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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 1 of the other outcomes listed in the definition 
above. These events, including those that may result in disability/incapacity, usually are 
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.
5.5.2.1 Always Serious Adverse Events
The sponsor has a list of events that they classify as “always serious” events.  If an AE is 
reported that is considered by the sponsor to be an SAE per this classification as “always 
serious”, additional information on the event (e.g., investigator confirmation of seriousness, 
causality) will be requested.  
5.5.3
Criteria for Causal Relationship to Study Vaccine
A medically qualified investigator is obligated to assess the relationship between the study 
vaccine and each occurrence of each (S)AE. This medically qualified investigator will use 
medical judgment as well as the Reference Safety Information to determine the relationship. 
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements.
The medically qualified investigator is requested to provide an explanation for the causality 
assessment for each (S)AE and must document in the medical notes that he/she has reviewed 
the (S)AE and has provided an assessment of causality.
Following a review of the relevant data, the causal relationship between the study vaccine 
and each (S)AE will be assessed by answering ‘yes’ or ‘no’ to the question “Do you 
consider that there is a reasonable possibility that the event may have been caused by 
the study vaccine”.
When making an assessment of causality, the following factors are to be considered when 
deciding if there is evidence and/or arguments to suggest there is a ‘reasonable possibility’ 
that an (S)AE may have been caused by the study vaccine (rather than a relationship cannot 
be ruled out) or if there is evidence to reasonably deny a causal relationship:
●
Plausible temporal relationship between exposure to the study vaccine and (S)AE onset 
and/or resolution. Has the subject actually received the study vaccine? Did the (S)AE 
occur in a reasonable temporal relationship to the administration of the study vaccine? 
●
Plausibility; i.e., could the event been caused by the study vaccine? Consider biologic 
and/or pharmacologic mechanism, half-life, literature evidence, drug/vaccine class, 
preclinical and clinical study data, etc.
●
Laboratory or other test results; a specific lab investigation supports the assessment of 
the relationship between the (S)AE and the study vaccine (e.g., based on values pre-, 
during and post-immunization).

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●
Available alternative explanations independent of study vaccine exposure; such as other 
concomitant drugs, past medical history, concurrent or underlying disease, risk factors 
including medical and family history, season, location, etc., and strength of the 
alternative explanation.
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that 
the medically qualified investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the sponsor. With limited or insufficient 
information about the event to make an informed medical judgment and in absence of any 
indication or evidence to establish a causal relationship, a causality assessment of ‘no’ is to 
be considered. In such instance, the investigator is expected to obtain additional information 
regarding the event as soon as possible and to re-evaluate the causality upon receipt of 
additional information. The medically qualified investigator may revise his/her assessment of 
causality in light of new information regarding the SAE and shall send an SAE follow-up 
report and update the eCRF with the new information and updated causality assessment. 
5.5.4
Criteria for Defining the Severity of an Adverse Event
The investigator will use the following definitions to rate the severity of each AE:
●
Mild: No disruption of normal daily activities
●
Moderate: Affect normal daily activities
●
Severe: Inability to perform daily activities
●
Potentially life threatening: Emergency room visit or hospitalization 
5.5.5
Reporting of Serious Adverse Events (SAEs)
The collection of AEs will continue until 30 days after study vaccine administration in all 
groups.  The expedited reporting of SAEs will start following receipt of the ICF and will 
continue until 180 days after study vaccine administration in Groups 1 and 2 and until 30 
days after study vaccine administration in Group 3, or until the subject is determined to be a 
screen failure or withdraws from the study.
In the case of an SAE, the investigator must contact the sponsor by fax or email immediately 
(within 24 hours of awareness).
The investigator must complete and submit an SAE worksheet containing all information that 
is required by local and/or regional regulations to the sponsor by email or fax immediately 
(within 24 hours of awareness).
The SAE worksheet must be signed by a medically qualified investigator (as identified 
on Delegation of Authority Log). Signature confirms accuracy and completeness of the 
SAE data as well as the investigator causality assessment including the explanation for 
the causality assessment.
If the SAE is associated with emergency unblinding as outlined in [Section 4.4.4 Breaking 
the Study Vaccine Assignment Code for Emergency], this is to be recorded on the SAE 

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worksheet. Within the SAE worksheet, the investigator is to include when unblinding took 
place in association with the SAE. 
For contact details, see [Section II Contact Details of Key Sponsor's Personnel]. Fax or email 
the SAE/Special Situations Worksheet to:
Astellas Pharma Global Development – United States
Pharmacovigilance
Fax number 847-317-1241
Email: safety-us@astellas.com 
The following minimum information is required:
●
International Study Number/Study number, 
●
Subject number, sex and age,
●
The date of report,
●
A description of the SAE (event, seriousness criteria), 
●
Causal relationship to the study vaccine (including reason), and
●
The drug provided (if any) (blinded regimen is also an option)
The sponsor or sponsor’s designee will medically evaluate the SAE and determine if the report 
meets the requirements for expedited reporting based on seriousness, causality and expectedness 
of the events (e.g., Suspected Unexpected Serious Adverse Reaction [SUSAR] reporting) 
according to current local/regional regulatory requirements in participating countries. The 
sponsor or sponsor's designee will submit expedited safety reports (e.g., Investigational New 
Drug [IND] Safety Reports, SUSAR, Council for International Organizations of Medical 
Sciences [CIOMS-I]) to Competent Authorities (CA) and concerned Ethics Committee (cEC) 
per current local regulations, and will inform the investigators of such regulatory reports as 
required. Investigators must submit safety reports as required by their IRB within timelines set 
by regional regulations (e.g., EMA, FDA) where required.  Documentation of the submission to 
and receipt by the IRB of expedited safety reports should be retained by the site.
The sponsor will notify all investigators responsible for ongoing clinical studies with the study 
vaccine of all SUSARs, which may require submission per local requirements to the site IRB.
The investigators or designee should provide written documentation of IRB notification for 
each report to the sponsor.
The investigator may contact the sponsor's medical monitor/study physician for any other 
problem related to the safety, welfare, or rights of the subject.
5.5.6
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 by the investigator. 
If after the protocol defined AE collection period [Section 5.5.1 Definition of Adverse 
Event], an AE progresses to an SAE, or the investigator learns of any (S)AE including death, 

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where he/she considers there is reasonable possibility it is related to the study vaccine 
treatment or study participation, the investigator must promptly notify the sponsor.
5.5.7
Monitoring of Common Serious Adverse Events
For this phase 1/2 clinical study, there is no list of common SAEs for which a single 
occurrence will be excluded from IND safety reporting.
5.5.8
Special Situations 
Certain Special Situations observed in association with the study vaccine(s), such as incorrect 
administration (e.g., wrong dose of study vaccine, comparator, or background therapy) are 
collected in the eCRF, as Protocol Deviation per [Section 8.3 Major Protocol Deviations] or 
may require special reporting, as described below. These Special Situations are not 
considered AEs, but do require to be communicated to Astellas as per the timelines defined 
below.
If a Special Situation is associated with, or results in, an AE, the AE is to be assessed 
separately from the Special Situation and captured as an AE in the eCRF. If the AE meets the 
definition of a SAE, the SAE is to be reported as described in [Section 5.5.5 Reporting of 
Serious Adverse Events] and the details of the associated Special Situation are to be included 
in the clinical description on the SAE worksheet.
The Special Situations are:
●
Pregnancy 
●
Medication error, overdose and “off-label use”
●
Misuse/abuse
●
Occupational exposure
●
(Suspicion of) Transmission of infectious agent 
●
Suspected drug-drug interaction
5.5.8.1 Pregnancy
If a female subject becomes pregnant within 28 days of immunization, the investigator is to 
report the information to Astellas according to the timelines in [Section 5.5.5 Reporting of 
Serious Adverse Events] using the Pregnancy Reporting Form and in the eCRF. 
The investigator will attempt to collect pregnancy information on any female partner of a 
male subject who becomes pregnant within 28 days of immunization and report the 
information to Astellas according to the timelines in [Section 5.5.5 Reporting of Serious 
Adverse Events] using the Pregnancy Reporting Form. 
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.
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
termination (including elective termination) of a pregnancy is to be reported for a female 
study subject as an AE in the eCRF or SAE per [Section 5.5.5 Reporting of Serious Adverse 

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Events]. For (S)AEs experienced by a female partner of a male subject, (S)AEs are to be 
reported via the Pregnancy Reporting Form. 
Additional information regarding the outcome of a pregnancy when also categorized as an 
SAE is mentioned below:
●
“Spontaneous abortion” includes miscarriage, abortion and missed abortion.
●
Death of a newborn or infant within 1 month after birth is to be reported as an SAE 
regardless of its relationship with the study vaccine.
●
If an infant dies more than 1 month after the birth, is to be reported if a relationship 
between the death and intrauterine exposure to the study vaccine is judged as “possible”
by the investigator.
●
Congenital anomaly (including anomaly in miscarried fetus)
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. (S)AEs 
experienced by the newborn/infant should be reported via the Pregnancy Reporting Form. 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated delivery 
date.
5.5.8.2 Medication Error, Overdose and “Off-Label Use”
If a medication error, overdose or “off-label use” (i.e., use outside of what is stated in the 
protocol) is suspected, refer to [Section 8.3 Major Protocol Deviations]. Any associated 
(S)AEs are to be reported in the eCRF.  If the AE meets the definition of a SAE, the SAE is 
also to be reported as described in [Section 5.5.5 Reporting of Serious Adverse Events] 
together with the details of the medication error, overdose and/or “off-label use”.
In the event of suspected ASP3772 overdose, the subject should receive supportive care and 
monitoring. The medical monitor/expert should be contacted as applicable. 
5.5.8.3 Misuse
If misuse of the study vaccine(s) is suspected, the investigator must forward the Special 
Situation worksheet Astellas Pharma Inc. by fax or email immediately (within 24 hours of 
awareness). Any associated (S)AEs are to be reported in the eCRF. If the AE meets the 
definition of a SAE, the SAE is also to be reported as described in [Section 5.5.5 Reporting 
of Serious Adverse Events] together with details of the misuse or abuse of the study 
vaccine(s).
5.5.8.4 Occupational Exposure
If occupational exposure (e.g., inadvertent exposure to the study vaccine(s) of site staff whilst 
preparing it for administration to the patient) to the study vaccine(s) occurs, the investigator 
must forward the Special Situation worksheet to Astellas Pharma Inc. by fax or email 
immediately (within 24 hours of awareness).  Any associated (S)AEs occurring to the 
individual associated with or resulting from the Special Situation are to be reported on the 
Special Situations worksheet.

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5.5.8.5 (Suspicion of) Transmission of infectious agent
If transmission of an infectious agent associated with the study vaccine(s) is suspected, the 
investigator must forward the Special Situation worksheet to Astellas Pharma Inc. by fax or 
email immediately (within 24 hours of awareness) and any associated (S)AEs are to be 
reported in the eCRF.  If the AE meets the definition of a SAE, the SAE is also to be reported 
as described in [Section 5.5.5 Reporting of Serious Adverse Events] together with the details 
of the suspected transmission of infectious agent.
5.5.8.6 Suspected Drug-Drug Interaction
If a suspected drug-drug interaction associated with the study vaccine(s) is suspected, the 
investigator must forward the Special Situation worksheet Astellas Pharma Inc. by fax or 
email immediately (within 24 hours of awareness). Any associated (S)AEs are to be reported 
in the eCRF. If the AE meets the definition of a SAE, the SAE is also to be reported as 
described in [Section 5.5.5 Reporting of Serious Adverse Events] together with details of the 
suspected drug-drug interaction.
5.5.9
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. 
The investigator will also inform the subjects, who will be required to sign an updated ICF in 
order to continue in the clinical study.
5.5.10
Urgent Safety Measures 
An Urgent Safety Measure (USM) is an intervention, which is not defined by the protocol 
and can be put in place with immediate effect without needing to gain prior approval by the 
sponsor, relevant CA, IRB/IEC, where applicable, in order to protect study participants from 
any immediate hazard to their health and/or safety. Either the investigator or the sponsor can 
initiate an USM. The cause of an USM can be safety, product or procedure related.
5.5.11
Reporting Urgent Safety Measures
In the event of a potential USM, the investigator must contact the Astellas study physician 
(within 24 hours of awareness).  Full details of the potential USM are to be recorded in the 
subject’s medical records.  The sponsor may request additional information related to the 
event to support their evaluation. 
If the event is confirmed to be an USM the sponsor will take appropriate action to ensure the 
safety and welfare of the patients.  These actions may include, but are not limited to, a change 
in study procedures or study treatment, halting further enrollment in the trial, or stopping the 
study in its entirety.  The sponsor or sponsor's designee will notify CA and cEC within the 
timelines required per current local regulations, and will inform the investigators as required. 

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When required, investigators must notify their IRB/IEC within timelines set by regional 
regulations.
Test Drug Concentration
Measurement of study vaccine concentrations is not applicable to this study.
Other Measurements, Assessments or Methods
Not applicable.
Total Amount of Blood
The approximate total amount of blood to be collected for central laboratory assessment per 
subject is presented in below tables.  Repeat and additional blood samples may be taken if 
required, however the maximum blood volume drawn from the subject will not exceed 550 mL 
over the course of the study.  Refer to laboratory manual for more details regarding blood 
collection.
Stage 1 
Sample Type
Number of Samples
Sample Volume (mL)
Total Volume (mL)
Clinical Laboratory Tests
4
10.0
40.0
T-cell response (PBMCs) 
3
20.0
60.0
Anti-biotin 
2
10.0
20.0
Anti-1500+0785
2
10.0
20.0
IgG and OPA
2
10.0
20.0
Total
IgG: immunoglobulin G; OPA: opsonophagocytic activity; PBMC: peripheral blood mononuclear cells; 
CCI
CCI
CCI
CCI
CCI

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Stage 2
Group 2
Sample Type
Number of Samples
Sample Volume (mL)
Total Volume (mL)
Clinical Laboratory Tests 
4
10.0
40.0
T-cell response (PBMCs) 
3
20.0
60.0
Anti-biotin 
2
10.0
20.0
Anti-1500+0785 
2
10.0
20.0
IgG and OPA
2
10.0
20.0
Total
IgG: immunoglobulin G; OPA: opsonophagocytic activity; PBMC: peripheral blood mononuclear cells; 
Group 3
Sample Type
Number of Samples
Sample Volume (mL)
Total Volume (mL)
Clinical Laboratory Tests 
3
10.0
30.0
IgG and OPA
2
10.0
20.0
Total
IgG: immunoglobulin G; OPA: opsonophagocytic activity;
6
DISCONTINUATION
Discontinuation of Individual Subject(s) From Study 
Individual subjects will be discontinued from the study if:
●
Subject is lost-to-follow-up despite reasonable efforts by the investigator to locate the 
subject.
●
Subject can voluntarily withdraw from the study at any time for any reason. 
The reason for discontinuation from study must be documented in the subject’s medical 
records.
Any subject who has received immunization, but withdraws consent, will be asked to 
complete the day 30 study assessments at the time of their withdrawal if possible. 
6.1.1
Lost to Follow Up
Every reasonable effort is to be made to contact any subject lost to follow-up during the 
course of the study to complete study-related assessments and record outstanding data. 
Discontinuation of the Site
If an investigator intends to discontinue participation in the study, the investigator must 
immediately inform the sponsor.
CCI
CCI
CCI
CCI
CCI
CCI

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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 
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 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. Any changes from the analyses planned in SAP will be 
justified in the clinical study report.
In general, continuous data will be summarized with descriptive statistics (number of subjects, 
mean, standard deviation, geometric mean and geometric standard deviation (GSD) where 
applicable, minimum, median and maximum), and frequency and percentage for categorical 
data. Percentages by categories will be based on the number of subjects with no missing data, 
i.e., the percentages will sum to 100%.
Baseline will be defined as the last observation prior to first dose, unless otherwise specified.
Sample Size
In Stage 1, approximately 120 evaluable adults 18 to 64 years of age are planned to be enrolled.  
This sample size in is considered sufficient to obtain preliminary estimates in a phase 1 study of 
safety and reactogenicity in the adult population, ages 18 to 64. In Stage 2, approximately 495 
evaluable adult subjects from 65 to 85 years of age are planned to be enrolled.  For each PCV13 
serotype the OPA titer-1 responses (geometric mean titer [GMT] and GSD) in subjects 60 to 
64 years of age administered PCV13 (Source Prevnar13® label) were assumed to be 
representative of the response following immunization with ASP3772.  The width of 95% 
confidence intervals for each serotype with 30, 100 and 150 subjects were calculated. A sample 
size of 100 subjects at each dose level treated with ASP3772 under these assumptions was 
considered sufficient to provide good estimates of OPA titer-1 responses.  The sample size and 
dose level for the phase 3 study will be determined based on the responses in Stage 2 elderly 
subjects. 
Analysis Sets
The Safety Analysis Set (SAF) will consist of all subjects who receive an immunization in 
this study with either ASP3772, PCV13, or PPSV23.  The Full Analysis Set (FAS) will 
consist of all subjects who receive an immunization in this study with either ASP3772, 
PCV13 or PPSV23 and have at least 1 postimmunization measurement.
For each ASP3772, PCV13 or PPSV23 immunization group, the number and percentage of 
subjects in each analysis set will be given for all randomized (ASP3772 or PCV13) or 
enrolled (PPSV23) subjects.

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7.2.1
Full Analysis Set (FAS)
The FAS will be used for summaries and primary analyses of immunogenicity data.
7.2.2
Per Protocol Set (PPS)
The PPS will be used to assess immunologic response and will serve as a supportive analysis. 
The PPS will exclude the following subjects:
●
Subjects who are given antibiotics within 7 days prior to the 30-day blood draw to assess 
immunogenicity in the ASP3772 immunization group since these may interfere with the 
immunogenicity assay
●
Subjects who have their 30-day blood draw 14 or more days after the 30 day post 
immunization scheduled blood collection
●
Subjects who receive immunosuppressants as this may interfere with their ability to 
mount a response to the vaccine
●
Subjects who have newly diagnosed immunologic abnormalities within the first 2 weeks 
after receiving the immunization.
7.2.3
Safety Analysis Set (SAF)
The SAF will be used for most summaries of demographic and baseline characteristics and 
all safety and tolerability related variables.  There are a limited number of displays that will 
use all subjects who gave informed consent or all subjects who were randomized.
Demographics and Baseline Characteristics 
Demographics and baseline characteristics (age, sex, race, ethnicity, weight, height and body 
mass index) will be summarized by dose cohort and immunization group (ASP3772 or 
PCV13) and for all PCV13 subjects combined.  Summaries will be given separately for the 
adults (18 to 64 years) and elderly (65 to 84 years).  A summary will be provided for the 
PPSV23 enrolled subjects.
7.3.1
Subject Disposition 
Disposition (consented, discontinued before randomization, randomized, vaccinated) will be 
provided by stage (adults, elderly), dose cohort (1 µg, 2 µg, 5 µg) and immunization group 
(ASP3772 or PCV13) and for all PCV13 subjects combined. A summary will be provided for 
the PPSV23 enrolled subjects.
The number and percentage of subjects who completed the study, those who discontinued the 
study and the reasons for study discontinuation (AE, death, lost to follow-up, protocol 
deviation, withdrawal by subject, non-compliance with study, other) will be presented for 
SAF subjects for each stage (adults, elderly).  All disposition details and dates of first and last 
evaluations for each subject will be listed.
7.3.2
Previous and Concomitant Medications 
All previous and concomitant medications for each subject will be listed.

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7.3.3
Medical History 
Medical history for each subject will be listed.
Analysis of Immunogenicity 
Assessment of immunological response following ASP3772 administration relative to 
PCV13 is a secondary objective for this study.
Stage 1:
The following measures in adults 18 to 64 years of age will be used to characterize the 
immunological response 30 days following administration of either ASP3772 or PCV13. 
These measures will be provided for each immunization group (PCV13 vs ASP3772) and 
dose level (ASP3772: 1, 2, 5 µg). 
●
The GMT, GSD and 95% confidence interval (CI) for functional OPA for each serotype 
will be calculated.  
●
The ratio of the OPA GMT (each ASP3772 dose level/PCV13) and 95% CI will be provided.  
●
The geometric mean concentration (GMC), GSD and 95% CI for serotype-specific IgG 
for each of the serotypes will be calculated.
●
The ratio of the IgG GMC (each ASP3772 dose level/PCV13) and 95% CI will be provided.  
●
The GMFR, GSD and 95% CI in anticapsular polysaccharide IgG and OPA titer will be 
calculated for each of the serotypes unique to ASP3772.  
●
The proportion of subjects with a 4-fold increase in anticapsular polysaccharide IgG 
and OPA relative to baseline will be calculated. 
Stage 2 Group 2:
The following measures in adults 65 to 84 years of age will be used to characterize the 
immunological response 30 days following vaccine administration. These measures will be 
provided by dose cohort for ASP3772 and for PCV13 as a single group for each serotype.
●
The GMT, GSD and 95% CI for functional OPA activity for each serotype will be calculated.  
●
The ratio of the GMT for functional OPA (each ASP3772 dose level/PCV13) for each 
serotype and the 95% CI will be provided.
●
The GMC, GSD and 95% CI for serotype-specific IgG for each of the serotypes will be 
calculated.  
●
The ratio of the IgG GMC (each ASP3772 dose level/PCV13) and 95% CI will be provided 
for each serotype.
●
The GMFR, GSD and 95% CI in anticapsular polysaccharide IgG and OPA titer will be 
calculated for each of the serotypes unique to ASP3772.  
●
The proportion of subjects with a 4-fold increase in anticapsular polysaccharide IgG 
and OPA relative to baseline will be calculated  
●
To assess the impact of ASP3772 dose, an analysis of covariance (ANCOVA) model 
with age (65 to 74 years, 75 to 85 years) as the covariate and immunization (ASP3772 1, 

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2, 5 μg or PCV13) as the factor of interest will be conducted on the natural logarithm 
(log) of pneumococcal OPA titers and the natural log of the IgG concentrations. 
In addition, for both Stage 1 Group 1 and Stage 2 Group 2, SP1500+0785 levels (ng/mL) will 
be collected for those subjects given either ASP3772 or PCV13. Levels of the following 
cytokines will be collected for subjects given ASP3772 or PCV13: Th17, IL-17, 
, IL-22, 
 The units for all are pg/mL. Non-parametric 
methods will be used for these analyses. A Kruskal-Wallis test will be used to test for overall 
differences between the 3 dose levels and PCV13. All treatment groups in Stage 1 will be 
compared, followed by paired comparisons between each of the ASP3772 dose levels and 
PCV13 using a Wilcoxon Test.  The same set of comparisons will be made for subjects in 
Stage 2, Group 2.
Stage 2; Group 3: 
For the 11 serotypes contained in PPSV23 and not in PCV13, immunological response will 
be evaluated by the following endpoints at 30 days after administration of PPSV23: 
●
The GMFR, GSD and 95% CI in anticapsular polysaccharide IgG and OPA titer 
●
The proportion of subjects with a # 4-fold increase in anticapsular polysaccharide IgG 
and OPA relative to baseline 
●
The GMT, GSD and 95% CI for the OPA titers 
●
The GMC, GSD and 95% CI for serotype-specific IgG levels.   
Analysis of Safety
Safety and tolerability of ASP3772 are the primary objectives in Stage 1 and Stage 2 of this 
study and will be assessed by: 
●
TEAEs (including SAEs, MAAEs, PIMCCs and NOCDs)
●
Laboratory assessments
●
Vital signs (body temperature, blood pressure and pulse rate)
●
Physical examination
●
ECG
●
Reactogenicity
Safety analyses will be performed on the SAF; all subjects who receive study immunization.  
Data from PCV13 subjects in each cohort will be pooled.  
For each local and systemic solicited reaction the percentage of subjects who reported each 
symptom by grade (None, Grade 1, 2, 3 or 4) will be summarized (n, %) by immunization 
group (PCV13 vs ASP3772) and dose level (ASP3772: 1, 2, 5 μg) and the percentage of 
subjects who reported any symptom.
CCI
CCI

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7.5.1
Adverse Events 
A TEAE is defined as an AE observed after study immunization and up to 30 days 
postimmunization.  SAEs will be monitored for up to 180 days postimmunization (Group 1 
and Group 2).
For each immunization arm, the frequencies and percentages will be displayed for the 
following TEAEs (coded using the Medical Dictionary for Regulatory Activities [MedDRA]) 
by system organ class and preferred term:
●
Overall
●
Serious
●
Related (yes or no) to study vaccine
The number and percentage of subjects with TEAEs, SAEs, AEs and AEs related to study 
vaccine will be summarized by system organ class, preferred term and immunization group.  
The number and percentage of AEs by severity will also be summarized.  MAAEs including 
PIMMCs and NOCDs, if any, will be summarized. All AEs will be listed. 
7.5.2
Laboratory Assessments 
Descriptive statistics for each laboratory test (e.g., hematology, biochemistry and urinalysis) 
and vital signs will be tabulated by immunization group, dose level for ASP3772 and 
scheduled time point.  
Shifts relative to normal ranges from baseline to each time point during the immunization 
period in laboratory tests will also be tabulated.  Laboratory data will be listed.
7.5.3
Vital Signs 
Descriptive statistics will be used to summarize vital sign results and changes from baseline 
for subjects in the SAF by immunization group and time point. 
Vital signs data will be displayed in listings.
7.5.4
Physical Examination 
Physical examination findings will be listed by immunization group.
7.5.5
Routine 12-lead Electrocardiograms
The 12-lead ECG results will be listed by immunization group.
Analysis of Pharmacokinetics
Pharmacokinetic analysis is not applicable in this study.
Analysis of Pharmacodynamics
Pharmacodynamic analysis is not applicable in this study.

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Major Protocol Deviations and Other Analyses 
Major protocol deviations as defined in [Section 8.3 Major Protocol Deviations] will be 
summarized for all randomized subjects by immunization group and total as well as by site.  
A data listing will be provided by site and subject.
The major 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 immunization or incorrect dose
PD4 – Received excluded concomitant treatment
Interim Analysis (and Early Discontinuation of the Clinical Study)
No formal interim analysis for efficacy is planned. Safety data will be provided for DEC 
review after each dose cohort for the adult and elderly populations for dose escalation 
decisions. Prior to initiating the enrollment of the elderly subjects, the DEC will review the 
available data through 30 days post immunization in adult subjects. Details will be provided 
in the DEC Charter.
Handling of Missing Data, Outliers, Visit Windows and Other 
Information
As a general principle, no imputation of missing data will be done. Exceptions are the start 
and stop dates of AEs and concomitant medications if they are missing on day of first dose. 
The imputed dates will be used to assess if the AEs or concomitant medications are 
treatment-emergent or concomitant, respectively.  Listings of the AEs and concomitant 
medications will present the actual partial dates; imputed dates will not be shown.
8
OPERATIONAL CONSIDERATIONS
Data Collection
The investigator or site designee will enter data collected using an electronic data capture 
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’s visit.  The investigator or site designee will be required to expedite 
recording of data in the eCRF preferably within 24 hours for data required for dose escalation 
decisions.  The investigator or site designee will also be required to expedite recording of 
data in the eCRF when last subject of Stage 1 Cohort 3 completes day 30 (visit 4) in order to 
make the Stage 1 up-to-day-30 visit data for all subjects available for DEC review. 

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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 a central laboratory. Central Laboratory data will be 
transferred electronically to the sponsor or designee at predefined intervals during the study. 
The Central laboratory will provide the sponsor or designee with a complete and clean copy 
of the data. 
ECGs are performed at a site ECG reader device. ECG read data will be reviewed by the 
investigator for the entry in eCRF.
The investigator or designee must record all protocol-required data in the provided eCRF. In 
the interest of collecting data in the most efficient manner, the investigator or site designee 
should record data (including laboratory values, if applicable) onto the eCRF as soon as 
possible after the subject visit. eCRFs and any supporting documents should be available for 
retrieval by the sponsor/delegated CRO at any given time. The monitor should verify the data 
in the eCRFs with source documents to confirm that there are no inconsistencies between 
them. If the monitor finds no inconsistencies, the appropriate eCRFs are collected, ensuring a 
copy remains at site. The originals should be submitted to the sponsor or designee.
If any inconsistency is detected on the collected eCRFs, the monitor or data manager should 
query the investigator/subinvestigator. The investigator/subinvestigator should provide an 
answer to the query and provide the resolved query to the sponsor.
The monitor should verify the revised data of the eCRFs with source documents and confirm 
that there are no inconsistencies between them, and also check that appropriate records on the 
correction/addition of data are maintained.
All procedures conducted under the protocol must be documented. For screen failures, the 
minimum demographic data (sex, birth date, race and informed consent date), outcome of 
eligibility assessment (inclusion and exclusion criteria), reason for screen failure and AEs 
details must be documented.
The investigator or designee will be responsible for eCRF completion and that all data and 
queries are accurate, complete and are verifiable with the source. The source should be 
appropriately maintained by the clinical unit.
Electronic data sources and any supporting documents should be available for 
review/retrieval by the sponsor/designee at any given time.
Electronic Patient Reported Outcome:
Subject diaries and questionnaires as described in [Section 5.4.3 Reactogenicity] will be 
completed by the subject from day 1 through day 7 on an electronic device and the collected 
electronic source data will be hosted at the vendor. The investigator or site designee will

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review the diaries and questionnaire data throughout the  study to ensure completion and 
protocol compliance. The diary and questionnaire data will be transferred electronically to 
sponsor or designee at predefined intervals during the study. The vendor will provide the 
investigator with a complete and clean copy of the site’s data and will provide the sponsor or 
designee with a complete and clean copy of the study data.  The ownership of this data is 
with the investigator and subsequently any changes requested to the non-subject reported data 
will be made using a Data Clarification Form (DCF) to the vendor.  The requested change 
must be supported by documented evidence at site.  For this study, it has been decided that 
there are justifiable scientific reasons (e.g., recall bias) for not allowing changes after the 
original daily data has been entered or not allowing additional data entered after the daily 
24-hour window has expired as these changes could potentially impact the data integrity of 
this study.  Data not collected by the subject in his/her ePRO diary will be noted as missing 
in the dataset.
Screen Failures
For screen failures the demographic data, reason for failing, informed consent, inclusion and 
exclusion criteria and AEs will be collected in the eCRF.
Major Protocol Deviations
A major 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 study 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.  The major protocol 
deviation criteria are described in [Section 7.8 Major Protocol Deviations and Other 
Analyses].
When a major 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 major 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.  

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9
END OF TRIAL 
Study completion occurs with the last visit of the last subject in the study. The End of Study 
is defined as the date on which the independent DEC completes their assessment of the study 
data.  
10
STUDY ORGANIZATION
Dose Escalation Committee (DEC)
For this clinical study, the Astellas DEC and the investigator/designee are responsible for dose 
escalation decisions.  Progression to higher dose level cohorts will be determined by the DEC, 
which may consist of representatives from Astellas Medical Science, Pharmacovigilance and 
Statistics personnel, as well as external independent safety physician(s).  For detailed 
information on the dose-escalation decision process, refer to DEC Charter.

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11
REFERENCES 
ASP3772 Investigator’s Brochure, Current edition.
Buller HR, Halperin J, Hankey GJ, Pillion G, Prins MH, Raskob GE. Comparison of idrabiotaparinux 
with vitamin K antagonists for prevention of thromboembolism in patients with atrial 
ﬁbrillation: the Borealis-Atrial Fibrillation Study. J Thromb Haemost. 2014;12: 824-30.
CDC Morbidity and Mortaility Weekly Report. Preventing pneumococcal disease among infants and 
young children. Vol 49. Oct 6, 2000.
CDC Morbidity and Mortaility Weekly Report. Prevention of pneumococcal disease among infants 
and children - use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal 
polysaccharide vaccine. Vol 59. Dec 10, 2010.
FDA Guidance for Industry: Toxicity grading scale of healthy adult and adolescent volunteers 
enrolled in preventive vaccine clinical trials. 2007.
Gruber MF, Pratt D, Haase M. Licensing of pneumococcal conjugate vaccines for children and adults: 
regulatory perspective from the European Medicines Agency and the U.S. Food and Drug 
Administration. In : Siber GR, et al editors. Pneumococcal Vaccines: the Impact of Conjugate 
Vaccine. ASM Press, Washington D.C. 2008;183-96.
Helppolainen SH, Nurminen KP, Määttä JA, Halling KK, Slotte JP, Huhtala T, et al. Rhizavidin from 
Rhizobium etli: the first natural dimer in the avidin protein family. Biochem J. 
2007;405(3):397-405.
Lazzeri E, Pauwels EK, Erba PA, Volterrani D, Manca M, Bodei L, et al. Clinical feasibility of two-
step streptavidin/111In-biotin scintigraphy in patients with suspected vertebral osteomyelitis. 
Eur J Nucl Med Mol Imaging. 2004;31(11):1505-11.
Paty I, Trellu M, Destors J-M, Cortez P, Boëlle E, Sanderink G. Reversibility of the anti-FXa activity 
of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion. J Throm Haemost. 
2010;8:722-9.
PNEUMOVAX 23 (prescribing information). Merck and Co., Inc. Kenilworth, NJ. 2017.
PREVNAR 13 (prescribing information). Pfizer, Inc. New York, NY. 2017.
Richter SS, Diekema DJ, Heilmann KP, Dohrn CL, Riahi F, Doern GV. Changes in pneumococcal 
serotypes and antimicrobial resistance after introduction of the 13-valent conjugate vaccine in 
the United States. Antimicrob Agents Chemother. 2014;58(11):6484-9. 
Zhang F, Lu Y-J, Malley R. Multiple antigen-presenting system (MAPS) to induce comprehensive B-
and T-cell immunity. PNAS. 2013;110(33):13564-9.

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12
APPENDICES
Ethical, Regulatory and Study Oversight Considerations
12.1.1
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. 
12.1.2
Institutional Review Board (IRB) 
GCP requires that the clinical protocol, any protocol amendments, the IB, the ICF 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 IRB.  The IRB will review 
the ethical, scientific and medical appropriateness of the study before it is conducted.  IRB 
approval of the protocol, ICF and subject information and/or advertising, as relevant, will be 
obtained prior to the authorization of drug shipment to a study site.
Any substantial amendments to the protocol will require IRB approval before 
implementation, except for changes necessary to eliminate an immediate hazard to subjects.
The investigator will be responsible for the following:
●
Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies and procedures established by 
the IRB
●
Notifying the IRB of SAEs or other significant safety findings as required by IRB 
procedures
●
Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB, European regulation 536/2014 for clinical studies 
(if applicable), and all other applicable local regulations
12.1.3
Protocol Amendment and/or Revision
Amendments to this protocol must be signed by the sponsor and the investigator. Written 
verification of IRB approval will be obtained before any amendment is implemented. 
Modifications to the protocol that are administrative in nature do not require IRB approval, 
but will be submitted to the IRB for their information, if required by local regulations.
If there are changes to the ICF, written verification of IRB approval must be forwarded to the 
sponsor.  An approved copy of the new ICF must also be forwarded to the sponsor.
12.1.4
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.

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12.1.5
Informed Consent of Subjects
12.1.5.1 Subject Information and Consent
The investigator or his/her representative will explain the nature of the study to the subject 
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, the person who administered the informed consent and 
any other signatories according to local requirements. A copy of the signed ICF 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.
12.1.5.2 Supply of New and Important Information Influencing the Subject’s Consent 
and Revision of the Written Information
1.
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 drug reaction). The communication must be 
documented in the subject’s medical records and whether the subject is willing to remain 
in the study or not must be confirmed and documented.
2.
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 ICF.  A copy of the 
signed ICF 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.
12.1.6
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 investigator is responsible for ensuring the source data are attributable, legible, 
contemporaneous, original, accurate and complete whether the data are hand-written on paper 
or entered electronically. If source data are created (first entered), modified, maintained, 
achieved, retrieved or transmitted electronically via computerized systems (and/or other kind 
of electric devices) as part of regulated clinical trial activities, such systems must be 

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compliant with all applicable laws and regulations governing use of electronic records and/or 
electronic signatures. Such systems may include, but are not limited to, electronic 
medical/health records, protocol related assessments, AE tracking and/or drug accountability. 
Paper records from electronic systems used in place of electronic format must be certified 
copies. A certified copy must be an exact copy and must have all the same attributes and 
information as the original. Certified copies must include signature and date of the individual 
completing the certification. Certified copies must be a complete and chronological set of 
study records (including notes, attachments and audit trail information, if applicable). All 
printed records must be kept in the subject file and available for archive. 
12.1.7
Record Retention
The investigator will archive all study data (e.g., subject identification code list, source data, 
eCRFs 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, 2 years after 
approval of the NDA or discontinuation of the IND). The sponsor will notify the 
site/investigator if the NDA/MAA/J-NDA is approved or if the IND/IMPD/CHIKEN 
TODOKE 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.
The documents of the Efficacy and Safety Evaluation Committee (minutes and SOPs and 
others) and the judgment committee outside the study sites (minutes and SOPs and others) 
shall be retained by the sponsor.
12.1.8
Subject Confidentiality and Privacy
Individual subject medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited unless otherwise the subject provides 
written consent or approval. Additional medical information may be given only after 
approval of the subject to the investigator 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.
Even though any individuals involved in the study, including the study monitors and auditors, 
may get to know matters related to subject's privacy due to direct access to source documents, 
or from other sources, they may not leak the content to third parties. 
The sponsor affirms the subject's right to protection against invasion of privacy. Only a 
subject identification number 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.

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The sponsor agrees to comply and process personal data in accordance with all applicable 
privacy laws and regulations, including, without limitation, the Personal Information 
Protection Law in Japan and Privacy laws in the US.  If the services will involve the 
collection or processing of personal data (as defined by applicable data protection legislation) 
within the European Economic Area (EEA), then sponsor shall serve as the controller of such 
data, as defined by the EU Data Protection Directive, and investigator and/or third party shall 
act only under the instructions of the sponsor in regard to personal data.  If sponsor is not 
based in the EEA, sponsor must appoint a third party to act as its local data protection 
representative or arrange for a co-controller established in the EU for data protection 
purposes in order to comply with the Directive.
12.1.9
Arrangement for Use of Information and Publication of the Clinical Study
Information concerning the study vaccine, patent applications, processes, unpublished 
scientific data, the IB 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 drug 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. 
12.1.10 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.

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Procedure for Clinical Study Quality Control
12.2.1
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/subinvestigator 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.  
12.2.2
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 including source documents 
when they are requested by the sponsor monitors and auditors, the IRB/IEC, or regulatory 
authorities. The confidentiality of the subject's identities shall be well protected consistent 
with local and national regulations when the source documents are subject to direct access.
12.2.3
Data Management
Data Management will be coordinated by the Astellas Global Data Manager in accordance 
with the SOPs for data management. All study-specific processes and definitions will be 
documented by Data Management. eCRF completion will be described in the eCRF 
instructions. Coding of medical terms and medications will be performed using MedDRA 
and WHO Drug Dictionary, respectively.
12.2.4
Quality Assurance
The sponsor is implementing and maintaining quality assurance and quality control systems 
with written SOPs to ensure that studies are conducted and data are generated, documented, 
recorded, and reported in compliance with the protocol, GCP and applicable regulatory 
requirement(s). Where applicable, the quality assurance and quality control systems and 
written SOPs of the CRO will be applied.
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, eCRFs and source documents. Direct access to these documents will be required 
by the auditors.

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Contraception Requirements
WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Schedule of Assessments.
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND METHODS OF 
CONTRACEPTION DEFINITIONS (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile. 
Women in the following categories are not considered WOCBP
●
Premenarchal
●
Premenopausal female with 1 of the following:
○Documented hysterectomy
○Documented bilateral salpingectomy
○Documented bilateral oophorectomy
●
Post-menopausal
Documentation of any of these categories can come from the site personnel’s review of the 
female subject’s medical records, medical examination, or medical history interview.
A postmenopausal state is defined as at least 12 months after last regular menstrual bleeding 
without an alternative medical cause. 
●
In case the last regular menstrual bleeding cannot be clearly determined, confirmation 
with repeated follicle stimulating hormone (FSH) measurements of at least > 40 IU/L (or 
higher per local institutional guidelines), is required. 
Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt 
will be required to use 1 of the non-estrogen hormonal highly effective contraception 
methods if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status by repeated FSH 
measurements before study enrollment.
CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF CHILD 
BEARING POTENTIAL
One of the highly effective methods of contraception listed below is required at the time of 
informed consent and until the end of relevant systemic exposure, defined as 28 days after the 
study vaccine administration.*
Highly Effective Contraceptive Methods (Failure rate of < 1% per year when used 
consistently and correctly)a
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation
●
oral
●
intravaginal

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●
transdermal
Progestogen-only hormonal contraception associated with inhibition of ovulation
●
oral
●
injectable
●
implantable 
Hormonal methods of contraception containing a combination of estrogen and progesterone:
●
vaginal ring 
●
injectables
●
implants 
●
intrauterine hormone-releasing system
●
intrauterine device
Bilateral tubal occlusion/ligation is considered as a highly effective contraception method. 
Vasectomized partner: A vasectomized partner is a highly effective contraception method 
provided that the partner is the sole male sexual partner of the WOCBP and the absence of 
sperm has been confirmed. If not, an additional highly effective method of contraception 
should be used.
Sexual abstinence: Sexual abstinence is considered a highly effective method only if defined 
as refraining from heterosexual intercourse during the entire period of risk associated with 
the study vaccine. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the participant. It is not 
necessary to use any other method of contraception when complete abstinence is elected.
* Local laws and regulations may require use of alternative and/or additional contraception methods.
a Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants participating 
in clinical studies.
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S) 
OF CHILD BEARING POTENTIAL.
Male participants with female partners of childbearing potential are eligible to participate if 
they agree to the following during the study and until the end of relevant systemic exposure 
defined as 28 days after study vaccine administration.*
●
Inform any and all partner(s) of their participation in a clinical drug study and the need to 
comply with contraception instructions as directed by the investigator.
●
Male participants are required to use a condom during the study and until end of relevant 
systemic exposure defined 28 days after study immunization.
●
Female partners of male participants who have not undergone a vasectomy with the 
absence of sperm confirmed or a bilateral orchiectomy should consider use of effective 
methods of contraception until the end of relevant systemic exposure, defined as 28 days 
after study immunization.

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List of Excluded Concomitant Medications
Subjects must not use any of the following:
●
Vaccines, blood product, immunosuppressants including systemic steroids (topical steroids 
will be allowed) from the day of study administration until 30 days postimmunization.
●
Subjects may receive other routine immunizations at the 30-day follow-up visit after the 
completion of all study procedures at each site’s discretion; however routine vaccines 
should not be given in less than 30 days post-study immunization.
●
Acetaminophen and NSAIDs are allowed during the study, but not within 24 hours prior 
to immunization and collection of serum samples for immunogenicity.
●
Use of any systemically absorbed antibiotics during the 30-day period prior to collection 
of the immunogenicity samples should be restricted unless clinically warranted (e.g., 
avoid prophylaxis) to avoid interference with the immunoassay. If a subject has been 
treated with any systemically absorbed antibiotics between day 1 and day 30, the 30-day 
follow-up visit should take place at least 7 days after the last dose of the antibiotics.

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Laboratory Assessment
Laboratory Test
Visit
Parameters to be Analyzed
Hematology
Screening (Visit 1) or 
Dosing (Visit 2), 
day 7 (Visit 3) and 
day 30 (Visit 4)

Hemoglobin (HGB)

Hematocrit (HCT)

Erythrocytes (RBC)

Leukocytes (WBC) 

Differential WBC

Platelets (PLT)
Biochemistry
Screening (Visit 1) or 
Dosing (Visit 2),
day 7 (Visit 3) and 
day 30 (Visit 4)

Sodium (Na)

Potassium (K)

Calcium (Ca)

Chloride (Cl)

Glucose (Gluc)

Total cholesterol (TC)

Triglycerides (TG)

Blood Urea Nitrogen (BUN)

Creatinine (Cr)

Creatine kinase (CK)

Total protein (TP)

Uric acid (UA)

Albumin (Alb)

C-reactive protein
Coagulation Profile
Screening (Visit 1) or 
Dosing (Visit 2), 
day 7 (Visit 3) and 
day 30 (Visit 4) 

Prothrombin Time (PT)

Activated Partial Thromboplastin Time (aPTT)

Fibrinogen
Hepatic Profile
Screening (Visit 1) or 
Dosing (Visit 2), 
day 7 (Visit 3) and 
day 30 (Visit 4) 

Alkaline phosphatase (ALP)

Aspartate transaminase (AST)

Alanine transaminase (ALT)

Gamma Glutamyl Transferase (GGT)

Total bilirubin (TBL)

Lactate dehydrogenase (LDH)
Urinalysis
Screening (Visit 1) or 
Dosing (Visit 2), 
day 7 (Visit 3) and 
day 30 (Visit 4) 
Using dipstick

Protein

Glucose

pH

Blood

Leukocytes

Urobilinogen

Bilirubin

Ketones

Nitrite
Microscopy (Optional)

Casts

Crystals

Epithelial cells

Leucocytes

Erythrocytes

Bacteria
Table continued on next page

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Laboratory Test
Visit
Parameters to be Analyzed
Pregnancy Test (females 
of childbearing potential 
only)
Screening (Visit 1) –
serum, 
Dosing (Visit 2) – urine,
Day 30 (Visit 4) – urine
∀
Human Chorionic Gonadotropin (hCG)
Urine Drug Screening
Screening (Visit 1) or
Dosing (Visit 2) 
∀
Amphetamines
∀
Barbiturates
∀
Benzodiazepines
∀
Cannabinoids
∀
Cocaine
Virology
Screening (Visit 1) or 
Dosing (Visit 2)
∀
Anti-HAV (IgM)
∀
HBsAg
∀
Anti-HCV (reflex testing/HCV-RNA)
∀
Anti-HIV-1 and 2
Immunogenicity
Dosing (Visit 2) and 
day 30 (Visit 4)
∀
Anti-biotin
∀
Anti-1500+0785
∀
IgG and OPA
Immunogenicity
Dosing (Visit 2), 
day 7 (Visit 3) and 
day 30 (Visit 4)
∀
T-cell response (PBMCs)
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Grading of Local Reactogenicity 
Stage 1 Group 1 and Stage 2 Group 2 subjects will be asked to record the below local 
reactogenicity along with body temperature through day 7 following study immunization.
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
ER visit or 
hospitalization
Tenderness 
Mild discomfort 
to touch
Discomfort with 
movement
Significant 
discomfort at rest
ER visit or 
hospitalization
Erythema/Redness†*
2.5 – 5 cm
5.1 – 10 cm
> 10 cm
Necrosis or 
exfoliative 
dermatitis
Induration/Swelling‡*
2.5 – 5 cm 
and does not 
interfere with 
activity
5.1 – 10 cm 
or interferes with 
activity
> 10 cm 
or prevents daily 
activity
Necrosis
ER: emergency room
† In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable. 
‡ Induration/Swelling should be evaluated and graded using the functional scale, as well as the actual 
measurement. 
* A measurement tool will be provided to the subjects to measure the diameter of the erythema/redness and 
induration/swelling.  

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Grading of Signs of Systemic Reactogenicity 
Vital signs measurements will be monitored for reactogenicity through 1 hour postdose in all 
Stage 1 Group 1 and Stage 2 Group 2 subjects. Oral temperature will be recorded by the 
subjects daily through day 7 postimmunization.
Vital Signs†
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
(bpm)
101 – 115
116 – 130
> 130
ER visit or 
hospitalization for 
arrhythmia
Bradycardia
(bpm)§
50 – 54
45 – 49
< 45
ER visit or 
hospitalization for 
arrhythmia
Hypertension 
(systolic) 
(mm Hg)
141 – 150
151 – 155
> 155
ER visit or 
hospitalization for 
malignant 
hypertension
Hypertension 
(diastolic) 
(mm Hg)
91 – 95
96 – 100
> 100
ER visit or 
hospitalization for 
malignant 
hypertension
Hypotension 
(systolic ) (mm
Hg)
85 – 89
80 – 84
< 80
ER visit or 
hospitalization for 
hypotensive shock
Respiratory 
Rate (breaths 
per min)
17 – 20
21 – 25
> 25
Intubation
bpm: beats per minute; ER: emergency room
† Subject should be at rest for all vital sign measurements.
‡ Oral temperature; no recent hot or cold beverages or smoking. Subjects will be provided with a digital 
thermometer to record oral temperature daily though day 7 postimmunization.
§ When resting heart rate is between 60 and 100 bpm. Use clinical judgment when characterizing bradycardia 
among some healthy subject populations, e.g., conditioned athletes.

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Stage 1 Group 1 and Stage 2 Group 2 subjects will be asked to record the below systemic 
reactogenicity through day 7 following study immunization.
Systemic
(General)
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially
Life-threatening
(Grade 4)
Nausea/
Vomiting
No interference with 
activity or 1 – 2 
episodes/24 hours
Some interference with 
activity or 
> 2 episodes/24 hours
Prevents daily activity, 
requires outpatient IV 
hydration
ER visit or 
hospitalization for 
hypotensive shock
Diarrhea
2 – 3 loose stools or 
< 400 g/24 hours
4 – 5 stools or 
400 – 800 g/24 hours
6 or more watery 
stools or > 800 g/24 
hours or requires 
outpatient IV hydration
ER visit or 
hospitalization
Headache
No interference with 
activity
Repeated use of non-
narcotic pain reliever 
> 24 hours or some 
interference with 
activity
Significant; any use of 
narcotic pain reliever 
or prevents daily 
activity
ER visit or 
hospitalization
Fatigue
No interference with 
activity
Some interference with 
activity
Significant; prevents 
daily activity
ER visit or 
hospitalization
Arthralgia*
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
Illness or clinical 
AE (as defined 
according to 
applicable 
regulations) †
No interference with 
activity
Some interference with 
activity not requiring 
medical intervention
Prevents daily activity 
and requires medical 
intervention
ER visit or 
hospitalization
AE: adverse event; ER: emergency room; IV: intravenous.
* Stage 1, subjects will be questioned on day 7 visit if they experienced any joint pain/arthralgia through day 7 
and if yes, the site personnel will report it as a clinical event using this grading scale. Stage 2 subjects will 
report arthralgia daily on electronic diary through day 7 postimmunization. 
† Subjects will be questioned on day 7 if they experienced any other illness through day 7 postimmunization 
and if yes, the site personal will report it as a clinical event using this grading scale. 
Reference
Guidance for Industry titled “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials” issued by US Department of Health and Human 
Services Food and Drug Administration Center for Biologics Evaluation and Research on 
September 2007.

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Grading of Laboratory Abnormalities
Clinical laboratory test results will be graded and used for dose escalation decisions and for 
analysis of safety at the end of the study. The laboratory values within the grading scale 
provided in the FDA guidance have been modified based on ICON Central Laboratories 
reference ranges. These values will be provided to the DEC.
Reference
Guidance for Industry titled “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials” issued by US Department of Health and Human 
Services Food and Drug Administration Center for Biologics Evaluation and Research on 
September 2007.

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Liver Safety Monitoring and Assessment 
Any subject enrolled in a clinical study with active drug therapy and reveals an increase of 
serum aminotransferases (AT) to > 3 × upper limit of normal (ULN) or bilirubin > 2 × ULN 
should undergo detailed testing for liver enzymes (including at least ALT, AST, alkaline 
phosphatase and total bilirubin [TBL]). Testing should be repeated within 72 hours of 
notification of the test results. For studies for which a central laboratory is used, alerts will be 
generated by the central laboratory regarding moderate and severe liver abnormality to 
inform the investigator and study team. 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 × ULN 
Or
> 2 × ULN
Severe
> 3 × ULN
And
> 2 × 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 International Normalized Ratio (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 staff is to complete the liver abnormality 
case report form (LA-CRF). Subjects with confirmed abnormal liver function testing should 
be followed as described below.
Confirmed moderately abnormal liver function tests should be repeated 2 to 3 times weekly 
then weekly or less if abnormalities stabilize or the study vaccine 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 SAE.  The 

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sponsor should be contacted and informed of all subjects for whom severe hepatic liver 
function abnormalities possibly attributable to study vaccine 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 is to be recorded as “AEs” within the eCRF. Illnesses and 
conditions such as hypotensive events, and decompensated cardiac disease that may lead 
to secondary liver abnormalities should be noted. Nonalcoholic steatohepatitis is seen in 
obese hyperlipoproteinemic and/or diabetic patients, and may be associated with 
fluctuating AT levels.   The investigator should ensure that the medical history form 
captures any illness that predates study enrollment that may be relevant in assessing 
hepatic function. 
●
Obtain a history of concomitant drug use (including nonprescription medication, 
complementary and alternative medications), alcohol use, recreational drug use and 
special diets.  Medications, is to be entered in the eCRF.  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: 
o
Acute viral hepatitis (A, B, C, D, E or other infectious agents), 
o
Ultrasound or other imaging to assess biliary tract disease,
o
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.
*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 to 50% mortality 
(or transplant). 
The 2 “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 × ULN (“2 × ULN elevations are too common in 
treated and untreated patients to be discriminating”). 
2) Cases of increased bilirubin (at least 2 × ULN) with concurrent transaminase elevations at 
least 3 × ULN and no evidence of intra- or extra-hepatic bilirubin obstruction (elevated 
alkaline phosphatase [ALP]) or Gilbert’s syndrome [Temple, 2006].
FDA Guidance for Industry, “Drug-Induced Liver Injury: Premarketing Clinical Evaluation,” 
2009:
1. The drug causes hepatocellular injury, generally shown by a higher incidence of 3-fold or 
greater elevations above the ULN of ALT or AST than the (nonhepatotoxic) control drug 
or placebo.

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2. Among trial subjects showing such AT elevations, often with ATs much greater than 3 ×
ULN, 1 or more also show elevation of serum TBL to > 2 × ULN, without initial findings 
of cholestasis (elevated serum ALP).
3. No other reason can be found to explain the combination of increased AT and TBL, such 
as viral hepatitis A, B, or C; preexisting or acute liver disease; or another drug capable of 
causing the observed injury. [Guidance for Industry titled “Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation” issued by FDA on July 2009]
References
Temple R. Hy’s law: Predicting Serious Hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006 
April;15(Suppl 4):241-3.
Guidance for Industry titled “Drug-Induced Liver Injury: Premarketing Clinical Evaluation” issued by 
FDA on July 2009.  

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Common Serious Adverse Events
For this phase 1/2 clinical study, there is no list of common SAEs for which a single 
occurrence will be excluded from IND safety reporting.

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CCI

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INFORMATION DISCLOSURE TO THE SUBJECTS
CCI

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13
ATTACHMENT 1:  NONSUBSTANTIAL AMENDMENT 2
I.  The purpose of this amendment is:
Non-Substantial Changes
1.
Minor Administrative-type Changes
DESCRIPTION OF CHANGE: 
Include minor administrative-type changes, e.g., typos, format, numbering, consistency 
throughout the protocol.  
RATIONALE:
To provide clarifications to the protocol and to ensure complete understanding of study 
procedures.
2.
Update Planned Study Period
DESCRIPTION OF CHANGE:
The planned study period for this Stage 2 of this trial is moved out a quarter. 
RATIONALE:
This revision is made due to reflect the current study timelines.
3.
Increase in Number of Study Sites
DESCRIPTION OF CHANGE:
The number of study sites for both Stage 1 and Stage 2 is increased.
RATIONALE:
The site numbers are increased to support subject recruitment in Stage 2 Group 2.
4.
Modification to Exclusion Criterion #11
DESCRIPTION OF CHANGE:
Exclusion criterion #11 is revised to remove the requirement to exclude subjects who are 
positive for hepatitis B core antibody (HBc) during serology testing. 
RATIONALE:
It was determined that hepatitis B surface antigen (HBsAg) is sufficient to confirm evidence 
of chronic hepatitis B virus infection.
5.
Extension of Screening Period
DESCRIPTION OF CHANGE:
The screening period for Stage 2, Groups 2 and 3, is extended to 40 days before dosing.

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RATIONALE:
The screening period is extended for Groups 2 and 3 to minimize the number of subjects who 
may require rescreening procedures due to the timing of cohort data reviews. 
6.
Modification to Stopping Rules
DESCRIPTION OF CHANGE:
The formal stopping rules for cohorts is updated such that enrollment/dosing will be stopped 
when 1 of the sentinel subjects experiences an ASP3772-related adverse event (AE) of severe 
intensity only when sentinel subjects are required. 
RATIONALE:
Based on the dose escalation committee review of safety data in previous cohorts, it was 
decided that sentinel subjects will no longer be required for Cohort 5 onward.
II.  Amendment Summary of Changes:
IIa. Non-substantial Changes
II.
Contact Details of Key Sponsor’s Personnel
WAS:
Clinical Research Contacts:
, MBBS, MS
Clinical Study Manager 
Astellas Pharma Global Development, Inc.
1 Astellas Way, Northbrook, IL 60062
Tel: 
Cell/Mobile: 
Email:
Project Manager
ICON Clinical Research
2100 Pennbrook Parkway, North Wales, PA 19454
Tel: 
Cell/Mobile: 
Email: 
IS AMENDED TO:
Clinical Research Contacts:
, MBBS, MS
Senior Clinical Study Manager 
Astellas Pharma Global Development, Inc.
1 Astellas Way, Northbrook, IL 60062
Tel: 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Cell/Mobile: 
Email:
Project Manager
ICON Clinical Research
2100 Pennbrook Parkway, North Wales, PA 19454
Tel: 
Cell/Mobile:
Email: 
IV Synopsis
Planned Study Period
WAS:
Stage 1:  1Q2019 – 2Q2019 
Stage 2:  2Q2019 – 2Q2020
IS AMENDED TO:
Stage 1:  1Q2019 – 2Q2019 
Stage 2:  2Q2019 – 2Q2020 3Q2019 – 3Q2020
IV Synopsis
Planned Total Number of Study Centers and Location(s)
WAS:
Stage 1: Approximately 5 sites in United States
Stage 2: Approximately 10 sites (includes sites from Stage 1) in United States
IS AMENDED TO:
Stage 1: Approximately 5 10 sites in United States
Stage 2: Approximately 10 25 sites (includes sites from Stage 1) in United States
IV Synopsis, Exclusion Criteria and 3 Study Population
3.3 Exclusion Criterion #11
WAS:
11. Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis B 
core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), hepatitis C 
virus antibodies (anti-HCV) confirmed by reflex testing (HCV-RNA) or antibodies to 
human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
IS AMENDED TO:
11. Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis B 
core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), hepatitis C 
virus antibodies (anti-HCV) confirmed by reflex testing (HCV-RNA) or antibodies to 
human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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V  Flow Chart and Schedule of Assessments
Flow Chart B
WAS:
Stage 2
DEC: Dose Escalation Committee; ESV: end-of-study visit; ET: early termination; PCV13: Prevnar 13; PE: physical examination; PPSV23: Pneumovax 23
† DEC will review day 7 data for sentinel subjects before opening full cohort
PCV13 Naïve 
(Group 2)  
Days -28 to -3
Informed 
consent. PE and 
screening labs 
and inclusion
and exclusion 
criteria
Week 1
Day 7
Reactogenicity/ 
safety/immune 
response
Week 4
Day 30/ ET
Immune 
response, safety 
DEC Review†
(Reactogen
icity/safety 
data day 7)
Proceed with  
Cohort or 
sentinel 
subjects of 
Next Cohort
Week 1
Day 1
Randomization, 
vaccine dose
ASP3772 or 
PCV13, safety, 
immune 
response
PCV13 > 10 months 
< 2 years (Group 3)
Days -28 to -3
Informed consent, PE 
and screening labs 
and inclusion and 
exclusion criteria
Week 4
Day 30/ESV
Immune response, 
safety 
Week 1
Day 1
Vaccine – PPSV23, 
immune response 
Week 26
Day 180/ESV
Safety follow-up 
(Visit conducted as 
a phone call unless 
anti-biotin 
antibodies were 
elevated at day 30 
visit)

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Version 2.1 Nonsubstantial Amendment 2
IS AMENDED TO:
Stage 2
DEC: Dose Escalation Committee; ESV: end-of-study visit; ET: early termination; PCV13: Prevnar 13; PE: physical examination; PPSV23: Pneumovax 23
† DEC will review day 7 data for sentinel subjects before opening full cohort
PCV13 Naïve 
(Group 2)  
Days -28 -40 to 
-3
Informed 
consent. PE and 
screening labs 
and inclusion 
and exclusion 
Week 1
Day 7
Reactogenicity/ 
safety/immune 
response
Week 4
Day 30/ ET
Immune 
response, safety 
DEC Review†
(Reactogen
icity/safety 
data day 7)
Proceed with  
Cohort or 
sentinel 
subjects of 
Next Cohort
Week 1
Day 1
Randomization, 
vaccine dose
ASP3772 or 
PCV13, safety, 
immune 
response
PCV13 > 10 months 
< 2 years (Group 3)
Days -28 -40 to -3
Informed consent, PE 
and screening labs 
and inclusion and 
exclusion criteria
Week 4
Day 30/ESV
Immune response, 
safety 
Week 1
Day 1
Vaccine – PPSV23, 
immune response 
Week 26
Day 180/ESV
Safety follow-up 
(Visit conducted as 
a phone call unless 
anti-biotin 
antibodies were 
elevated at day 30 
visit)

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V  Flow Chart and Schedule of Assessments
Table 1  Schedule of Assessments - Stage 1: Subjects 18 to 64 Years of Age (Group 1)
WAS:
f.
Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), HCV 
antibody (anti-HCV) confirmed by reflex testing (HCV-RNA) and HIV antigen/antibody (type 1 and/or type 2) at screening.
IS AMENDED TO:
f.
Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), HCV 
antibody (anti-HCV) confirmed by reflex testing (HCV-RNA) and HIV antigen/antibody (type 1 and/or type 2) at screening.
V  Flow Chart and Schedule of Assessments
Table 2  Schedule of Assessments - Stage 2: Subjects 65 to 85 Years of Age, PCV13 Naïve (Group 2)
WAS:
Assessments
Screeninga
Dosing
Follow-up
Visit Number
1
2
3
4
5
Visit Day (Window)
-28 to -3
1
7 (+1)
30 (±2)*
180 (±14)§
a. Screening will be completed up to 28 days prior to study immunization. Subjects will be assigned a subject number for use throughout the study at the 
screening visit via the Interactive Response Technology (IRT) system.
e. A physical examination will be performed at the screening visit (days -28 thru -3), prior to study immunization (day 1) and day 30 visits.
f. Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), HCV 
antibody (anti-HCV) confirmed by reflex testing (HCV-RNA) and HIV antigen/antibody (type 1 and/or type 2) at screening.
g. Body temperature, blood pressure and pulse rate will be assessed in a sitting position.  At the dosing visit, body temperature, blood pressure, pulse rate 
and respiratory rate will assessed predose and approximately 30 min and 1 hour postdose.  Predose vitals should be collected close to the 
immunization and should not be more than 30 minutes prior to the dose administration.  Body temperature will be collected by the subject daily 
through day 7 following the study immunization.

Sponsor:  APGD
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Version 2.1 Nonsubstantial Amendment 2
IS AMENDED TO:
Assessments
Screeninga
Dosing
Follow-up
Visit Number
1
2
3
4
5
Visit Day (Window)
-28 -40 to -3
1
7 (+1)
30 (±2)*
180 (±14)§
a. Screening will be completed up to 28 40 days prior to study immunization. Subjects will be assigned a subject number for use throughout the study at 
the screening visit via the Interactive Response Technology (IRT) system.
e. A physical examination will be performed at the screening visit (days -28 -40 thru -3), prior to study immunization (day 1) and day 30 visits.
f. Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), HCV 
antibody (anti-HCV) confirmed by reflex testing (HCV-RNA) and HIV antigen/antibody (type 1 and/or type 2) at screening.
g. Body temperature, blood pressure and pulse rate will be assessed in a sitting position.  At the dosing visit, body temperature, blood pressure, pulse rate 
and respiratory rate will assessed predose and at approximately 30 min and 1 hour postdose.  Predose vitals should be collected close to the 
immunization and should not be more than 30 minutes prior to the dose administration.  Body temperature will be collected by the subject daily 
through day 7 following the study immunization.
V  Flow Chart and Schedule of Assessments
Table 3  Schedule of Assessments - Stage 2: Subjects 65 to 85 Years of Age and Received PCV13 Within a Year of Randomization (Group 3)
WAS:
Assessments
Screeninga
Dosing
Follow-up
Visit Number
1
2
3
Visit Day (Window)
-28 to -3
1
30 (±2)
a. Screening will be completed up to 28 days prior to study immunization. Subjects will be assigned a subject number for use throughout the study at the 
screening visit via the Interactive Response Technology (IRT) system.
f. Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), HCV 
antibody (anti-HCV) and HIV antigen/antibody (type 1 and/or type 2) at screening.

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02 Dec 2019
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Version 2.1 Nonsubstantial Amendment 2
IS AMENDED TO:
Assessments
Screeninga
Dosing
Follow-up
Visit Number
1
2
3
Visit Day (Window)
-28 -40 to -3
1
30 (±2)
a. Screening will be completed up to 28 40 days prior to study immunization. Subjects will be assigned a subject number for use throughout the study at 
the screening visit via the Interactive Response Technology (IRT) system.
f. Perform tests for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), HCV 
antibody (anti-HCV) and HIV antigen/antibody (type 1 and/or type 2) at screening.

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Version 2.1 Nonsubstantial Amendment 2
5  Immunizations and Evaluation
5.1.5  Criteria for Continuation of Immunization
WAS:
Formal Stopping Rules for Cohorts:
No additional subjects will be randomized or dosed in the study until the events below 
occurring in a subject who received ASP3772 are reviewed by the DEC and it is acceptable 
to resume cohort immunization. 
●
Unexplained death of a subject.
●
Acute hypersensitivity reaction in a subject.
●
One of the sentinel subjects experiences an AE of severe intensity related to ASP3772.
●
An SAE of the same character occurs in at least 2 subjects or 1 subject experiences a 
vaccine-related SAE. 
●
Grade 3 or higher lab abnormality considered related to the immunization occurs in 2 or 
more subjects [FDA Guidance for Industry, 2007].
●
The same type of reactogenicity event assessed as Grade 3 or higher occurs in 2 or more 
subjects, or 1 of the sentinel subjects experiences a reactogenicity event assessed as 
Grade 3 or higher, using the FDA toxicity grading scale for preventative vaccines [FDA 
Guidance for Industry, 2007].
●
An imbalance of unsolicited AEs between ASP3772 and PCV13 is observed.
IS AMENDED TO:
Formal Stopping Rules for Cohorts:
No additional subjects will be randomized or dosed in the study until the events below 
occurring in a subject who received ASP3772 are reviewed by the DEC and it is acceptable 
to resume cohort immunization. 
●
Unexplained death of a subject.
●
Acute Serious acute hypersensitivity reaction in a subject.
●
One of the sentinel subjects experiences an AE of severe intensity related to ASP3772, 
when sentinel subjects are required.
●
An SAE of the same character occurs in at least 2 subjects or 1 subject experiences a 
vaccine-related SAE. 
●
Grade 3 or higher lab abnormality considered related to the immunization occurs in 2 or 
more subjects [FDA Guidance for Industry, 2007].
●
The same type of reactogenicity event assessed as Grade 3 or higher occurs in 2 or more 
subjects, or 1 of the sentinel subjects experiences a reactogenicity event assessed as 
Grade 3 or higher, using the FDA toxicity grading scale for preventative vaccines [FDA 
Guidance for Industry, 2007].
●
An imbalance of unsolicited AEs between ASP3772 and PCV13 is observed.
5  Immunizations and Evaluation
5.2.1  Demographics
WAS:

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Demographic information will be collected for all subjects (where permitted) at the screening 
visit (day -28 to day-3) and will include age, date of birth, sex, race and ethnicity.
IS AMENDED TO:
Demographic information will be collected for all subjects (where permitted) at the screening 
visit (day -28 to day-3) and will include age, date of birth, sex, race and ethnicity.
5  Immunizations and Evaluation
5.2.2  Medical History
WAS:
Medical history will be collected at the screening visit (day -28 to day-3) in order to assess 
Inclusion/Exclusion criteria and will be reconfirmed prior to study immunization (if 
screening was performed > 7 days from study immunization [day 1]).
IS AMENDED TO:
Medical history will be collected at the screening visit (day -28 to day-3) in order to assess 
Inclusion/Exclusion criteria and will be reconfirmed prior to study immunization (if 
screening was performed > 7 days from study immunization [day 1]).
5  Immunizations and Evaluation
5.4.6  Physical Examination
WAS:
A physical examination consisting of an examination of general appearance, eyes, nose 
throat, neck (including thyroid), lymph nodes, chest, lungs, cardiovascular, abdomen, skin, 
extremities, musculoskeletal and neurological system including mental status will be 
conducted at the screening visit (days -28 to -3), prior to study immunization (day 1) and at 
the day 30 follow-up visit. A symptom-directed physical exam may be performed at any 
other time, if necessary.  The screening physical examination also includes evaluation of 
significant, ongoing medical conditions. Any changes between screening and randomization 
will be captured in the medical/surgical history.
IS AMENDED TO:
A physical examination consisting of an examination of general appearance, eyes, nose 
throat, neck (including thyroid), lymph nodes, chest, lungs, cardiovascular, abdomen, skin, 
extremities, musculoskeletal and neurological system including mental status will be 
conducted at the screening visit (days -28 to -3), prior to study immunization (day 1) and at 
the day 30 follow-up visit. A symptom-directed physical exam may be performed at any 
other time, if necessary.  The screening physical examination also includes evaluation of 
significant, ongoing medical conditions. Any changes between screening and randomization 
will be captured in the medical/surgical history.
12  Appendices
12.5  Laboratory Assessment
WAS:

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Version 2.1 Nonsubstantial Amendment 2
Laboratory Test
Visit
Parameters to be Analyzed
Virology
Screening (Visit 1) or 
Dosing (Visit 2)

Anti-HAV (IgM)

HBsAg

Anti-HBc

Anti-HCV (reflex testing/HCV-RNA)

Anti-HIV-1 and 2
IS AMENDED TO:
Laboratory Test
Visit
Parameters to be Analyzed
Virology
Screening (Visit 1) or 
Dosing (Visit 2)

Anti-HAV (IgM)

HBsAg

Anti-HBc

Anti-HCV (reflex testing/HCV-RNA)

Anti-HIV-1 and 2

Sponsor:  APGD
ISN/Protocol 3772-CL-1001
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02 Dec 2019
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Version 2.1 Nonsubstantial Amendment 2
14
COORDINATING INVESTIGATOR’S SIGNATURE 
A Phase 1/2, Randomized, Single Ascending Dose Study in Adults (Stage 1) and 
Randomized, Single Ascending Dose-Finding Study (Stage 2) in Elderly Subjects with 
ASP3772, a Pneumococcal Vaccine 
ISN/Protocol 3772-CL-1001
Version 2.1 Incorporating Nonsubstantial Amendment 2
02 Dec 2019
I have read all pages of this clinical study protocol for which Astellas is the sponsor. I agree that it 
contains all the information required to conduct this study.
Coordinating Investigator:
Signature:
<Insert name, department/affiliation, name of institution>
Date (DD Mmm YYYY)
Printed Name:
Address:

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Astellas
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Version 2.1 Nonsubstantial Amendment 2
15
SPONSOR SIGNATURES

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Clinical Study Protocol
Study Statistician Approval
Reissue v2.1, 02Dec2019
12/04/2019 23:14:52
(For Disclosure) Responsible Officer
N/A
12/03/2019 20:55:42
N/A
MGC1901015
3772-CL-1001
2.0
N/A
PPD
PPD
PPD
PPD