A Randomized, Observer-Blind, Controlled Phase 1/2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of Different Doses of a Stand-alone Trivalent, Inactivated Poliomyelitis Vaccine From Sabin Strains in Healthy Infants, With a Safety and Tolerability Age-Step Down Lead-in in Healthy Adults Followed by Healthy Toddlers
Phase: PHASE1
Conditions: Poliomyelitis
Sponsor: Takeda

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

Title: A Randomized, Observer-Blind, Controlled Phase 1/2 Trial to Evaluate the Safety, 
Tolerability and Immunogenicity of Different Doses of a Stand-alone Trivalent, Inactivated 
Poliomyelitis Vaccine from Sabin Strains in Healthy Infants, with a Safety and Tolerability Age-
Step Down Lead-in in Healthy Adults followed by Healthy Toddlers
NCT Number: NCT03092791
Protocol Approve Date: 11 April 2017 
Certain information within this protocol has been redacted (ie, specific content is masked irreversibly from 
view with a black/blue bar) to protect either personally identifiable information (PPD) or company 
confidential information (CCI). 
This may include, but is not limited to, redaction of the following: 
Named persons or organizations associated with the study.
Proprietary information, such as scales or coding systems, which are considered confidential 
information under prior agreements with license holder.
Other information as needed to protect confidentiality of Takeda or partners, personal information, or 
to otherwise protect the integrity of the clinical study.

 TITLE PAGE 
TITLE PAGE 
A Randomized, Observer-Blind, Controlled Phase 1/2 Trial to Evaluate the Safety, Tolerability 
and Immunogenicity of Different Doses of a Stand-alone Trivalent, Inactivated Poliomyelitis 
Vaccine from Sabin Strains in Healthy Infants, with a Safety and Tolerability Age-Step Down 
Lead-in in Healthy Adults followed by Healthy Toddlers 
IPV-102 Safety, Tolerability and Immunogenicity of TAK-195 
in Healthy Infants, Toddlers and Adults 
Sponsor: 
Takeda Vaccines Inc., 
One Takeda Parkway 
Deerfield, IL 60015 
USA 
Study Identifier: 
IPV-102 
IND Number: 
Not applicable 
EudraCT Number: 
Not applicable 
Vaccine Name: 
Investigational vaccine: Stand-alone Trivalent Sabin Inactivated 
Poliomyelitis Vaccine (sIPV) candidate 
Control vaccines:  
Adult cohort: Placebo 
Toddler and infant cohorts: Reference Inactivated Poliomyelitis 
Vaccine (IPV). 
Date: 
11 April 2017 
Version: 
2.0 The current version supersedes Version 1.0 dated 23 November 
2016 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
2 of 104 
Protocol Version 2.0  
11 April 2017 
1.0
ADMINISTRATIVE INFORMATION 
1.1 
Contacts 
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Table 1.a 
Contact Information 
Issue
Contact
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
3 of 104 
Protocol Version 2.0  
11 April 2017 
1.2
Approval 
REPRESENTATIVES OF TAKEDA 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
4 of 104 
Protocol Version 2.0  
11 April 2017 
 
INVESTIGATOR AGREEMENT 
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, and 
any other product information provided by the sponsor. I agree to conduct this trial in accordance 
with the requirements of this protocol and also protect the rights, safety, privacy, and well-being 
of trial subjects in accordance with the following: 
• The ethical principles that have their origin in the Declaration of Helsinki. 
• International Council on Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use (ICH), ICH Harmonised Guideline, Integrated Addendum to ICH(R1): Guideline 
for Good Clinical Practice E6(R2). 
• All applicable laws and regulations, including, but not limited to those related to data privacy 
and clinical trial disclosure. 
• Regulatory requirements for reporting serious adverse events defined in Section 10.4 of this 
protocol. 
• Terms outlined in the Clinical Study Site Agreement. 
• Appendix A – Responsibilities of the Investigator. 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix C of this protocol. 
 
Signature of Investigator 
Date 
Investigator Name (print or type) 
Investigator’s Title 
Location of Facility (City, State) 
Location of Facility (Country) 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
Trial No. IPV-102 
5 of 104 
Protocol Version 2.0  
11 April 2017 
1.3 
Protocol Amendment Summary of Changes 
This document describes the changes in reference to the Protocol Incorporating Amendment 
No.1. 
The primary purpose of this substantial amendment is to update the protocol regarding the 
reference IPV to be used in the toddler and infant cohorts (controls) as locally licensed vaccine is 
not available. As pentavalent DTP-HBV-Hib vaccine is not licensed/available at the study sites, 
this vaccine will now also be sourced by Takeda and becomes a trial vaccine.  
An error in the secondary endpoints for the infant cohort has also been corrected. 
Full details on changes of text are given in Section 1.3.1 
1.3.1 Amendment History 
Date 
Amendment Number 
Amendment Type 
Region 
23 November 2016 
Initial Protocol 
Not applicable 
Global 
11 April 2017 
1 
Substantial 
Global 
1.3.2 Summary of Changes 
Amendment to Protocol Version 1.0 23 November 2016 
Rationale for the Amendment: 
The primary purpose of this substantial amendment is to update the protocol regarding the reference IPV to be 
used in the toddler and infant cohorts (controls) as locally licensed vaccine is not available. As pentavalent DTP-
HBV-Hib vaccine is not licensed/available at the study sites, this vaccine will now also be sourced by Takeda and 
becomes a trial vaccine.  
An error in the secondary endpoints for the infant cohort has also been corrected. 
Reference to ICH E6 guidance has been updated throughout. 
2.0 
The Trial Summary had been adapted to reflect the changes in the body of the protocol. 
2.1 
Table 2a 
Errors in the table and footnotes have been corrected with additional cross-references added 
in the table where appropriate. The footnotes now read: 
ET: Early Termination. Use of (X) indicates samples or procedures that generally will not 
be performed but may be performed to investigate an AE, or at the time of premature 
discontinuation.  
(a) In women of childbearing potential, a pregnancy test will be performed on Day 1 prior
to enrollment.
(ab) Eligibility by review of relevant inclusion/exclusion criteria will be documented before 
enrollment. 
(bc) Physical exam at on Day 1 (Section 9.1.4). All subsequent physical examinations may 
be performed if deemed necessary and will be symptom-directed and should assess 
clinically significant changes from the baseline examination. For any procedures at the site, 
the investigator shall follow his/her standard practice. 
(cd)Vital signs: as defined in Section 9.1.5.
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
6 of 104 
Protocol Version 2.0  
11 April 2017 
 
(e) After vaccination, subjects will be observed for at least 30 minutes including 
observation for immediate reactions and body temperature measurement. 
(df) Diary cards will be distributed on the day of vaccination, and will be collected at the 
return visit 7 days later. 
(eg) Solicited local and systemic adverse events (AEs: Section 10.1.2) and unsolicited AEs 
will be recorded daily in diary cards for Days 1-7, and unsolicited AEs for Days 1-28, after 
vaccination.  
(fh) AEs leading to Early Termination will be recorded by the investigator. 
(gi) SAEs will be collected for the duration of the trial and will be reported to the Sponsor 
within 24 hours of the investigator becoming aware of the event. 
 
Table 2b 
Errors in the table and footnotes have been corrected with additional cross-references added 
in the table where appropriate. The footnotes now read: 
 
ET: Early Termination. Use of (X) indicates samples or procedures that generally will not 
be performed but may be performed to investigate an AE, or at the time of premature 
discontinuation.  
(a) Eligibility by review of relevant inclusion/exclusion criteria will be documented before 
enrollment.  
(b) Only vaccines administered since the last visit should be recorded. 
(bc) Physical exam on Day 1 (Section 9.1.4). All subsequent physical examinations may be 
performed if deemed necessary and will be symptom-directed and should assess clinically 
significant changes from the baseline examination. For any procedures at the site, the 
investigator shall follow his/her standard practice. 
(cd) Vital signs: as defined in Section 9.1.5. 
(de) sIPV or reference IPV. After vaccination, subjects will be observed for at least 30 
minutes including observation for immediate reactions and body temperature 
measurement. 
(ef) Diary cards will be distributed on the day of vaccination, and collected at the return 
visit on Day 29. 
(fg) Solicited local and systemic adverse events (AEs: Section 10.1.2) will be recorded 
daily in diary cards for Days 1-7, and unsolicited AEs for Days 1-28.  
(gh) AEs leading to Early Termination will be recorded by the investigator. 
(hi) SAEs will be collected for the duration of the trial and will be reported to the Sponsor 
within 24 hours of the investigator becoming aware of the event. 
(ij) Blood should be drawn prior to vaccination 
 
Table 2c 
Errors in the table and footnotes have been corrected with additional cross-references added 
in the table where appropriate. Information on vaccines administered will be collected at all 
visits. Adverse events will be collected on Days 36, 64, 372 and 393; an "X" has been 
added. Demographics will not be recorded at Day 365/Visit 9; ("X") removed. "Anchor to 
Study Visit 1" has been corrected to "Anchor to Study Visits". The footnotes now read:  
ET: Early Termination. Use of (X) indicates samples or procedures that generally will not 
be performed but may be performed to investigate an AE, or at the time of premature 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
7 of 104 
Protocol Version 2.0  
11 April 2017 
 
discontinuation.  
(a) Eligibility by review of relevant inclusion/exclusion criteria will be documented before 
enrollment. Continuing eligibility (by review of relevant inclusion/exclusion criteria and 
criteria for delay of vaccination) will be documented before each vaccination. 
(b) Only vaccines administered since the last visit should be recorded. 
(bc) Physical exam on Day 1 (Section 9.1.4). All subsequent physical examinations may be 
performed if deemed necessary and will be symptom-directed and should assess clinically 
significant changes from the baseline examination. For any procedures at the site, the 
investigator shall follow his/her standard practice. 
(cd) Vital signs: as defined in Section 9.1.5. 
(de) sIPV or reference IPV. Polio vaccine should be administered concomitantly with 
DTP-HBV-Hib on Days 1, 29 and 57. After vaccination, subjects will be observed for at 
least 30 minutes including observation for immediate reactions and body temperature 
measurement. 
(ef) Diary cards will be distributed on the day of each vaccination, and will be collected at 
the return visit 28 days later. 
(fg) Solicited local and systemic adverse events (AEs: Section 10.1.2) will be recorded 
daily in diary cards for Days 1-7, and unsolicited AEs for Days 1-28, after each 
vaccination.  
(gh) AEs leading to Early Termination will be recorded by the investigator. 
(hi) SAEs will be collected for the duration of the trial and will be reported to the Sponsor 
within 24 hours of the investigator becoming aware of the event. 
(ij) Blood should be drawn prior to vaccination. 
3.3 
National Program on Immunization (NPI) was added to the list of abbreviations 
4.1 
This trial will assess the safety and tolerability as well as the immunogenicity of Takeda’s 
stand-alone sIPV candidate to identify the optimal formulation that meets with the currently 
available standard of care to take forward into advanced stage studies to show the 
immunogenicity and safety of the final candidate vaccine. 
4.2 
Following a lead-in study of the safety and tolerability of the highest anticipated dosage in 
primed (after full primary poliovirus vaccination) adults followed by toddlers, the 
descriptive dosage-ranging study in infants will allow selection of the dosage to take 
forward into advanced stage studies powered to show the non-inferiority of the final 
candidate vaccine against the current standard of care, i.e. licensed IPV vaccine. This 
decision will be based on the WHO recommendations for assessment of IPV vaccines [4], 
and will use the seroconversion rate after completion of the three-dose primary schedule as 
primary measure. 
A control group will receive a licensed, reference IPV to allow for descriptive comparison 
with the normal standard of care.  
In the infant dose ranging cohort, the control group will provide a comparator for the safety 
and tolerability of the different sIPV dosages. Assessing immunogenicity in the comparator 
control arm in the infant cohort will provide background information to show that the three 
groups who that receive the different dosages of sIPV all achieve adequate levels of 
immunity, similar to that provided by the current standard of care, and so are not put at risk 
of poliovirus infection. 
The primary endpoint for the immunogenicity analysis is the seroconversion rate achieved 
in infants four weeks after the last of three primary doses of sIPV, in accordance with 
WHO recommendations for the assessment of IPV [4]. The study is not powered for 
statistical comparisons, and all comparisons will be descriptive. It is only designed to select 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
8 of 104 
Protocol Version 2.0  
11 April 2017 
 
a dosage formulation from consideration of an interim analysis performed on the data 
obtained 28 days after the third primary immunizations at Day 85. The selected formulation 
will be taken into larger phase 3 trials for advanced stage clinical development to show the 
immunogenicity and safety of the final candidate vaccine. 
5.1.2 
Subsections in Section 5.1.2 
Safety amended to Safety and tolerability 
5.2 
Immunogenicity, separately for poliovirus types 1, 2, and 3 for both Sabin and Salk strains 
Infant dose ranging cohort 
• 
SCR on Day 393 (28 days after booster vaccination). 
• 
Seropositivity/seroprotection rate (SPR, defined as the percentage of subjects with 
antibody titers ≥ 8) on Days 85, 365, and 393 (28 days after booster vaccination). 
6.1 
B). Toddler lead-in cohort  
The second lead-in cohort of 60 healthy toddlers at 12–15 months of age inclusive, will be 
enrolled and randomized to two equal groups. Each group will receive, in an observer-blind 
fashion, a single intramuscular injection of high dose sIPV containing 3, 100, and 100 DU 
of poliovirus types 1, 2, and 3, respectively (Day 1), or a licensed, reference IPV. Polio 
vaccines previously received for primary immunization of these children will be recorded. 
Routine infant childhood vaccines other than poliovirus vaccine for booster immunization 
recommended for children at approximately 12 months of age according to national 
guidelines the NPI (eg, measles-containing vaccine) are to be given at least 4 weeks after 
apart from sIPV / reference IPV booster vaccination. Routine infant vaccines according to 
the national immunization program NPI-recommended childhood vaccines other than 
poliomyelitis vaccine will be given outside the trial. 
Individual titers pre and post booster vaccination will be assessed. Toddlers who receive 
sIPV and who have no neutralizing antibodies to any of the three poliovirus serotypes (titer 
<8) on Day 29 as well as those with no titer increase between Day 1 and Day 29 will be 
offered re-vaccination with a single dose of a locally-available standard polio vaccine the 
reference IPV (note: toddlers that have received bivalent OPV exclusively for primary 
immunization may not achieve seropositivity to poliovirus type 2. Therefore, subjects with 
documented primary immunization against serotypes 1 and 3 only who do not respond to 
serotype 2 post sIPV booster will not be offered re-vaccination). 
C). Infant dose ranging cohort 
Routine infant vaccines according to the national immunization program NPI other than 
poliovirus vaccine for primary immunization and for booster vaccination are to be given 
according to national guidelines outside the trial. Inactivated / oral routine infant vaccines 
should be given on the same day as sIPV / reference IPV. Injectable live-attenuated 
vaccines (eg, measles-containing vaccine) should be given at least 4 weeks apart from 
sIPV / reference IPV. 
Infants who receive sIPV and who have no neutralizing antibodies to any of the three 
poliovirus serotypes (titer <8) on Day 393 will be offered re-vaccination with a single 
series of three primary immunizations of a locally-available standard polio vaccine of 
reference IPV after the unblinding occurs and serological results become available, and 
outside of the IPV-102 clinical trial. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
9 of 104 
Protocol Version 2.0  
11 April 2017 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
10 of 104 
Protocol Version 2.0  
11 April 2017 
 
8.1.1 
In this protocol, study medication refers to the trivalent polio vaccine sIPV, the reference 
IPV, pentavalent infant vaccine, and placebo. Study medication outer cartons/kits will be 
packaged and labelled with a tamper seal. The inner primary packaging will be unblinded 
and dose preparation will be carried out by unblinded site personnel.  
This trial will involve the use of three sIPV trivalent polio vaccine formulations for 
intramuscular administration that were manufactured and filled at Takeda’s manufacturing 
plant in Hikari, Japan. In addition, a reference IPV (toddler and infant cohorts only) and 
placebo (adult cohort only) will be provided for control groups and a pentavalent DTP-
HBV-Hib vaccine will be provided for the infant dose ranging cohort to complete 
childhood immunizations. In case the reference IPV and / or the pentavalent vaccine 
cannot be sourced locally, Takeda will import these vaccines from a country/countries 
where the respective vaccine(s) is/are licensed. 
8.1.1.1 
Study medications described in this protocol (sIPV, reference IPV, pentavalent infant 
vaccine, and placebo) will be supplied by the sponsor.  
The Takeda sIPV single-dose vials will be supplied in a labeled, single-use vial and carton 
(0.5 mL) dose for intramuscular injection, preferably in the right limb. Each vial and carton 
will contain a label that includes pertinent trial information and caution statements. The 
label text will be in the specific country language, depending on local requirements. The 
vaccine to be used will be identifiable by a unique identification number and managed by 
the interactive response technology (IRT) system. 
Depending on the IPV in use in the country selected for the study, tThe reference IPV will 
be presented in a blinded or open label carton. Should the primary container/packaging be 
open label, unblinded pharmacy and administration teams at the site will be required for 
dose preparation, administration and accountability. Each reference IPV and carton will 
contain a label that includes pertinent trial information and caution statements. The label 
text, which includes pertinent trial information and caution statements, will be in the 
specific country language, depending on local requirements and will be included in the 
Pharmacy Manual and in the ICF for the toddler lead-in and infant dose ranging 
cohorts. 
The placebo (saline control) will be 0.9% sodium chloride for injection without 
preservatives.  
Vaccination against D, T, P, HBV and Hib will be given as pentavalent combination 
vaccine (DTP-HBV-Hib). The pentavalent infant vaccine will be sourced as trial vaccine.  
All doses should be prepared at the time of administration by the unblinded administrator 
(and/or pharmacist) per the Pharmacy Manual. 
8.1.1.2 
Routine Infant Vaccines for Primary Immunizations and Booster Vaccinations 
Appropriate medication for the local vaccination schedule NPI-recommended routine 
vaccines (other than poliomyelitis vaccine and pentavalent vaccine, see above) will be 
sourced locally by the site and administered in accordance with the approved package 
labeling. Additional injectable routine infant vaccines given concomitantly will be 
administered in a limb different from that of the sIPV / reference IPV vaccination. 
8.1.3 
An additional cross-reference has been added, with its corresponding footnote:  
(b) Subjects will also receive DTP-HBV-Hib vaccine at the same visit; pentavalent 
vaccine will be administered in a limb different from that of the sIPV / reference IPV 
vaccination. 
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8.4 
The trial vaccine blind will be maintained using IRT. 
This trial is an observer-blind study. The subjects, data collectors (eg investigator), and 
data evaluators (eg trial statisticians) are blinded to the material administered. The 
investigational product assignment will be maintained by the unblinded site staff 
designee. 
All care must be taken to ensure that the unblinded reports and documents are shared 
only with unblinded personnel and properly stored in a secured area, accessible only by 
authorized personnel. 
8.5 
If any subject is unblinded, the subject must be withdrawn from the trial, and their data no 
longer evaluated. However, further doses of trial vaccine are to be administered to ensure 
completion of the nationally NPI-recommended schedule, and they should be monitored 
for safety parameters. 
8.6 
The investigator or designee must ensure that the sponsor-supplied vaccine is used in 
accordance with the approved protocol and is administered only to subjects enrolled in the 
trial. To document appropriate use of sponsor-supplied vaccines (sIPV, reference IPV, and 
placebo, and DTP-HBV-Hib), the investigator must maintain records of all sponsor-
supplied vaccine delivery to the site, site inventory, administration and use by each subject, 
and return to the sponsor or designee. 
The investigator must record the current inventory of all sponsor-supplied vaccines (sIPV, 
reference IPV, and placebo, and DTP-HBV-Hib) on a sponsor-approved vaccine 
accountability log. The following information will be recorded at a minimum: protocol 
number and title, name of investigator, site identifier and number, description of sponsor-
supplied vaccines, expiry date and amount. The IRT should include all required 
information as a separate entry for each subject to whom sponsor-supplied vaccine is 
administered. 
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9.1.2 
Demographic information to be obtained will include age date of birth, sex, and race as 
described by the subject or the subject’s LAR. 
Medical History will also be collected, including but not limited to any medical history that 
may be relevant to subject eligibility for trial participation such as gestational age and birth 
weight (for infants in the dose ranging cohort only), prior vaccinations, concomitant 
medications, and previous and ongoing illnesses or injuries. Relevant medical history can 
also include any medical history that contributes to the understanding of an AE that occurs 
during trial participation, if it represents an exacerbation of an underlying 
disease/preexisting problem. 
All medications, vaccines and blood products taken or received by the subjects within: 
a) 
Medications: 4 weeks prior to the start of the trial 
b) 
Vaccines: 4 weeks prior to the start of the lead-in study. Infants in the dose 
ranging study should only have received any routine vaccines recommended by 
the NPI at birth. Information on previous polio vaccinations should be collected 
for toddlers in the lead-in cohort.  
c) 
Blood products: 4 weeks prior to the start of the trial 
are to be recorded on the Prior and Concomitant Medications eCRF. The use of antipyretics 
and/or analgesic medications within 24 hours prior to vaccination must be identified and 
the reason for their use (prophylaxis versus treatment) must be described in the source 
documents or the eCRF. Trial vaccination should be delayed if subjects have used 
antipyretics/analgesic medications within 24 hours prior to vaccine administration. 
9.1.5 
Vital signs to be measured in this study are respiratory and heart rates, height and weight, 
and temperature (preferably measured as oral temperature for the adult cohort and rectal 
temperature for the toddler and infant cohorts).  
For the adult lead-in cohort, height and weight are measured at enrollment only; for the 
toddler lead-in cohort, height and weight are measured at enrollment and at the last 
study visit. For the infant dose ranging cohort, height and weight are measured at each 
visit. 
9.1.8 
For female subjects of childbearing potential, urine pregnancy testing will be performed on 
Day 1 prior to vaccination enrollment. Subjects will be provided with information on 
acceptable methods of contraception as part of the subject informed consent process and 
will be asked to sign a consent form stating that they understand the requirements for 
avoidance of pregnancy and donation of ova. Women of childbearing potential will receive 
guidance with respect to the avoidance of pregnancy as part of the trial procedures (Section 
2.1). 
9.1.9 
Should a pregnancy occur after the administration of a blinded trial vaccine, the 
investigator must inform the subject of their right to receive treatment information. If the 
subject chooses to receive unblended unblinded treatment information, the individual blind 
should be broken by the investigator and procedures must be followed as described in 
Section 8.5. 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
13 of 104 
Protocol Version 2.0  
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9.3.1 
1. 
Confirm informed consent and complete signing of informed consent form. 
2. 
Demographics. 
 
a)3.   Prior and concomitant medication. This should include the vaccines that will 
be concomitantly administered with the trial vaccine at this visit. 
 
b)4.   Medical history. 
3. 
Review of systems: Review of systems is a structured interview that queries the 
subject (adult cohort) or the subject’s LAR (toddler and infant cohorts) as to any 
complaints the subject has experienced across each organ system. 
45. 
“Complete” physical examination and temperature. Physical examination. 
56. 
Vital signs.  
67. 
Review of eligibility criteria. 
78. 
Enrollment/randomization. 
9. 
Randomization. 
9. 
Blood sampling for toddler lead-in and infant dose ranging cohorts. Blood should be 
taken from the subject in the infant cohort using an aseptic venipuncture technique 
for serological immunogenicity testing.  
9.3.9 
No post-trial care will be provided, except to ensure that all subjects in the toddler lead-in 
and infant dose ranging cohorts receive their complete number of polio vaccine doses as 
recommended by the national scheduleNPI, and that toddlers from both the lead-in cohort 
and the dose ranging cohort (after their booster dose) who received the trial sIPV vaccine 
are seropositive or have demonstrated a vaccine response which shows seroprotection. 
Toddlers from the lead-in cohort who do not meet these criteria will be offered a single 
dose of a locally-available standard polio vaccine the reference IPV (note: toddlers that 
have received bivalent OPV exclusively for primary immunization may not achieve 
seropositivity to poliovirus type 2. Therefore, subjects with documented primary 
immunization against serotypes 1 and 3 only who do not respond to serotype 2 post sIPV 
booster will not be offered re-vaccination). Toddlers in the dose ranging cohort, who 
received sIPV as infants in their primary series and their toddler booster dose, and who 
have no neutralizing antibodies to any of the three poliovirus serotypes (titer <8) on Day 
393 will be offered re-vaccination with a single series of three primary immunizations of a 
locally-available standard polio vaccine the reference IPV after the unblinding occurs and 
serological results become available, and outside of the IPV-102 clinical trial. 
11.2.1 
Details of the independent DMC will be captured in a charter prior to the start of the trial. 
The DMC will have study-specific responsibilities to review IPV-102 data and decide on 
the enrollment of the toddler and infant cohorts after reviewing 7 days of safety and 
tolerability follow-up post vaccination in adults in the lead-in cohort. In addition, the 
DMC will evaluate the overall tolerability and safety of Takeda’s sIPV on an ongoing 
basis. The DMC will be entitled to stop enrollment of additional subjects or to stop 
administration of additional sIPV doses. The composition, role and responsibilities of the 
DMC are presented in a separate DMC Charter. 
15.0 
ICH Harmonized Tripartite Guideline for GCP 
Appendix D 
To permit flexibility in testing, Viroclinics Biosciences has been added to the contract 
laboratories in the Serology Plan. 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
14 of 104 
Protocol Version 2.0  
11 April 2017 
 
TABLE OF CONTENTS 
1.0 
ADMINISTRATIVE INFORMATION ..............................................................................2 
1.1 
Contacts..........................................................................................................................2 
1.2 
Approval ........................................................................................................................3 
1.3 
Protocol Amendment Summary of Changes..................................................................5 
1.3.1 
Amendment History ............................................................................................5 
1.3.2 
Summary of Changes ..........................................................................................5 
2.0 
TRIAL SUMMARY ..........................................................................................................19 
2.1 
Schedule of Trial Procedures .......................................................................................32 
3.0 
TRIAL REFERENCE INFORMATION ...........................................................................36 
3.1 
Trial-Related Responsibilities ......................................................................................36 
3.2 
Principal Investigator/Coordinating Investigator .........................................................36 
3.3 
List of Abbreviations ...................................................................................................37 
3.4 
Corporate Identification ...............................................................................................39 
4.0 
INTRODUCTION .............................................................................................................40 
4.1 
Background ..................................................................................................................40 
4.2 
Rationale for the Proposed Trial ..................................................................................43 
5.0 
TRIAL OBJECTIVES AND ENDPOINTS ......................................................................45 
5.1 
Objectives ....................................................................................................................45 
5.1.1 
Primary Objective .............................................................................................45 
5.1.2 
Secondary Objectives........................................................................................45 
5.1.3 
Exploratory Objectives .....................................................................................46 
5.2 
Endpoints .....................................................................................................................46 
6.0 
TRIAL DESIGN AND DESCRIPTION ...........................................................................50 
6.1 
Trial Design .................................................................................................................50 
6.2 
Justification for Trial Design, Dose, and Endpoints ....................................................53 
6.3 
Duration of Subject’s Expected Participation in the Entire Trial ................................53 
6.4 
Premature Termination or Suspension of Trial or Investigational Site .......................53 
6.4.1 
Criteria for Premature Termination or Suspension of the Trial ........................53 
6.4.2 
Criteria for Premature Termination or Suspension of Investigational Sites .....54 
6.4.3 
Procedures for Premature Termination or Suspension of the Trial or the 
Participation of Investigational Site(s)..............................................................54 
7.0 
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS ...............55 
7.1 
Inclusion Criteria .........................................................................................................55 
7.2 
Exclusion Criteria ........................................................................................................56 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
15 of 104 
Protocol Version 2.0  
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7.3 
Criteria for Delay of Vaccination and/or Blood Sampling ..........................................58 
7.4 
Criteria for Early Study Termination of a Subject .......................................................59 
7.5 
Criteria for Premature Discontinuation of Trial Vaccine Administration ...................59 
8.0 
CLINICAL TRIAL MATERIAL MANAGEMENT .........................................................61 
8.1 
Trial Vaccines and Materials .......................................................................................61 
8.1.1 
Dosage Form, Manufacturing, Packaging, and Labeling .................................61 
8.1.2 
Storage ..............................................................................................................62 
8.1.3 
Dose and Regimen ............................................................................................62 
8.2 
Trial Vaccine Assignment and Dispensing Procedures ...............................................63 
8.3 
Randomization Code Creation and Storage .................................................................64 
8.4 
Trial Vaccine Blind Maintenance ................................................................................64 
8.5 
Unblinding Procedure ..................................................................................................64 
8.6 
Accountability and Destruction of Sponsor-Supplied Vaccines ..................................65 
9.0 
TRIAL PLAN ....................................................................................................................67 
9.1 
Trial Procedures ...........................................................................................................67 
9.1.1 
Informed Consent Form ....................................................................................67 
9.1.2 
Demographics, Medical History and Prior Medications ...................................67 
9.1.3 
Documentation of Trial Entrance/Randomization ............................................68 
9.1.4 
Physical Examination........................................................................................68 
9.1.5 
Vital Signs .........................................................................................................68 
9.1.6 
Immunogenicity Assessments ...........................................................................68 
9.1.7 
Safety Assessments ...........................................................................................69 
9.1.8 
Contraception and Pregnancy Avoidance Procedure ........................................69 
9.1.9 
Pregnancy ..........................................................................................................69 
9.1.10 
Documentation of Subjects who are not Randomized ......................................69 
9.2 
Monitoring Subject Treatment Compliance.................................................................70 
9.3 
Schedule of Observations and Procedures ...................................................................70 
9.3.1 
Pre-Vaccination Procedures (Day 1) ................................................................70 
9.3.2 
Pre-Vaccination Procedures (Days 29, 57 and 365) .........................................70 
9.3.3 
Vaccination Procedures (Days 1, 29, 57 and 365) ............................................71 
9.3.4 
Post Vaccination procedures (Days 1, 29, 57 and 365) ....................................71 
9.3.5 
Clinic Visits after Vaccination (Day 8 in the adult lead-in cohort, Day 29 in 
the toddler lead-in cohort and Days 85 and 393 in the infant dose ranging 
cohort) ...............................................................................................................73 
9.3.6 
Phone Contacts - Reminder Calls (Days 8, 36, 64 and 372).............................73 
9.3.7 
Phone Contacts – Safety Call (Days 183 and 547) ...........................................73 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
16 of 104 
Protocol Version 2.0  
11 April 2017 
 
9.3.8 
Final (End of Trial) Visit ..................................................................................74 
9.3.9 
Post-Trial Care ..................................................................................................74 
9.4 
Biological Sample Retention and Destruction .............................................................74 
10.0 
ADVERSE EVENTS .........................................................................................................76 
10.1 
Definitions....................................................................................................................76 
10.1.1 
Adverse Events (AEs) .......................................................................................76 
10.1.2 
Solicited Adverse Events ..................................................................................76 
10.1.3 
Serious Adverse Events (SAEs)........................................................................80 
10.2 
Causality of AEs ..........................................................................................................80 
10.2.1 
Relationship to Trial Procedures .......................................................................80 
10.2.2 
Outcome of AEs ................................................................................................81 
10.3 
Additional Points to Consider for AEs ........................................................................81 
10.4 
Procedures ....................................................................................................................82 
10.4.1 
Collection and Reporting of AEs ......................................................................82 
10.4.2 
Collection and Reporting of Solicited AEs .......................................................83 
10.4.3 
Collection and Reporting of SAEs ....................................................................83 
10.5 
Follow-up Procedures ..................................................................................................84 
10.5.1 
AEs ....................................................................................................................84 
10.5.2 
SAEs .................................................................................................................84 
10.5.3 
Safety Reporting to Investigators, IRBs or IECs, and Regulatory 
Authorities.........................................................................................................84 
10.5.4 
Post-Trial Events ...............................................................................................84 
11.0 
TRIAL-SPECIFIC REQUIREMENT(S) ...........................................................................85 
11.1 
Halting Rules ...............................................................................................................85 
11.2 
Trial-Specific Committees ...........................................................................................85 
11.2.1 
Data Monitoring Committee .............................................................................85 
12.0 
DATA HANDLING AND RECORDKEEPING ..............................................................86 
12.1 
Electronic CRFs (eCRF) ..............................................................................................86 
12.2 
Record Retention .........................................................................................................86 
13.0 
STATISTICAL METHODS ..............................................................................................88 
13.1 
Statistical and Analytical Plans ....................................................................................88 
13.1.1 
Analysis Sets .....................................................................................................88 
13.1.2 
Analysis of Demographics and Other Baseline Characteristics .......................88 
13.1.3 
Immunogenicity Analysis .................................................................................88 
13.1.4 
Safety Analysis .................................................................................................89 
13.2 
Interim Analysis and Criteria for Early Termination ...................................................89 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
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17 of 104 
Protocol Version 2.0  
11 April 2017 
 
13.3 
Determination of Sample Size .....................................................................................89 
14.0 
QUALITY CONTROL AND QUALITY ASSURANCE .................................................90 
14.1 
Trial-Site Monitoring Visits .........................................................................................90 
14.2 
Protocol Deviations ......................................................................................................90 
14.3 
Quality Assurance Audits and Regulatory Agency Inspections ..................................90 
15.0 
ETHICAL ASPECTS OF THE TRIAL .............................................................................91 
15.1 
IRB and/or IEC Approval ............................................................................................91 
15.2 
Subject Information, Informed Consent (ICF), and Subject Authorization .................91 
15.3 
Subject Confidentiality ................................................................................................92 
15.4 
Publication, Disclosure, and Clinical Trial Registration Policy ..................................93 
15.4.1 
Publication and Disclosure ...............................................................................93 
15.4.2 
Clinical Trial Registration.................................................................................93 
15.4.3 
Clinical Trial Results Disclosure ......................................................................93 
15.5 
Insurance and Compensation for Injury .......................................................................94 
16.0 
REFERENCES ..................................................................................................................95 
 
LIST OF IN-TEXT TABLES 
Table 1.a 
Contact Information .................................................................................................2 
Table 2.a 
Adult Lead-In Cohort .............................................................................................32 
Table 2.b. 
Toddler Lead-In Cohort .........................................................................................33 
Table 2.c. 
Infant Dose Ranging Cohort ..................................................................................34 
Table 8.a 
Sponsor-Supplied Vaccines and Reference ...........................................................63 
Table 10.a 
Local and Systemic AEs ........................................................................................77 
Table 10.b 
Solicited Safety Parameters - Adult Lead-In Cohort .............................................78 
Table 10.c 
Solicited Safety Parameters - Toddler Lead-In Cohort and Infant Dose 
Ranging Cohort ......................................................................................................79 
 
LIST OF IN-TEXT FIGURES 
Figure 6.a 
Schematic of Trial Design .....................................................................................52 
 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
18 of 104 
Protocol Version 2.0  
11 April 2017 
 
LIST OF APPENDICES 
Appendix A 
Responsibilities of the Investigator ........................................................................96 
Appendix B 
Elements of the Subject Informed Consent ...........................................................98 
Appendix C 
Investigator Consent to Use of Personal Information ..........................................101 
Appendix D 
Serology Plan .......................................................................................................102 
 
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19 of 104 
Protocol Version 2.0  
11 April 2017 
 
2.0 
TRIAL SUMMARY 
Name of Sponsor(s): 
Takeda Vaccines, Inc. 
One Takeda Parkway 
Deerfield, IL 60015 
USA 
Product Name: 
Stand-alone Trivalent Sabin Inactivated Poliomyelitis 
Vaccine (sIPV) 
(TAK-195) 
Trial Title: A Randomized, Observer-Blind, Controlled Phase 1/2 Trial to Evaluate the Safety, Tolerability and 
Immunogenicity of Different Doses of a Stand-alone Trivalent, Inactivated Poliomyelitis Vaccine from Sabin 
Strains in Healthy Infants, with a Safety and Tolerability Age-Step Down Lead-in in Healthy Adults followed by 
Healthy Toddlers. 
IND No.: Not applicable 
EudraCT No.: Not applicable 
Study Identifier: IPV-102 
Phase: 1/2 
Trial Blinding Schema: Observer-blind 
Background and Rationale: 
Poliomyelitis is an acute infectious disease caused by any of 3 poliovirus serotypes (types 1, 2, or 3), spread by 
fecal-to-oral and oral-to-oral routes. Approximately 25% of those infected develop transient minor symptoms 
including fever, headache, malaise, nausea, vomiting, and sore throat, and on rare occasions is complicated with 
signs suggestive of aseptic meningitis. After infection, an average of 1 in 200 susceptible individuals develops 
paralytic poliomyelitis - depending on age and serotype - of whom 5-10% suffer viral destruction of bulbar cells 
resulting in respiratory paralysis and death. 
Immunity acquired following infection is considered to provide serotype-specific lifelong protection against 
paralytic poliomyelitis. Similarly, induction of circulating antibodies through vaccination is an excellent 
indicator of protection against clinical disease, so post-vaccination seropositivity rates are considered to equate 
with seroprotection rates. Currently, two types of vaccines against poliomyelitis are available to control the 
disease in most parts of the world: injectable Inactivated Poliomyelitis Vaccine (IPV), and live Oral 
Poliomyelitis Vaccine (OPV). The introductions of IPV in 1955 (Jonas Salk) and OPV in 1963 (Albert Sabin) 
have led to a near eradication in poliomyelitis worldwide. Since the Global Polio Eradication Initiative (GPEI) 
was initiated by the World Health Assembly (WHA) in 1988, cases of polio have decreased by over 99%. One of 
the three serotypes, poliovirus type 2, was officially declared to be globally eradicated in September 2015, the 
last case being reported in 1999, and no cases of type 3 wild poliovirus have been reported since November 
2012. Wild type 1 poliovirus is currently circulating in only three countries, Afghanistan, Pakistan and Nigeria.  
With the global eradication of wild-type 2 poliovirus, trivalent OPV has been withdrawn globally since April 
2016, and only bivalent OPVs (types 1 and 3) are now in use. Currently, OPV is used in polio-endemic countries, 
in countries at high risk for importation of polio and/or intermediate-to-high potential for transmission. OPV has 
several advantages over IPV: it is easy to administer in resource-poor settings, it allows for the vaccine virus to 
spread to contacts resulting in contact immunity beyond the vaccinated individual, and it elicits a better intestinal 
immunity. In addition, it is safer and, hence, easier and cheaper to manufacture as it does not involve the 
amplification of wild poliovirus, which reduces production costs. However, on rare occasions, the attenuated 
Sabin strains can cause vaccine-associated paralytic poliomyelitis (VAPP). A further risk is the occurrence of 
mutations that can revert the attenuated strain into a neurovirulent form of poliovirus leading to circulating 
vaccine-derived poliovirus (cVDPV), with the potential of outbreaks of VAPP. For this reason, OPV is not 
suitable for long-term control of polio and IPV will be the cornerstone towards final eradication.  
The GPEI Polio Eradication and Endgame Strategic Plan 2013–2018 is a comprehensive, long-term strategy that 
calls for all countries to introduce at least one dose of IPV into their national routine immunization schedules 
together with the replacement of trivalent OPV with bivalent OPV from April 2016, before the eventual 
withdrawal of all forms of OPV immunization. The GPEI recommendation that all children receive at least one 
dose of IPV with the introduction of bOPV which will help to:  
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
21 of 104 
Protocol Version 2.0  
11 April 2017 
 
Trial Design: 
This is a Phase 1/2, randomized, observer-blind, safety, tolerability, and dose ranging trial on a stand-alone 
trivalent inactivated poliomyelitis vaccine derived from Sabin strains in healthy infants with a lead-in in healthy 
adults followed by healthy toddlers. 
The trial will start with an adult cohort (n = 40) in a safety and tolerability lead-in of the highest dosage of sIPV 
compared with placebo. Unblinded safety and tolerability assessments post vaccination will be reviewed by an 
independent Data Monitoring Committee (DMC) who will recommend whether or not vaccination of younger 
cohorts can proceed. The toddler lead-in cohort (n  = 60) is designed to evaluate the safety and tolerability of the 
highest dosage of sIPV given as booster vaccination compared with the reference IPV. Blinded safety data from 
this cohort will be reviewed internally by Takeda before initiating the recruitment of the infant dose ranging 
cohort. 
 
In the adult lead-in cohort, 40 healthy adults, 18-49 years of age inclusive, will be recruited to receive in an 
observer-blind fashion a single intramuscular injection of high dose sIPV containing 3, 100, and 100 D-antigen 
units (DU) of poliovirus types 1, 2, and 3, respectively (Day 1), or placebo. Subjects must have completed 
primary immunization against poliomyelitis according to local recommendations. Safety and tolerability will be 
assessed 7 days post vaccine administration.  
The total follow-up duration will be 7 days for adults in this cohort; they will have 2 clinical visits.  
In the toddler lead-in cohort, 60 toddlers at 12 to 15 months of age inclusive, will be recruited to receive in an 
observer-blind fashion a single intramuscular injection of high dose sIPV containing 3, 100, and 100 DU for 
poliovirus types 1, 2, and 3, respectively (Day 1), or the reference IPV. Polio vaccines previously received for 
primary immunization will be recorded. Other routine vaccines for toddler immunizations as recommended by 
the locally applicable National Program on Immunization (NPI) for children shall be given at least 4 weeks apart 
from the sIPV / reference IPV booster vaccination. Safety and tolerability will be assessed 7 and 28 days post 
IPV administration. In addition, a final safety visit will be scheduled for 6 months post IPV booster 
administration. 
Individual poliovirus neutralizing antibody titers pre and post booster vaccination will be assessed. Toddlers who 
receive sIPV and who have no neutralizing antibodies to any of the three poliovirus serotypes (titer <8) on Day 
29 as well as those with no titer increase between Day 1 and Day 29 will be offered re-vaccination with a single 
dose of the reference IPV (note: toddlers that have received bivalent OPV exclusively for primary immunization 
may not achieve seropositivity to poliovirus type 2. Therefore, subjects with documented primary immunization 
against serotypes 1 and 3 only who do not respond to serotype 2 post- sIPV booster will not be offered re-
vaccination). 
The total follow-up duration will be 182 days for toddlers in the lead-in cohort, who will have 2 clinical visits 
and 2 telephone contacts. 
In the infant dose ranging cohort, a total of 240 infants at 6 to 8 weeks of age, inclusive, with no previous 
history of poliomyelitis vaccination, will be enrolled and randomized to 4 equal study arms to receive 3 doses 4 
weeks apart (on Day 1, Day 29, and Day 57) of either i) low concentration (0.75, 25, and 25 Du, formulation ‘L’, 
Arm 1), ii) medium concentration (1.5, 50, and 50 DU, formulation ‘M’, Arm 2), iii) high concentration (3, 100, 
and 100 DU, formulation ‘H’, Arm 3) sIPV, or iv) or a reference IPV (controls, Arm 4). The 3-dose primary IPV 
administrations will be performed concomitantly with routine NPI-recommended infant vaccinations. Solicited 
adverse events (AEs) will be assessed for 7 days and unsolicited adverse events for 28 days after each of the 
three vaccinations. Additional safety assessments will be performed 6 months (Day 183) and 12 months post first 
dose (Day 365) of the primary immunization. Serious adverse events (SAEs) will be recorded throughout the 
entire study period. Neutralizing antibodies to each of the three poliovirus types will be assessed before the first 
vaccination, and 28 days after the second and third primary vaccinations on Day 57 and Day 85. 
Twelve months (Day 365) after first dose received for primary immunization, all subjects recruited in the dose 
ranging cohort will receive a booster vaccination containing the same sIPV formulation that was allocated for 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
22 of 104 
Protocol Version 2.0  
11 April 2017 
 
their primary immunization (Arms 1-3) or the reference IPV (Arm 4), concomitantly with NPI-recommended 
booster vaccinations. Solicited adverse events will be assessed for 7 days and unsolicited adverse events for 28 
days after this booster vaccination, and SAEs will be recorded throughout the entire study period. Neutralizing 
antibodies to each of the three poliovirus types will be assessed before (Day 365) and 28 days after the booster 
vaccination (Day 393).  Infants who receive sIPV and who have no neutralizing antibodies to any of the three 
poliovirus serotypes (titer <8) on Day 393 will be offered re-vaccination with a single series of three primary 
immunizations of the reference IPV after the unblinding occurs and serological results become available, and 
outside of the IPV-102 clinical trial. 
Total follow-up duration will be 546 days for infants in the dose ranging cohort, who will have 6 clinical visits 
and 6 telephone contacts.  
Primary evaluation of the trial objectives is planned at Day 85, 28 days after the third dose of a series of three 
IPV (sIPV or reference IPV) doses given for primary immunization in the infant dose ranging cohort.  
An interim analysis will be performed when the safety, tolerability and immunogenicity data until Day 85 
(28 days after the third dose of the primary immunization series) are available. The interim analysis will be 
performed by a separate set of unblinded statisticians who will have access to individual treatment assignments, 
but will not be involved in subsequent study conduct. Other personnel involved in the conduct of the study, 
including those at Takeda, the contract research organization (CRO), and the study sites, will remain blinded to 
the individual subject data (including treatment assignments) until unblinding after database lock post Day 547.  
The figure below illustrates numbers of subjects as well as planned procedures / visits for the adult and toddler 
lead-in cohorts and the infant dose ranging cohort. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
23 of 104 
Protocol Version 2.0  
11 April 2017 
 
 
Primary Objective: 
Infant dose ranging cohort only 
To select for further development, the optimal antigen concentrations of the three Sabin poliovirus strains (types 
1, 2, and 3) of the stand-alone trivalent sIPV by comparing the three sIPV study arms based on two parameters: 
• 
the safety and tolerability profile after each dose of primary immunization  
• 
the seroconversion rates (SCR) for poliovirus types 1, 2, and 3 for both Sabin and Salk strains, after the final 
dose of a three dose primary immunization series (Day 85) 
Day 29 safety & tolerability data assessment by Takeda safety team before proceeding with dose ranging cohort
Lead-in Arm 2 [control] – reference IPV (n = 30)
1:1
Day 29
Day 183
Visit
1
2
3
4
Day 8
Lead-in Arm 1 [‘H’] – sIPV D-Ag 3:100:100 (n = 30) 
60 toddlers
12 to15 months 
of age, inclusive
A) Lead-in, adults
1:1
Day 1
Visit
1
2
Day 8
40 adults
18-49 years 
of age, inclusive
Lead-in Arm 1 – [‘H’] – sIPV D-Ag 3:100:100 (n = 20)
Day 8 safety & tolerability data assessment by DMC before proceeding with toddler lead-in
Lead-in Arm 2 – [control] – placebo (n = 20)
B) Lead-in, toddlers
Day 1
240 infants
6 to 8 weeks of 
age, inclusive
Arm 1 [‘L’] - sIPV D-Ag 0.75:25:25 (n = 60)
Day 8
Primary immunizations
Arm 2 [‘M’] - sIPV D-Ag 1.5:50:50 (n = 60)
Arm 3 [‘H’] - sIPV D-Ag 3:100:100 (n = 60)
1:1:1:1
Day 57
Day 29
Day 1
Day 85
Day 365
Primary endpoint 
Day 393
Day 183
Visit
Booster immunization
C) Dose ranging, infants
Day 372
1 2
3 4
5 6
7
8
9 10
11
Day 547
12
Day 36
Day 64
Arm 4 [control] – reference IPV (n = 60)
= IPV vaccination
= pivotal endpoints analysis points
= safety & tolerability assessments
= blood draw
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
24 of 104 
Protocol Version 2.0  
11 April 2017 
Secondary Objectives: 
Safety and tolerability: 
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Immunogenicity: 
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Exploratory Objectives: 
Subject Populations:
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Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
25 of 104 
Protocol Version 2.0  
11 April 2017 
 
Adult lead-in cohort:  
Healthy subjects: yes 
Planned Minimum Age: 18 years 
Planned Number of Subjects: 40  
Planned Number of Arms: 2 (randomly allocated, n = 20 per arm) 
o 
Arm 1: sIPV formulation ‘H’, high concentration (3.0, 100, and 100 DU) 
o 
Arm 2: placebo 
Toddler lead-in cohort:  
Healthy subjects: yes 
Planned Minimum Age: 12 months 
Planned Number of Subjects: 60  
Planned Number of Arms: 2 (randomly allocated, n = 30 per arm) 
o 
Arm 1: sIPV formulation ‘H’, high concentration (3.0, 100, and 100 DU) 
o 
Arm 2: reference IPV. 
Infant dose ranging cohort:  
Healthy subjects: yes 
Planned Minimum Age: 6 weeks 
Planned Number of Subjects: 240  
Planned Number of Arms: 4 (randomly allocated, n = 60 per arm) 
o 
Arm 1: sIPV formulation ‘L’, low concentration (0.75, 25, and 25 DU) 
o 
Arm 2: sIPV formulation ‘M’, medium concentration (1.5, 50, and 50 DU) 
o 
Arm 3: sIPV formulation ‘H’, high concentration (3.0, 100, and 100 DU) 
o 
Arm 4: reference IPV. 
Criteria for Inclusion: 
Adult Lead-in Cohort 
• 
Male and female adults aged 18 to 49 years, inclusive, at the time of enrollment. 
• 
Individuals who are in good health at the time of entry into the trial as determined by medical history, 
physical examination (including vital signs) and clinical judgment of the investigator. 
• 
The subject signs and dates a written, informed consent form (ICF) and any required privacy authorization 
prior to the initiation of any trial procedures, after the nature of the trial has been explained according to 
local regulatory requirements. 
• 
Individuals who can comply with trial procedures and are available for the duration of follow-up. 
• 
Completed primary immunization against poliomyelitis according to local recommendations. 
 
Toddler lead-in cohort: 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
26 of 104 
Protocol Version 2.0  
11 April 2017 
 
• 
Male and female toddlers, aged 12 to 15 months, inclusive, at the time of enrollment. 
• 
Toddlers in good health at the time of entry into the trial as determined by medical history, physical 
examination (including vital signs) and clinical judgment of the investigator. 
• 
The toddler’s legally authorized representative (LAR) signs and dates a written ICF and any required 
privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been 
explained according to local regulatory requirements. 
• 
Toddlers and their LAR can comply with trial procedures, are available for the duration of the trial, and a 
suitable telephone contact is available. 
• 
Completed primary immunization against poliomyelitis, preferably with IPV, according to local 
recommendations. 
 
Infant dose ranging cohort: 
• 
Male and female infants, aged 6 to 8 weeks (42 – 55 days, inclusive) at the time of enrollment. 
• 
Infants in good health at the time of entry into the trial as determined by medical history, physical 
examination (including vital signs) and clinical judgment of the investigator. 
• 
Infants must have been born full term (37-42 weeks of gestation).  
• 
The infant’s LAR signs and dates a written ICF and any required privacy authorization prior to the initiation 
of any trial procedures, after the nature of the trial has been explained according to local regulatory 
requirements. 
• 
Infants and their LAR can comply with trial procedures, are available for the duration of follow-up, and a 
suitable telephone contact is available. 
Criteria for Exclusion: 
Adult lead-in cohort 
• 
Individuals with body mass index (BMI) greater than or equal to 35 kg/m2 (= weight in kg / [height in 
meters * height in meters]. 
• 
Individuals with history of substance or alcohol abuse within the past 2 years. 
• 
Female subjects who are pregnant or breastfeeding 
 
Toddler lead-in cohort: 
• 
Last polio vaccination (either inactivated or oral) received within 5 months prior to first trial visit. 
• 
Household member/sibling who had received or is/are scheduled to receive OPV in the previous 3 months 
until 5 weeks post subject's inclusion in the study. 
• 
Prior vaccination with booster dose of diphtheria, tetanus, pertussis (acellular or whole cell), polio (either 
inactivated or oral), or Haemophilus influenzae type b (Hib) vaccines. 
 
Infant dose ranging cohort:  
• 
Infants with low birth weight according to local standards. 
• 
Prior vaccination with polio vaccines (either inactivated or oral). 
• 
Household member/sibling that had received or is/are scheduled to receive OPV in the previous 3 months 
until 5 weeks after the third dose of the primary immunization series. 
• 
Prior vaccination with any diphtheria, tetanus, pertussis (acellular or whole cell), Haemophilus influenzae 
type b (Hib) vaccine or polio vaccine (OPV or IPV). Note, BCG at birth and prior vaccination with Hepatitis 
B vaccine given at least 28 days prior to first trial visit are not exclusion criteria. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
27 of 104 
Protocol Version 2.0  
11 April 2017 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
28 of 104 
Protocol Version 2.0  
11 April 2017 
 
Toddler lead-in cohort: 
Routine childhood vaccines other than poliomyelitis vaccine for booster immunization recommended for 
children at approximately 12 months of age according to the NPI (eg, measles-containing vaccine) are to be 
given at least 4 weeks apart from sIPV / reference IPV booster vaccination. NPI-recommended childhood 
vaccines other than poliomyelitis vaccine will be given outside the trial. 
Infant dose ranging cohort: 
Vaccination against diphtheria (D), tetanus (T), pertussis (P), hepatitis B (HBV) and Haemophilus influenzae 
type b (Hib) will be given as pentavalent combination vaccine (DTP-HBV-Hib). The pentavalent vaccine will be 
sourced and provided by Takeda as trial vaccine.  
All other routine infant vaccines (other than poliomyelitis vaccine and pentavalent vaccine) for primary 
immunization and for booster vaccination at approximately 12 months of age will be given concordant with NPI 
recommendations outside the trial. Inactivated / oral routine infant vaccines should be given on the same day as 
sIPV / reference IPV. Injectable live-attenuated vaccines (eg, measles-containing vaccine) should be given at 
least 4 weeks apart from sIPV / reference IPV. 
 
Route of administration: sIPV / reference IPV / placebo will be administered by IM injection, preferably in the 
right limb. Additional injectable inactivated routine infant vaccines given concomitantly to infants in the dose 
ranging cohort will be administered in a limb/limbs different from the one used for sIPV / reference IPV 
vaccination. 
Duration of the Trial: 
Adult lead-in cohort: approximately 1 week 
Toddler lead-in cohort: approximately 6 months  
Infant dose ranging cohort: approximately 18 months 
Period of Evaluation: 
Adult lead-in cohort: 7 days 
Toddler lead-in cohort: 182 days  
Infant dose ranging cohort: 546 days 
Main Criteria for Evaluation and Analyses: 
The co-primary endpoints for this trial are in the infant dose ranging cohort only:  
Safety: 
• 
Percentage of subjects with solicited local reactions on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after each primary immunization dose of 
sIPV.  
• 
Percentage of subjects with solicited systemic AEs on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after each primary immunization dose of 
sIPV.  
• 
Percentage of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-day period (including 
day of vaccination) after each primary immunization dose of sIPV.  
• 
Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period (including day of 
vaccination) after each primary immunization dose of sIPV.  
• 
Percentage of subjects experiencing SAEs throughout the entire trial duration in the sIPV study arms. 
Immunogenicity, separately for poliovirus types 1, 2, and 3 for both Sabin and Salk strains for the three study 
arms: 
• 
SCR = percentage of subjects in each arm who seroconvert, which is defined as: 
i) initially seronegative infants (titer <8 at Day 1) having a titer ≥ 8 at Day 85, or  
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
29 of 104 
Protocol Version 2.0  
11 April 2017 
 
ii) initially seropositive infants (titer ≥ 8 at Day 1) with a 4-fold rise in antibody titers over the expected 
level of maternal antibodies at Day 85, calculated using a decline from the Day 1 titer with a half-life of 
28 days. 
Secondary endpoints: 
Safety and tolerability: 
Infant dose ranging cohort 
• 
Percentage of subjects with solicited local reactions on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after each primary immunization dose of 
sIPV or IPV. 
• 
Percentage of subjects with solicited systemic AEs on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after each primary immunization dose of 
sIPV or IPV. 
• 
Percentage of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-day period (including 
day of vaccination) after each primary immunization dose of sIPV or IPV. 
• 
Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period (including day of 
vaccination) after each primary immunization dose of sIPV or IPV. 
• 
Percentage of subjects experiencing SAEs throughout the entire trial duration in the sIPV and IPV study 
arms. 
• 
Percentage of subjects with solicited local reactions on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after booster vaccination. 
• 
Percentage of subjects with solicited systemic AEs on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after booster vaccination. 
• 
Percentage of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-day period (including 
day of vaccination) after booster vaccination. 
• 
Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period (including day of 
vaccination) after booster vaccination. 
 
Toddler lead-in cohort 
• 
Percentage of subjects with solicited local reactions on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after booster vaccination. 
• 
Percentage of subjects with solicited systemic AEs on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after booster vaccination. 
• 
Percentage of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-day period (including 
day of vaccination) after booster vaccination. 
• 
Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period (including day of 
vaccination) after booster vaccination. 
• 
Percentage of subjects experiencing SAEs throughout the entire trial duration. 
 
Adult lead-in cohort 
• 
Number of subjects with solicited local reactions on a symptom by symptom basis, in each severity 
category, during the 7-day period (including day of vaccination) after a single dose of sIPV or placebo. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
30 of 104 
Protocol Version 2.0  
11 April 2017 
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Immunogenicity, separately for poliovirus types 1, 2, and 3 for both Sabin and Salk strains: 
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Exploratory endpoints: 
Statistical Considerations:
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
31 of 104 
Protocol Version 2.0  
11 April 2017 
 
protocol violations will be identified as part of the blinded data review prior to the unblinding of subject’s 
investigational trial vaccine assignment. The categories of major protocol violations include: (1) not meeting 
selected entry criteria, (2) receiving a wrong trial vaccine or an incorrect regimen, (3) receiving prohibited 
therapies, and (4) other major protocol violations that may be identified during blinded data reviews. 
All summaries and analyses of safety data will be based on subjects in the Safety Set. The primary 
immunogenicity analyses will be based on the PPS, and additional sensitivity analyses will be based on the FAS. 
Analysis of Demographics and Other Baseline Characteristics 
Summaries of age, gender, race, and other baseline characteristics will be presented by formulation arm. 
Immunogenicity Analysis 
Descriptive statistics for the primary, secondary, and exploratory immunogenicity endpoints, including estimates 
and 95% confidence intervals for SCR, SPR, VRR, and GMT will be provided by study arm and by poliovirus 
type. For the dose ranging cohort only, estimates and 95% confidence intervals for differences in SCR, SPR, and 
VRR, as well as ratios in GMT, will be provided for each pair of study arms by poliovirus type.  
Safety Analysis 
Reactogenicity will be assessed for 7 days following each vaccination (including day of vaccination) via daily 
collection of solicited AEs, including local reactions (injection site: pain, erythema, induration, and swelling) and 
systemic adverse events of headache, asthenia, malaise, arthralgia and myalgia for the adult lead-in cohort and 
irritability/fussiness, drowsiness, loss of appetite for the toddler lead-in and infant dose ranging cohorts. In 
addition, body temperature (preferably measured as oral temperature in the adult lead-in cohort and as rectal 
temperature in the toddler lead-in and infant dose ranging cohorts) as indicator of reactogenicity will be collected 
(with fever defined as body temperature ≥ 38°C).  
For each solicited AE and fever, the percentage of subjects will be summarized by event severity for each day for 
the 7 days after each vaccination and overall. For subjects with more than 1 episode of the same event, the 
maximum severity will be used for tabulations. 
Unsolicited AEs, and SAEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
and summarized by system organ class (SOC) and preferred term (PT) for each formulation arm. 
Sample Size Justification: 
This trial is designed to be descriptive and is not based on testing formal null hypotheses, and therefore the 
sample size was not determined based on formal statistical power calculations. 
Interim Analysis: 
An interim analysis will be performed on data from Day 85 (28 days after the last dose of the primary 
immunization series in the infant dose ranging cohort). The interim analysis will be performed by a separate set 
of unblinded statisticians and programmers who will have access to individual treatment assignments but will not 
be involved in subsequent study conduct. Results of the interim analysis will be used to inform the choice of 
antigen dose to be used in subsequent phase 3 studies of the sIPV.  
More details on the analyses will be provided in the SAP. 
Independent Data Monitoring Committee:  
An independent program level DMC will be established. The DMC will have study-specific responsibilities to 
review IPV-102 data and decide on the enrollment of the toddler and infant cohorts after reviewing 7 days of 
safety and tolerability follow-up post vaccination in adults in the lead-in cohort. In addition, the DMC will 
evaluate the overall tolerability and safety of Takeda’s sIPV on an ongoing basis. The DMC will be entitled to 
stop enrollment of additional subjects or to stop administration of additional sIPV doses. The composition, role 
and responsibilities of the DMC are presented in a separate DMC Charter. 
IPV-102 Version 2.0 (11 April 2017) 
 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
32 of 104 
Protocol Version 2.0  
11 April 2017 
 
2.1 
Schedule of Trial Procedures 
Table 2.a 
Adult Lead-In Cohort 
Day 
Day 1 
Day 8 
ET 
Anchor to Study Visit 1 
-/- 
Visit 1 
+  
7 days 
 
Visit Number  
1 
2 
 
Acceptable Visit Window (before/after) (days) 
NA 
0/+4 
 
Clinical Visit (at site) 
X 
X 
 
Signed Informed Consent Form 
X 
 
 
Pregnancy Test(a) 
X 
 
 
Assessment of Eligibility Criteria(b) 
X 
 
 
Demographics 
X 
 
 
Medical History 
X 
 
 
Prior Medications 
X 
 
 
Concomitant Medications 
X 
X 
(X) 
Physical Examination 
Complete(c) 
X 
 
 
Symptom Directed(c) 
 
(X) 
(X) 
Vital Signs(d) 
X 
(X) 
(X) 
Randomization 
X 
 
 
IPV/placebo administration(e) 
X 
 
 
Diary Card  
Distribution(f) 
X 
 
 
Collection(f) 
 
X 
(X) 
Adverse Events(g) 
X 
X 
(X)(h) 
Serious Adverse Events(i) 
X 
X 
(X) 
ET: Early Termination. Use of (X) indicates samples or procedures that generally will not be performed but may 
be performed to investigate an AE, or at the time of premature discontinuation.  
(a) In women of childbearing potential, a pregnancy test will be performed on Day 1 prior to enrollment. 
(b) Eligibility by review of relevant inclusion/exclusion criteria will be documented before enrollment. 
(c) Physical exam on Day 1 (Section 9.1.4). All subsequent physical examinations may be performed if deemed 
necessary and will be symptom-directed and should assess clinically significant changes from the baseline 
examination. For any procedures at the site, the investigator shall follow his/her standard practice. 
(d) Vital signs: as defined in Section 9.1.5.  
(e) After vaccination, subjects will be observed for at least 30 minutes including observation for immediate 
reactions and body temperature measurement. 
(f) Diary cards will be distributed on the day of vaccination, and will be collected at the return visit 7 days later. 
(g) Solicited local and systemic adverse events (AEs: Section 10.1.2) and unsolicited AEs will be recorded daily in 
diary cards for Days 1-7 after vaccination.  
(h) AEs leading to Early Termination will be recorded by the investigator. 
(i) SAEs will be collected for the duration of the trial and will be reported to the Sponsor within 24 hours of the 
investigator becoming aware of the event. 
 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
33 of 104 
Protocol Version 2.0  
11 April 2017 
 
Table 2.b. 
Toddler Lead-In Cohort 
Day 
Day 1 
Day 8 
Day 29 
Day 183 
ET 
Anchor to Study Visit 1 
-/- 
Visit 1 
+  
7 days 
Visit 1 
+  
28 days 
Visit 1 
+  
182 days 
 
Visit Number  
1 
2 
3 
4 
 
Acceptable Visit Window (before/after) (days) 
NA 
0/+4 
0/+4 
0/+4 
 
Clinical Visit (at site) 
X 
 
X 
 
 
Telephone Contact 
 
X 
 
X 
(X) 
Signed Informed Consent Form 
X 
 
 
 
 
Assessment of Eligibility Criteria(a) 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Prior Medications 
X 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X(b) 
(X)(b) 
Physical Examination 
Complete(c) 
X 
 
 
 
 
Symptom Directed(c) 
 
 
(X) 
 
(X) 
Vital Signs(d) 
X 
 
X 
 
(X) 
Randomization 
X 
 
 
 
 
IPV administration(e) 
X 
 
 
 
 
Diary Card  
Distribution(f) 
X 
 
 
 
 
Collection(g) 
 
 
X 
 
(X) 
Adverse Events(h) 
X 
X 
X 
 
(X)(h) 
Serious Adverse Events(i) 
X 
X 
X 
X 
(X) 
Blood Draw (5 mL)  
X(j) 
 
X 
 
 
ET: Early Termination. Use of (X) indicates samples or procedures that generally will not be performed but may be 
performed to investigate an AE, or at the time of premature discontinuation.  
(a) Eligibility by review of relevant inclusion/exclusion criteria will be documented before enrollment. 
(b) Only vaccines administered since the last visit should be recorded. 
(c) Physical exam on Day 1 (Section 9.1.4). All subsequent physical examinations may be performed if deemed 
necessary and will be symptom-directed and should assess clinically significant changes from the baseline 
examination. For any procedures at the site, the investigator shall follow his/her standard practice.  
(d) Vital signs: as defined in Section 9.1.5.  
(e) sIPV or reference IPV. After vaccination, subjects will be observed for at least 30 minutes including observation 
for immediate reactions and body temperature measurement.  
(f) Diary cards will be distributed on the day of vaccination, and collected at the return visit on Day 29.  
(g) Solicited local and systemic adverse events (AEs: Section 10.1.2) will be recorded daily in diary cards for Days 
1-7, and unsolicited AEs for Days 1-28.  
(h) AEs leading to Early Termination will be recorded by the investigator.  
(i) SAEs will be collected for the duration of the trial and will be reported to the Sponsor within 24 hours of the 
investigator becoming aware of the event.  
(j) Blood should be drawn prior to vaccination. 
 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
34 of 104 
Protocol Version 2.0 
11 April 2017 
 
Table 2.c. 
Infant Dose Ranging Cohort 
Day 
Day 
1 
Day 
8 
Day 
29 
Day 
36 
Day 
57 
Day 
64 
Day 
85 
Day 
183 
Day 
365 
Day 
372 
Day 
393 
Day 
547 
ET 
Anchor to Study Visits  
-/- 
Visit 1 
+ 
7 days 
Visit 1 
+ 
28 days 
Visit 3 
+ 
7 days 
Visit 3 
+ 
28 days 
Visit 5 
+ 
7 days 
Visit 5 
+ 
28 days 
Visit 1 
+ 
182 days 
Visit 1 
+ 
364 days 
Visit 9 
+ 
7 days 
Visit 9 
+ 
28 days 
Visit 9 
+ 
182 days 
 
Visit Number  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
 
Acceptable Visit Window (before/after) 
(days) 
NA 
0/+4 
0/+4 
0/+4 
0/+4 
0/+4 
0/+4 
-7/+7 
-7/+14 
0/+4 
0/+4 
-7/+14 
 
Clinical Visit (at site) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Telephone Contact 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Signed Informed Consent Form 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of Eligibility Criteria (a) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Medications 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications(b) 
X 
X 
X 
X 
X 
X 
X 
X(b) 
X(b) 
X(b) 
X(b) 
X(b) 
(X) 
Physical 
Exam 
Complete (c) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom Directed (c) 
 
 
(X) 
 
(X) 
 
(X) 
 
(X) 
 
(X) 
 
(X) 
Vital Signs (d) 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
(X) 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IPV administration (e) 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Diary Card  
Distribution (f) 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Review/Collection 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
Adverse Events (g) 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
(X)(h) 
Serious Adverse Events (i) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(X) 
Blood Draw (5 mL)  
X(j) 
 
 
 
X(j) 
 
X 
 
X(j) 
 
X 
 
 
ET: Early Termination. Use of (X) indicates samples or procedures that generally will not be performed but may be performed to investigate an AE, or at the 
time of premature discontinuation.  
(a) Eligibility by review of relevant inclusion/exclusion criteria will be documented before enrollment. Continuing eligibility (by review of relevant 
inclusion/exclusion criteria and criteria for delay of vaccination) will be documented before each vaccination. 
(b) Only vaccines administered since the last visit should be recorded. 
(c) Physical exam on Day 1 (Section 9.1.4). All subsequent physical examinations may be performed if deemed necessary and will be symptom-directed and 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
35 of 104 
Protocol Version 2.0 
11 April 2017 
 
should assess clinically significant changes from the baseline examination. For any procedures at the site, the investigator shall follow his/her standard 
practice. 
(d) Vital signs: as defined in Section 9.1.5. 
(e) sIPV or reference IPV. Polio vaccine should be administered concomitantly with DTP-HBV-Hib on Days 1, 29 and 57. After vaccination, subjects will be 
observed for at least 30 minutes including observation for immediate reactions and body temperature measurement. 
(f) Diary cards will be distributed on the day of each vaccination, and will be collected at the return visit 28 days later. 
(g) Solicited local and systemic adverse events (AEs: Section 10.1.2) will be recorded daily in diary cards for Days 1-7, and unsolicited AEs for Days 1-28, 
after each vaccination.  
(h) AEs leading to Early Termination will be recorded by the investigator. 
(i) SAEs will be collected for the duration of the trial and will be reported to the Sponsor within 24 hours of the investigator becoming aware of the event. 
(j) Blood should be drawn prior to vaccination 
 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
36 of 104 
Protocol Version 2.0 
11 April 2017 
 
3.0 
TRIAL REFERENCE INFORMATION 
3.1 
Trial-Related Responsibilities 
The sponsor will perform all trial-related activities with the exception of those identified in the 
Trial-Related Responsibilities template. The identified vendors in the template for specific trial-
related activities will perform these activities in full or in partnership with the sponsor. 
3.2 
Principal Investigator/Coordinating Investigator 
The sponsor will select a Signatory Principal Investigator / Coordinating Investigator from the 
investigators who participate in the trial. Selection criteria for this investigator will include 
significant knowledge of the trial protocol, the investigational vaccine, their expertise in the 
therapeutic area and the conduct of clinical research as well as trial participation. The Signatory 
Principal Investigator / Coordinating Investigator will be required to review and sign the clinical 
study report and by doing so agrees that it accurately describes the results of the trial. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
37 of 104 
Protocol Version 2.0 
11 April 2017 
 
3.3 
List of Abbreviations 
AE 
Adverse Event 
Al(OH)3 
Aluminum Hydroxide 
bOPV 
bivalent Oral Poliomyelitis Vaccine 
CI 
Confidence Interval 
eCRF 
electronic Case Report Form  
CRO 
Contract Research Organization 
cVDPV 
circulating Vaccine-Derived Poliovirus 
DTaP 
Diphtheria, Tetanus, acellular Pertussis combination vaccine 
DTaP-IPV 
Diphtheria, Tetanus, acellular Pertussis, Inactivated Poliomyelitis 
combination vaccine 
DMC 
Data Monitoring Committee 
DU 
D-Antigen Units 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
EMA 
European Medicines Agency 
EPI 
Expanded Programme on Immunization 
FAS 
Full Analysis Set 
FSFV 
First Subject First Visit 
GAVI 
Global Alliance for vaccines and Immunization 
GCP 
Good Clinical Practice 
GMT 
Geometric Mean Titer 
GPEI 
Global Polio Eradication Initiative 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
IM 
Intramuscular 
IPV 
Inactivated Poliomyelitis Vaccine 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intention-To-Treat 
IUD 
Intrauterine Device 
JPRI 
Japanese Poliomyelitis Research Institute 
LAR 
Legally Authorized Representative 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
38 of 104 
Protocol Version 2.0 
11 April 2017 
 
LLN 
Lower Limit of Normal 
LSLV 
Last Subject Last Visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
NPI 
National Program on Immunization 
OPV 
Oral Poliomyelitis Vaccine 
PP 
Per Protocol 
PPS 
Per-Protocol Analysis Set 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SCR 
Seroconversion Rate 
sIPV 
Sabin-based Inactivated Poliomyelitis Vaccine 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SPR 
Seropositivity/Seroprotection Rate 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
ULN 
Upper Limit of Normal 
VAPP 
Vaccine-Associated Paralytic Poliomyelitis 
WHA 
World Health Assembly  
WHO 
World Health Organization 
VRR 
Vaccine Response Rate 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
39 of 104 
Protocol Version 2.0 
11 April 2017 
 
3.4 
Corporate Identification 
TV 
Takeda Vaccines, Inc. 
VBU 
Vaccines Business Unit 
 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
40 of 104 
Protocol Version 2.0 
11 April 2017 
 
4.0 
INTRODUCTION 
4.1 
Background 
Poliomyelitis is an acute infectious disease caused by any of 3 poliovirus serotypes (types 1, 2, or 
3), spread by fecal-to-oral and oral-to-oral routes. Approximately 25% of those infected develop 
transient minor symptoms including fever, headache, malaise, nausea, vomiting, and sore throat, 
and on rare occasions is complicated with signs suggestive of aseptic meningitis. After infection, 
an average of 1 in 200 susceptible individuals develops paralytic poliomyelitis—depending on 
age and serotype—of whom 5–10% suffer viral destruction of bulbar cells resulting in 
respiratory paralysis and death [2]. 
Immunity acquired following infection is considered to provide serotype-specific lifelong 
protection against paralytic poliomyelitis [3]. Similarly, induction of circulating antibodies 
through vaccination is an excellent indicator of protection against clinical disease, so post-
vaccination seropositivity rates are considered to equate with seroprotection rates [4]. Currently, 
two types of vaccines against poliomyelitis are available to control the disease in most parts of 
the world: injectable Inactivated Poliomyelitis Vaccine (IPV), and live Oral Poliomyelitis 
Vaccine (OPV). The introductions of IPV in 1955 (Jonas Salk) and OPV in 1963 (Albert Sabin) 
have led to a significant decrease in poliomyelitis worldwide. Since the Global Polio Eradication 
Initiative (GPEI) was initiated by the World Health Assembly (WHA) in 1988, cases of polio 
have decreased by over 99%. One of the three serotypes, poliovirus type 2, was officially 
declared to be globally eradicated in September 2015, the last case being reported in 1999, and 
no cases of type 3 wild poliovirus have been reported since November 2012. Wild type 1 
poliovirus is currently circulating in only three countries, Afghanistan, Pakistan and Nigeria [5].  
With the global eradication of wild-type 2 poliovirus, trivalent OPV has been withdrawn globally 
since April 2016 and only bivalent OPVs (types 1 and 3) are now in use. Currently, OPV is used 
in polio-endemic countries, in countries at high risk for importation of polio and/or intermediate-
to-high potential for transmission. OPV has several advantages over IPV: it is easy to administer 
in resource-poor settings, it allows for the vaccine virus to spread to contacts resulting in contact 
immunity beyond the vaccinated individual, it elicits a better intestinal immunity. In addition, it 
is safer and, hence, easier and cheaper to manufacture as it does not involve the amplification of 
wild poliovirus which reduces production costs. However, on rare occasions, the attenuated 
Sabin strains cause vaccine-associated paralytic poliomyelitis (VAPP). A further risk is the 
occurrence of mutations that can revert the attenuated strain into a neurovirulent form of 
poliovirus leading to circulating vaccine-derived poliovirus (cVDPV) with the potential of 
outbreaks of VAPP. For this reason, OPV is not suitable for long-term control of polio and IPV 
will be the cornerstone towards final eradication. 
The GPEI Polio Eradication and Endgame Strategic Plan 2013–2018 [6] is a comprehensive, 
long-term strategy that calls for all countries to introduce at least one dose of IPV into their 
national routine immunization schedules together with the replacement of trivalent OPV with 
bivalent OPV from April 2016, before the eventual withdrawal of all forms of OPV 
immunization. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
41 of 104 
Protocol Version 2.0 
11 April 2017 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
42 of 104 
Protocol Version 2.0 
11 April 2017 
Clinical experience with sIPV 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
43 of 104 
Protocol Version 2.0 
11 April 2017 
 
This trial will assess the safety and tolerability as well as the immunogenicity of Takeda’s stand-
alone sIPV candidate to identify the optimal formulation to take forward into advanced stage 
studies to show the immunogenicity and safety of the final candidate vaccine. 
4.2 
Rationale for the Proposed Trial 
With the imminent global eradication of wild-type polioviruses, the routine vaccination of 
infants and toddlers with IPV will be necessary for several years to maintain sufficient 
population immunity to prevent polio disease outbreaks due to circulating vaccine-derived 
poliovirus (cVDPV). Current constraints on cost, capacity and safety of manufacturing of IPV 
can be alleviated by use of stand-alone vaccines such as Takeda’s sIPV, particularly for GAVI-
supported countries to complement other Expanded Programme on Immunization (EPI)-
recommended vaccines. This phase 1/2 trial is intended to show the safety, tolerability and 
provide a first indication of antigen dosage of Takeda’s sIPV in the target population of 
unvaccinated infants. 
Following a lead-in study of the safety and tolerability of the highest anticipated dosage in 
primed (after full primary poliovirus vaccination) adults followed by toddlers, the descriptive 
dosage-ranging study in infants will allow selection of the dosage to take forward into advanced 
stage studies. This decision will be based on the WHO recommendations for assessment of IPV 
vaccines [4], and will use the seroconversion rate after completion of the three-dose primary 
schedule as primary measure. 
In the adult and toddler lead-ins, the focus will be to ensure no unanticipated reactions or AEs 
are observed following one dose of the highest dosage formulation, which will be administered 
as a booster in adults and children who have previously been primed with a full primary 
poliomyelitis vaccination series according to the local recommendations. Immunogenicity will 
not be assessed in the adult cohort. In the toddler lead-in cohort, immunogenicity will be 
assessed after children receive this “booster” dose of sIPV to ensure they all have antibodies 
against at least serotypes 1 and 3 (as immune response to type 2 poliovirus may be incomplete in 
toddlers who had received their primary immunization with bOPV). A control group will receive 
a reference IPV for descriptive comparison. 
In the infant dose ranging cohort, the control group will provide a comparator for the safety and 
tolerability of the different sIPV dosages. Assessing immunogenicity in the comparator control 
arm in the infant cohort will provide background information to show that the three groups that 
receive the different dosages of sIPV all achieve adequate levels of immunity and so are not put 
at risk of poliovirus infection.  
The primary endpoint for the immunogenicity analysis is the seroconversion rate achieved in 
infants four weeks after the last of three primary doses of sIPV, in accordance with WHO 
recommendations for the assessment of IPV [4]. The study is not powered for statistical 
comparisons, and all comparisons will be descriptive. It is only designed to select a dosage 
formulation from consideration of an interim analysis performed on the data obtained 28 days 
after the third primary immunizations at Day 85. The selected formulation will be taken into 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
44 of 104 
Protocol Version 2.0 
11 April 2017 
 
larger phase 3 trials for advanced stage clinical development to show the immunogenicity and 
safety of the final candidate vaccine.  
The trial will be conducted in accordance with the protocol, ICH-GCP Guidelines and applicable 
regulatory requirements. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
45 of 104 
Protocol Version 2.0 
11 April 2017 
 
5.0 
TRIAL OBJECTIVES AND ENDPOINTS 
5.1 
Objectives 
5.1.1 Primary Objective 
Infant dose ranging cohort only 
To select for further development, the optimal antigen concentrations of the three Sabin 
poliovirus strains (types 1, 2, and 3) of the stand-alone trivalent sIPV by comparing the three 
sIPV study arms based on two parameters: 
• the safety and tolerability profile after each dose of primary immunization  
• the seroconversion rates (SCR) for poliovirus types 1, 2, and 3 for both Sabin and Salk 
strains, after the final dose of a three dose primary immunization series (Day 85) 
5.1.2 Secondary Objectives 
Safety and tolerability 
Adult lead-in cohort  
• To compare the safety and tolerability profile in the high dose sIPV arm with the control 
arm in adults after a single vaccination. 
Toddler lead-in cohort  
• To compare the safety and tolerability profile in the high dose sIPV arm with the 
reference IPV (control) arm in toddlers after a single booster vaccination. 
Infant dose ranging cohort  
• To compare the safety and tolerability profile of each sIPV study arm with the reference 
IPV (control) arm after each primary immunization. 
• To compare the safety and tolerability profile between sIPV study arms, and between 
each sIPV study arm and the reference IPV (control) arm, after booster vaccination. 
Immunogenicity 
Infant dose ranging cohort 
• To compare between each sIPV study arm and the reference IPV (control) arm, the SCR 
separately for poliovirus types 1, 2, and 3 for both Sabin and Salk strains, after the final 
dose out of a series of three doses for primary immunization (Day 85).  
• To compare between sIPV study arms, and between each sIPV study arm and the 
reference IPV (control) arm, the seropositivity/seroprotection rates (SPR) separately for 
poliovirus types 1, 2, and 3 for both Sabin and Salk strains, after the final dose out of a 
series of three doses for primary immunization (Day 85).  
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
46 of 104 
Protocol Version 2.0 
11 April 2017 
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5.1.3 Exploratory Objectives 
5.2 
Endpoints 
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Safety and tolerability 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
47 of 104 
Protocol Version 2.0 
11 April 2017 
 
• Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period 
(including day of vaccination) after each primary immunization dose of sIPV. 
• Percentage of subjects experiencing SAEs throughout the entire trial duration in the sIPV 
study arms. 
Immunogenicity, separately for poliovirus types 1, 2, and 3 for both Sabin and Salk strains, in 
the three study arms 
• SCR = percentage of subjects in each arm who seroconvert, which is defined as: 
i. initially seronegative infants (titer <8 at Day 1) having a titer ≥8 at Day 85, or  
ii. initially seropositive infants (titer ≥8 at Day 1) with a 4-fold rise in antibody titers 
over the expected level of maternal antibodies at Day 85, calculated using a decline 
from the Day 1 titer with a half-life of 28 days. 
Secondary Endpoints 
Safety and tolerability 
Infant dose ranging cohort 
• Percentage of subjects with solicited local reactions on a symptom by symptom basis, in 
each severity category, during the 7-day period (including day of vaccination) after each 
primary immunization dose of sIPV or IPV. 
• Percentage of subjects with solicited systemic AEs on a symptom by symptom basis, in 
each severity category, during the 7-day period (including day of vaccination) after each 
primary immunization dose of sIPV or IPV. 
• Percentage of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-
day period (including day of vaccination) after each primary immunization dose of sIPV 
or IPV. 
• Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period 
(including day of vaccination) after each primary immunization dose of sIPV or IPV. 
• Percentage of subjects experiencing SAEs throughout the entire trial duration in the sIPV 
and IPV study arms. 
• Percentage of subjects with solicited local reactions on a symptom by symptom basis, in 
each severity category, during the 7-day period (including day of vaccination) after 
booster vaccination. 
• Percentage of subjects with solicited systemic AEs on a symptom by symptom basis, in 
each severity category, during the 7-day period (including day of vaccination) after 
booster vaccination. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
48 of 104 
Protocol Version 2.0 
11 April 2017 
 
• Percentage of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-
day period (including day of vaccination) after booster vaccination. 
• Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period 
(including day of vaccination) after booster vaccination. 
Toddler lead-in cohort 
• Percentage of subjects with solicited local reactions on a symptom by symptom basis, in 
each severity category, during the 7-day period (including day of vaccination) after 
booster vaccination. 
• Percentage of subjects with solicited systemic AEs on a symptom by symptom basis, in 
each severity category, during the 7-day period (including day of vaccination) after 
booster vaccination. 
• Percentage of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-
day period (including day of vaccination) after booster vaccination. 
• Percentage of subjects experiencing non-serious unsolicited AEs during the 28-day period 
(including day of vaccination) after booster vaccination. 
• Percentage of subjects experiencing SAEs throughout the entire trial duration. 
Adult lead-in cohort 
• Number of subjects with solicited local reactions on a symptom by symptom basis, in 
each severity category, during the 7-day period (including day of vaccination) after a 
single dose of sIPV or placebo. 
• Number of subjects with solicited systemic AEs on a symptom by symptom basis, in each 
severity category, during the 7-day period (including day of vaccination) after a single 
dose of sIPV or placebo. 
• Number of subjects with a body temperature ≥ 38°C (defined as fever) during the 7-day 
period (including day of vaccination) after a single dose of sIPV or placebo. 
• Number of subjects experiencing non-serious unsolicited AEs during the 7-day period 
(including day of vaccination) after a single dose of sIPV or placebo. 
• Number of subjects experiencing SAEs during the 7-day period (including day of 
vaccination) after a single dose of sIPV or placebo. 
Immunogenicity, separately for poliovirus types 1, 2, and 3 for both Sabin and Salk strains 
Infant dose ranging cohort 
• Seropositivity/seroprotection rate (SPR, defined as the percentage of subjects with 
antibody titers ≥ 8) on Days 85, 365, and 393 (28 days after booster vaccination). 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
49 of 104 
Protocol Version 2.0 
11 April 2017 
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Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
50 of 104 
Protocol Version 2.0 
11 April 2017 
 
6.0 
TRIAL DESIGN AND DESCRIPTION 
6.1 
Trial Design 
This observer-blind, randomized trial has three separately enrolled cohorts starting with an adult 
cohort (n = 40) in a safety and tolerability lead-in of the highest dosage of sIPV compared with 
placebo. Unblinded safety and tolerability assessments over the first 7 days post vaccination will 
be reviewed by an independent Data Monitoring Committee (DMC) who will recommend 
whether or not vaccination of younger cohorts can proceed. The toddler lead-in cohort (n = 60) is 
designed to evaluate the safety and tolerability of the highest dosage of sIPV given as booster 
vaccination compared with the reference IPV. Blinded safety data from this cohort will be 
reviewed internally by Takeda before initiating the recruitment of the infant dose ranging cohort.  
A schematic of the trial design is included as Figure 6.a. A schedule of trial procedures is 
provided in Section 2.1. 
A). Adult lead-in cohort 
The first lead-in cohort will consist of 40 healthy adults, 18-49 years of age inclusive. Subjects 
will be enrolled and randomized to two equal groups to receive, in an observer-blind fashion, a 
single intramuscular injection of high dose sIPV containing 3, 100, and 100 DU of poliovirus 
types 1, 2, and 3, respectively (Day 1), or placebo. To be eligible, subjects must have completed 
primary immunization against poliomyelitis according to local recommendations.  
Safety and tolerability will be assessed 7 days post vaccine administration.  
B). Toddler lead-in cohort  
The second lead-in cohort of 60 healthy toddlers at 12–15 months of age inclusive, will be 
enrolled and randomized to two equal groups. Each group will receive, in an observer-blind 
fashion, a single intramuscular injection of high dose sIPV containing 3, 100, and 100 DU of 
poliovirus types 1, 2, and 3, respectively (Day 1), or reference IPV. Polio vaccines previously 
received for primary immunization of these children will be recorded. Routine childhood 
vaccines other than poliovirus vaccine for booster immunization recommended for children at 
approximately 12 months of age according to the NPI (eg, measles-containing vaccine) are to be 
given at least 4 weeks apart from sIPV / reference IPV booster vaccination. NPI-recommended 
childhood vaccines other than poliomyelitis vaccine will be given outside the trial.  
Safety and tolerability will be assessed 7 and 28 days post IPV administration. In addition, a final 
safety contact is scheduled for six months post IPV administration.  
Individual titers pre and post booster vaccination will be assessed. Toddlers who receive sIPV 
and who have no neutralizing antibodies to any of the three poliovirus serotypes (titer <8) on 
Day 29 as well as those with no titer increase between Day 1 and Day 29 will be offered re-
vaccination with a single dose of the reference IPV (note: toddlers that have received bivalent 
OPV exclusively for primary immunization may not achieve seropositivity to poliovirus type 2. 
Therefore, subjects with documented primary immunization against serotypes 1 and 3 only who 
do not respond to serotype 2 post sIPV booster will not be offered re-vaccination). 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
51 of 104 
Protocol Version 2.0 
11 April 2017 
 
C). Infant dose ranging cohort 
A cohort of 240 healthy infants at 6 to 8 weeks of age, inclusive, with no previous history of 
poliomyelitis vaccination, will be enrolled and randomized to four equal groups. Each group will 
receive three vaccinations, at four week intervals, with one of the three different dosages of sIPV 
or the reference IPV, in an observer-blind fashion.  
Safety and tolerability will be assessed 7 and 28 days post each vaccination with a further safety 
contact scheduled for six months post sIPV / reference IPV administration (Day 183). 
Blood samples drawn before the first vaccination (Day 1) and 28 days after the second (Day 57) 
and third (Day 85) doses will be used to assess neutralization antibodies.  
All children will then receive a fourth (booster) dose of sIPV or reference IPV 12 months 
(Day 365) after their last primary series vaccination. 
Routine infant vaccines according to the NPI other than poliovirus vaccine for primary 
immunization and for booster vaccination are to be given according to national guidelines 
outside the trial. Inactivated / oral routine infant vaccines should be given on the same day as 
sIPV / reference IPV. Injectable live-attenuated vaccines (eg, measles-containing vaccine) should 
be given at least 4 weeks apart from sIPV / reference IPV. 
Safety and tolerability will be assessed for 7 and 28 days post booster vaccination with a further 
safety contact scheduled one year post sIPV / reference IPV administration (Day 547). 
Infants who receive sIPV and who have no neutralizing antibodies to any of the three poliovirus 
serotypes (titer <8) on Day 393 will be offered re-vaccination with a series of three 
immunizations of reference IPV after the unblinding occurs and serological results become 
available, and outside of the IPV-102 clinical trial. 
Blood samples drawn before (Day 365) and 28 days after booster vaccination (Day 393) will be 
used to assess neutralization antibodies.  
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
52 of 104 
Protocol Version 2.0 
11 April 2017 
 
Figure 6.a 
Schematic of Trial Design 
 
 
Day 29 safety & tolerability data assessment by Takeda safety team before proceeding with dose ranging cohort
Lead-in Arm 2 [control] – reference IPV (n = 30)
1:1
Day 29
Day 183
Visit
1
2
3
4
Day 8
Lead-in Arm 1 [‘H’] – sIPV D-Ag 3:100:100 (n = 30) 
60 toddlers
12 to15 months 
of age, inclusive
A) Lead-in, adults
1:1
Day 1
Visit
1
2
Day 8
40 adults
18-49 years 
of age, inclusive
Lead-in Arm 1 – [‘H’] – sIPV D-Ag 3:100:100 (n = 20)
Day 8 safety & tolerability data assessment by DMC before proceeding with toddler lead-in
Lead-in Arm 2 – [control] – placebo (n = 20)
B) Lead-in, toddlers
Day 1
240 infants
6 to 8 weeks of 
age, inclusive
Arm 1 [‘L’] - sIPV D-Ag 0.75:25:25 (n = 60)
Day 8
Primary immunizations
Arm 2 [‘M’] - sIPV D-Ag 1.5:50:50 (n = 60)
Arm 3 [‘H’] - sIPV D-Ag 3:100:100 (n = 60)
1:1:1:1
Day 57
Day 29
Day 1
Day 85
Day 365
Primary endpoint 
Day 393
Day 183
Visit
Booster immunization
C) Dose ranging, infants
Day 372
1 2
3 4
5 6
7
8
9 10
11
Day 547
12
Day 36
Day 64
Arm 4 [control] – reference IPV (n = 60)
= IPV vaccination
= pivotal endpoints analysis points
= safety & tolerability assessments
= blood draw
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
53 of 104 
Protocol Version 2.0 
11 April 2017 
6.2
Justification for Trial Design, Dose, and Endpoints 
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6.3 
Duration of Subject’s Expected Participation in the Entire Trial 
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6.4
Premature Termination or Suspension of Trial or Investigational Site 
6.4.1
Criteria for Premature Termination or Suspension of the Trial 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
54 of 104 
Protocol Version 2.0 
11 April 2017 
 
• New information or other evaluation regarding the safety or efficacy of the investigational 
vaccine that indicates a change in the known risk/benefit profile, such that the risk/benefit is 
no longer acceptable for subjects participating in the trial. 
• The DMC recommends that the trial should be suspended or terminated.  
• Significant deviation from Good Clinical Practice (GCP) that compromises the ability to 
achieve the primary trial objectives or compromises subject safety. 
6.4.2 Criteria for Premature Termination or Suspension of Investigational Sites 
A trial site may be terminated prematurely or suspended if the site (including the investigator) is 
found in significant deviation from GCP, protocol, or contractual agreement, is unable to ensure 
adequate performance of the trial, or as otherwise permitted by the contractual agreement. 
6.4.3 Procedures for Premature Termination or Suspension of the Trial or the 
Participation of Investigational Site(s) 
In the event that the sponsor, an institutional review board (IRB)/independent ethics committee 
(IEC) or regulatory authority elects to terminate or suspend the trial or the participation of an 
investigational site, a trial-specific procedure for early termination or suspension will be 
provided by the sponsor; the procedure will be followed by applicable investigational sites 
during the course of termination or trial suspension. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
55 of 104 
Protocol Version 2.0 
11 April 2017 
 
7.0 
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS 
All entry criteria, including test results, need to be confirmed prior to randomization.  
7.1 
Inclusion Criteria 
Subject eligibility is determined according to the following criteria: 
Adult Lead-in Cohort 
1. Male and female adults aged 18 to 49 years, inclusive, at the time of enrollment. 
2. Individuals who are in good health at the time of entry into the trial as determined by 
medical history, physical examination (including vital signs) and clinical judgment of the 
investigator.  
3. The subject signs and dates a written, informed consent form (ICF) and any required 
privacy authorization prior to the initiation of any trial procedures, after the nature of the 
trial has been explained according to local regulatory requirements (Appendix B).  
4. Individuals who can comply with trial procedures and are available for the duration of 
follow-up. 
5. Completed primary immunization against poliomyelitis according to local 
recommendations. 
Toddler Lead-in Cohort 
1. Male and female toddlers, aged 12 to 15 months, inclusive, at the time of enrollment. 
2. Toddlers in good health at the time of entry into the trial as determined by medical history, 
physical examination (including vital signs) and clinical judgment of the investigator.  
3. The toddler’s legally authorized representative (LAR) signs and dates a written ICF and any 
required privacy authorization prior to the initiation of any trial procedures, after the nature 
of the trial has been explained according to local regulatory requirements (Appendix B). 
4. Toddlers and their LAR can comply with trial procedures, are available for the duration of 
the trial, and a suitable telephone contact is available.  
5. Completed primary immunization against poliomyelitis, preferably with IPV, according to 
local recommendations. 
Infant Dose Ranging Cohort  
1. Male and female infants, aged 6 to 8 weeks (42–55 days, inclusive) at the time of 
enrollment. 
2. Infants are in good health at the time of entry into the trial as determined by medical 
history, physical examination (including vital signs) and clinical judgment of the 
investigator. 
3. Infants must have been born full term (37-42 weeks of gestation). 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
56 of 104 
Protocol Version 2.0 
11 April 2017 
 
4. The infant’s LAR signs and dates a written ICF and any required privacy authorization 
prior to the initiation of any trial procedures, after the nature of the trial has been explained 
according to local regulatory requirements (Appendix B). 
5. Infants and their LAR can comply with trial procedures, are available for the duration of 
follow-up, and a suitable telephone contact is available. 
7.2 
Exclusion Criteria 
Any subject who meets any of the following criteria will not qualify for entry into the trial: 
Adult Lead-in Cohort 
1. Individuals with body mass index (BMI) greater than or equal to 35 kg/m2 (= weight in kg / 
[height in meters * height in meters]. 
2. Individuals with history of substance or alcohol abuse within the past 2 years. 
3. Female subjects who are pregnant or breastfeeding. 
4. If female subject of childbearing potential, sexually active, and has not used any of the 
“acceptable contraceptive methods” for at least 2 months prior to trial entry: 
a) Of childbearing potential is defined as status post onset of menarche and not meeting 
any of the following conditions: menopausal for at least 2 years, status after bilateral 
tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after 
hysterectomy. 
b) Acceptable birth control methods are defined as one or more of the following: 
I.  
Hormonal contraceptive (such as oral, injection, transdermal patch, implant, 
cervical ring). 
II.  
Barrier (condom with spermicide or diaphragm with spermicide) each and every 
time during intercourse. 
III. 
Intrauterine device (IUD). 
IV. 
Monogamous relationship with vasectomized partner. Partner must have been 
vasectomized for at least 6 months prior to the subject’s trial entry. 
5. If female subject of childbearing potential and sexually active, refusal to use an “acceptable 
contraceptive method” through to 1 month after the last dose of trial vaccine. In addition, 
they must be advised not to donate ova during this period (Section 9.1.8). 
6. Any positive or indeterminate pregnancy test. 
Toddler Lead-in Cohort 
1. Last polio vaccination (either inactivated or oral) received within 5 months prior to first 
trial visit. 
2. Household member/sibling who had received or is/are scheduled to receive OPV in the 
previous 3 months until 5 weeks post subject's inclusion in the study. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
57 of 104 
Protocol Version 2.0 
11 April 2017 
 
3. Prior vaccination with booster dose of diphtheria, tetanus, pertussis (acellular or whole 
cell), polio (either inactivated or oral), or Haemophilus influenzae type b (Hib) vaccines. 
Infant Dose Ranging Cohort 
1. Infants with low birth weight according to local standards. 
2. Prior vaccination with polio vaccines (either inactivated or oral). 
3. Household member/sibling that had received or is/are scheduled to receive OPV in the 
previous 3 months until 5 weeks after the third dose of the primary immunization series. 
4. Prior vaccination with any diphtheria, tetanus, pertussis (acellular or whole cell), 
Haemophilus influenzae type b (Hib) vaccine or polio vaccine (OPV or IPV). Note, BCG at 
birth and prior vaccination with Hepatitis B vaccine given at least 4 weeks prior to first trial 
visit are not exclusion criteria. 
All Cohorts 
1. Known hypersensitivity or allergy to any of the vaccine components (including excipients) 
or standard infant vaccines, as summarized in Section 6.1. 
2. Any significant chronic infection. 
3. Any clinically significant active infection (as assessed by the investigator) or temperature 
≥38.0°C (>100.4°F), within 3 days of intended trial vaccination. 
4. Subjects who received any vaccine within 28 days prior to enrollment in this trial. 
5. Any serious chronic or progressive disease according to the judgment of the investigator 
(eg, cardiac, renal or hepatic disease). 
6. Individuals with history, eg, convulsions/febrile convulsions, or any illness, that, in the 
opinion of the investigator, might interfere with the results of the trial or pose additional 
risk to the subjects due to participation in the trial. 
7. Known or suspected impairment/alteration of immune function, including: 
a) Chronic use of oral steroids (equivalent to 20 mg/day prednisone for ≥12 
weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1 (use of 
inhaled, intranasal, or topical corticosteroids is allowed). 
b) Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg 
body weight/day for ≥2 weeks) within 60 days prior to Day 1. 
c) Administration of immunoglobulins and/or any blood or blood products within the 3 
months preceding the administration of the trial vaccine or planned administration during 
the trial (consider whether applicable as an exclusion criterion or criterion for delay, see 
Section 7.3). 
d) Receipt of immunostimulants within 60 days prior to Day 1. 
e) Genetic immunodeficiency. 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
58 of 104 
Protocol Version 2.0 
11 April 2017 
 
8. Individuals with a known bleeding diathesis, or any condition that may be associated with a 
prolonged bleeding time. 
9. Individuals participating in any clinical trial with another investigational product 30 days 
prior to first trial visit or intent to participate in another clinical trial at any time during the 
conduct of this trial. 
10. Individuals with first degree relatives involved in the trial conduct. 
There may be instances when individuals meet all entry criteria except one that relates to 
transient clinical circumstances (eg, temperature elevation or recent use of excluded medication). 
Under these circumstances, eligibility for trial enrollment may be considered if the appropriate 
window for delay has not passed, inclusion/exclusion criteria have been rechecked, and if the 
subject is confirmed to be eligible. 
7.3 
Criteria for Delay of Vaccination and/or Blood Sampling 
After enrollment, subjects may encounter clinical circumstances that warrant a delay in the 
administration of trial vaccination. These situations are listed below. In the event that a subject 
meets a criterion for delay of vaccination, the subject may receive trial vaccination once the 
window for delay has passed as long as the subject is otherwise eligible for trial participation.  
• Individuals with a clinically significant active infection (as assessed by the investigator) or 
temperature ≥ 38.0°C / 100.4°F, within 3 days of intended trial vaccination (consider whether 
applicable as a criterion for delay or as an exclusion criterion, see Section 7.2). 
• Individuals who have received blood, blood products and/or plasma derivatives or any 
parenteral immunoglobulin preparation within the past 3 months prior to any dose (consider 
whether applicable as a criterion for delay or as an exclusion criterion, see Section 7.2). 
• Individuals who received any other vaccines within 28 days prior to planned vaccination or 
blood sampling. 
• Individuals who have used antipyretics/analgesic medications within 24 hours prior to 
planned vaccine administration. 
If vaccinations cannot be given within the visit window as defined by the protocol, the subject 
may receive the vaccination outside the visit window. This will be considered as a protocol 
deviation. All subjects should receive all vaccinations necessary to fulfill the locally 
recommended NPI schedule. 
There are also circumstances under which receipt of further vaccines is a contraindication in this 
trial. These circumstances include anaphylaxis or severe hypersensitivity reactions following the 
initial vaccination. If these reactions occur, the subject must not receive additional vaccinations 
but is encouraged to continue in trial participation for safety reasons.  
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
59 of 104 
Protocol Version 2.0 
11 April 2017 
 
7.4 
Criteria for Early Study Termination of a Subject 
Under some circumstances, a subject’s trial participation may be terminated early. This means 
that no further trial procedures (including data collection) will be performed on that subject 
beyond the specific date of early termination. The primary reason for early termination of the 
subject from the trial should be recorded in the electronic case report form (eCRF “end of study 
visit” page) using the following categories. For screen failure subjects, refer to Section 9.1.10. 
1. Adverse Event: The subject has experienced an AE (irrespective of being related / unrelated 
to the Trial Vaccine or trial-related procedures) that requires early termination because 
continued participation imposes an unacceptable risk to the subject’s health and / or the 
subject is unwilling to continue participation because of the AE. If the subject (adult cohort) 
or the subject’s LAR (toddler and infant cohorts) is unwilling to continue because of the AE 
the primary reason for early termination in this case will be ‘withdrawal due to AE’ and not 
‘withdrawal of consent’, see below. Any ongoing AEs leading to early termination should be 
followed by the investigator until resolution or stabilization. 
2. Lost to follow-up: The subject did not return to the clinic and at least three attempts to 
contact the subject (adult cohort) or the subject’s LAR (toddler and infant cohorts) were 
unsuccessful. Attempts to contact the subject or the subject’s LAR must be documented. 
3. Withdrawal of consent: The subject (adult cohort) or the subject’s LAR (toddler and infant 
cohorts) wishes to withdraw from the trial. The primary reason for early termination will be 
‘withdrawal of consent” if the subject is withdrawn from participation due to a non-medical 
reason (ie, reason other than AE). The reason for withdrawal, if provided, should be recorded 
in the eCRF. 
Note: All attempts should be made to determine the underlying reason for the withdrawal 
and, where possible, the primary underlying reason should be recorded.  
4. Premature study termination by sponsor, a regulatory agency, the EC/IRB, or any other 
authority. 
If the clinical study is prematurely terminated by the sponsor, the investigator is to promptly 
inform the study subjects and local EC/IRB and should assure appropriate follow up for the 
subjects. The primary reason for early termination in this case will be ‘trial termination”. 
5. Subject’s death during trial participation. 
6. Other. 
Note: The specific reasons should be recorded in the “specify” field of the eCRF. 
7.5 
Criteria for Premature Discontinuation of Trial Vaccine Administration 
Early study termination of a subject will by default prevent the subject from continued Trial 
Vaccine administration, as the subject will no longer be participating in the study. In addition to 
early termination (see Section 7.4) criteria, other situations may apply in which subjects may 
continue participating in the trial (eg, contributing safety data according to protocol) but Trial 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
60 of 104 
Protocol Version 2.0 
11 April 2017 
 
Vaccine administration is discontinued selectively. Regardless of the reasons for discontinuation 
of Trial Vaccine administration, this must be documented as protocol deviation. Even if the 
subject is deemed ineligible to receive Trial Vaccine, all efforts should be made to continue the 
collection of safety data according to protocol. In addition, the one primary reason for premature 
discontinuation of Trial Vaccine application should be recorded in the electronic case report 
form (eCRF, “end of Trial Vaccine application” page) using the following categories. 
1.  Adverse Event: The subject has experienced an AE (irrespective of being related / unrelated 
to the Trial Vaccine or trial-related procedures) for which subsequent Trial Vaccine 
applications impose an unacceptable risk to the subject’s health, but the subject may continue 
trial participation for safety, or a subset of other study procedures.  
2. Lost to follow-up: The subject did not return to the clinic and at least three attempts to 
contact the subject were unsuccessful. Attempts to contact the subject must be documented. 
3. Withdrawal of consent: The subject (adult cohort) wishes to withdraw from the trial or the 
subject’s LAR (toddler and infant cohorts) wishes to withdraw the subject from the trial. The 
primary reason for early termination will be ‘withdrawal of consent” if the subject is 
withdrawn from participation due to a non-medical reason (ie, reason other than AE). The 
reason for withdrawal, if provided, should be recorded in the eCRF. 
4. Premature study termination by sponsor, a regulatory agency, the IEC/IRB, or any other 
authority. 
If the clinical study is prematurely terminated by the sponsor, the investigator is to promptly 
inform the study subjects and local IEC/IRB and should assure appropriate follow up for the 
subjects. The primary reason for early termination in this case will be ‘trial termination”. 
5. Subject´s death during trial participation. 
6. Protocol deviation: A protocol deviation is any change, divergence, or departure from the 
study design or procedures of a study protocol. The subject may remain in the trial unless 
continuation in the trial jeopardizes the subject’s health, safety or rights (see Section 7.4). 
7. Other. 
Note: The specific reasons should be recorded in the “specify” field of the eCRF. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
61 of 104 
Protocol Version 2.0 
11 April 2017 
8.0
CLINICAL TRIAL MATERIAL MANAGEMENT 
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Trial Vaccines and Materials 
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Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
62 of 104 
Protocol Version 2.0 
11 April 2017 
 
The Takeda sIPV single-dose vials will be supplied in a labeled, single-use vial and carton 
(0.5 mL) dose for intramuscular injection, preferably in the right limb. Each vial and carton will 
contain a label that includes pertinent trial information and caution statements. The label text will 
be in the specific country language, depending on local requirements. The vaccine to be used 
will be identifiable by a unique identification number and managed by the interactive response 
technology (IRT) system. 
The reference IPV will be presented in a blinded or open label carton. Should the primary 
container/packaging be open label, unblinded pharmacy and administration teams at the site will 
be required for dose preparation, administration and accountability. Each reference IPV and 
carton will contain a label. The label text, which includes pertinent trial information and caution 
statements, will be in the specific country language, depending on local requirements and will be 
included in the Pharmacy Manual and in the ICF for the toddler lead-in and infant dose-ranging 
cohorts. 
The placebo (saline control) will be 0.9% sodium chloride for injection without preservatives.  
Vaccination against D, T, P, HBV and Hib will be given as pentavalent combination vaccine 
(DTP-HBV-Hib). The pentavalent infant vaccine will be sourced as trial vaccine.  
All doses should be prepared at the time of administration by the unblinded administrator (and/or 
pharmacist) per the Pharmacy Manual. 
8.1.1.2 Routine Vaccines for Primary Immunizations and Booster Vaccinations 
NPI-recommended routine vaccines (other than poliomyelitis vaccine and pentavalent vaccine, 
see above) will be sourced locally by the site and administered in accordance with the approved 
package labeling. Additional injectable routine infant vaccines given concomitantly will be 
administered in a limb different from that of the sIPV / reference IPV vaccination. 
Refer to Section 8.4 for investigational vaccine blind maintenance. 
8.1.2 Storage 
Vaccine will be shipped in refrigerated containers. From receipt and prior to use, the vaccine 
must be stored at 2°C to 8°C in a refrigerator. 
All clinical trial material must be kept in an appropriate, limited-access, secure place until it is 
used or returned to the sponsor or designee for destruction. All sponsor-supplied vaccines must 
be stored under the conditions specified on the label, and remain in the original container until 
dispensed. A daily temperature log of the vaccine storage area must be maintained every 
working day. Temperature excursions must be reported to the sponsor as soon as possible and 
use of these vaccines requires sponsor approval. 
8.1.3 Dose and Regimen 
Each subject who meets all the inclusion criteria and none of the exclusion criteria will be 
randomly assigned to receive either sIPV or reference IPV/placebo via the IRT. In all parts of the 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
63 of 104 
Protocol Version 2.0 
11 April 2017 
 
study (adult lead-in, toddler lead-in and infant dose ranging), trial vaccines should be prepared 
by site personnel who are unblinded while maintaining the blind for other study personnel. 
Table 8.a describes the dose(s) that will be provided to each group. 
Table 8.a 
Sponsor-Supplied Vaccines and Reference 
Treatment 
Group 
Dose 
Treatment 
Description 
Timing 
Vaccine 
Dose 1(b) 
Dose 2(b) 
Dose 3(b) 
Dose 4 
A) Adult lead-in 
Arm 1 
High-dose(a) 
sIPV H 
Day 1 
- 
- 
- 
Arm 2 
Placebo 
Placebo 
Day 1 
- 
- 
- 
B) Toddler lead-in 
Arm 1 
High-dose(a) 
sIPV H 
Day 1 
- 
- 
- 
Arm 2 
Reference IPV 
IPV Reference 
Day 1 
- 
- 
- 
C) Infant dose ranging 
Arm 1 
Low-dose(a) 
sIPV L 
Day 1 
Day 29 
Day 57 
Day 365 
Arm 2 
Medium-dose(a) 
sIPV M 
Day 1 
Day 29 
Day 57 
Day 365 
Arm 3 
High-dose(a) 
sIPV H 
Day 1 
Day 29 
Day 57 
Day 365 
Arm 4 
Reference IPV 
IPV Reference 
Day 1 
Day 29 
Day 57 
Day 365 
(a) Low-dose = 0.75, 25, and 25 DU; Medium-dose = 1.5, 50, and 50 DU; High-dose = 3, 100, and 100 DU 
(b) Subjects will also receive DTP-HBV-Hib vaccine at the same visit; pentavalent vaccine will be administered in a 
limb different from that of the sIPV / reference IPV vaccination. 
8.2 
Trial Vaccine Assignment and Dispensing Procedures 
Each subject will be assigned a unique study number supplied by the sponsor. Subjects will be 
assigned to receive their treatment according to the schedule allocated to the study site. The 
investigator or investigator’s designee will access the IRT to obtain the subject number at 
screening. 
Vaccination will be performed by suitably qualified and authorized study personnel. Blinded 
personnel must not be present during dose preparation or at point of administration. An 
unblinded nurse or administrator will be required to administer the vaccines to the infants and 
toddlers. 
If sponsor-supplied vaccine is lost or damaged, the site can request a replacement via IRT (refer 
to IRT manual separately). Expired vaccines must not be administered. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
64 of 104 
Protocol Version 2.0 
11 April 2017 
 
PRECAUTIONS TO BE OBSERVED IN ADMINISTERING THE TRIAL VACCINE: 
Prior to vaccination, a subject must be determined to be eligible for trial vaccination and it must 
be clinically appropriate in the judgment of the investigator to vaccinate. Eligibility for 
vaccination prior to first trial vaccine administration is determined by evaluating the entry 
criteria outlined in this protocol (Sections 7.1 and 7.2). 
Eligibility for subsequent trial vaccination is determined by following the criteria outlined in 
Section 7.0. 
Trial vaccines should not be administered to individuals with known hypersensitivity to any 
component of the vaccines. 
Standard immunization practices are to be observed and care should be taken to administer the 
injection intramuscularly. In addition, WHO recommendations to reduce anxiety and pain at the 
time of vaccination should be followed [9]. Before administering the vaccine, the vaccination 
site is to be disinfected with a skin disinfectant (eg, 70% alcohol). Allow the skin to dry. DO 
NOT inject intravascularly. 
As with all injectable vaccines, trained medical personnel and appropriate medical treatment 
should be readily available in case of anaphylactic reactions following vaccination. For example, 
epinephrine 1:1000, diphenhydramine, and/or other medications for treating anaphylaxis should 
be available. 
8.3 
Randomization Code Creation and Storage 
Randomization personnel of the sponsor or designee will generate the randomization schedule 
for the adult lead-in, the toddler lead-in and the infant dose ranging cohorts. Randomization 
information will be stored in a secured area, accessible only by authorized personnel. At the 
Randomization Visit, all qualified subjects will be randomized to one of the 2 (adult and toddler 
lead-ins) or 4 (infant dose ranging) arms in a 1:1 or a 1:1:1:1 ratio, respectively, using IRT. 
8.4 
Trial Vaccine Blind Maintenance 
This trial is an observer-blind study. The subjects, data collectors (eg investigator), and data 
evaluators (eg trial statisticians) are blinded to the material administered. The investigational 
product assignment will be maintained by the unblinded site staff designee. 
All care must be taken to ensure that the unblinded reports and documents are shared only with 
unblinded personnel and properly stored in a secured area, accessible only by authorized 
personnel. 
8.5 
Unblinding Procedure 
The trial vaccine blind shall not be broken by the investigator unless information concerning the 
trial vaccine is necessary for the medical treatment of the subject. In the event of a medical 
emergency, if possible, the medical monitor should be contacted before the trial vaccine blind is 
broken to discuss the need for unblinding. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
65 of 104 
Protocol Version 2.0 
11 April 2017 
 
For unblinding a subject, the trial vaccine blind can be obtained by the investigator, by accessing 
the IRT. The sponsor’s Pharmacovigilance Department must be notified as soon as possible if 
the trial vaccine blind is broken by the investigator and the completed SAE form must be sent 
within 24 hours. The date, time, and reason the blind is broken must be recorded in the source 
document and the same information (except the time) must be recorded on the eCRF. 
If any subject is unblinded, the subject must be withdrawn from the trial, and their data no longer 
evaluated. However, further doses of vaccine are to be administered to ensure completion of the 
NPI-recommended schedule, and they should be monitored for safety parameters. 
8.6 
Accountability and Destruction of Sponsor-Supplied Vaccines 
Vaccine supplies will be counted and reconciled at the site before being returned to the sponsor 
or designee as noted below. Sites will maintain source documents in addition to entering data in 
the IRT. 
The investigator or designee must ensure that the sponsor-supplied vaccine is used in accordance 
with the approved protocol and is administered only to subjects enrolled in the trial. To 
document appropriate use of sponsor-supplied vaccines (sIPV, reference IPV, placebo and DTP-
HBV-Hib), the investigator must maintain records of all sponsor-supplied vaccine delivery to the 
site, site inventory, administration and use by each subject, and return to the sponsor or designee. 
Upon receipt of sponsor-supplied vaccine(s), the investigator or designee must verify the 
contents of the shipments against the packing list. The verifier should ensure that the quantity is 
correct, the trial vaccine is received within the labeled storage conditions (ie, no cold chain break 
has occurred during transit), and is in good condition. If quantity and conditions are acceptable, 
investigator or designee will acknowledge receipt of the shipment. 
If there are any discrepancies between the packing list versus the actual product received, the 
sponsor or designee must be contacted to resolve the issue. The packing list should be filed in the 
investigator’s essential document file. 
The investigator must maintain 100% accountability for all sponsor-supplied vaccines [including 
challenge agents, ancillary materials, as applicable] received and administered during their entire 
participation in the trial. Proper vaccine accountability includes, but is not limited to: 
• Verifying that actual inventory matches documented inventory. 
• Verifying that the log is completed for the vaccine lot (or Vaccine Med ID or job number) 
used to prepare each dose. 
• Verifying that all containers used are documented accurately on the log. 
• Verifying that required fields are completed accurately and legibly. 
If any dispensing errors or discrepancies are discovered, the sponsor must be notified 
immediately. 
The investigator must record the current inventory of all sponsor-supplied vaccines (sIPV, 
reference IPV, placebo and DTP-HBV-Hib) on a sponsor-approved vaccine accountability log. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
66 of 104 
Protocol Version 2.0 
11 April 2017 
 
The following information will be recorded at a minimum: protocol number and title, name of 
investigator, site identifier and number, description of sponsor-supplied vaccines, expiry date and 
amount. The IRT should include all required information as a separate entry for each subject to 
whom sponsor-supplied vaccine is administered. 
Prior to site closure or at appropriate intervals throughout the trial, before any clinical trial 
materials are returned to the sponsor or its designee for destruction, a representative from the 
sponsor or its designee will perform clinical trial material accountability and reconciliation. The 
investigator will retain a copy of the documentation regarding clinical trial material 
accountability, return, and/or destruction, and originals will be sent to the sponsor or designee. 
The pharmacist (or designated individual) at each site will be responsible for vaccine 
accountability and will document receipt, use, return, or destruction of trial vaccines. Vaccine 
accountability documentation will be reviewed by the unblinded monitor during clinical 
monitoring visits. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
67 of 104 
Protocol Version 2.0 
11 April 2017 
 
9.0 
TRIAL PLAN 
9.1 
Trial Procedures 
The following sections describe the trial procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same investigator or site personnel whenever possible. The 
Schedule of Trial Procedures is located in Section 0. 
9.1.1 Informed Consent Form 
The requirements of the informed consent form are described in Section 15.2. 
Informed consent from the subject or the subject's LAR must be obtained prior to the subject 
entering into the trial, and before any protocol-directed procedures are performed. 
A unique subject number will be assigned to each subject after informed consent is obtained 
from the IRT. If all eligibility criteria are fulfilled, this subject number will be used throughout 
the trial. Subject numbers assigned to subjects who fail screening should not be reused (Section 
9.1.10). 
9.1.2 Demographics, Medical History and Prior Medications 
Demographic information to be obtained will include date of birth, sex, and race as described by 
the subject or the subject’s LAR. 
Medical History will also be collected, including but not limited to any medical history that may 
be relevant to subject eligibility for trial participation such as gestational age and birth weight 
(for infants in the dose ranging cohort only), prior vaccinations, concomitant medications, and 
previous and ongoing illnesses or injuries. Relevant medical history can also include any medical 
history that contributes to the understanding of an AE that occurs during trial participation, if it 
represents an exacerbation of an underlying disease/preexisting problem. 
All medications, vaccines and blood products taken or received by the subjects within: 
a) Medications: 4 weeks prior to the start of the trial 
b) Vaccines: 4 weeks prior to the start of the lead-in study. Infants in the dose ranging study 
should only have received any routine vaccines recommended by the NPI at birth. 
Information on previous polio vaccinations should be collected for toddlers in the lead-in 
cohort. 
c) Blood products: 4 weeks prior to the start of the trial 
are to be recorded on the Prior and Concomitant Medications eCRF. The use of antipyretics 
and/or analgesic medications within 24 hours prior to vaccination must be identified and the 
reason for their use (prophylaxis versus treatment) must be described in the source documents or 
the eCRF. Trial vaccination should be delayed if subjects have used antipyretics/analgesic 
medications within 24 hours prior to vaccine administration. 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Stand-alone Trivalent Sabin Inactivated Polio Vaccine 
 
Trial No. IPV-102 
68 of 104 
Protocol Version 2.0 
11 April 2017 
 
Medications taken for prophylaxis are those intended to prevent the onset of AEs following 
vaccination. Medications taken for treatment are intended to reduce or eliminate the presence of 
symptoms that are present. 
Assess and record concomitant therapy (prescription medications ONLY) and vaccine history 
from 1 month prior to Day 1 in the subject’s source document. 
Prohibited Therapies: Refer to Section 7.2. 
These data must be written in the source documents. 
Medical history (including corresponding medication) to be obtained will include any significant 
conditions or diseases that have disappeared or resolved at or prior to signing of informed 
consent form. 
9.1.3 Documentation of Trial Entrance/Randomization 
Only subjects who have a signed informed consent form, meet all of the inclusion criteria and 
none of the exclusion criteria are eligible for entrance/randomization into the vaccination phase. 
The randomization schedule will be created and processed by the IRT provider. The 
randomization specification will be approved by the sponsor's trial statistician, or designee. 
If the subject is found to be ineligible for randomization/trial phase, the investigator should 
record the primary reason for failure on the subject enrollment log. 
9.1.4 Physical Examination 
Physical examinations must be performed by a qualified health professional in accordance with 
local regulations and licensing requirements designated within the Site Responsibility Delegation 
Log. Complete physical exam will be performed on Day 1 according to the investigator’s 
standard practice. Additional physical examinations may be performed if indicated by review of 
the subject’s medical history. The findings should be documented in the subject’s source 
document. 
Symptom-directed physical examination may be performed if deemed necessary. 
9.1.5 Vital Signs 
Vital signs to be measured in this study are respiratory and heart rates, and temperature 
(preferably measured as oral temperature for the adult cohort and rectal temperature for the 
toddler and infant cohorts).  
For the adult lead-in cohort, height and weight are measured at enrollment only; for the toddler 
lead-in cohort, height and weight are measured at enrollment and at the last study visit. For the 
infant dose ranging cohort, height and weight are measured at each visit. 
9.1.6 Immunogenicity Assessments 
Subjects in the toddler lead-in and the infant dose ranging cohorts (all vaccine arms) will 
undergo blood sampling for serological immunogenicity testing before their first primary 
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vaccination and 28 days after their second and third primary vaccination in the infant dose 
ranging cohort, and before and 28 days after booster vaccination in the infant dose ranging and 
toddler lead-in cohorts. All samples will be collected in accordance with acceptable laboratory 
procedures. The maximum volume of blood taken at any single visit is approximately 5 mL, and 
the approximate total volume of blood for the trial is maximum 10 mL for toddlers in the lead-in 
cohort and 25 mL for infants in the dose ranging cohort. Blood samples will be processed and 
stored at the trial site in accordance with the Laboratory Guidelines. 
9.1.7 Safety Assessments 
Safety assessments will include collection and recording of solicited local (injection site) and 
systemic AEs, and unsolicited AEs (serious and non-serious). Refer to Section 10.1 for safety 
definitions. Details on collection and reporting of AEs are in Section 10.5. 
9.1.8 Contraception and Pregnancy Avoidance Procedure 
For female subjects of childbearing potential, pregnancy testing will be performed on Day 1 
prior to enrollment. Subjects will be provided with information on acceptable methods of 
contraception as part of the subject informed consent process and will be asked to sign a consent 
form stating that they understand the requirements for avoidance of pregnancy and donation of 
ova. Women of childbearing potential will receive guidance with respect to the avoidance of 
pregnancy as part of the trial procedures (Section 2.1). 
9.1.9 Pregnancy 
Adult lead-in cohort 
To ensure subject safety and the safety of the unborn child, each pregnancy in a subject having 
received a trial vaccine must be reported to the sponsor within 24 hours of the site learning of its 
occurrence. The pregnancy must be followed to determine outcome, including spontaneous or 
voluntary termination, details of birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications. This follow-up should 
occur even if the intended duration of safety follow-up for the trial has ended. 
Any pregnancy occurring following trial vaccine administration should be reported immediately, 
using a pregnancy notification form, to the contact listed in the Investigator Site File. 
Should a pregnancy occur after the administration of a blinded trial vaccine, the investigator 
must inform the subject of their right to receive treatment information. If the subject chooses to 
receive unblinded treatment information, the individual blind should be broken by the 
investigator and procedures must be followed as described in Section 8.5. 
9.1.10 Documentation of Subjects who are not Randomized 
Investigators must account for all subjects who have a signed informed consent form. If the 
subject is found to be not eligible at this visit, the investigator should complete the eCRF. The 
IRT supplier should be contacted as a notification of non-randomization. 
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The primary reason for non-randomization is recorded in the eCRF using the following 
categories: 
• Screen failure (did not meet one or more inclusion criteria or did meet one or more exclusion 
criteria), 
• Withdrawal by the subject or the subject’s LAR,  
• Trial terminated by sponsor. 
Subject numbers assigned to subjects who fail screening should not be reused. 
9.2 
Monitoring Subject Treatment Compliance 
The investigator records all injections of trial vaccine given to the subject in the eCRF. 
9.3 
Schedule of Observations and Procedures 
The schedule for all trial-related procedures for all evaluations is shown in Section 2.1. 
Assessments should be completed at the designated visit/time point(s). 
9.3.1 Pre-Vaccination Procedures (Day 1) 
1. Confirm informed consent and complete signing of informed consent form. 
2. Demographics. 
3. Prior and concomitant medication. This should include the vaccines that will be 
concomitantly administered with the trial vaccine at this visit. 
4. Medical history. 
5.  Physical examination. 
6. Vital signs.  
7. Review of eligibility criteria. 
8. Enrollment/randomization. 
9. Blood sampling for toddler lead-in and infant dose ranging cohorts. Blood should be taken 
from the subject in the infant cohort using an aseptic venipuncture technique for serological 
immunogenicity testing.  
9.3.2 Pre-Vaccination Procedures (Days 29, 57 and 365) 
Temperature will be taken pre-vaccination and in case of fever a delay of vaccination should be 
considered (see Section 7.3). Symptom-directed physical examination is to be performed in case 
of symptoms prior to each vaccination. Concomitant medication, including the vaccines that will 
be concomitantly administered with the trial vaccine at the visit, should be recorded.  
Blood sampling should be taken for subjects in the infant dose ranging cohort; blood sampling 
will be performed before vaccination on Day 57 and Day 365. 
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9.3.3 Vaccination Procedures (Days 1, 29, 57 and 365) 
After confirming eligibility and enrolling the subject (on Day 1), perform vaccination according 
to the assigned trial vaccine in all cohorts and according to the procedures described in Section 
8.2. At later clinic visits in the infant dose ranging cohort that involve vaccination (Days 29, 57 
and 365), confirm that the subject does not meet any criteria for delaying or cancelling additional 
trial vaccination, as described in Section 7.3.  
9.3.4 Post Vaccination procedures (Days 1, 29, 57 and 365) 
The following post-vaccination procedures will be performed on Day 1: 
• Careful training of the subject (adult cohort) or subject’s LAR (toddler and infant cohorts) on 
how to measure local AEs and body temperature, how to complete the diary card and how 
often to complete the diary card. Training should be directed at the individual(s) who will 
perform the measurements of local AEs and those who will enter the information into the 
diary card. In the toddler and infant cohorts, this individual may or may not be the subject’s 
LAR, but if a person other than the subject’s LAR enters information into the diary card, this 
person’s identity must be documented in the trial file and this person must receive training on 
the diary card. Training of the subject (adult cohort) or subject’s LAR (toddler and infant 
cohorts) on how to measure an injection site AE should be performed while the subject is 
under observation after vaccination. 
Diary card instructions must include the following: 
• The subject (adult cohort) or subject’s LAR (toddler and infant cohorts) must understand that 
timely completion of the diary card on a daily basis is a critical component of trial 
participation. The subject or subject’s LAR should also be instructed to write clearly and to 
complete the diary card in pen. Any corrections to the diary card that are performed by the 
person completing the diary card should include a single strikethrough line with a brief 
explanation for any change and be initialed and dated. 
Please note: 
Diary cards will be the only source document allowed for remote collection of solicited local and 
systemic AEs (including body temperature measurements). The following additional rules apply 
to the documentation of safety information collected by diary card: 
• The diary card should be reviewed with the subject (adult cohort) or subject’s LAR (toddler 
and infant cohorts). 
• No corrections or additions to the diary card will be allowed after it is reviewed with the 
investigator/designee. 
• Any data that is identified as implausible or incorrect, and confirmed by the subject (adult 
cohort) or subject’s LAR (toddler and infant cohorts) to be a transcription error should be 
corrected by the subject or subject’s LAR on the diary card (the correction should include a 
single strikethrough line and should be initialed and dated by the subject or subject’s LAR). 
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• Any blank or illegible fields on the diary card not otherwise corrected as above will be 
missing in the eCRF. 
• The site must enter all readable entries on the diary card into the eCRF. 
• Any newly described solicited safety information should be added to the diary card by the 
subject (adult cohort) or subject’s LAR (toddler and infant cohorts) and initialed and dated. 
Any new unsolicited safety information would be recorded in the subject source document as 
a verbally reported event and therefore captured as an AE and recorded in the eCRF. 
• Starting on the day of vaccination, the subject (adult cohort) or subject’s LAR (toddler and 
infant cohorts) will check for specific types of events at the injection site (solicited local 
AEs), any specific generalized symptoms (solicited systemic AEs), body temperature (any 
method), any other symptoms or change in the subject’s health status, and any medications 
taken (excluding vitamins and minerals). These solicited AEs and body temperature will be 
recorded in the diary. Assessments should preferably take place in the evening at day’s end. 
• Temperature measurement (preferrably by the oral route for the adult cohort and by the rectal 
route for the toddler and infant cohorts) is to be performed using the thermometer provided 
by the site. If the subject feels unusually hot or cold during the day, the subject or subject’s 
LAR should check their temperature. If the subject has fever, the highest body temperature 
observed that day should be recorded on the diary card. 
• The measurement of solicited local AEs (erythema, swelling, and induration) is to be 
performed using the ruler provided by the site. 
• The collection on the diary card of body temperature, solicited local AEs, and solicited 
systemic AEs will continue for a total of 7 days following vaccine administration. The 
collection on the diary card of unsolicited AEs and medications will continue for 28 days 
following vaccine administration by Diary Card. 
After vaccination, the subject will be observed for at least 30 minutes including observation for 
immediate reactions and body temperature measurement. Information should be recorded in the 
eCRF as immediate reactions. The investigator or delegate will take the opportunity to remind 
the subject (adult cohort) or subject’s LAR (toddler and infant cohorts) how to measure solicited 
AEs and body temperature as part of this observation period. All safety data will be collected in 
the subject’s source documents. 
The site should schedule the next trial activity with the subject (adult cohort) or subject’s LAR 
(toddler and infant cohorts). 
The subject (adult cohort) or subject’s LAR (toddler and infant cohorts) will receive a written 
reminder of the next planned trial activity. The subject or subject’s LAR will be reminded to 
complete the Diary Card daily and to contact the site if there are any questions and to contact the 
site immediately (or as soon as the subject is medically stable) if the subject has a medical 
condition that leads to a hospitalization or an emergency room visit. All contact details will be 
provided to the subject or subject's LAR. 
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9.3.5 Clinic Visits after Vaccination (Day 8 in the adult lead-in cohort, Day 29 in the 
toddler lead-in cohort and Days 85 and 393 in the infant dose ranging cohort) 
Clinic visits that do NOT include a vaccination will be performed on Day 8 in the adult lead-in 
cohort, Day 29 in the toddler lead-in cohort, and Days 85 and 393 in the infant dose ranging 
cohort. At the clinic visit, the Diary Card will be reviewed. The healthcare professional 
reviewing these data will discuss the AEs (if any) reported by the subject or subject’s LAR and 
will determine if any additional diagnoses and/or AEs are present and/or concomitant 
medications have been used. 
The site should schedule the next trial activity with the subject’s LAR for all subjects in the 
toddler lead-in and infant dose ranging cohorts. 
The subject’s LAR will receive a written reminder of the next planned trial activity. The 
subject’s LAR will be reminded to contact the site if there are any questions and to contact the 
site immediately (or as soon as the subject is medically stable) if the subject has a medical 
condition that leads to a hospitalization or an emergency room visit. 
9.3.6 Phone Contacts - Reminder Calls (Days 8, 36, 64 and 372) 
Post-vaccination reminder phone calls will be performed 7 days after each vaccination (Day 8 in 
the toddler lead-in cohort, Days 8, 36, 64 and 372 in the infant dose ranging cohort). The purpose 
is to remind the subject’s LAR about completion of the diary card. If the subject’s LAR wishes 
to describe safety information, this information should only be collected by a trained healthcare 
professional at the site, and the safety data described must be written down in source documents. 
The subject’s LAR should be reminded to write the information down in the diary card and to 
contact the site via the telephone number provided in the informed consent form to discuss 
medical questions. 
9.3.7 Phone Contacts – Safety Call (Days 183 and 547) 
A safety call will be performed on Day 183 in both the toddler lead-in and infant dose ranging 
cohorts, and additionally on Day 547 in the infant dose ranging cohort. Safety calls are calls 
made to the subject or subject’s LAR by a trained healthcare provider. The subject or subject’s 
LAR will be interviewed according to a script, and information relating to SAEs and/or AEs 
leading to trial or vaccine withdrawal and concomitant medications or vaccinations associated 
with those events will be collected. All safety information described by the subject or subject’s 
LAR must be written down in a designated location within the source documents and not written 
on the script used for the telephone call.  
The site should schedule the next clinic visit with the subject’s LAR, as appropriate.  
The subject’s LAR will be reminded to contact the site if there are any questions and to contact 
the site immediately (or as soon as the subject is medically stable) if the subject has a medical 
condition that leads to a hospitalization or an emergency room visit.  
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For subjects in the adult lead-in cohort, the investigator should inform and educate the subject 
that any adverse medical occurrence being perceived as serious up to 6 months after vaccination 
should be reported (passive follow up for safety).  
9.3.8 Final (End of Trial) Visit 
Adult lead-in cohort 
The Final Study Visit will be on Day 8. For all subjects, the investigator must complete the End 
of Trial eCRF page. 
Toddler lead-in cohort 
The Final Site Visit will be on Day 29, but the Final Study Visit is a telephone call on Day 183. 
If a subject terminates earlier, end of trial visit procedures should be performed if possible. For 
all subjects, the investigator must complete the End of Trial eCRF page. 
Infant dose ranging cohort 
The Final Study Visit will be performed on Day 393. If a subject terminates earlier, end of trial 
visit procedures should be performed if possible. For all subjects, the investigator must complete 
the End of Trial eCRF page. 
9.3.9 Post-Trial Care 
No post-trial care will be provided, except to ensure that all subjects in the toddler lead-in and 
infant dose ranging cohorts receive their complete number of polio vaccine doses as 
recommended by the NPI, and that toddlers from both the lead-in cohort and the dose ranging 
cohort (after their booster dose) who received the trial sIPV vaccine are seropositive or have 
demonstrated a vaccine response which shows seroprotection. Toddlers from the lead-in cohort 
who do not meet these criteria will be offered a single dose of the reference IPV (note: toddlers 
that have received bivalent OPV exclusively for primary immunization may not achieve 
seropositivity to poliovirus type 2. Therefore, subjects with documented primary immunization 
against serotypes 1 and 3 only who do not respond to serotype 2 post sIPV booster will not be 
offered re-vaccination). Toddlers in the dose ranging cohort, who received sIPV as infants in 
their primary series and their toddler booster dose, and who have no neutralizing antibodies to 
any of the three poliovirus serotypes (titer <8) on Day 393 will be offered re-vaccination with a 
single series of three immunizations of the reference IPV after the unblinding occurs and 
serological results become available, and outside of the IPV-102 clinical trial. 
9.4 
Biological Sample Retention and Destruction 
In this trial, specimens for immune response testing will be collected for subjects enrolled in the 
toddler lead-in and infant dose ranging cohorts as described in Section 9.1.6. After blood draw 
and serum processing, the serum samples will be preserved and retained at a central laboratory 
that was contracted by the sponsor for this purpose for up to but not longer than 20 years or as 
required by applicable law. The sponsor has put into place a system to protect the subjects’ 
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personal information to ensure optimal confidentiality and defined standard processes for sample 
and data collection, storage, analysis, and destruction. 
Serum samples will be used for the analyses defined in this protocol, but can also, with 
permission from the subject’s LAR, be used to assess, improve or develop tests related to the 
disease(s) or the vaccine(s) under trial that will allow more reliable measurement of the response 
to the vaccine(s). 
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10.0 
ADVERSE EVENTS 
10.1 
Definitions 
10.1.1 Adverse Events (AEs) 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a trial vaccine; it does not necessarily have to have a causal relationship with trial 
vaccine administration. 
An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant 
abnormal laboratory finding), symptom, or disease temporally associated with the administration 
of a trial vaccine whether or not it is considered related to the trial vaccine. 
AEs will be graded by the investigator in the following manner: 
Mild 
Grade 1 
• 
Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities. Relieved with or without symptomatic treatment. 
Moderate 
Grade 2 
• 
Sufficient discomfort is present to cause interference with normal activity. Only 
partially relieved with symptomatic treatment. 
Severe 
Grade 3 
• 
Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities. Not relieved with symptomatic treatment 
10.1.2 Solicited Adverse Events 
The occurrence of selected indicators of safety (Table 10.a) will be measured/collected for the 
7 days after vaccination (including the day of vaccination) and will be recorded on the “Local 
and Systemic AEs” eCRF as applicable. These will be summarized in the final report under the 
category “solicited adverse events” to differentiate them from other AEs which were not 
solicited. Any solicited local or systemic AE observed as continuing on Trial Day 8 will be 
recorded as an AE on the Adverse Event eCRF.  
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Table 10.a 
Local and Systemic AEs  
Local AEs (injection site): 
Pain 
Erythema 
Induration 
Swelling 
Systemic AEs (adult lead-in cohort): 
Fever(a) 
Headache 
Asthenia 
Malaise 
Arthralgia 
Myalgia 
Systemic AEs (toddler lead-in and infant dose ranging cohorts): 
Drowsiness 
Irritability/fussiness 
Loss of appetite 
Fever(a) 
(a) Body temperature will be collected and recorded. Fever is defined as greater than or equal to 38°C (100.4°F) 
regardless of method used [10]. 
The intensity of solicited safety parameters will be assessed as described in Table 10.b (adult 
cohort) and Table 10.c (toddler and infant cohorts). 
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Table 10.b 
Solicited Safety Parameters - Adult Lead-In Cohort 
Adverse Event 
Intensity grade 
Severity/Intensity 
Pain at injection site 
0 
None 
1 
Mild: No interference with daily activity 
2 
Moderate: Interference with daily activity with or without treatment 
3 
Severe: Prevents daily activity with or without treatment 
Erythema at injection 
site (a) 
0 
<25 mm 
1 
Mild: >25 – ≤ 50 mm 
2 
Moderate: > 50 – ≤ 100 mm 
3 
Severe: > 100 mm 
Induration at injection 
site (a) 
0 
<25 mm 
1 
Mild: >25 – ≤ 50 mm 
2 
Moderate: > 50 – ≤ 100 mm 
3 
Severe: > 100 mm 
Swelling at injection 
site (a) 
0 
<25 mm 
1 
Mild: >25 – ≤ 50 mm  
2 
Moderate: > 50 – ≤ 100 mm 
3 
Severe: > 100 mm 
Headache 
0 
None 
1 
Mild: No interference with daily activity 
2 
Moderate: Interference with daily activity with or without treatment 
3 
Severe: Prevents normal activity with or without treatment 
Asthenia 
0 
None 
1 
Mild: No interference with daily activity 
2 
Moderate: Interference with daily activity 
3 
Severe: Prevents daily activity 
Malaise  
0 
None 
1 
Mild: No interference with daily activity 
2 
Moderate: Interference with daily activity 
3 
Severe: Prevents daily activity 
Arthralgia 
1 
None 
2 
Mild: No interference with daily activity 
3 
Moderate: Interference with daily activity 
4 
Severe: Prevents daily activity 
Myalgia 
0 
None 
1 
Mild: No interference with daily activity 
2 
Moderate: Interference with daily activity 
3 
Severe: Prevents daily activity 
Fever(b) 
Record body temperature in °C/°F 
(a) Subjects are to record greatest surface diameter in mm in the Diary. 
(b) Fever is defined as greater than or equal to 38°C (100.4°F) regardless of method taken. 
 
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Table 10.c 
Solicited Safety Parameters - Toddler Lead-In Cohort and Infant Dose 
Ranging Cohort 
Adverse Event 
Intensity 
grade 
Severity/Intensity 
Pain at injection site 
0 
None 
1 
Mild: Minor reaction to touch 
2 
Moderate: Cries/protests on touch 
3 
Severe: Cries when limb is moved/spontaneously painful 
Erythema at injection site (a) 
0 
<10 mm 
1 
Mild: >10 – ≤ 20 mm 
2 
Moderate: > 20 – ≤ 40 mm 
3 
Severe: > 40 mm 
Induration at injection site (a) 
0 
<10 mm 
1 
Mild: >10 – ≤ 20 mm 
2 
Moderate: > 20 – ≤ 40 mm 
3 
Severe: > 40 mm 
Swelling at injection site (a) 
0 
<10 mm 
1 
Mild: >10 – ≤ 20 mm  
2 
Moderate: > 20 – ≤ 40 mm 
3 
Severe: > 40 mm 
Drowsiness 
0 
Behavior as usual 
1 
Mild: Drowsiness easily tolerated 
2 
Moderate: Drowsiness that interferes with normal activity 
3 
Severe: Drowsiness that prevents normal activity 
Irritability/fussiness 
0 
Behavior as usual 
1 
Mild: Crying more than usual/no effect on normal activity 
2 
Moderate: Crying more than usual/interferes with normal 
activity 
3 
Severe: Crying that cannot be comforted/prevents normal 
activity 
Loss of appetite 
0 
Appetite as usual 
1 
Mild: Eating less than usual/no effect on normal activity 
2 
Moderate: Eating less than usual/interferes with normal 
activity 
3 
Severe: Not eating at all 
Fever(b) 
Record body temperature in °C/°F 
(a) Subject's LARs are to record greatest surface diameter in mm in the Diary. 
(b) Fever is defined as greater than or equal to 38°C (100.4°F) regardless of method taken. 
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10.1.3 Serious Adverse Events (SAEs) 
An SAE is defined as any untoward medical occurrence that: 
1. Results in DEATH. 
2. Is LIFE THREATENING. 
• The term “life threatening” refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event that hypothetically might have caused 
death if it were more severe. 
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization. 
4. Results in persistent or significant DISABILITY/INCAPACITY. 
5. Is an IMPORTANT MEDICAL EVENT that satisfies any of the following: 
• May require intervention to prevent items 1 through 4 above. 
• May expose the subject to danger, even though the event is not immediately life 
threatening or fatal or does not result in hospitalization. 
10.2 
Causality of AEs 
Relatedness (causality) to vaccine will also be assessed by the investigator. The relationship of 
each AE, including solicited systemic AEs (solicited local AEs are considered as related) to trial 
vaccine(s) will be assessed using the following categories: 
Related: 
There is suspicion that there is a relationship between the trial vaccine and 
the AE (without determining the extent of probability); there is a reasonable 
possibility that the trial vaccine contributed to the AE. 
Not Related: 
There is no suspicion that there is a relationship between the trial vaccine 
and the AE; there are other more likely causes and administration of the trial 
vaccine is not suspected to have contributed to the AE. 
10.2.1 Relationship to Trial Procedures 
Relationship (causality) to trial procedures should be determined for all AEs. 
The relationship should be assessed as “Yes” if the investigator considers that there is reasonable 
possibility that an event is due to a trial procedure. Otherwise, the relationship should be 
assessed as “No”. 
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10.2.2 Outcome of AEs 
Resolved: 
The subject has fully recovered from the event or the condition has 
returned to the level observed at baseline 
Resolving: 
The event is improving but the subject is still not fully recovered 
Not resolved: 
The event is ongoing at the time of reporting and the subject has still 
not recovered 
Resolved with 
sequelae: 
As a result of the AE, the subject suffered persistent and significant 
disability/incapacity (eg, became blind, deaf or paralysed) 
Fatal: 
The subject died due to the event. If the subject died due to other 
circumstances than the event, the outcome of the event per se should 
be stated otherwise (eg, Not Resolved or Resolving) 
Unknown: 
If outcome is not known or not reported. 
10.3 
Additional Points to Consider for AEs 
An untoward occurrence generally may: 
• Indicate a new diagnosis or unexpected worsening of a pre-existing condition. Intermittent 
events for pre-existing conditions or underlying disease should not be considered as AEs. 
• Necessitate therapeutic intervention. 
• Require an invasive diagnostic procedure. 
• Require vaccine discontinuation or a change in concomitant medication. 
• Be considered unfavorable by the investigator for any reason. 
Diagnoses vs. signs and symptoms: 
• Each event should be recorded to represent a single diagnosis. Accompanying signs 
(including abnormal laboratory values) or symptoms should NOT be recorded as additional 
AEs. If a diagnosis is unknown, signs or symptoms should be recorded appropriately as AEs. 
Worsening of AEs: 
• If the subject experiences a worsening or complication of an AE after starting administration 
of the trial vaccine, the worsening or complication should be recorded as a new AE. 
Investigators should ensure that the AE term recorded captures the change in the condition 
(eg, “worsening of…”). 
• If the subject experiences a worsening or complication of an AE after any change in trial 
vaccine, the worsening or complication should be recorded as a new AE. Investigators should 
ensure that the AE term recorded captures the change in the condition (eg, “worsening 
of…”). 
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Changes in severity of AEs: 
• If the subject experiences changes in severity of an AE, the event should be captured once 
with the maximum severity recorded. 
Preplanned surgeries or procedures: 
• Preplanned procedures (surgeries or therapies) that were scheduled prior to signing of 
informed consent form are not considered AEs. Complications resulting from any planned 
surgery should be reported as AEs. 
Elective surgeries or procedures: 
• Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as AEs, but should be documented in the subject’s source documents. 
Complications resulting from an elective surgery should be reported as AEs. 
10.4 
Procedures 
10.4.1 Collection and Reporting of AEs 
All AEs, whether considered related with the use of the trial vaccine or not, must be monitored 
until symptoms subside and any abnormal laboratory values have returned to baseline, or until 
there is a satisfactory explanation for the changes observed, or until death, in which case a full 
pathologist’s report should be supplied, if possible. All findings must be reported on an AE 
eCRF and on the SAE form, if necessary (see Section 10.4.2). All findings in subjects 
experiencing AEs must also be reported in the subject’s source documents. Any unsolicited AEs 
will be collected for 7 days (adult lead-in cohort) or 28 days (toddler lead-in and infant dose 
ranging cohorts) after each vaccination via diary cards. 
The following information will be documented for each event: 
• Reported term for the Adverse Event, 
• Start and end date, 
• Serious (Y/N), 
• Severity, 
• Investigator’s opinion of the causality (relationship) between the event and administration of 
trial vaccine(s) (“related” or “not related”), 
• Investigator’s opinion of the causality (relationship) to trial procedure(s), including the 
details of the suspected procedure, 
• Action taken with the trial treatment (trial vaccine), 
• Outcome of event. 
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10.4.2 Collection and Reporting of Solicited AEs 
The occurrence of selected indicators of safety will be collected on diary cards by the subject 
(adult cohort) or the subject’s LAR (toddler and infant cohorts) for 7 days post-vaccination and 
will be recorded on the “Local and Systemic AEs” eCRF, as appropriate.  
In the toddler lead-in and in the infant dose ranging cohorts, any solicited local or systemic AE 
observed as continuing on trial Day 8 will be recorded as an unsolicited AE on the Adverse 
Event eCRF. Any solicited local or systemic AE that resolved before Day 7 but recurs at a later 
time (ie, if discontinues), will be recorded as an unsolicited AE on the Adverse Event eCRF. 
Any solicited AE that meets any of the following criteria must be entered as an AE on the 
Adverse Event eCRF. 
• Solicited local or systemic AEs that lead the subject’s withdrawal from the trial. 
• Solicited local or systemic AEs that lead to the subject being withdrawn from the trial by the 
Investigator. 
• Solicited local and systemic AEs that otherwise meet the definition of an SAE (see 
Section 10.1.2). 
10.4.3 Collection and Reporting of SAEs 
Collection of SAEs will commence from the time that the subject is first administered the trial 
vaccine (Day 1). Routine collection of SAEs will continue until the end of the trial (Day 8 in the 
adult lead-in cohort, Day 183 in the toddler lead-in cohort and Day 547 in the infant dose ranging 
cohort). 
SAEs should be reported according to the following procedure: 
A sponsor SAE form must be completed, in English, and signed by the investigator immediately 
or within 24 hours of first onset or notification of the event. The information should be 
completed as fully as possible but contain, at a minimum: 
• A short description of the event and the reason why the event is categorized as serious. 
• Subject identification number. 
• Investigator’s name. 
• Name of the trial vaccine(s) – if no unblinding is necessary, in a blinded way. 
• Causality assessment. 
The SAE form should be transmitted within 24 hours to the attention of the contact(s) in the list 
provided to each site. 
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10.5 
Follow-up Procedures 
10.5.1 AEs 
All AEs will be monitored until resolution or a stable status is reached or until a formal diagnosis 
can be made or until the end of the trial, whichever occurs first. 
10.5.2 SAEs 
If information not available at the time of the first report becomes available at a later date, the 
investigator should complete a follow-up SAE form or provide other written documentation and 
fax it immediately within 24 hours of receipt. Copies of any relevant data from the hospital notes 
(eg, laboratory tests, discharge summary, postmortem results) should be sent to the sponsor. 
All SAEs should be followed up until resolution or permanent outcome of the event or is 
otherwise explained. Ongoing SAEs could potentially be followed outside of this trial or in a 
planned extension trial. The timelines and procedure for follow-up reports are the same as those 
for the initial report. 
10.5.3 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities 
The sponsor or designee will be responsible for the reporting of all suspected unexpected serious 
adverse reactions (SUSARs) and any other applicable SAEs to regulatory authorities, 
investigators and IRBs or IECs, as applicable, in accordance with national regulations in the 
countries where the trial is conducted. Relative to the first awareness of the event by/or further 
provision to the sponsor or sponsor’s designee, SUSARs will be submitted within 7 days for fatal 
and life-threatening events and 15 days for other SUSARs, unless otherwise required by national 
regulations. The sponsor will also prepare an expedited report for other safety issues where these 
might materially alter the current benefit-risk assessment of an investigational medicinal product 
or that would be sufficient to consider changes in the trial vaccine administration or in the overall 
conduct of the trial. The investigational site also will forward a copy of all expedited reports to 
their IRB or IEC in accordance with national regulations. 
10.5.4 Post-Trial Events 
Adult lead-in cohort 
The investigator should inform and educate the subjects that any adverse medical occurrence 
being perceived as serious up to 6 months after vaccination should be reported (passive follow 
up for safety). The investigator must report these SAEs to the sponsor. 
Toddler lead-in and infant dose ranging cohorts 
Any AE that occurs outside of the protocol-specified observation period or after the end of the 
trial must be reported to the sponsor. These AEs will be processed by the sponsor’s 
Pharmacovigilance Department. Instructions for how to submit these AEs will be provided in a 
handout in the Investigator Site File. 
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11.0 
TRIAL-SPECIFIC REQUIREMENT(S) 
No trial-specific committee is planned for this trial. 
11.1 
Halting Rules 
No specific halting rules have been defined for this trial. 
11.2 
Trial-Specific Committees 
11.2.1 Data Monitoring Committee 
The DMC will have study-specific responsibilities to review IPV-102 data and decide on the 
enrollment of the toddler and infant cohorts after reviewing 7 days of safety and tolerability 
follow-up post vaccination in adults in the lead-in cohort. In addition, the DMC will evaluate the 
overall tolerability and safety of Takeda’s sIPV on an ongoing basis. The DMC will be entitled 
to stop enrollment of additional subjects or to stop administration of additional sIPV doses. The 
composition, role and responsibilities of the DMC are presented in a separate DMC Charter. 
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12.0 
DATA HANDLING AND RECORDKEEPING 
The full details of procedures for data handling will be documented in the Data Management 
Plan. AEs, medical history, and concurrent conditions will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA [SOC, HLGT, HLT, LL, PT, and their 
corresponding descriptive terms]). Drugs will be coded using the World Health Organization 
(WHO) Drug Dictionary. 
12.1 
Electronic CRFs (eCRF) 
Completed eCRFs are required for each subject who provides a signed informed consent form. 
The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor 
will make arrangements to train appropriate site staff in the use of the eCRF. These forms are 
used to transmit the information collected in the performance of this trial to the sponsor and 
regulatory authorities. eCRFs must be completed in English. Data are entered directly onto 
eCRFs. 
After completion of the entry process, computer logic checks will be run to identify items, such 
as inconsistent dates, missing data, and questionable values. Queries may be issued by sponsor 
personnel (or designees) and will be answered by the site. 
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for change. 
The principal investigator or designee must review the eCRFs for completeness and accuracy 
and must sign and date the appropriate eCRFs as indicated. Furthermore, the investigator must 
retain full responsibility for the accuracy and authenticity of all data entered on the eCRFs. 
eCRFs will be reviewed for completeness and acceptability at the trial site during periodic visits 
by trial monitors. The sponsor or its designee will be permitted to review the subject’s medical 
and hospital records pertinent to the trial to ensure accuracy of the eCRFs. The completed eCRFs 
are the sole property of the sponsor and should not be made available in any form to third parties, 
except for authorized representatives of appropriate governmental health or regulatory 
authorities, without written permission of the sponsor. 
12.2 
Record Retention 
The investigator agrees to keep the records stipulated in Section 12.0 and those documents that 
include (but are not limited to) the trial-specific documents, the identification log of all 
participating subjects, medical records. Temporary media such as thermal sensitive paper should 
be copied and certified, source worksheets, all original signed and dated informed consent forms, 
subject authorization forms regarding the use of personal health information (if separate from the 
informed consent forms), electronic copy of eCRFs, including the audit trail, and detailed records 
of vaccine disposition to enable evaluations or audits from regulatory authorities, the sponsor or 
its designees. Furthermore, International Council on Harmonization (ICH) E6 Section 4.9.5 
requires the investigator to retain essential documents specified in ICH E6 (Section 8) until at 
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least 2 years after the last approval of a marketing application for a specified vaccine indication 
being investigated or, if an application is not approved, until at least 2 years after the 
investigation is discontinued and regulatory authorities are notified. In addition, ICH E6 Section 
4.9.5 states that the trial records should be retained until an amount of time specified by 
applicable regulatory requirements or for a time specified in the Clinical Study Site Agreement 
between the investigator and sponsor. 
Refer to the Clinical Study Site Agreement for the sponsor’s requirements on record retention. 
The investigator should contact and receive written approval from the sponsor before disposing 
of any such documents. 
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13.0 
STATISTICAL METHODS 
13.1 
Statistical and Analytical Plans 
A statistical analysis plan (SAP) will be prepared and finalized prior to unblinding of subject’s 
treatment assignment. This document will provide further details regarding the definition of 
analysis variables and analysis methodology to address all trial objectives. 
A blinded data review will be conducted prior to unblinding of subject’s vaccination assignment. 
This review will assess the accuracy and completeness of the trial database, subject evaluability, 
and appropriateness of the planned statistical methods. 
13.1.1 Analysis Sets 
Safety Set: The Safety Set will consist of all subjects who received at least one dose of the trial 
vaccines. 
Full Analysis Set (FAS): The FAS will include all subjects who were randomized and received at 
least one dose of the trial vaccines. 
Per–Protocol Set (PPS): The PPS will include all subjects in the FAS who have no major 
protocol violations. The major protocol violation criteria will be defined in the Statistical 
Analysis Plan (SAP). Subjects with major protocol violations will be identified as part of the 
blinded data review prior to the unblinding of subject’s investigational trial vaccine assignment. 
The categories of major protocol violations include: (1) not meeting selected entry criteria, (2) 
receiving a wrong trial vaccine or an incorrect regimen, (3) receiving prohibited therapies, and 
(4) other major protocol violations that may be identified during blinded data reviews. 
All summaries and analyses of safety data will be based on subjects in the Safety Set. The 
primary immunogenicity analyses will be based on the PPS, and additional sensitivity analyses 
will be based on the FAS.  
13.1.2 Analysis of Demographics and Other Baseline Characteristics 
Descriptive summaries of age, gender, race, and other baseline characteristics will be presented 
by formulation arm. Unless specified otherwise, number of subjects with non-missing 
observations, mean, standard deviation (SD), median, minimum and maximum will be presented 
for continuous data; and frequency and percent will be presented for categorical data.  
13.1.3 Immunogenicity Analysis  
Descriptive statistics for the primary, secondary, and exploratory immunogenicity endpoints, 
including estimates and 95% confidence intervals for SCR, SPR, VRR, and GMT will be 
provided by study arm and by poliovirus type. For the dose ranging cohort only, estimates and 
95% confidence intervals for differences in SCR, SPR, and VRR, as well as ratios in GMT, will 
be provided for each pair of study arms by poliovirus type. 
More specific details about the immunogenicity analyses will be provided in the SAP. 
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13.1.4 Safety Analysis 
Reactogenicity will be assessed for 7 days following each vaccination (including day of 
vaccination) via collection of solicited AEs, including local reactions (injection site: pain, 
erythema, induration, and swelling) and systemic AEs of irritability/fussiness, drowsiness, loss 
of appetite, for children in both cohorts daily. In addition, body temperature as indicator of 
reactogenicity will be collected (with fever defined as body temperature ≥38°C).  
For each solicited AE and fever, the percentage of subjects will be summarized by event severity 
for each day for the 7 days after each vaccination and overall. For subjects with more than one 
episode of the same event, the maximum severity will be used for tabulations. 
Unsolicited AEs, and SAEs, will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) and summarized by system organ class (SOC) and preferred term (PT) for 
each formulation arm. 
In general, unsolicited AEs will be tabulated at each of the following levels: overall summary 
(subject with at least 1 AE), and by SOC and PT. Unsolicited AEs will be summarized as 
follows: by PT; by SOC and PT; by SOC, PT, and severity; by SOC, PT, and relationship 
(causality) to the investigational trial vaccine; and by SOC and PT, including events with 
frequency greater than a pre-defined frequency (the percentage will be specified in the SAP).  
13.2 
Interim Analysis and Criteria for Early Termination 
An interim analysis will be performed after the primary safety and immunogenicity data (28 days 
after the last dose of the primary immunization series in the infant dose ranging cohort) are 
available on Day 85. The interim analyses will be performed by a separate set of unblinded 
statisticians and programmers who will have access to individual treatment assignments but will 
not be involved in subsequent study conduct. The results of the interim analysis will be used, 
following the appropriate Takeda Vaccines guidance, to inform the choice of dose to be used in 
subsequent phase 3 studies of the sIPV. The rest of the personnel involved in the conduct of the 
study, including those at Takeda, the contract research organization (CRO) and the study sites, 
will remain blinded to the individual subject data (including treatment assignments) until 
unblinding after database lock (Day 547). 
More details on the analyses will be provided in the SAP. 
13.3 
Determination of Sample Size 
This trial is designed to be descriptive and is not based on testing formal null hypotheses, and 
therefore the sample size was not determined based on formal statistical power calculations. 
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14.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
14.1 
Trial-Site Monitoring Visits 
Monitoring visits to the trial site will be made periodically during the trial to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. 
The investigator and institution guarantee access to source documents by the sponsor or its 
designee (CRO) and by the IRB or IEC. 
All aspects of the trial and its documentation will be subject to review by the sponsor or designee 
(as long as blinding is not jeopardized), including but not limited to the Investigator’s Binder, 
trial vaccine, subject medical records, informed consent form documentation, documentation of 
subject authorization to use personal health information (if separate from the informed consent 
forms), and review of eCRFs and associated source documents. It is important that the 
investigator and other trial personnel are available during the monitoring visits and that sufficient 
time is devoted to the process. 
14.2 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to trial subjects. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the medical 
monitor (and IRB or IEC, as required) to determine the appropriate course of action. There will 
be no exemptions (a prospective approved deviation) from the inclusion or exclusion criteria. 
14.3 
Quality Assurance Audits and Regulatory Agency Inspections 
The trial site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an 
auditing visit. The auditor may ask to visit the facilities where laboratory samples are collected, 
where the vaccine is stored and prepared, and any other facility used during the trial. In addition, 
there is the possibility that this trial may be inspected by regulatory agencies, including those of 
foreign governments (eg, the United Kingdom Medicines and Healthcare products Regulatory 
Agency, the Pharmaceuticals and Medical Devices Agency of Japan). If the trial site is contacted 
for an inspection by a regulatory body, the sponsor should be notified immediately. The 
investigator and institution guarantee access for quality assurance auditors to all trial documents 
as described in Section 14.1. 
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15.0 
ETHICAL ASPECTS OF THE TRIAL 
This trial will be conducted with the highest respect for the individual participants (ie, subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of 
Helsinki, and the ICH Harmonized Guideline for GCP. Each investigator will conduct the trial 
according to applicable local or regional regulatory requirements and align his or her conduct in 
accordance with the “Responsibilities of the Investigator” that are listed in Appendix A. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities. 
15.1 
IRB and/or IEC Approval 
IRBs and IECs must be constituted according to the applicable national and local requirements of 
each participating region. The sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC 
has direct participation in this trial, written notification regarding his or her abstinence from 
voting must also be obtained. 
The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the informed consent form, and, if applicable, subject recruitment materials and/or 
advertisements and other documents required by all applicable laws and regulations, must be 
submitted to a central or local IRB or IEC for approval. The IRB’s or IEC’s written approval of 
the protocol and subject informed consent form must be obtained and submitted to the sponsor or 
designee before commencement of the trial (ie, before shipment of the sponsor-supplied Vaccine 
or trial specific screening activity). The IRB or IEC approval must refer to the trial by exact 
protocol title, number, and version date; identify versions of other documents (eg, informed 
consent form) reviewed; and state the approval date. The sponsor will notify the site once the 
sponsor has confirmed the adequacy of site regulatory documentation and, when applicable, the 
sponsor has received permission from the competent authority to begin the trial. Until the site 
receives [notification] no protocol activities, including screening may occur. 
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the informed consent 
form, recruitment materials intended for viewing by subjects, local safety reporting requirements, 
reports and updates regarding the ongoing review of the trial at intervals specified by the 
respective IRB or IEC, and submission of the investigator’s final status report to IRB or IEC. All 
IRB and IEC approvals and relevant documentation for these items must be provided to the 
sponsor or its designee. 
Subject incentives should not exert undue influence for participation. Payments to subjects must 
be approved by the IRB or IEC and sponsor. 
15.2 
Subject Information, Informed Consent (ICF), and Subject Authorization 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
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applicable laws and regulations. The ICF, subject authorization form (if applicable), and subject 
information sheet (if applicable) describe the planned and permitted uses, transfers, and 
disclosures of the subject’s personal and personal health information for purposes of conducting 
the trial. 
The investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF 
and if applicable, the subject authorization form. The ICF, subject authorization form (if 
applicable), and subject information sheet (if applicable) must be approved by both the IRB or 
IEC and the sponsor prior to use. 
The ICF, subject authorization form (if applicable), and subject information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective subject’s LAR. It is the 
responsibility of the investigator to explain the detailed elements of the ICF, subject 
authorization form (if applicable), and subject information sheet (if applicable) to the subject’s 
LAR. Information should be given in both oral and written form whenever possible and in the 
manner deemed appropriate by the IRB or IEC.  
The subject (adult cohort) or the subject’s LAR (toddler and infant cohorts) must be given ample 
opportunity to: (1) inquire about details of the trial and (2) decide whether or not to allow their 
child to participate in the trial. If the subject determines that he/she will participate or if the 
subject’s LAR determines their child will participate in the trial, then the ICF and subject 
authorization must be signed and dated by the subject or subject’s LAR at the time of consent 
and prior to the subject entering into the trial. The subject or subject’s LAR should be instructed 
to sign using their legal names, not nicknames, using blue or black ballpoint ink. The investigator 
must also sign and date the ICF and subject authorization at the time of consent and prior to 
subject entering into the trial; however, the sponsor may allow a designee of the investigator to 
sign to the extent permitted by applicable law. 
Once signed, the original ICF, subject authorization form, and subject information sheet (if 
applicable) will be stored in the investigator’s site file. The investigator must document the date 
the subject or subject’s LAR signs the ICF in the subject’s medical record and eCRF. Copies of 
the signed ICF, the signed subject authorization form (if applicable), and subject information 
sheet (if applicable) shall be given to the subject or subject’s LAR. 
All revised ICFs must be reviewed and signed by the subject or relevant subject’s LAR in the 
same manner as the original ICF. The date the revised consent was obtained should be recorded 
in the subject’s medical record and eCRF, and the subject or subject’s LAR should receive a 
copy of the revised ICF. 
15.3 
Subject Confidentiality 
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this trial, a subject’s source data will only be linked to 
the sponsor’s clinical trial database or documentation via a unique identification number. As 
permitted by all applicable laws and regulations, limited subject attributes, such as sex, age, or 
date of birth, and subject initials may be used to verify the subject and accuracy of the subject’s 
unique identification number. 
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To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the 
sponsor requires the investigator to permit its monitor or designee’s monitor, representatives 
from any regulatory authority (eg, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals and Medical Devices Agency), the sponsor’s designated auditors, and the 
appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission 
and discharge summaries for hospital admissions occurring during a subject’s trial participation, 
and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject’s LAR as part of the ICF process (see Section 15.2). 
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (ie, subject name, address, and other identifier fields 
not collected on the subject’s eCRF). 
15.4 
Publication, Disclosure, and Clinical Trial Registration Policy 
15.4.1 Publication and Disclosure 
The results of this trial are expected to be published in a scientific journal. It is anticipated that 
clinical and laboratory co-investigators will participate in authorship. The order of authorship 
and choice of journal will be proposed by the sponsor to the PIs, to be eventually agreed upon by 
all authors. The data analysis center for this trial will provide the analyses needed for 
publication. Information regarding this trial will be posted on ClinicalTrials.gov. 
15.4.2 Clinical Trial Registration 
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable law, regulation and guidance, the sponsor will, at a minimum register all 
clinical trials conducted in subjects that it sponsors anywhere in the world on ClinicalTrials.gov 
or other publicly accessible websites before trial initiation. The sponsor contact information, 
along with investigator’s city, country, and recruiting status will be registered and available for 
public viewing. 
15.4.3 Clinical Trial Results Disclosure 
The sponsor will post the results of this clinical trial, regardless of outcome, on 
ClinicalTrials.gov or other publicly accessible websites, as required by applicable laws and/or 
regulations. 
Trial completion corresponds to the date on which the final subject was examined or received an 
intervention for the purposes of final collection of data for the primary outcome, whether the 
clinical trial concluded according to the pre-specified protocol or was terminated. 
In line with EC Regulation N° 1901/2006 [11], the sponsor will submit a pediatric trial within six 
months of their completion and irrespective of whether it is part of a completed or not yet 
completed Pediatric Investigation Plan (PIP) or not, or whether it is intended for submission later 
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on as part of a variation, extension or new stand-alone marketing-authorization application or 
not. 
15.5 
Insurance and Compensation for Injury 
Each subject in the trial must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical trial insurance against the risk of injury to clinical trial subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject 
compensation and treatment for injury. If the investigator has questions regarding this policy, he 
or she should contact the sponsor or sponsor’s designee. 
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16.0 
REFERENCES 
1. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH). ICH Harmonised Guideline. Integrated Addendum to ICH E6(R1): 
Guideline for Good Clinical Practice E6(R2) 9 November 2016. 
2. World Health Organization (WHO). Polio vaccines WHO Position paper. Wkly Epidemiol 
Rec 2016; 12: 145-168. 
3. Sutter RW, Pallansch MA, Sawyer LA, Cochi SL, Hadler SC. Defining surrogate serologic 
tests with respect to predicting protective vaccine efficacy: Poliovirus vaccination. Ann NY 
Acad Sci 1995; 754: 289–299. 
4. World Health Organization (WHO) Expert Committee on Biological Standardization. 65th 
Report. Annex 3. Recommendations to assure the quality, safety and efficacy of 
poliomyelitis vaccines (inactivated). WHO Technical Report Series 993. 2015 
5. World Health Organization (WHO). Government of Nigeria reports 2 wild polio cases, first 
since July 2014. Available at: http://www.who.int/mediacentre/news/releases/2016/nigeria-
polio/en/  
6. Polio Eradication and Endgame Strategic Plan 2013–2018. Available at: 
http://polioeradication.org/wp-content/uploads/2016/07/PEESP_EN_A4.pdf 
7. Shimizu H. Development and introduction of inactivated poliovirus vaccines derived from 
Sabin strains in Japan. Vaccine 2016; 34:1975-1985. 
8. Verdijk P, Rots NY, Bakker WA. Clinical development of a novel inactivated poliomyelitis 
vaccine based on attenuated Sabin poliovirus strains. Exp Rev Vacc 2011; 10:635–644. 
9. World Health Organization (WHO). Reducing pain at the time of vaccination: WHO 
position paper – September 2015. Wkly Epidemiol Rec 2015; 90:505–510. 
10. Marcy SM, Kohl KS, Dagan R, et al. Fever as an adverse event following immunization: 
case definition and guidelines of data collection, analysis, and presentation. Vaccine 2004; 
22:551-556. 
11. EC Regulation N° 1901/2006 OF THE EUROPEAN PARLIAMENT AND OF THE 
COUNCIL of 12 December 2006 on medicinal products for pediatric use and amending 
Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and 
Regulation (EC) No 726/2004. 
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Appendix A Responsibilities of the Investigator 
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations. 
The investigator agrees to assume the following responsibilities: 
1. Conduct the trial in accordance with the protocol. 
2. Personally conduct or supervise the staff who will assist in the protocol. 
3. Ensure that trial related procedures, including trial specific (non-routine/non-standard 
panel) screening assessments are NOT performed on potential subjects, prior to the receipt 
of written approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the trial are informed 
of these obligations. 
5. Secure prior approval of the trial and any changes by an appropriate IRB/IEC that conform 
to ICH, and local regulatory requirements. 
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and 
approval of the protocol. Promptly report to the IRB/IEC all changes in research activity 
and all anticipated risks to subjects. Make at least yearly reports on the progress of the trial 
to the IRB/IEC, and issue a final report within 3 months of trial completion. 
7. Ensure that requirements for informed consent, as outlined in ICH and local regulations, are 
met. 
8. Obtain valid informed consent from the LAR of each subject who participates in the trial, 
and document the date of consent in the subject’s medical chart. Valid ICF is the most 
current version approved by the IRB/IEC. Each ICF should contain a subject authorization 
section that describes the uses and disclosures of a subject’s personal information 
(including personal health information) that will take place in connection with the trial. If 
an ICF does not include such a subject authorization, then the investigator must obtain a 
separate subject authorization form for each subject from the subject’s LAR. 
9. Prepare and maintain adequate case histories of all persons entered into the trial, including 
eCRFs, hospital records, laboratory results, etc, and maintain these data for a minimum of 
2 years following notification by the sponsor that all investigations have been discontinued 
or that the regulatory authority has approved the marketing application. The investigator 
should contact and receive written approval from the sponsor before disposing of any such 
documents. 
10. Allow possible inspection and copying by the regulatory authority of GCP-specified 
essential documents. 
11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
vaccines, and return all unused sponsor-supplied vaccines to the sponsor. 
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12. Report AEs to the sponsor promptly. In the event of an SAE, notify the sponsor within 
24 hours. 
13. Review and provide a signature as approval of the content of the clinical study report. 
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Appendix B Elements of the Subject Informed Consent  
In seeking the subject's (adult cohort) or the LAR’s (toddler and infant cohorts) consent, the 
following information shall be provided to each subject or subject’s LAR: 
1. A statement that the trial involves research. 
2. An explanation of the purposes of the research. 
3. The expected duration of the subject’s participation. 
4. A description of the procedures to be followed, including invasive procedures. 
5. The identification of any procedures that are experimental. 
6. The estimated number of subjects involved in the trial. 
7. A description of the subject or subject’s LAR’s responsibilities. 
8. A description of the conduct of the trial. 
9. A statement describing the vaccination(s) and the probability for random assignment to 
each treatment. 
10. A description of the possible side effects following vaccine administration that the subject 
may receive. 
11. A description of any reasonably foreseeable risks or discomforts to the subject and, when 
applicable, to an embryo, fetus, or nursing infant. 
12. A description of any benefits to the subject or to others that reasonably may be expected 
from the research. When there is no intended clinical benefit to the subject, the subject or 
the subject’s LAR should be made aware of this. 
13. Disclosures of appropriate alternative procedures or courses of treatment, if any, that might 
be advantageous to the subject and their important potential risks and benefits. 
14. A statement describing the extent to which confidentiality of records identifying the subject 
will be maintained, and a note of the possibility that regulatory agencies, auditor(s), 
IRB/IEC, and the monitor may inspect the records. By signing an ICF, the subject or 
subject’s LAR is authorizing such access. 
15. For research involving more than minimal risk, an explanation as to whether any 
compensation and an explanation as to whether any medical treatments are available if 
injury occurs and, if so, what they consist of or where further information may be obtained. 
16. The anticipated prorated payment(s), if any, to the subject for participating in the trial. 
17. The anticipated expenses, if any, to the subject for participating in the trial. 
18. An explanation of whom to contact for answers to pertinent questions about the research 
(investigator), subject’s rights, and IRB/IEC and whom to contact in the event of a 
research-related injury to the subject. 
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19. A statement that participation is voluntary, that refusal to participate will involve no penalty 
or loss of benefits to which the subject otherwise is entitled, and that the subject may 
discontinue participation or the subject’s LAR may discontinue participation of their child 
at any time without penalty or loss of benefits to which the subject is otherwise entitled. 
20. The consequences of a subject’s decision to withdraw from the research and procedures for 
orderly termination of participation by the subject. 
21. A statement that the subject or subject’s LAR will be informed in a timely manner if 
information becomes available that may be relevant to their willingness to continue 
participation in the trial. 
22. A statement that results of pharmacogenomic analysis will not be disclosed to an individual, 
unless prevailing laws require the sponsor to do so. 
23. The foreseeable circumstances or reasons under which the subject’s participation in the trial 
may be terminated. 
24. A written subject authorization (either contained within the ICF or provided as a separate 
document) describing to the subject or subject’s LAR the contemplated and permissible 
uses and disclosures of the subject’s personal information (including personal health 
information) for purposes of conducting the trial. The subject authorization must contain the 
following statements regarding the uses and disclosures of the subject’s personal 
information: 
a) that personal information (including personal health information) may be processed by or 
transferred to other parties in other countries for clinical research and safety reporting 
purposes, including, without limitation, to the following: (1) Takeda, its affiliates, and 
licensing partners; (2) business partners assisting Takeda, its affiliates, and licensing 
partners; (3) regulatory agencies and other health authorities; and (4) IRBs/IECs; 
b) it is possible that personal information (including personal health information) may be 
processed and transferred to countries that do not have data protection laws that offer 
subjects the same level of protection as the data protection laws within this country; 
however, Takeda will make every effort to keep your or your child’s personal 
information confidential, and your or your child’s name will not be disclosed outside the 
clinic unless required by law; 
c) that personal information (including personal health information) may be added to 
Takeda’s research databases for purposes of developing a better understanding of the 
safety and effectiveness of the investigational vaccine(s), studying other therapies for 
patients, developing a better understanding of disease, and improving the efficiency of 
future clinical studies; 
d) that the subject or subject’s LAR agrees not to restrict the use and disclosure of their or 
their child’s personal information (including personal health information) upon 
withdrawal from the trial to the extent that the restricted use or disclosure of such 
information may impact the scientific integrity of the research; and 
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e) that the subject’s identity will remain confidential in the event that trial results are 
published. 
25. A statement that clinical trial information from this trial will be publicly disclosed in a 
publicly accessible website, such as ClinicalTrials.gov. 
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Appendix C Investigator Consent to Use of Personal Information 
Takeda will collect and retain personal information of investigator, including his or her name, 
address, and other personally identifiable information. In addition, investigator’s personal 
information may be transferred to other parties located in countries throughout the world (eg, the 
United Kingdom, United States, and Japan), including the following: 
• Takeda, its affiliates, and licensing partners. 
• Business partners assisting Takeda, its affiliates, and licensing partners. 
• Regulatory agencies and other health authorities. 
• IRBs and IECs. 
Investigator’s personal information may be retained, processed, and transferred by Takeda and 
these other parties for research purposes including the following: 
• Assessment of the suitability of investigator for the trial and/or other clinical studies. 
• Management, monitoring, inspection, and audit of the trial. 
• Analysis, review, and verification of the trial results. 
• Safety reporting and pharmacovigilance relating to the trial. 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the trial. 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other vaccines used in other clinical studies that may contain 
the same chemical compound present in the investigational vaccine. 
• Inspections and investigations by regulatory authorities relating to the trial. 
• Self-inspection and internal audit within Takeda, its affiliates, and licensing partners. 
• Archiving and audit of trial records. 
• Posting investigator site contact information, trial details and results on publicly accessible 
clinical trial registries, databases, and websites. 
Investigator’s personal information may be transferred to other countries that do not have data 
protection laws that offer the same level of protection as data protection laws in investigator’s 
own country. Investigator acknowledges and consents to the use of his or her personal 
information by Takeda and other parties for the purposes described above. 
 
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Appendix D Serology Plan 
Assay 
Validation 
status 
required for 
the assay(b) 
Sample 
type 
Analytical 
readout of 
assay data 
Sample 
volume/ time 
point/ 
assay(c) 
Sample volume 
reserved as 
backup (min.)(c) 
Subset 
of 
Subjects 
Time 
points(d) 
Total 
# of 
time 
points 
Total 
# of tests/ 
assays/ 
study 
Study Objective: 
(Primary, 
Secondary or 
Exploratory) 
Contract 
Testing Lab Comments 
CCI
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le
ints
nts
Total
otal
# of tests
of tes
assay
ass
s
pli
pli
pli
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D
E
F
G
CCI
CCI
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th
ble Terms of Use
le
th
the applicab

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Primary sample required per time point (e.g. blood draw): 
Time point 
Primary sample type  secondary 
sample type 
Primary sample volume or 
amount per time point 
Expected secondary sample 
volume or amount 
D1, 29  
(Toddler lead-in 
cohort) 
Blood → Serum 
5 mL 
2000 µL 
D1, 57, 85, 365, 393 
(Infant dose ranging 
cohort) 
Blood → Serum 
5 mL 
2000 µL 
 
Total blood drawn in study for Serology      10 mL/ 25 mL 
 
In this table primary sample means e.g. blood, corresponding secondary sample means e.g. serum 
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