A Multi-country, Multi-center, Open-labelled, Randomized, Controlled, Extended Phase Ⅲ Clinical Trial to Evaluate the Immunogenicity and Tolerability of Sabin Strain Inactivated Poliovirus Vaccine Administered With or Without Routine Infant Vaccines
Phase: PHASE3
Conditions: Poliomyelitis, Polio
Sponsor: Sinovac Biotech Co., Ltd



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TABLE OF CONTENTS 
PROTOCOL APPROVAL–SPONSOR SIGNATORY ................................................................................5 
DECLARATION OF INVESTIGATOR .........................................................................................................6 
DECLARATION OF INVESTIGATOR .........................................................................................................7 
1. 
PROTOCOL SUMMARY ...................................................................................................................... 13 
1.1 
Synopsis .................................................................................................................................... 13 
1.2 
Trial Schema ............................................................................................................................ 17 
1.3 
Schedule of Activities and Timeline .................................................................................. 18 
2. 
INTRODUCTION .................................................................................................................................... 21 
2.1 
Study Rationale ....................................................................................................................... 21 
2.2 
Background .............................................................................................................................. 21 
2.2.1 
Product Summary ........................................................................................................ 22 
2.2.2 
Summary of Existing Immunogenicity Data ....................................................... 22 
2.2.2.1 
Immunogenicity data for sIPV-only vaccination schedule ............................ 22 
2.2.2.2 
Immunogenicity data for sIPV & bOPV sequential vaccination schedule 22 
2.2.3 
Summary of Existing Safety Data ........................................................................... 23 
2.3 
Benefit-risk assessment ......................................................................................................... 23 
2.3.1 
Risks related to study participation ....................................................................... 23 
2.3.2 
Benefit/risk assessment ............................................................................................. 24 
3. 
OBJECTIVES AND ENDPOINTS ...................................................................................................... 24 
4. 
STUDY DESIGN ...................................................................................................................................... 25 
4.1 
Overall Design ........................................................................................................................ 25 
4.2 
Rationale for Study Design .................................................................................................. 27 
4.3 
Justification for Dose ............................................................................................................. 27 
4.4 
End-of-study Definition ........................................................................................................ 27 
5. 
STUDY POPULATION .......................................................................................................................... 27 
5.1 
Inclusion Criteria .................................................................................................................... 27 
5.2 
Exclusion Criteria ................................................................................................................... 28
5.3 
Exclusion Criteria for the Subsequent Vaccination ........................................................ 28 
5.4 
Lifestyle Considerations ....................................................................................................... 28 
5.5 
Screening Failures .................................................................................................................. 29 
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY .................................................... 29 
6.1 
Investigational Vaccines Administered .............................................................................. 29 
6.2 
Preparation/Handling/Storage/Accountability ................................................................. 29 
6.3 
Measures to Minimize Bias: Randomization and Blinding .......................................... 30 
6.4 
Study Treatment Compliance .............................................................................................. 30 
6.5 
Dose Modification .................................................................................................................. 30 
6.6 
Treatment of Overdose .......................................................................................................... 30 
6.7 
Concomitant Medications and Therapies .......................................................................... 30 
7. 
DELAY/DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................................................... 31 
7.1 
Participants Discontinuation/Withdrawal from the Study............................................. 31 
7.2 
Lost to Follow-up ................................................................................................................... 31 

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7.3 
Study Vaccination Pausing Rules ....................................................................................... 32 
7.4 
Study Early Termination Rules ........................................................................................... 32 
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................. 32 
8.1 
Immunogenicity Assessments.............................................................................................. 32 
8.1.1 
Blood Collection and Laboratory Testing ............................................................ 32 
8.1.2 
Sample Management ................................................................................................. 33 
8.2 
Safety Assessments ................................................................................................................ 33 
8.3 
Physical Examinations .......................................................................................................... 33 
8.4 
Vital Signs ................................................................................................................................ 33 
8.5 
AEs, SAEs, and Other Safety Reporting ........................................................................... 34 
8.5.1 
Definitions ...................................................................................................................... 34 
8.5.2 
Outcomes of Adverse Events................................................................................... 35 
8.5.3 
Causality .......................................................................................................................... 35 
8.5.4 
Grading Scale for Adverse Events .......................................................................... 36 
8.5.5 
Safety Follow-up .......................................................................................................... 37 
8.5.6 
Regulatory Reporting Requirements for Serious Adverse Events ............... 38 
8.5.7 
Safety Oversight ........................................................................................................... 39 
8.6 
Study Procedures .................................................................................................................... 39 
8.6.1 
Co-administration group (group C1/C2) ............................................................ 39 
8.6.2 
Staggered administration group (group S1/S2) ............................................... 41 
9. 
STATISTICAL CONSIDERATIONS .................................................................................................. 45 
9.1 
Sample Size Determination .................................................................................................. 45 
9.2 
Analysis Sets ........................................................................................................................... 45 
9.3 
Statistical Methods ................................................................................................................. 46 
9.3.1 
General Considerations ............................................................................................. 46 
9.3.2 
Disposition of Participants ........................................................................................ 46 
9.3.3 
Demographic and Baseline Characteristics ......................................................... 46 
9.3.4 
Immunogenicity Analysis .......................................................................................... 46
9.3.5 
Safety Analysis .............................................................................................................. 47 
9.4 
Subgroup Analysis ................................................................................................................. 47 
9.5 
Multiplicity .............................................................................................................................. 47 
9.6 
Method of Missing Data Handling ..................................................................................... 47 
10. 
DATA COLLECTION AND MANAGEMENT ....................................................................... 47 
10.1 
Data Collection ....................................................................................................................... 47 
10.2 
Safety Follow-up Method ..................................................................................................... 48 
10.3 
Study Records Retention ...................................................................................................... 48 
10.4 
Publication and Data Sharing .............................................................................................. 48 
11. 
QUALITY ASSURANCE ............................................................................................................. 48 
11.1 
General Consideration ........................................................................................................... 48 
11.2 
Study Monitoring.................................................................................................................... 49 
12. 
REFERENCES ................................................................................................................................. 49 
13. 
ANNEX.............................................................................................................................................. 51 
 

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LIST OF ABBREVIATION
AE
Adverse Event
AR 
Adverse Reaction
ASaT
All Subjects as Treated
bOPV 
Bivalent Oral Poliovirus Vaccine 
CRO
Contract Research Organization
eCRF
Electronic Case Report Form
EPI 
Expanded Programme on Immunization 
FAS
Full Analysis Set
FHA 
Filamentous Hemagglutinin 
GCP
Good Clinical Practice
GMC
Geometric Mean Concentration
GMT 
Geometric Mean Titers 
GMFR
Geometric Mean Fold Increase
GPEI 
Global Polio Eradication Initiative
IB
Investigator’s Brochure
ICF 
Informed Consent Form
ICH 
International Conference on Harmonization 
IEC
Independent Ethics Committee
IRB
Institutional Review Board
IP 
Investigational Product
IPV
Inactivated Poliovirus Vaccine
LOCF
Last Observation Carried Forward
MedDRA 
Medical Dictionary for Regulatory Activities 
NMPA
National Medical Products Administration 
OPV 
Oral Polio Vaccine
PPS
Per-Protocol Set 
PRN
Pertussis Antigen Pertactin
PT 
Preferred Term
PT 
Pertussis Toxin
QA 
Quality Assurance 
QC
Quality Control
VAPP
Vaccine-Associated Paralytic Poliomyelitis
VDPV
Vaccine-Derived Poliovirus
wIPV
Wild Strain Inactivated Poliovirus Vaccine 
SAE
Serious Adverse Event
SAR
Serious Adverse Reaction
sIPV 
Poliomyelitis Vaccine (Vero cells), Inactivated, Sabin Strains
SoA 
Schedule of Activities
SOC
System Organ Class
SS 
Safety Set
TEAE
Treatment-Emergent Adverse Events
tOPV
Trivalent Oral Poliovirus Vaccine

March 27 2024