A Phase III, Open-label, Randomized, Controlled Study to Evaluate the Immunogenicity and Safety of Inactivated Poliovirus Vaccine (IPV) When Co-administered With Porcine Circovirus (PCV)-Free Liquid Formulation of an Oral Live Attenuated Human Rotavirus (HRV) Vaccine in Healthy Chinese Infants
Phase: PHASE3
Conditions: Gastroenteritis
Sponsor: GlaxoSmithKline

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218485 (ROTA-098) 
Protocol Amendment 1 Final 
25 Oct 2023 
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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Primary study intervention 
Porcine circovirus (PCV)-free liquid formulation of 
GSK oral live attenuated human rotavirus (HRV) 
vaccine (444563) 
Other study intervention 
Inactivated Poliomyelitis Vaccine Made From Sabin 
Strains (Vero Cells) 
eTrack study number and 
abbreviated title 
218485 (ROTA-098) 
EudraCT number 
2022-000708-36 
Date of protocol 
20 January 2023 
Date of protocol amendment 
Amendment 1 Final: 25 Oct 2023 
Title 
A phase III, open-label, randomized, controlled study 
to evaluate the immunogenicity and safety of 
inactivated poliovirus vaccine (IPV) when co-
administered with Porcine circovirus (PCV)-free 
liquid formulation of an oral live attenuated human 
rotavirus (HRV) vaccine in healthy Chinese infants. 
Brief title 
A study on the immunogenicity and safety of 
inactivated poliovirus vaccine (IPV) when co-
administered with Porcine circovirus (PCV)-free 
liquid formulation of an oral live attenuated human 
rotavirus (HRV) vaccine in healthy Chinese infants. 
Sponsor signatory 
Md Ahsan Habib, Clinical Project Lead, Live viral 
vaccines 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.3 
©2023 GSK group of companies or its licensor. 

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218485 (ROTA-098) 
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Protocol Amendment 1 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GSK. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 
• 
That I will comply with the terms of the site agreement. 
• 
To comply with local bio-safety legislation. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To supervise any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site. 
• 
To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the participant and/or the participant’s legally acceptable representative (LAR). 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• 
To co-operate with representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the study. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator(s)’ ownership interest 
in the sponsor or the investigational intervention(s), and more generally about their 
financial ties with the sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 

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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 

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eTrack study number and 
abbreviated title 
218485 (ROTA-098) 
EudraCT number 
2022-000708-36 
Date of protocol 
20 January 2023 
Date of protocol amendment 
Amendment 1 Final: 25 Oct 2023 
Title 
A phase III, open-label, randomized, controlled study 
to evaluate the immunogenicity and safety of 
inactivated poliovirus vaccine (IPV) when co-
administered with Porcine circovirus (PCV)-free 
liquid formulation of an oral live attenuated human 
rotavirus (HRV) vaccine in healthy Chinese infants. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 

CONFIDENTIAL 
218485 (ROTA-098) 
Protocol Amendment 1 Final 
25 Oct 2023 
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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA (GSK) 
Rue de l’Institut, 89 
1330 Rixensart 
Belgium 
2. Sponsor medical expert for the study 
Refer to the local study contact information document. 
3. Sponsor study monitor 
Refer to the local study contact information document. 
4. Sponsor study contact for reporting of Serious Adverse Events (SAEs) 
GSK central back up study contact for reporting SAEs: refer to Section 8.3.3.1. 
Study contact for reporting SAEs: refer to the local study contact information 
document. 

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218485 (ROTA-098) 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 1 
25 Oct 2023 
Original Protocol 
20 January 2023 
Amendment 1 (25 Oct 2023) 
Overall rationale for the current Amendment:  The distribution of the paper diary 
only at the first visit, followed by its return at the last visit, carries the risk of loss of the 
dairy card/incorrect data entry. Hence, distributing the paper diaries at each visit for 
intervention, and their return at the subsequent visit, would remediate the risk of loss of 
the dairy card and the corresponding solicited data between two visits. For this reason, 
the protocol is currently being amended. 
List of main changes in the protocol and their rationale: 
Section # and 
title 
Description of change 
Brief rationale 
1.3: Schedule of 
activities 
Paper dairy card to be distributed at 
each visit for intervention and be 
collected at the next visit 
To remediate the risk of loss of 
the dairy card and solicited data 
between two visits 
Throughout the 
document 
The term “SPM” or “Study Procedures 
Manual” has been replaced with 
“Pharmacy Manual” 
To align with the current protocol 
template 

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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 5 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 6 
List of main changes in the protocol and their rationale: ........................................... 6 
1. 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1. 
Synopsis ..................................................................................................... 13 
1.2. 
Schema ...................................................................................................... 13 
1.3. 
Schedule of Activities (SoA) ........................................................................ 14 
2. 
INTRODUCTION .................................................................................................... 21 
2.1. 
Study rationale ............................................................................................ 21 
2.2. 
Background ................................................................................................ 21 
2.3. 
Benefit/Risk assessment ............................................................................. 22 
3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ................................................... 22 
4. 
STUDY DESIGN .................................................................................................... 23 
4.1. 
Overall design ............................................................................................. 23 
4.2. 
Scientific rationale for study design ............................................................. 25 
4.3. 
Justification for dose ................................................................................... 26 
4.4. 
EoS definition ............................................................................................. 26 
5. 
STUDY POPULATION ........................................................................................... 26 
5.1. 
Inclusion criteria .......................................................................................... 27 
5.2. 
Exclusion criteria ......................................................................................... 27 
5.2.1. 
Medical conditions ....................................................................... 27 
5.2.2. 
Prior/Concomitant therapy ........................................................... 28 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 28 
5.2.4. 
Other exclusions .......................................................................... 28 
5.3. 
Lifestyle considerations ............................................................................... 28 
5.4. 
Screening failures ....................................................................................... 29 
5.5. 
Criteria for temporarily delaying enrolment and/or study intervention 
administration ............................................................................................. 29 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 29 
6.1. 
Study interventions administered ................................................................ 30 
6.2. 
Preparation, handling, storage, and accountability ...................................... 31 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 31 
6.3.1. 
Participant identification ............................................................... 31 
6.3.2. 
Randomization to study intervention ............................................ 31 
6.3.3. 
Intervention allocation to the participant ....................................... 31 
6.3.4. 
Blinding and unblinding ................................................................ 32 
6.4. 
Study intervention compliance .................................................................... 32 
6.5. 
Dose modification ....................................................................................... 32 
6.6. 
Continued access to study intervention after the end of the study ............... 32 
6.7. 
Treatment of overdose ................................................................................ 32 
6.8. 
Concomitant therapy ................................................................................... 32 

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7. 
DISCONTINUATION OF STUDY INTERVENTIONS AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 33 
7.1. 
Discontinuation of study interventions ......................................................... 33 
7.1.1. 
Contraindications to subsequent study interventions 
administration .............................................................................. 33 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 34 
7.3. 
Lost to follow-up.......................................................................................... 35 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 35 
8.1. 
Immunogenicity assessments ..................................................................... 36 
8.1.1. 
Biological samples ....................................................................... 37 
8.1.2. 
Laboratory assays ....................................................................... 37 
8.1.3. 
Immunological read-outs .............................................................. 38 
8.1.4. 
Immunological correlates of protection ......................................... 38 
8.2. 
Safety assessments .................................................................................... 38 
8.2.1. 
Pre-intervention administration procedures .................................. 39 
8.2.1.1. 
Collection of demographic data .................................. 39 
8.2.1.2. 
Medical/vaccination history ......................................... 39 
8.2.1.3. 
Physical examination .................................................. 39 
8.2.1.4. 
Warnings and precautions to administration of 
study interventions...................................................... 40 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and other 
safety reporting ........................................................................................... 40 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information ............................................................... 40 
8.3.2. 
Method of detecting AEs and SAEs ............................................. 41 
8.3.3. 
Regulatory reporting requirements for SAEs ................................ 42 
8.3.3.1. 
Contact information for reporting SAEs ....................... 43 
8.3.4. 
Treatment of expedited adverse events (SAE) ............................. 43 
8.3.5. 
Participant card ............................................................................ 43 
8.3.6. 
Medical device deficiencies ......................................................... 43 
8.3.6.1. 
Detection, follow-up, and prompt reporting of 
medical device deficiency ........................................... 43 
8.3.6.2. 
Regulatory reporting of medical device 
deficiency when used as combination product ............ 44 
8.4. 
Pharmacokinetics ....................................................................................... 44 
8.5. 
Genetics ..................................................................................................... 44 
8.6. 
Biomarkers ................................................................................................. 44 
8.7. 
Immunogenicity assessments ..................................................................... 44 
8.8. 
Health outcomes ......................................................................................... 44 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 45 
9.1. 
Statistical hypotheses ................................................................................. 45 
9.2. 
Analysis sets ............................................................................................... 45 
9.2.1. 
Criteria for elimination from analysis ............................................ 46 
9.3. 
Statistical analyses ..................................................................................... 46 
9.3.1. 
Primary endpoint analysis ............................................................ 46 
9.3.2. 
Secondary immunogenicity endpoints analysis ............................ 46 
9.4. 
Analysis of safety ........................................................................................ 47 
9.4.1. 
Within groups assessment ........................................................... 47 
9.5. 
Other analyses ........................................................................................... 48 
9.5.1. 
Demographic and baseline characteristics analyses .................... 48 

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9.6. 
Interim analyses .......................................................................................... 48 
9.7. 
Sample size determination .......................................................................... 48 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 49 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 49 
10.1.1. 
Regulatory and ethical considerations ......................................... 49 
10.1.2. 
Financial disclosure ..................................................................... 50 
10.1.3. 
Informed consent process ............................................................ 50 
10.1.4. 
Data protection ............................................................................ 51 
10.1.5. 
Committees structure ................................................................... 51 
10.1.6. 
Dissemination of clinical study data ............................................. 51 
10.1.7. 
Data quality assurance ................................................................ 52 
10.1.8. 
Source documents ....................................................................... 53 
10.1.9. 
Study and site start and closure ................................................... 53 
10.1.10. Publication policy ......................................................................... 54 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 54 
10.2.1. 
Protocol required immunogenicity laboratory assessments .......... 54 
10.3. 
Appendix 3: AE: definitions and procedures for recording, 
evaluating, follow-up, and reporting ............................................................ 55 
10.3.1. 
Definition of an AE ....................................................................... 55 
10.3.1.1. Events Meeting the AE Definition ............................... 55 
10.3.1.2. Events NOT Meeting the AE Definition ....................... 56 
10.3.2. 
Definition of an SAE ..................................................................... 56 
10.3.3. 
Solicited events............................................................................ 57 
10.3.4. 
Unsolicited AE ............................................................................. 57 
10.3.5. 
SAEs related to Study Participation ............................................. 58 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 58 
10.3.6.1. Recording and follow-up of AEs and SAEs ................. 58 
10.3.6.2. Time period for collecting and recording AEs 
and SAEs ................................................................... 59 
10.3.6.3. Follow-up of AEs, SAEs or any other events of 
interest ....................................................................... 59 
10.3.6.3.1. Follow-up during the study ...................... 60 
10.3.6.3.2. Follow-up after the participant is 
discharged from the study ...................... 60 
10.3.6.4. Updating of SAE information after removal of 
write access to the participant’s eCRF ........................ 60 
10.3.7. 
Assessment of intensity and causality .......................................... 60 
10.3.7.1. Assessment of intensity .............................................. 60 
10.3.7.2. Assessment of causality ............................................. 62 
10.3.7.3. Medically attended visits ............................................. 63 
10.3.7.4. Assessment of outcomes............................................ 63 
10.3.8. 
Reporting of SAEs and other events ............................................ 63 
10.3.8.1. Events requiring expedited reporting to GSK .............. 63 
10.3.8.2. Back up system in case the electronic reporting 
system does not work ................................................. 64 
10.4. 
Appendix 4: Contraceptive guidance and collection of pregnancy 
information .................................................................................................. 64 
10.5. 
Appendix 5: Genetics .................................................................................. 64 

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10.6. 
Appendix 6: Definition of medical device AE, adverse device effect 
(ADE), serious adverse device effect (SADE) and unanticipated 
SADE (USADE) .......................................................................................... 64 
10.6.1. 
Definition of medical device AE and ADE..................................... 64 
10.6.2. 
Definition of medical device SAE, SADE and USADE .................. 65 
10.6.3. 
Recording and reporting of medical device AE, ADEs, 
SADEs and USADE ..................................................................... 65 
10.6.4. 
Reporting of Medical Device Deficiencies for Associated 
Person ......................................................................................... 66 
10.7. 
Appendix 7: Country-specific requirements ................................................. 66 
10.8. 
Appendix 8: Abbreviations and glossary of terms ........................................ 66 
10.8.1. 
List of abbreviations ..................................................................... 66 
10.8.2. 
Glossary of terms ......................................................................... 69 
10.9. 
Appendix 9: Protocol Amendment change history ....................................... 73 
11. REFERENCES ....................................................................................................... 73 

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LIST OF TABLES 
PAGE 
Table 1 
SoA for Co-administration group ............................................................ 14 
Table 2 
SoA for Staggered group ........................................................................ 17 
Table 3 
Intervals between study visits for Co-administration group ..................... 20 
Table 4 
Intervals between study visits for Staggered group ................................ 20 
Table 5 
Study objectives, endpoints and estimands ............................................ 22 
Table 6 
Study groups, intervention and blinding .................................................. 25 
Table 7 
Study interventions administered ........................................................... 30 
Table 8 
Biological samples ................................................................................. 37 
Table 9 
Laboratory assays .................................................................................. 37 
Table 10 
Immunological read-outs ........................................................................ 38 
Table 11 
Timeframes for collecting and reporting of safety information ................. 41 
Table 12 
Timeframes for submitting SAE and other events reports to GSK .......... 42 
Table 13 
Contact information for reporting SAEs .................................................. 43 
Table 14 
Study objective and null hypothesis........................................................ 45 
Table 15 
Analysis sets .......................................................................................... 45 
Table 16 
Probability that the lower limit of the 95% CI around group 
difference in the percentage of participants with anti-poliovirus 
types 1, 2 and 3 antibody seroconversion 1 month post Dose 3 of 
IPV (Co-administration group minus Staggered group) is greater 
than or equal to -10% ............................................................................. 49 
Table 17 
Solicited systemic events ....................................................................... 57 
Table 18 
Intensity scales to be used by the parent(s)/LAR(s) for solicited 
symptoms during the solicited follow-up period ...................................... 60 
Table 19 
Intensity scales for diarrhea, vomiting and fever in infants ...................... 61 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 24 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale: GlaxoSmithKline Biologicals SA’s (GSK) Rotarix liquid vaccine is currently 
approved in all European Economic Area (EEA) countries, United Kingdom (UK), 
United States (US), Japan, as well as over 90 other countries. GSK intends to register 
Rotarix Porcine circovirus (PCV)-free liquid vaccine (hereafter referred as Rotarix PCV-
free) in China. “PCV-free” is defined as no detection of PCV-1 and PCV-2 according to 
the limit of detection of the tests used. 
In China, under the National Immunization Programme (NIP), a 3-dose primary 
vaccination against poliovirus is currently recommended during the first year of life in a 
2, 3 and 4 months of age schedule and a booster vaccine is recommended at 4 years of 
age. Inactivated poliovirus vaccine (IPV) is used for the first 2 doses, and oral poliovirus 
vaccine (OPV) is used for the third and the fourth dose. 
This study is designed to evaluate the immunogenicity and safety of IPV when 
co-administered with Rotarix PCV-free, in healthy Chinese infants. 
Objectives, endpoints and estimands: See Table 5-Study objectives and endpoints from 
Section 3. 
1.2. 
Schema 
See Figure 1 from Section 4.1. 

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1.3. 
Schedule of Activities (SoA) 
Table 1 
SoA for Co-administration group 
Age at time of study enrolment 
6-10 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 a 
Visit 4 
Visit 5 a 
Visit 6 
Visit 7 
 
Timepoints 
Day 1 
Month 0.5 
Month 1 
Month 1.5 
Month 2 
Month 2.5 
Month 3.5 
Informed consent by parent(s)/LAR(s) 
● 
 
 
 
 
 
 
See Section 10.1.3 for details 
Check inclusion/exclusion criteria 
● 
 
 
 
 
 
 
See Section 5.1 for Inclusion 
criteria and Section 5.2 for 
Exclusion criteria 
Collect demographic data and gestational age 
● 
 
 
 
 
 
 
See Section 8.2.1.1 for more 
information 
Medical and vaccination history 
● 
 
 
 
 
 
 
See Section 8.2.1.2 for more 
information 
Physical examination 
● 
 
 
 
 
 
 
See Section 8.2.1.3 for more 
information 
Measure/record height and weight 
● 
 
 
 
 
 
 
See Section 8.2.1.3 for more 
information 
Study intervention 
Check contraindications, warnings and precautions 
to study intervention administration 
 
● 
 
● 
 
● 
 
See Sections 7.1.1 and 8.2.1.4 for 
more information 
Randomization 
● 
 
 
 
 
 
 
See Section 6.3 for more 
information 
Check criteria for temporary delay for enrolment 
and/or study intervention administration 
O 
O 
 
O 
 
O 
 
See Section 5.5 for more 
information 
Study group and intervention number allocation 
O 
 
 
 
 
 
 
See Sections 6.3.2 and 6.3.3 for 
more information 
Allocation of treatment number for subsequent 
dose 
 
 
 
● 
 
● 
 
See Section 6.3.3 for more 
information 
Body temperature before study intervention 
administration 
 
● 
 
● 
 
● 
 
See Section 8.2.1.3 for more 
information. 
The preferred route for measuring 
temperature will be axillary. Fever 
is defined as temperature ≥37.5°C 

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Age at time of study enrolment 
6-10 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 a 
Visit 4 
Visit 5 a 
Visit 6 
Visit 7 
 
Timepoints 
Day 1 
Month 0.5 
Month 1 
Month 1.5 
Month 2 
Month 2.5 
Month 3.5 
Administration of study intervention: Rotarix PCV-
free 
 
● 
 
● 
 
 
 
See Section 6.1 for more 
information 
Administration of study intervention: IPV 
 
● 
 
● 
 
● 
 
See Section 6.1 for more 
information 
Recording of administered intervention number 
 
● 
 
● 
 
● 
 
 
Recording of regurgitation/vomiting 
 
● 
 
● 
 
 
 
If regurgitation or vomiting occurs 
within 30 minutes after study 
intervention administration, 
administration of a replacement 
dose is not recommended. This 
information on regurgitation or 
vomiting should be recorded in the 
electronic Case Report Form 
(eCRF). The participant should 
continue to participate in the study 
Distribution of ‘Participant card’ 
 
O 
 
 
 
 
 
See Section 8.3.5 for more 
information 
Distribution of diary cards 
 
● 
 
● 
 
 
 
 
Laboratory Assessment 
Blood sampling for antibody determination (at least 
2 mL) 
 
●^ 
 
 
 
●^ 
● 
^Blood sampling to be done before 
study intervention administration. 
Volume of the blood sample 
should be between 2 and 2.5 mL.  
See Section 8.1.1 for more 
information 
Safety assessments 
Record any concomitant medications/vaccinations 
 
● 
●* 
● 
●* 
● 
● 
See Section 6.8 for more 
information 
Recording of solicited events post Dose 1 and 
Dose 2 of study intervention administration (Days 
1-14*) 
 
● 
 
● 
 
 
 
See Section 10.3.3 and Section 
10.3.6.1 for more information 
Recording of unsolicited AEs after each dose of 
Rotarix administration (Days 1-31) 
 
● 
●* 
● 
●* 
● 
 
See Section 10.3.4 and Section 
10.3.6.1 for more information 

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Age at time of study enrolment 
6-10 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 a 
Visit 4 
Visit 5 a 
Visit 6 
Visit 7 
 
Timepoints 
Day 1 
Month 0.5 
Month 1 
Month 1.5 
Month 2 
Month 2.5 
Month 3.5 
Record any intercurrent medical conditions b 
 
● 
●* 
● 
●* 
● 
● 
See Section 9 for more information 
Recording of AEs that led to withdrawal from study 
● 
● 
●* 
● 
●* 
● 
● 
See Section 10.3.6.1 for more 
information. 
 
Recording of SAEs 
● 
● 
●* 
● 
●* 
● 
● 
See Section 10.3.6.1 for more 
information 
Recording of SAEs related to study participation, 
or to a concurrent GSK medication/vaccine 
● 
● 
●* 
● 
●* 
● 
● 
See Section 10.3.6.1 for more 
information. 
The collection and reporting 
periods start once the participants’ 
parents/LARs informed consent is 
obtained 
Return of diary cards 
 
 
 
● 
 
● 
 
 
Diary card transcription by investigator or designee 
 
 
 
● 
 
● 
● 
 
Study Conclusion 
 
 
 
 
 
 
● 
See Section 4.4 for more 
information 
AE: Adverse Event; IPV: Inactivated poliovirus vaccine; LAR: Legally Acceptable Representative; PCV: Porcine circovirus; PCV-free: no detection of PCV-1 and PCV-2 according to the 
limit of detection of the tests used; SAE: Serious Adverse Event; mL: milliliter 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
●* is used to indicate documentation activity that does not involve any site visit. These activities can be recorded by the participant and will be collected at the next site visit. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
a Visit 3 and Visit 5 are not applicable for the Co-administration group. 
b immunosuppressive or immunodeficient conditions. 
Note: Details of COVID-19 infection-related signs and symptoms should also be recorded in a separate eCRF page. 
*Number of days for recording of solicited events after each dose of study intervention is defined by Chinese authorities [NMPA, 2019a].  

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Table 2 
SoA for Staggered group 
Age at time of study enrolment 
6-10 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Timepoints 
Day 1 
Month 0.5 
Month 1 
Month 1.5 
Month 2 
Month 2.5  
Month 3.5 
Informed consent by parent(s)/LAR(s) 
● 
 
 
 
 
 
 
See Section 10.1.3 for details 
Check inclusion/exclusion criteria 
● 
 
 
 
 
 
 
See Section 5.1 for Inclusion 
criteria and Section 5.2 for 
Exclusion criteria 
Collect demographic data and gestational age 
● 
 
 
 
 
 
 
See Section 8.2.1.1 for more 
information 
Medical and vaccination history 
● 
 
 
 
 
 
 
See Section 8.2.1.2 for more 
information 
Physical examination 
● 
 
 
 
 
 
 
See Section 8.2.1.3 for more 
information 
Measure/record height and weight 
● 
 
 
 
 
 
 
See Section 8.2.1.3 for more 
information 
Study intervention 
Check contraindications, warnings and 
precautions to study intervention administration 
● 
● 
● 
● 
 
● 
 
See Sections 7.1.1 and 8.2.1.4 
for more information 
Randomization 
● 
 
 
 
 
 
 
See Section 6.3 for more 
information 
Check criteria for temporary delay for enrolment 
and study intervention administration 
O 
O 
O 
O 
 
O 
 
See Section 5.5 for more 
information 
Study group and intervention number allocation 
O 
 
 
 
 
 
 
See Sections 6.3.2 and 6.3.3 for 
more information 
Allocation of treatment number for subsequent 
dose 
 
● 
● 
● 
 
● 
 
See Section 6.3.3 for more 
information 
Body temperature before study intervention 
administration 
● 
● 
● 
● 
 
● 
 
See Section 8.2.1.3 for more 
information. 
The preferred route for 
measuring temperature will be 
axillary. Fever is defined as 
temperature ≥ 37.5°C 
Administration of study intervention: Rotarix 
PCV-free 
● 
 
● 
 
 
 
 
See Section 6.1 for more 
information 

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Age at time of study enrolment 
6-10 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Timepoints 
Day 1 
Month 0.5 
Month 1 
Month 1.5 
Month 2 
Month 2.5  
Month 3.5 
Administration of study intervention: IPV 
 
● 
 
● 
 
● 
 
See Section 6.1 for more 
information 
Recording of administered intervention number 
● 
● 
● 
● 
 
● 
 
 
Recording of regurgitation/vomiting 
● 
 
● 
 
 
 
 
If regurgitation or vomiting occurs 
within 30 minutes after study 
intervention administration, 
administration of a replacement 
dose is not recommended. This 
information on regurgitation or 
vomiting should be recorded in 
the eCRF. The participant should 
continue to participate in the 
study 
Distribution of ‘Participant card’ 
O 
 
 
 
 
 
 
See Section 8.3.5 for more 
information 
Distribution of diary cards 
● 
● 
● 
● 
 
 
 
 
Laboratory Assessment  
Blood sampling for antibody determination (at 
least 2 mL) 
●^ 
 
 
 
● 
 
● 
^Blood sampling before study 
intervention administration. 
Volume of the blood sample 
should be between 2 and 2.5 mL 
See Section 8.1.1 for more 
information 
Safety assessments 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
See Section 6.8 for more 
information 
Recording of solicited events post Dose 1 and 
Dose 2 of study intervention (Days 1-14*) 
● 
● 
● 
● 
● 
 
 
See Section 10.3.3 and Section 
10.3.6.1 for more information 
Recording of unsolicited AEs after each dose of 
Rotarix administration (Days 1-31) 
● 
● 
● 
● 
● 
 
 
See Section 10.3.4 and Section 
10.3.6.1 for more information 
Record any intercurrent medical conditions a 
● 
● 
● 
● 
● 
● 
● 
See Section 9 for more 
information 

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Age at time of study enrolment 
6-10 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Timepoints 
Day 1 
Month 0.5 
Month 1 
Month 1.5 
Month 2 
Month 2.5  
Month 3.5 
Recording of AEs that led to withdrawal from 
study 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.6.1 for more 
information. 
Recording of SAEs 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.6.1 for more 
information 
Recording of SAEs related to study participation, 
or to a concurrent GSK medication/vaccine 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.6.1 for more 
information. 
The collection and reporting 
periods start once the 
participants’ parents/LARs 
informed consent is obtained. 
Return of diary cards 
 
● 
● 
● 
 
● 
 
 
Diary cards transcription by investigator or 
designee 
 
● 
● 
● 
● 
● 
 
 
Study Conclusion 
 
 
 
 
 
 
● 
See Section 4.4 for more 
information 
AE: Adverse Event; IPV: Inactivated poliovirus vaccine; LAR: Legally Acceptable Representative; PCV: Porcine circovirus; PCV-free: no detection of PCV-1 and PCV-2 according to the 
limit of detection of the tests used; SAE: Serious Adverse Event; mL: milliliter 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
a immunosuppressive or immunodeficient conditions. 
Note: Details of COVID-19 infection-related signs and symptoms should also be recorded in a separate eCRF page. 
*Number of days for recording of solicited events after each dose of study intervention is defined by Chinese authorities [NMPA, 2019a].  

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Table 3 
Intervals between study visits for Co-administration group 
Interval 
Optimal interval 
Allowed interval range 
Allowed interval during special 
circumstances# 
Visit 1→Visit 2 
15 days 
14-18 days between study enrolment 
and Dose 1 of IPV and Rotarix PCV-
free 
14-45 days 
Visit 2→Visit 4 
30 days 
28-36† days between Dose 1 of IPV 
and Rotarix PCV-free and Dose 2 of 
IPV and Rotarix PCV-free 
28-60 days 
Visit 4→Visit 6 
30 days 
28-36† days between Dose 2 of IPV 
and Rotarix PCV-free and Dose 3 of 
IPV and BS for assessment of 
Rotavirus Ab, IgA 
28-60 days 
Visit 6→Visit 7 
30 days 
30-36† days between Dose 3 of IPV 
and BS for assessment of anti-
poliovirus types 1, 2 and 3 Ab 
30-60 days 
Ab: Antibody; BS: Blood sampling; IgA: Immunoglobulin A; IPV: Inactivated poliovirus vaccine; PCV: Porcine circovirus; 
PCV-free: no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used 
† Participants will not be eligible for inclusion in the Per Protocol Set for immunogenicity if they make the study visit 
outside this interval. Interval is computed as the difference between the 2 dates of the study procedure. 
# Refer to Section 8 for more details on special circumstances (e.g., COVID-19 pandemic). 
Table 4 
Intervals between study visits for Staggered group 
Interval 
Optimal interval 
Allowed interval range 
Allowed interval during special 
circumstances# 
Visit 1→Visit 2 
15 days 
14-18† days between Dose 1 of Rotarix 
PCV-free and Dose 1 of IPV 
14-45 days 
Visit 1→Visit 3 
30 days 
28-36† days between Dose 1 and Dose 
2 of Rotarix PCV-free 
28-60 days 
Visit 2→Visit 4 
30 days 
28-36† days between Dose 1 and Dose 
2 of IPV 
28-60 days 
Visit 3→Visit 5 
30 days 
28-36† days between Dose 2 of Rotarix 
PCV-free and BS for assessment of 
Rotavirus Ab, IgA 
28-60 days 
Visit 4→Visit 6 
30 days 
28-36† days between Dose 2 and Dose 
3 of IPV 
28-60 days 
Visit 6→Visit 7 
30 days 
30-36† days between Dose 3 of IPV 
and BS for assessment of anti-
poliovirus types 1, 2 and 3 Ab 
30-60 days 
Ab: Antibody; BS: Blood sampling; IgA: Immunoglobulin A; IPV: Inactivated poliovirus vaccine; PCV: Porcine circovirus; 
PCV-free: no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used 
† Participants may not be eligible for inclusion in the Per Protocol Set for immunogenicity if they make the study visit 
outside this interval. Interval is computed as the difference between the 2 dates of the study procedure. 
# Refer to Section 8 for more details on special circumstances (e.g., COVID-19 pandemic). 

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2. 
INTRODUCTION 
2.1. 
Study rationale 
GSK’s Rotarix liquid vaccine is currently approved in all EEA countries, UK, US, Japan, 
as well as over 90 other countries. GSK intends to register Rotarix PCV-free liquid 
vaccine (hereafter referred as Rotarix PCV-free) in China. “PCV-free” is defined as no 
detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. 
In China, under the NIP, a 3-dose primary vaccination against poliovirus is currently 
recommended during the first year of life in a 2, 3 and 4 months of age schedule and a 
booster vaccine is recommended at 4 years of age. IPV is used for the first 2 doses, and 
OPV is used for the third and the fourth dose. 
This study is designed to evaluate the immunogenicity and safety of IPV when 
co-administered with Rotarix PCV-free, in healthy Chinese infants.  
2.2. 
Background 
RV infects almost every child before they reach the age of 3 to 5 years and is the leading 
cause of acute gastroenteritis (GE) and diarrhea, which can lead to severe dehydration 
[Atherly, 2009]. Prior to the introduction of RV vaccines in 2006, RV was accountable 
for an estimated 528 000 deaths worldwide annually, with the largest number of deaths 
occurring in the Sub-Saharan Africa region [WHO position paper, 2021; Tate, 2016; 
Bányai, 2018]. In 2013, several years after the launch of RV vaccines, it has been 
estimated that approximately 215 000 deaths (95% confidence interval [CI]: 197 000, 
233 000) were caused by RV infection. India, Nigeria, Pakistan, and Democratic 
Republic of Congo accounted for approximately half (49%) of all the estimated RV 
deaths in 2013 [Dennehy, 2008; Tate, 2016]. In China, 42.6% of all the hospitalizations 
for severe GE, 32.5% of outpatient visits for diarrhea and 9.3% of all diarrhea episodes in 
community settings are caused by RV [Fu, 2018]. 
The World Health Organization (WHO) recognizes RV vaccination as an effective 
measure to prevent RV infection and to reduce disease burden, and recommends its 
inclusion into all national infant immunization programs, particularly in countries where 
RVGE-associated fatality rates are high among children aged <5 years (e.g., South and 
South-Eastern Asia and Sub-Saharan Africa) [WHO position paper, 2021]. 
GSK HRV vaccine (Rotarix) is registered in around 130 countries and more than 790 
million doses of the vaccine (lyophilized and liquid formulations) are estimated to have 
been distributed worldwide from its launch until July 2022. 
Please refer to the current investigator’s brochure (IB) for information regarding the 
preclinical studies, clinical studies and epidemiology studies of Rotarix vaccine. 

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2.3. 
Benefit/Risk assessment 
Detailed information about the known and expected benefits and risks and expected 
adverse events of Rotarix can be found in the IB and of IPV can be found in the 
Prescribing Information (PI). 
3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
Table 5 
Study objectives, endpoints and estimands 
Objectives 
Endpoints and estimands 
Primary (Confirmatory) 
• To demonstrate the immunological non-inferiority of 
IPV when co-administered with Rotarix PCV-free 
compared with IPV administered alone. 
• Anti-poliovirus types 1, 2 and 3 neutralizing Ab 
seroconversion rate* 1 month post Dose 3 of IPV in 
the Co-administration and Staggered groups. 
Secondary (Descriptive) 
• To evaluate the immunogenicity of IPV when co-
administered with Rotarix PCV-free and when 
administered alone. 
• Anti-poliovirus types 1, 2 and 3 neutralizing Ab 
GMTs at 1 month post Dose 3 of IPV in the Co-
administration and Staggered groups. 
• Percentage of participants with anti-poliovirus types 
1, 2 and 3 neutralizing Ab titers ≥1:8 and ≥1:64 at 
1 month post Dose 3 of IPV in the Co-administration 
and Staggered groups. 
• To evaluate the immunogenicity of Rotarix PCV-free 
when co-administered with IPV and when 
administered alone. 
• Anti-RV IgA Ab seroconversion rate** 1 month post 
Dose 2 in the Co-administration and Staggered 
groups. 
• Anti-RV IgA Ab GMCs at 1 month post Dose 2 of 
Rotarix PCV-free in the Co-administration and 
Staggered groups. 
• Percentage of participants with anti-RV IgA Ab 
concentrations ≥90 U/mL at 1 month post Dose 2 of 
Rotarix PCV-free in the Co-administration and 
Staggered groups. 
• To evaluate the reactogenicity of Rotarix PCV-free 
and IPV in terms of solicited systemic events. 
• To assess the safety of Rotarix PCV-free in terms of 
unsolicited AEs and serious adverse events (SAEs) 
and safety of IPV in terms of SAEs. 
• Solicited AEs 
− For each solicited systemic event, percentage of 
participants reporting the occurrence of the event 
within 14 days (Day 1- Day 14) after Dose 1 and 
Dose 2 of Rotarix and IPV  
• Unsolicited AEs 
− Percentage of participants reporting the occurrence 
of unsolicited AEs within 31 days (Day 1- Day 31) 
after each dose of Rotarix, according to the 
MedDRA classification. 
• SAEs: 
− Percentage of participants reporting SAEs from the 
first dose of the study intervention up to study end in 
the Co-administration and Staggered groups. 

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Ab: Antibody; GMC: Geometric mean Ab concentration; GMT: Geometric mean Ab titer; IgA: Immunoglobulin A; 
IPV: Inactivated poliovirus vaccine; MedDRA: Medical Dictionary for Regulatory Activities; mL: milliliter; PCV: Porcine 
circovirus; SAE: Serious Adverse Event; U: Unit 
*Seroconversion rate for IPV neutralizing Ab is defined as percentage of participants with 
- 
Titer 1:8 at 1 month after 3 dose primary schedule of IPV in participants with titer <1:8 pre-vaccination 
- 
Titer 4-fold increase in titer 1 month after 3 dose primary vaccination schedule in participants with titer 
1:8 pre-vaccination. 
Note: the 4-fold increase will take into consideration the expected decline in maternal antibodies with 
estimated half-life of 28 days. 
**Seroconversion rate for anti-RV IgA Ab is defined as the percentage of participants who were initially seronegative 
(i.e., with anti-RV IgA Ab concentration <20 U/mL prior the first dose of Rotarix) and developed anti-RV IgA Ab 
concentration 20 U/mL at 1 month post Dose 2. 
Refer to Section 8 for details on SAEs. 
Refer to Section 9.3 and Section 9.4 for additional details on statistical analyses. 
Details related to attributes of estimand covering intercurrent events, population and 
treatment definition are provided in the Section 9. 
4. 
STUDY DESIGN 
4.1. 
Overall design 
The study design is presented in Figure 1. 

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Figure 1 
Study design overview 
 
AE: Adverse Event; IPV: Inactivated poliovirus vaccine; PCV: Porcine circovirus; PCV-free: no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used; SAE: 
Serious Adverse Event; N: Total number of participants planned to be enrolled; n: Planned number of participants in each group. 
Study interventions: IPV (Co-administered vaccine) and Rotarix PCV-free (Study vaccine). 
$ Refer to the Schedule of activities (SoA; Section 1.3) for Co-administration group. Note: For the Co-administration group, unsolicited AEs will be collected from visit 2 till visit 6. 
+ Visit not applicable for participants in the Co-administration group. 
^ Blood sampling to be done before study intervention administration. 
° Blood sample for anti-poliovirus types 1, 2 and 3 antibodies measurement. 
* Blood sample for anti-RV IgA antibody measurement. 

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• 
Experimental design: Phase III, open-label, randomized, controlled study with 2 
groups (see Figure 1). 
• 
Duration of the study: The total duration of the study, per participant, will be 
approximately 3.5 months. 
• 
Control: active comparator, i.e., staggered administration of licensed IPV and 
Rotarix PCV-free. 
• 
Blinding: Open-label. Refer to Section 6.3.4 for details. 
• 
Data collection: Standardized electronic Case Report Form (eCRF). Solicited 
systemic events will be collected using a diary card. Refer to Section 10.3.6.1 for 
details on recording and follow-up of SAEs. 
• 
Primary Completion Date (PCD): Visit 7 (Month 3.5). 
• 
End of Study (EoS): EoS is defined as last subject last visit (LSLV) (Visit 7) or date 
of the last testing/reading released of the Human Biological Samples, related to 
primary and secondary endpoints, whichever occurs later. EoS must be achieved no 
later than 8 months after LSLV. EoS cannot be before LSLV. Refer to Section 4.4 
for details. 
Table 6 
Study groups, intervention and blinding 
Study groups 
Number of 
participants 
Age (Min-Max) 
Study interventions 
Blinding 
Co-administration 
200 
6-10 weeks* 
IPV, Rotarix PCV-free 
Open-label 
Staggered 
200 
6-10 weeks* 
IPV, Rotarix PCV-free 
Open-label 
IPV: Inactivated poliovirus vaccine; Max: maximum; Min: minimum; PCV: Porcine circovirus 
* 6-10 weeks at the time of study enrolment 
4.2. 
Scientific rationale for study design 
In China, under the NIP, a 3-dose primary vaccination against poliovirus is currently 
recommended during the first year of life in a 2, 3 and 4 months of age schedule. Rotarix 
should be given in a 2-dose schedule between 6-24 weeks of age with an interval of at 
least 4 weeks between doses. Till date, there is no data available on the immunogenicity 
and safety of IPV when co-administered with Rotarix PCV-free, in healthy Chinese 
infants. 
The current study is therefore designed to assess the immunogenicity and safety of IPV 
when it is co-administered with Rotarix PCV-free, compared to administration of the 
vaccines separately. There are 2 parallel arms: 
• 
Co-administration group: participants will receive Rotarix PCV-free co-
administered with IPV at Month 0.5 and Month 1.5, and IPV at Month 2.5. 
• 
Staggered group: participants will receive Rotarix PCV-free at Day 1 and Month 1, 
and IPV at Month 0.5, Month 1.5, and Month 2.5. 

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The study will enroll infants 6-10 weeks of age. This will ensure compliance with the 
recommendations mentioned below, including for participants of the Co-administration 
group who will receive the first dose of Rotarix and IPV at 2 weeks after enrolment: 
• 
As per CDC recommendation, the first dose of Rotarix should be given before an 
infant is 15 weeks of age and the second dose before they turn 8 months old.  
• 
As per EU SmPC recommendation, the first dose of Rotarix may be administered 
from 6 weeks of age. There should be an interval of at least 4 weeks between doses. 
The second dose should preferably be given before 16 weeks of age but must be 
completed by the age of 24 weeks.  
• 
In China, IPV is recommended as 2 doses at the age of 2 and 3 months and no later 
than 13 weeks of age for the first dose. 
Please refer to the IB for further information on Rotarix. 
Please refer to the PI for further information on Beijing Biological Products Institute 
Co.,Ltd. IPV. 
4.3. 
Justification for dose 
Two oral doses of Rotarix PCV-free will be administered at approximately 1 month 
interval to participants, according to the immunization schedule of Rotarix licensed 
outside of China. 
Three doses of IPV will be administered in a 2, 3 and 4 months of age schedule, 
according to the recommended schedule for vaccination against poliovirus in China. 
4.4. 
EoS definition 
A participant is considered to have completed the study if the participant returns for the 
last visit or is available for the last scheduled procedure as described in the protocol. 
EoS is defined as LSLV (Visit 7) or date of the last testing/reading released of the Human 
Biological Samples, related to primary and secondary endpoints, whichever occurs later. 
EoS must be achieved no later than 8 months after LSLV. EoS cannot be before LSLV. 
5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardize the scientific 
integrity, regulatory acceptability of the study or safety of the participant. 

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5.1. 
Inclusion criteria 
All participants must satisfy ALL the following criteria at study entry: 
• 
Participants’ parent(s)/Legally Acceptable Representative(s) (LAR), who, in the 
opinion of the investigator, can and will comply with the requirements of the 
protocol. 
• 
Written or witnessed/thumb printed informed consent obtained from the 
parent(s)/LAR(s) of the participant prior to performance of any study specific 
procedure. 
• 
Healthy participants as established by medical history and clinical examination 
before entering into the study. 
• 
A male or female of Chinese origin, between and including, 6 and 10 weeks (42-76 
days) of age at the time of study enrolment. 
• 
Born after a gestation period of 36 to 42 weeks inclusive. 
5.2. 
Exclusion criteria 
The following criteria should be checked at the time of study entry. The potential 
participant MUST NOT be included in the study if ANY exclusion criterion applies: 
5.2.1. 
Medical conditions 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study interventions. 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required). 
• 
Hypersensitivity to latex. 
• 
History of severe combined immunodeficiency. 
• 
History of seizures or progressive neurological disease. 
• 
Family history of congenital or hereditary immunodeficiency. 
• 
Uncorrected congenital malformation (such as Meckel’s diverticulum) of the 
gastrointestinal tract that would predispose for intussusception (IS). 
• 
History of IS. 
• 
Major congenital defects, or serious chronic illness as assessed by the investigator. 
• 
Any contraindications to IPV. 
• 
Previous confirmed occurrence of rotavirus gastroenteritis (RVGE). 
• 
History of poliomyelitis. 
• 
Participants with confirmed or suspected Coronavirus Disease 2019 (COVID-19). 

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5.2.2. 
Prior/Concomitant therapy 
• 
Use of any investigational or non-registered product (drug, vaccine or invasive 
medical device) other than the study interventions during the period beginning 30 
days before the first dose of study interventions (Day -29 to Day 1), or planned use 
during the study period. 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 30 days before the first dose and ending 30 days after 
the last dose of study interventions administration*, with the exception of the 
inactivated influenza vaccine, which is allowed at any time during the study and 
other licensed routine childhood vaccinations. 
− 
*In case emergency mass vaccination for an unforeseen public health threat 
(e.g., a pandemic) is recommended and/or organized by public health authorities 
outside the routine immunization program, the time period described above can 
be reduced if, necessary for that vaccine, provided it is used according to the 
local governmental recommendations and that the Sponsor is notified 
accordingly. 
• 
Administration of long-acting immune-modifying drugs from birth or planned 
administration at any time during the study period (e.g., infliximab). 
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
from birth or planned administration during the study period. 
• 
Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs since birth. For 
corticosteroids, this will mean prednisone ≥0.5 milligram/kilogram (kg)/day, or 
equivalent. Inhaled, intra-articular and topical steroids are allowed. 
• 
Previous vaccination against RV. 
• 
Previous vaccination against poliomyelitis. 
5.2.3. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational intervention (drug, vaccine or invasive medical device). 
5.2.4. 
Other exclusions 
• 
Child in care. Please refer to the glossary of terms for the definition of child in care. 
5.3. 
Lifestyle considerations 
This section is not applicable. 

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5.4. 
Screening failures 
A screening failure is an individual who consents to participate in this study but is not 
entered in the study/randomized to a study intervention. 
Limited data for screening failures (including reason for screening failure) will be 
collected and reported in the eCRF. 
5.5. 
Criteria for temporarily delaying enrolment and/or study 
intervention administration 
Enrolment/study intervention administration may be postponed within the permitted time 
interval until transient conditions cited below are resolved: 
• 
Non-rotavirus GE within 7 days preceding the study intervention administration. 
• 
Acute disease and/or fever at the time of enrolment and/or study intervention 
administration. Refer to the SoA (Section 1.3) for fever definition and preferred 
location for measuring temperature in this study. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be enrolled and/or vaccinated at the discretion of the 
investigator. 
• 
Participants with known COVID-19 positive contacts within the past 14 days. 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Refer to the Glossary of terms for the definition of study intervention. 

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6.1. 
Study interventions administered 
Table 7 
Study interventions administered 
Study intervention name: 
Inactivated Poliomyelitis Vaccine Made From Sabin Strains 
(Vero Cells) (IPV) 
Rotarix PCV-free (HRV PCV-free) 
Study intervention formulation: 
 
HRV RIX4414 
 
 Sterile water 
Presentation: 
 
 
Type: 
Co-administered 
Study 
Product category: 
Combination product* 
Combination product* 
Route of administration:  
Intramuscular 
Oral 
Administration site: 
• 
Location 
Refer to the Pharmacy Manual for more details 
NA 
• 
Directionality 
Refer to the Pharmacy Manual for more details 
NA 
• 
Laterality 
Refer to the Pharmacy Manual for more details 
NA 
Number of doses to be administered: 
3 
2 
Volume to be administered by dose: 
0.5 mL 
1.5 mL 
Packaging and labeling: 
Refer to the Pharmacy Manual for more details 
Refer to the Pharmacy Manual for more details 
Manufacturer: 
Beijing Biological Products Institute Co.,Ltd. 
GSK 
DAgU: D antigen unit; HRV: human rotavirus; IPV: inactivated poliovirus vaccine; mL: milliliter; NA: Not applicable; PCV: Porcine circovirus; PCV-free: no detection of PCV-1 and PCV-
2 according to the limit of detection of the tests used 
*Combining a biological product and device 
Refer to Section 6.1 for schedule of study intervention administration. 
CCI
CCI
CCI
CCI
CCI

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Study participants must be observed closely for at least 30 minutes after the 
administration of the study interventions. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis, syncope. 
6.2. 
Preparation, handling, storage, and accountability 
The study interventions must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s). 
Only authorized study personnel should be allowed access to the study interventions. 
Storage conditions will be assessed by a sponsor study contact during pre-study activities. 
Refer to the Pharmacy Manual for more details on storage and handling of the study 
interventions. 
6.3. 
Measures to minimize bias: randomization and blinding 
6.3.1. 
Participant identification 
Participant identification numbers will be assigned sequentially to the participants who 
have consented to participate in the study, according to the range of participant 
identification numbers allocated to each study center. 
6.3.2. 
Randomization to study intervention 
Approximately 400 eligible participants will be randomly assigned (1:1) to the 2 study 
groups (Co-administration and Staggered). 
The numbering of Rotarix PCV-free and IPV supplies will be performed at GSK, using a 
block scheme randomization in MATerial EXcellence, a program developed by GSK. 
Entire blocks will be shipped to the study centers/warehouse(s). 
To allow GSK to take advantage of greater rates of recruitment than anticipated in this 
study and to thus reduce the overall study recruitment period, an over-randomization of 
supplies will be prepared. 
6.3.3. 
Intervention allocation to the participant 
The system’s randomization algorithm will use a minimization procedure accounting for 
center and the study as a whole as minimization factors. Minimization factors will have 
equal weight in the minimization algorithm. 
Once a participant identification number is allocated, the randomization system will 
determine study group and will provide the study intervention number to be used for the 
first dose. The study intervention number(s) to be used for subsequent dosing will be 
provided by the same automated Internet-based system (Source Data Base for Internet 
Randomization [SBIR]). 

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When SBIR is not available, please refer to the SBIR user guide or Pharmacy Manual for 
specific instructions. 
Refer to the Pharmacy Manual for additional information about the study intervention 
number allocation. 
6.3.4. 
Blinding and unblinding 
The study will be conducted in an open-label manner with respect to Rotarix PCV-free 
and IPV. 
6.4. 
Study intervention compliance 
Study intervention administration will be performed under medical supervision. The date 
of each dose administered in the study center will be recorded in the source documents 
and in the eCRF. 
6.5. 
Dose modification 
This section is not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study 
This section is not applicable. 
6.7. 
Treatment of overdose 
This section is not applicable. 
6.8. 
Concomitant therapy 
At each study visit, the investigator or their delegate should question the participant’s 
parent(s)/LAR(s) about all medications/products taken, and vaccinations received by the 
participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medications/products, except vitamins and dietary supplements, 
administered following each dose of study interventions (Day 1 to Day 31). 
• 
All concomitant vaccinations from Visit 1 up to the Visit 7 (blood sample visit).  
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines (Please refer to the 
sections 5.2.2 and 9.2.1 for further details). 

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• 
Prophylactic medication (i.e., medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the study intervention administration) 
e.g., an anti-pyretic is considered to be prophylactic when it is given in the absence 
of fever and any other symptom, to prevent fever from occurring [fever is defined as 
temperature ≥37.5°C. The preferred location for measuring temperature in this study 
will be the axilla]. 
• 
All concomitant medication which may explain/cause/be used to treat an SAE 
including vaccines/products, as defined in Sections 8.3.1 and 10.3.6.1. These must 
also be recorded in the Expedited AE report. 
The Local Medical Lead (LML) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7. 
DISCONTINUATION OF STUDY INTERVENTIONS AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study interventions 
‘Discontinuation’ of study interventions refers to any participant who has not received all 
planned doses of the study interventions. A participant who discontinued the study 
interventions may continue other study procedures (e.g., safety or immunogenicity), 
planned in the study protocol at the discretion of the investigator. 
The primary reason for premature discontinuation of the study interventions will be 
documented on the eCRF as follows: 
• 
AE requiring expedited reporting to GSK 
• 
Unsolicited nonserious AE 
• 
Solicited AE 
• 
Protocol deviation 
• 
Not willing to be vaccinated 
• 
Migrated/moved from study area 
• 
Other (specify). 
7.1.1. 
Contraindications to subsequent study interventions 
administration 
The eligibility for subsequent study interventions administration must be confirmed 
before administering any additional dose. 

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Participants who meet any of the criteria listed below or criteria listed in Section 5.2.1, 
Section 5.2.2, Section 5.2.3 and Section 5.2.4 should not receive additional doses of study 
intervention. Such participants should be encouraged to continue other study procedures, 
at the investigator’s discretion (Section 10.3.6.3). All relevant criteria for discontinuation 
of study intervention administration must be recorded in the eCRF. 
• 
Participants who experience any SAE judged to be possibly or probably related to 
study intervention or non-study concomitant vaccine/product, including 
hypersensitivity reactions. 
• 
Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participants if they continue to 
participate in the study. 
• 
Anaphylaxis following the administration of study interventions. 
• 
Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for them since the date of 
withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who did not 
return for the concluding visit planned in the protocol.  
Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. 
The primary reason for study withdrawal will be documented in the eCRF, based on the 
list below: 
• 
Adverse events requiring expedited reporting to GSK (please refer to the section 
10.3.8.1 for the details) 
• 
Unsolicited nonserious AE 
• 
Solicited AE 
• 
Protocol deviation 
• 
Withdrawal by participant, not due to an AE* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 

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• 
Sponsor study termination 
• 
Other (specify) 
*If a participant is withdrawn from the study because the participant’s parent(s)/LAR(s) 
has withdrawn consent and the reason for withdrawal was provided, the investigator must 
document this reason in the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.6.3). 
7.3. 
Lost to follow-up 
Participants will be considered ‘lost to follow-up’ if their parent(s)/LAR(s) fail to return 
for scheduled visits and cannot be contacted by the study site. 
Please refer to the Pharmacy Manual for a description of actions to be taken before 
considering the participant lost to follow-up. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant. 
Immediate safety concerns should be discussed with the sponsor as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarized in the SoA (Section 1.3). Adherence 
to the study design requirements, including those specified in the SoA, is essential and 
required for study conduct. 
All screening evaluations must be completed, and the results reviewed before confirming 
that potential participants meet all eligibility criteria. 
The investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for screening failure will be mentioned in 
this screening log. 
Procedures conducted as part of routine clinical management (e.g., hematologic profiles), 
and obtained before the participant’s parent(s)/LAR(s) signed the Informed Consent 
Form (ICF), may be used for screening and/or for establishing a clinical baseline 
(provided the procedure met protocol specified criteria and was performed within the 
time frame defined in the SoA [Section 1.3]).  
The Pharmacy Manual provides the investigator and site personnel with detailed 
administrative and technical information that does not impact participant safety. 

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During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, the 
following measures may be implemented for enrolled participants: 
• 
Biological samples may be collected at a different location* other than the study site 
or at participant’s home. Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use. 
• 
If despite best efforts it is not possible to collect the biological samples within the 
interval predefined in the protocol, then the interval may be extended up to a 
maximum length of 60 days (see Table 3 and Table 4). 
• 
If despite best efforts it is not possible to administer Dose 2 of Rotarix PCV-free 
according to the intervals defined in Table 3 and Table 4, a maximum age of 24 
weeks as per the label used outside of China may be used. 
*It is the investigator’s responsibility to identify an alternate location. The 
investigator should ensure that this alternate location meets International Council on 
Harmonization (ICH) Good Clinical Practice (GCP) requirements, such as adequate 
facilities to perform study procedures, appropriate training of the staff and 
documented delegation of responsibilities in this location. This alternate location 
should be covered by proper insurance for the conduct of study on participants by 
investigator and staff at a site other than the designated study site. Refer to EMA 
Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) 
pandemic (version 5, 10 February 2022) for more details. 
8.1. 
Immunogenicity assessments 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. 
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
Independent Ethics Committee (IEC)/ Institutional Review Board (IRB) approval, if 
required by local legislation. 
Information on further research and its rationale can be obtained from GSK.  
Sample testing will be done in accordance with the recorded consent of the individual 
participant’s parent(s)/LAR(s). 

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By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed and agreed 
with GSK. 
8.1.1. 
Biological samples 
Per participant, an overall volume of at least 6 mL (not more than 7.5 mL) will be 
collected during the entire study period. Refer to Table 8 and SoA (Section 1.3) for 
details of volumes collected for different assessments. 
Table 8 
Biological samples 
Group 
Sample type 
Quantity 
Unit 
Timepoint 
Co-administration 
Blood* 
At least 2** 
mL 
Visit 2 (Month 0.5) 
Visit 6 (Month 2.5) 
Visit 7 (Month 3.5) 
Staggered group 
Blood* 
At least 2** 
mL 
Visit 1 (Day 1) 
Visit 5 (Month 2) 
Visit 7 (Month 3.5) 
mL: milliliter 
*Blood sampling to be done before study intervention administration. 
**Volume of the blood sample should be between 2 and 2.5 mL. 
8.1.2. 
Laboratory assays 
Table 9 
Laboratory assays 
Test 
Classification 
System 
Component 
Method 
Laboratory* 
Humoral Immunity 
(Antibody 
determination) 
Serum 
Rotavirus Ab, IgA 
ELISA 
GSK designated lab in China 
IPV Ab, type 1 
IPV Ab, type 2 
IPV Ab, type 3 
Microneutralization 
assay 
GSK designated lab in China 
Ab: Antibody; IgA: Immunoglobulin A; IPV: Inactivated poliovirus vaccine; ELISA: Enzyme Linked Immunosorbent 
Assay 
*Refer to the list of clinical laboratories for details. 
Please refer to Section 10.2 for a brief description of the assays performed in the study. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 

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8.1.3. 
Immunological read-outs 
Table 10 
Immunological read-outs 
Blood sampling timepoint 
Subset name 
No. participants 
Component 
Type of contact 
and timepoint 
Sampling timepoint 
Visit 1 (Day 1) 
Pre-first Dose administration 
Staggered group 
200 
Rotavirus Ab, IgA 
IPV Ab, type 1 
IPV Ab, type 2 
IPV Ab, type 3 
Visit 2 (Month 0.5) 
Pre-first Dose administration 
Co-administration 
group 
200 
Rotavirus Ab, IgA 
IPV Ab, type 1 
IPV Ab, type 2 
IPV Ab, type 3 
Visit 5 (Month 2) 
Post Dose 2 of Rotarix PCV-free 
Staggered group 
200 
Rotavirus Ab, IgA 
Visit 6 (Month 2.5) Post Dose 2 of Rotarix PCV-free 
Co-administration 
group 
200 
Rotavirus Ab, IgA 
Visit 7 (Month 3.5) 
Post Dose 3 of IPV 
All participants 
(Co-administration 
group + Staggered 
group) 
400 
IPV Ab, type 1 
IPV Ab, type 2 
IPV Ab, type 3 
Ab: Antibody; IgA: Immunoglobulin A; IPV: Inactivated poliovirus vaccine; PCV: Porcine circovirus; PCV-free: no 
detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. 
8.1.4. 
Immunological correlates of protection 
No recognized immunological correlate of protection (CoP) has been established for the 
antigen used as part of the HRV vaccine. However, an analysis by Cheuvart et al. in 2014 
showed that post-vaccination anti-RV IgA seropositivity (Ab concentration ≥ 20 U/mL, 
measured by ELISA) is a correlate of vaccine efficacy in clinical trials of Rotarix 
[Cheuvart, 2014]. This was confirmed by an independent research group in 2020 
[Baker, 2020]. 
Antibodies against poliovirus types 1, 2 and 3 will be determined by a virus 
microneutralization test adapted from the WHO Guidelines for WHO/EPI Collaborative 
Studies on Poliomyelitis [WHO position paper, 1993]. Titers will be expressed in terms 
of the reciprocal of the dilution resulting in 50% inhibition. The lowest dilution at which 
serum samples will be tested is 1:8. Antibody titers greater than or equal to 1:8 will be 
considered as protective. 
The immunological assay results will be communicated to the investigator after the end 
of the study. 
8.2. 
Safety assessments 
The investigator(s) and their designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and designees 
are responsible for following up AEs that are serious, or that caused the participant’s 
withdrawal from the study interventions or study. 

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Note: Details of COVID-19 infection-related signs and symptoms will be recorded in a 
separate eCRF page. 
8.2.1. 
Pre-intervention administration procedures 
8.2.1.1. 
Collection of demographic data 
Record demographic data such as date of birth including gestational age, gender, race and 
ethnicity in the participants’ eCRF. 
Collection of race and ethnicity data is necessary to meet the inclusion criteria of the 
study participants, and to determine if the study participants are truly representative of the 
impacted population. 
8.2.1.2. 
Medical/vaccination history 
Obtain the participant’s medical/vaccination history by interviewing the parent(s)/LAR(s) 
and/or review of the participant’s medical records. Record any pre-existing conditions, 
signs and/or symptoms present prior to the first dose of study intervention administration 
in the eCRF. 
8.2.1.3. 
Physical examination 
• 
Axillary body temperature* of each participant needs to be measured prior to any 
study intervention administration and recorded in the eCRF. If the participant has 
fever (defined as temperature ≥37.5°C) on the day of administration of the study 
intervention, the study visit will be rescheduled within the allowed interval for this 
visit (see Table 3 and Table 4). 
*Axilla is the preferred route to measure temperature in China. If temperature is 
taken by other routes, conversion can be made as per local guidelines:  
− 
Axillary temperature  =  oral temperature - 0.2℃; 
− 
Axillary temperature  =  rectal temperature - 0.3℃. 
• 
Weight and height must be collected at Visit 1 and recorded in the eCRF. 
• 
Physical examination at each study visit subsequent to the first study intervention 
administration visit will be performed only if the participant’s parent(s)/LAR(s) 
indicates during questioning that there might be some underlying pathology(ies) or if 
deemed necessary by the investigator or delegate.  
• 
If the investigator determines that the participant’s health on the day of study 
intervention administration temporarily precludes dosing, the visit will be 
rescheduled.  
• 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. 

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8.2.1.4. 
Warnings and precautions to administration of study interventions 
Warnings and precautions to administration of study intervention must be checked at 
each visit with planned administration of study intervention as specified in SoA 
(Section 1.3). 
Refer to the approved product label/package insert. 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
other safety reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE and other 
safety information 
An overview of the protocol required reporting periods for safety information and for 
AEs/SAEs leading to withdrawal is given in Table 11 and Table 12. 
The investigator or designee will record and immediately report all SAEs in enrolled 
participants to the sponsor or designee via the Expedited AE Reporting Form. Reporting 
should, under no circumstances, occur later than 24 hours after the investigator becomes 
aware of an SAE, as indicated in Section 10.3.8. The investigator will submit any updated 
SAE data to the sponsor within 24 hours of it being available. 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting periods defined in Table 11. Investigators are not obligated to actively seek AEs 
or SAEs from former study participants. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
if the investigator considers the event to be reasonably related to the study intervention, 
the investigator will promptly notify the study contact for reporting SAEs mentioned in 
the Table 13. 

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Table 11 
Timeframes for collecting and reporting of safety information 
Event 
V1+ 
 
V2+ 
 
V3+ 
 
V4+ 
 
V5+ 
 
V6+ 
 
V7+ (Study 
Conclusion) 
D1 
 
M0.5 
M1 
 
M1.5 
M2 
 
M2.5 
 
M 3.5 
Solicited events 
Co-ad group 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Solicited events 
Staggered 
group 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
Co-ad group* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
Staggered 
group* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs that led to 
withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
study 
participation**  
or concurrent 
GSK 
medication/ 
vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE: Adverse Event; Co-ad: Co-administration group; V: Visit; D: Day, M: Month; SAE: Serious Adverse Event 
* Unsolicited AEs will be collected only post Rotarix administration. 
** Any SAEs assessed as related to study participation (e.g., protocol-mandated procedures, invasive tests, or change 
in existing therapy) or related to a GSK product will be recorded from the time a participant’s parent(s)/LAR consents to 
participate in the study. 
+ Refer to Table 3 (for Co-administration group) and Table 4 (for Staggered group) for information about optimal 
interval. 
8.3.2. 
Method of detecting AEs and SAEs 
Detection and recording of AE/SAE are detailed in Section 10.3.6.1. 
Assessment of AE/SAE intensity, causality and outcome are described in Section 10.3.7. 

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Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
non-leading verbal questioning of participants’ parent(s)/LAR(s) is the preferred method 
of acquiring information related to an AE/SAE. 
8.3.3. 
Regulatory reporting requirements for SAEs 
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE, it must be reported to GSK using the required documentation and 
within the timeframes mentioned in Table 12. This is essential for GSK to meet legal 
obligations and ethical responsibilities for participant safety and the safety of a study 
intervention under clinical investigation. 
For SAEs, the investigator must always provide an assessment of causality at the time of 
the initial report, as defined in the Section 10.3.7.2. 
Local regulatory requirements and sponsor policy for preparation of an investigator 
safety report of Suspected Unexpected Serious Adverse Reaction (SUSAR) must be 
followed. These reports will be forwarded to investigators as necessary. 
The sponsor has the legal responsibility to notify local authorities/regulatory agencies 
about the safety of an investigational study intervention. The sponsor will comply with 
country-specific regulatory requirements related to safety reporting to the regulatory 
authority, IRB/IEC and investigators. 
Please refer to Section 10.3.8 for further details regarding the reporting of SAEs. 
Table 12 
Timeframes for submitting SAE and other events reports to GSK 
Type of event 
Initial reports 
Follow-up of relevant information on a 
previous report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ ‡‡ 
paper/electronic Expedited 
Adverse Events Report 
24 hours* 
paper/electronic Expedited 
Adverse Events Report 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
‡ Paper Expedited Adverse Events Report will be dated and signed by the investigator (or designee). 
‡‡ For each SAE, the investigator(s) must document in the medical notes that they have reviewed the SAE and have 
provided an assessment of causality. 

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8.3.3.1. 
Contact information for reporting SAEs 
Table 13 
Contact information for reporting SAEs 
Study contact for questions regarding SAEs 
Refer to the local study contact information document 
Back up study contact for reporting SAEs 
Available 24/24 hours and 7/7 days: 
GSK Global Safety  
Outside US & Canada sites: 
Email address: ogm28723@gsk.com 
8.3.4. 
Treatment of expedited adverse events (SAE) 
Any medication administered for the treatment of an SAE should be recorded in the 
Expedited AE Report of the participant’s eCRF screen (refer to Section 10.3.8.1). 
8.3.5. 
Participant card 
The investigator (or designee) must provide the participant’s parent(s)/LAR(s) with a 
“participant card” containing information about the clinical study. The participant’s 
parent(s)/LAR(s) must be instructed to always keep the participant card in their 
possession for the duration of the study. In an emergency, this card serves to inform the 
responsible attending physician/LAR/caregiver/family member that the participant is in a 
clinical study and that relevant information may be obtained by contacting the 
investigator(s) or their back up. 
8.3.6. 
Medical device deficiencies 
Both study groups have study interventions that are a combination product constituted of 
a device 
 and biologic product. Refer to the Glossary of terms for 
the definition of combination product and medical device deficiency.  
8.3.6.1. 
Detection, follow-up, and prompt reporting of medical device 
deficiency 
The investigator is responsible for the detection, documentation and prompt reporting of 
any medical device deficiency occurring during the study to GSK. This applies to any 
medical device provided for the conduct of the study.  
Device deficiencies will be reported to GSK within 24 hours after the investigator 
determines that the event meets the protocol definition of a device deficiency. Refer to 
Section 10.6 for definitions and details on recording and reporting of these events.  
The investigator will ensure that follow-up includes any additional investigations to 
elucidate the nature and/or relatedness of the device deficiency to the incident.  
CCI

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New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator and reported to GSK within 24 hours. 
Medical device deficiencies and any associated AE/SAEs for associated person (i.e., 
spouse, caregiver, site staff) will also be collected. The associated person will be 
provided with a safety reporting information and authorization letter. 
Follow-up applies to all participants, including those who discontinue study intervention 
or the study, and associated persons. 
8.3.6.2. 
Regulatory reporting of medical device deficiency when used as 
combination product  
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study to GSK. GSK has a legal responsibility to notify 
appropriate regulatory authorities and other entities about safety information linked to 
medical devices being used in clinical studies. Refer to Section 10.6.3 for details of 
reporting. 
The investigator, or responsible person according to local requirements (e.g., the head of 
the medical institution), will comply with the applicable local regulatory requirements 
linked to the reporting of device deficiencies to the IRB/IEC. 
8.4. 
Pharmacokinetics 
This section is not applicable. 
8.5. 
Genetics 
This section is not applicable. 
8.6. 
Biomarkers 
This section is not applicable. 
8.7. 
Immunogenicity assessments 
Immunogenicity is described in Section 8.1. 
8.8. 
Health outcomes 
This section is not applicable. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
The study includes 1 confirmatory objective. The non-inferiority margin associated with 
the objective is provided in Table 14. 
Table 14 
Study objective and null hypothesis 
Primary objective 
Null hypothesis 
• 
To demonstrate the immunological non-inferiority of IPV 
when co-administered with Rotarix PCV-free compared 
with IPV administered alone. 
• 
The difference in seroconversion rate between 
the Co-administration group and (minus) the 
Staggered group is below -10% for at least 1 of 
the anti-poliovirus types 1, 2 and 3 Abs. 
Ab: Antibody; IPV: Inactivated poliovirus vaccine; PCV: Porcine circovirus 
The global type I error will be 2.5%. The primary objective will be achieved if the lower 
limit of the 2-sided 95% CI for the group difference (Co-administration group minus 
Staggered group) in seroconversion rate is greater than or equal to -10% for each of the 
anti-poliovirus types 1, 2 and 3 antibodies. 
9.2. 
Analysis sets 
Table 15 
Analysis sets 
Analysis set 
Description 
Screened 
All participants who were screened for eligibility. 
Enrolled Set 
• 
All participants who entered the study (who were randomized or received 
study intervention or underwent a post-screening study procedure). 
• 
Note: screening failures (who never passed screening even if rescreened) 
and participants screened but never enrolled into the study (Met eligibility 
but not needed) are excluded from the Enrolled Set as they did not enter the 
study. 
Exposed Set (ES) 
All participants with at least 1 dose of any of the 2 study interventions 
documented. Analysis per group is based on the administered intervention. 
Per Protocol Set (PPS) 
All eligible participants from the ES who meet all the following requirements: 
• 
who received the study interventions according to their random assignment 
and the expected study intervention administration schedule (see Table 3 
and Table 4), and without intercurrent conditions* that may interfere with 
immunogenicity and without prohibited concomitant medication/vaccination. . 
• 
for anti-poliovirus types 1, 2 and 3 analyses at 1 month post Dose 3 of IPV, 
participants should have pre- and post-vaccination immunogenicity results 
for at least 1 antigen and should have complied with interval between IPV 
Dose 3 and the post IPV Dose 3 blood sample. 
• 
for anti-RV IgA analyses at 1 month post Dose 2 of Rotarix PCV-free, 
participants should have pre- and post-vaccination immunogenicity results 
and should have complied with the interval between Rotarix Dose 2 and the 
post Rotarix PCV-free Dose 2 blood sample. 
* immunosuppressive or immunodeficient conditions identified before Visit 7. 

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9.2.1. 
Criteria for elimination from analysis 
If a participant meets one of the criteria mentioned in Table 15 or ones listed in the 
Section 7.1.1, they may be eliminated from PPS. 
9.3. 
Statistical analyses 
The statistical analysis will be detailed in the statistical analysis plan (SAP), which will 
be developed and finalized prior to the first subject first visit (FSFV). This section is a 
summary of the planned main statistical analyses of the primary/secondary 
immunogenicity, reactogenicity and safety endpoints and the descriptive analyses of 
demography summaries. 
The analysis of immunogenicity will be primarily based on the PPS. The analysis of 
safety will be based on the ES. 
9.3.1. 
Primary endpoint analysis 
The primary endpoints are described in Section 3. The Mittienen and Nurminen 95% CI 
for the group difference (Co-administration group minus Staggered group) in the 
seroconversion rate of anti-poliovirus types 1, 2 and 3 antibodies at Visit 7 will be 
computed. Refer to Section 9.1 for details on how this will be used to conclude whether 
the primary objective is reached. 
9.3.2. 
Secondary immunogenicity endpoints analysis 
The secondary endpoints are described in Section 3.  
Anti-RV IgA Ab seroconversion rate and the percentage of participants with anti-RV IgA 
antibody concentration ≥90 U/mL at 1 month post Dose 2 of Rotarix; and the percentage 
of participants with poliovirus types 1, 2 and 3 neutralizing antibody titers ≥1:8 and 
≥1:64 at 1 month post Dose 3 of IPV will be summarized by group with 95% CI.  
For all antigens and timepoints as applicable, GMT/GMC will be computed with 95% CI. 
The 95% CI will assume that log transformed titer/concentration is normally distributed. 
For the purpose of GMT/GMC computation, titer/concentration below the assay cut-off 
will be assigned half of the cut-off. 
For each of the anti-poliovirus types 1, 2 and 3, group GMT ratio at Visit 7 will be 
computed with 95% CI using an analysis of variance (ANOVA) model on log 
transformed titer in order to characterize the impact of co-administration on the IPV 
response. The group GMC ratio, the difference in seroconversion rates and the difference 
in the percentage of participants with concentration ≥90 U/mL will not be computed for 
anti-RV IgA antibody because a difference may be either attributed to co-administration 
of Rotarix PCV-free with IPV, or to the difference in administration schedule for Rotarix 
PCV-free (Month 0.5 and Month 1.5 in the Co-administration group, and Day 1 and 
Month 1 in the Staggered group). 
Reverse cumulative curve will be provided for each antigen and timepoint as applicable. 

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9.4. 
Analysis of safety 
Safety analysis will be performed on the ES. 
Participants who missed reporting events (solicited/unsolicited AEs or concomitant 
medications) will be treated as participants without the events (solicited/unsolicited AEs 
or concomitant medications, respectively). 
9.4.1. Within groups assessment 
The following calculations will be performed for each group: 
• 
The percentage of doses and participants reporting at least 1 AE (solicited or 
unsolicited) during the 14-day (Day 1 to Day 14) solicited follow-up period will be 
computed, along with exact 95% CI. The same calculations will be done for AEs 
(solicited or unsolicited) rated as Grade 3 in intensity and for AEs leading to a 
medically attended visit. 
• 
The percentage of doses and participants reporting each individual solicited systemic 
event will be computed, over the 14-day (Day 1 to Day 14) solicited follow-up 
period, following study intervention administration, along with exact 95% CI. The 
same calculations will be done for each individual solicited systemic event rated as 
Grade 3 in intensity and events leading to a medically attended visit. Temperature 
above specific thresholds will also be summarized with threshold defined by half 
degree increment. 
Note: Intensity of fever will be assessed by considering the grading scales recommended 
by the Chinese authorities [NMPA, 2019b]. 
• 
The verbatim reports of unsolicited AEs will be reviewed by a physician and will be 
coded according to MedDRA. Every verbatim term will be matched with the 
appropriate preferred term. The percentage of participants with unsolicited AEs 
occurring within 31-day (Day 1 to Day 31) follow-up period after any dose with its 
exact 95% CI will be tabulated by preferred term. The same calculations will be done 
for each AE rated as Grade 3 in intensity, for AEs leading to a medically attended 
visit and for AEs causally related to HRV as per the investigator assessment. 
• 
The percentages of participants who started taking at least 1 concomitant medication, 
by type (any, antipyretic), from Day 1 to Day 14 after study intervention 
administrations will be tabulated with exact 95% CI. The percentages of participants 
who started taking at least 1 concomitant medication, by type (any, antipyretic), 
within 1 month after each dose will also be tabulated with exact 95% CI. 
• 
SAEs and dropouts due to AEs will be described in detail.  

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9.5. 
Other analyses 
9.5.1. Demographic and baseline characteristics analyses 
The median, mean, range and standard deviation of age (in weeks) for each dose of study 
intervention and for gestational age (in weeks) will be computed by group. Median, mean 
and standard deviation of height in centimeter and weight in kg at Visit 1 will be 
computed by group. The geographical ancestry and sex composition will be presented.  
9.6. 
Interim analyses 
All analyses will be conducted on final data and therefore no statistical adjustment for 
interim analyses is required. 
9.7. 
Sample size determination 
A maximum of 400 participants (200 in the Co-administration group and 200 in the 
Staggered group) will be randomized such that approximately 160 evaluable participants 
complete the study, in each group for the evaluation of the primary objective assuming 
that approximately 20% of the enrolled participants will not be evaluable. 
Participants who withdraw from the study will not be replaced. 
The power calculation is based on the positive conversion rates of the Beijing Biological 
Products Institute Co.,Ltd. IPV, as mentioned in the package insert [Inactivated 
Poliomyelitis Vaccine Made From Sabin Strains (Vero Cells) package insert, 2019]. 
The positive conversion rate is defined as the percentage of participants at 1 month post 
Dose 3 of immunization with: 
• 
Neutralizing antibody titer > 1:8 for participants with titer < 1:8 pre-immunization or 
• 
At least 4 times increase in neutralizing antibody titer for participants with titer > 1:8 
pre-immunization. 
The definition of seroconversion used in this protocol differs slightly from the above 
definition of positive conversion by taking into account the expected decline in maternal 
antibodies between the pre-vaccination blood sample and the post IPV Dose 3 blood 
sample. By definition, the seroconversion rate will be at least equal to the positive 
conversion rate. Therefore, as a worst-case scenario, the observed positive conversion 
rates are used in the following sample size computations. 
The power presented in Table 16 is based on PASS 2019 (one-sided Non-Inferiority 
Tests for the Difference Between Two Proportions), under the alternative hypothesis of a 
96.23% (Polio 1), 93.83% (Polio 2), and 97.60% (Polio 3) seroconversion rate for the 
Staggered group and a true difference of 0% between the Co-administration group and 
Staggered group, using Miettinen and Nurminen’s Likelihood Score Test of the 
Difference. Under these conservative assumptions the overall power is above 90.4% (i.e., 
global type II error is conservatively computed as the sum of nominal type II errors). 

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Table 16 
Probability that the lower limit of the 95% CI around group difference 
in the percentage of participants with anti-poliovirus types 1, 2 and 3 
antibody seroconversion 1 month post Dose 3 of IPV (Co-
administration group minus Staggered group) is greater than or 
equal to -10% 
Ag 
True seroconversion 
rate (Co-
administrationgroup) 
* 
True seroconversion 
rate (Staggered 
group) * 
N evaluable 
(each group) 
Power 
Alpha 
Polio 1 
96.23% 
96.23% 
160 
98.2% 
0.025 
Polio 2 
93.83% 
93.83% 
160 
92.5% 
0.025 
Polio 3 
97.60% 
97.60% 
160 
99.7% 
0.025 
 
Overall 
90.4% 
 
Ag: Antigen; N: number of participants 
* Observed positive conversion rate from the Beijing Biological Products Institute Co.,Ltd. IPV package insert 
[Inactivated Poliomyelitis Vaccine Made From Sabin Strains (Vero Cells) package insert, 2019]. 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable ICH GCP Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator for review and 
approval. These documents will be signed and dated by the investigator before the 
study is initiated. 
• 
Any protocol amendments will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
GSK will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 

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• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
The investigator(s) or their representative(s) must fully explain the nature of the study to 
the participant’s parent(s) or participant’s LAR(s) and answer all questions regarding the 
study. 
Participants’ parent(s)/LAR(s) must be informed that their participation is voluntary. 
Freely given and written/witnessed/thumb printed informed consent must be obtained 
from each participant’s parent(s)/LAR(s)/witness as appropriate, prior to participation in 
the study. 
The content of the ICF must meet the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written or witnessed/thumb printed 
informed consent was obtained before the participant was enrolled in the study and the 
date the consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
Participants must be re-consented if a new version of the ICF(s) or an ICF addendum is 
released during their participation in the study. 
A copy of the ICF(s) must be provided to the participants’ parent(s)/LAR(s). 

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If follow-up information from a treating physician or other licensed medical practitioner 
is required for a medical device incident with an AE/SAE involving an associated 
person(s), the Associated Person Safety Reporting Information and Authorization Letter 
must be signed by the associated person to obtain consent. 
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the investigator. Any participant 
records or datasets transferred to the sponsor will contain only the identifier. Name and 
any other information which would identify the participant will not be transferred. 
GSK will ensure protection of the personal data of the investigator and site staff which is 
collected within the framework of and for the purpose of the study. 
The participants’ parent(s)/LAR(s) must be informed that: 
• 
Their child’s/ward’s study-related data will be used by the sponsor in accordance 
with local data protection law.  
• 
Their child’s/ward’s may be examined by Clinical Quality Assurance auditors or 
other authorized personnel appointed by the sponsor, by appropriate IRB/IEC 
members, and by inspectors from regulatory authorities. 
The participants’ parent(s)/LAR(s) must be notified about their rights regarding the use of 
their personal data in accordance with the data privacy section of the ICF. 
10.1.5. 
Committees structure 
GSK will obtain favorable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country. This includes IRBs/IECs for review and approval of 
the protocol and subsequent amendments, ICF and any other documentation. 
10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines. 
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical study registers. Where required by applicable regulatory requirements, 
an investigator signatory will be identified for the approval of the study report, and 
provided reasonable access to statistical tables, figures, and relevant reports. GSK will 
also provide the investigator with the full summary of the study results. The investigator 
is encouraged to share the summary results with the study participants, as appropriate. 

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GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis. 
GSK intends to make anonymized patient-level data from this study available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by study 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents. The document storage system used during the 
study and for archiving (irrespective of the type of media used) should provide for 
document identification, version history, search, and retrieval.  
Essential study documents may be added or removed where justified (in advance of study 
initiation) based on their importance and relevance to the study. When a copy is used to 
replace an original document (e.g., source documents, CRF), the copy should fulfill the 
requirements for certified copies. 
All participant data related to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee electronically (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
The investigator must maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the site’s study participants that 
supports information entered in the eCRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies for such review and inspection. 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data. 
Study monitors will perform ongoing source data verification to confirm that data entered 
in the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g., via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Quality tolerance limits (QTLs) will be predefined in the Study Management Plan to 
identify systematic issues that can impact participant safety and/or the reliability of study 
results. These predefined parameters will be monitored during the study. Important 
deviations from the QTLs and remedial actions taken will be summarized in the Clinical 
Study Report (CSR). 

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Study records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the investigator for 15 years from issuance of the final 
CSR/equivalent summary unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
10.1.8. 
Source documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The investigator should maintain a record of 
the location(s) of their source documents.  
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
Definitions of what constitutes source data and documents can be found in the Glossary 
of terms. 
10.1.9. 
Study and site start and closure 
First act of recruitment 
The start of study is defined as FSFV. 
Study/Site termination 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at its sole discretion, provided there is sufficient notice given to 
account for all participants safe exit from study. 
Regular closure of study sites will occur upon study completion. A study site is 
considered closed when all required data/documents and study supplies have been 
collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 

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• 
Discontinuation of further study intervention development 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform 
the investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication policy 
GSK aims to submit the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the LSLV for interventional studies and 
follows the guidance from the International Committee of Medical Journal Editors 
(ICMJE). 
10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
Protocol required immunogenicity laboratory assessments 
Anti-RV IgA antibody determination: 
The anti-RV antibody concentrations are determined by a validated anti-RV IgA ELISA. 
Microtiter plates (96-well) are coated with an anti-RV monoclonal antibody. The wells 
are washed and incubated with (positive wells) or without (negative wells) RV. 
Following incubation, the plates are washed and serum, standard and control dilutions are 
incubated in both types of wells (positive and negative). Bound anti-RV IgA in the wells 
are detected by incubation with peroxidase conjugated anti-human IgA polyclonal 
antibodies. Color development proportional to the quantity of bound anti-RV IgA occurs 
in the presence of a chromogen, TetraMethylBenzidine, and measured 
spectrophotometrically. Specific optical densities are calculated for each 
sample/control/standard dilution by measuring the difference between positive and 
negative wells, the use of negative wells allowing to assess non-specific IgA binding. The 
concentrations of the samples expressed in units per milliliter are calculated relative to 
the four-parameter logistic function generated from the standard curve. 
Anti-IPV type 1, type 2 and type 3 antibodies determination: 
The polio microneutralization assay measures neutralizing antibody titers to poliovirus 
types 1, 2, and 3 using 96-well microtiter plates. The principle of the test is that the anti-
poliovirus antibodies in a serum sample will bind to the virus and block infection of 
susceptible cells. Because poliovirus is cytopathic, virus that is not bound by antibody 
infects and lyses cells. The amount of neutralizing antibody is quantitated as a titer based 
on the last serum dilution to protect susceptible cell culture wells from poliovirus 
infection and cytopathic effect. 

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10.3. 
Appendix 3: AE: definitions and procedures for recording, 
evaluating, follow-up, and reporting 
10.3.1. 
Definition of an AE 
• 
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of a study intervention, whether or not considered related to 
the study intervention. 
• 
Note: an AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention. 
10.3.1.1. 
Events Meeting the AE Definition 
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 
• 
Signs, symptoms that require medical attention (e.g., hospital stays, physician 
visits and emergency room visits). 
• 
Significant failure of an expected pharmacologic or biological action. 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated 
procedures (i.e., invasive procedures, modification of participant’s previous 
therapeutic regimen). 
• 
Clinically significant abnormal laboratory findings or other abnormal assessments 
that are present at baseline and significantly worsen following the start of the study 
will also be reported as AEs or SAEs. 
• 
AEs to be recorded as solicited AEs are described in Section 10.3.3. All other AEs 
after administration of Rotarix will be recorded as unsolicited AEs. 
• 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfill the definition of an AE or SAE. 

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10.3.1.2. 
Events NOT Meeting the AE Definition 
• 
Situations where an untoward medical occurrence did not occur (e.g., social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.  
• 
Pre-existing conditions or signs and/or symptoms present in a participant before 
the first dose of study intervention. These events will be recorded in the medical 
history section of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
10.3.2. 
Definition of an SAE 
An SAE is any untoward medical occurrence that: 
a. 
Results in death. 
b. Is life-threatening. 
Note: the term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the participant was at risk of death at the time of the event. It does not refer 
to an event, which hypothetically might have caused death, had it been more 
severe. 
c. 
Requires hospitalization or prolongation of existing hospitalization. 
Note: in general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in disability/incapacity. 
Note: the term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza like illness, and accidental trauma 
(e.g., sprained ankle) which may interfere or prevent everyday life functions but do 
not constitute a substantial disruption. 

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e. 
Other situations. 
Medical or scientific judgment must be exercised in deciding whether reporting is 
appropriate in other situations. Important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition should be considered serious. 
Examples of such events are invasive or malignant cancers; intensive treatment in 
an emergency room or at home for allergic bronchospasm; blood dyscrasias; and 
convulsions that do not result in hospitalization. 
10.3.3. Solicited events 
Definition of solicited event 
• 
Solicited events are predefined events-administration site events and systemic 
events for which the participant’s parent(s) /LAR(s) is specifically questioned, and 
which are noted by the participant’s parent(s) /LAR(s)] in their diary/eDiary.  
 
Note: for this study solicited systemic events will be collected post Dose 1 and 
Dose 2 of study interventions administration. 
The following events will be solicited: 
Table 17 
Solicited systemic events 
Fever 
Diarrhea 
Vomiting 
Irritability/Fussiness 
Loss of appetite 
Cough/runny nose 
Note: participants’ parent(s)/LAR(s) will be instructed to measure and record the body 
temperature in the evening. Should additional temperature measurements be performed at 
other times of day, participants’ parent(s)/LAR(s) will be instructed to record the highest 
temperature in the diary card. 
10.3.4. Unsolicited AE 
Definition of unsolicited AE 
• 
An unsolicited AE is an AE that is either not included in the list of solicited events 
or is included in the list of solicited events but has an onset outside the specified 
period of follow-up for solicited events. Unsolicited AEs must be communicated 
by participant’s parent(s)/LAR(s) who has signed the informed consent. 
Unsolicited AEs include both serious and nonserious AEs. 

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• 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare 
provider). The participant’s parent(s)/LAR(s) will be instructed to contact the site 
as soon as possible to report medically attended event(s), as well as any events 
that, though not medically attended, are of participant’s parent(s) /LAR(s) concern. 
Detailed information about reported unsolicited AEs will be collected by qualified 
site personnel and documented in the participant’s records. 
• 
Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant’s parent(s)/LAR(s) will be collected during an interview with the 
participant’s parent(s)/LAR(s) and by review of available medical records at the 
next visit. 
• 
Note: for this study unsolicited AEs will be collected post Dose 1 and post Dose 2 
of Rotarix administration. 
10.3.5. 
SAEs related to Study Participation 
Any SAEs related to study participation (e.g., SAEs due to study mandated procedures, 
invasive tests or change in existing therapy) should be reported as per Section 8.3.3. 
10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs 
In the absence of a diagnosis, abnormal laboratory findings assessments (e.g., clinical 
chemistry, hematology, urinalysis) or other abnormal results the investigator considers 
clinically significant will be recorded as an AE or SAE, if they meet the definition of an 
AE or SAE (refer to Sections 10.3.1 and 10.3.2). 
The investigator must exercise their medical and scientific judgment in deciding whether 
an abnormal laboratory finding, or other abnormal assessment is clinically significant. 
10.3.6.1. 
Recording and follow-up of AEs and SAEs 
The participants’ parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should they experience any signs or symptoms they perceive as serious. 
When an AE/SAE occurs, it is the investigator’s responsibility to review all 
documentation (e.g., hospital progress notes, laboratory and diagnostics reports) related 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE on the electronic Expedited Adverse Events Report. The investigator may not 
send photocopies of the participant’s medical records to GSK instead of appropriately 
completing the electronic Expedited Adverse Events Report. 
There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers with the exception of the participant number, 
will be redacted on copies of the medical records prior to submission to GSK. 

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The investigator will attempt to establish a diagnosis pertaining to the event, based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE instead of individual signs/symptoms. 
A Paper Diary, hereafter referred to as Participant Diary will be used in this study to 
capture solicited systemic events. The participant should be trained on how and when to 
complete each field of the Participant Diary. 
Any individual(s) who performs the measurements of systemic events and who will enter 
the information into the Participant Diary should be trained on the use of the Diary. This 
training must be documented in the participant’s source record. If any individual other 
than the participant’s parent(s)/LAR(s) is making entries in the Participant Diary, their 
identity should be documented in the Participant Diary/participant’s source record. 
• 
Collect and verify completed diary cards during discussion with the participant’s 
parent(s)/LAR(s) as presented in the SoA Section 1.3. 
• 
Any unreturned diary cards will be sought from the participant’s parent(s)/LAR(s) 
through telephone call(s) or any other convenient procedure.  
The investigator or delegate will transcribe the required information into the eCRF in 
English.  
All solicited events and unsolicited AEs, SAEs, and AEs that led to withdrawal from the 
study will be collected and recorded in the eCRF. 
The verbatim reports of unsolicited AEs, SAEs and AEs leading to withdrawal will be 
reviewed by a physician and the signs and symptoms will be coded according to the 
Medical Dictionary for Regulatory Activities (MedDRA). Every verbatim term will be 
matched with the appropriate preferred term. 
10.3.6.2. 
Time period for collecting and recording AEs and SAEs 
All AEs and SAEs must be recorded into the appropriate section of the eCRF according 
to the timelines described in Table 11 of Section 8.3.1, irrespective of intensity or 
whether or not they are considered related to the study intervention. 
10.3.6.3. 
Follow-up of AEs, SAEs or any other events of interest 
After the initial AE/SAE or any other event of interest for the study, the investigator is 
required to proactively follow each participant at subsequent visits/contacts. All SAEs 
will be followed until the event is resolved, stabilized, otherwise explained, or the 
participant is lost to follow-up. 
Other nonserious AEs must be followed until 30 days after the last study intervention 
administration or until the participant is lost to follow-up. 

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10.3.6.3.1. Follow-up during the study 
AEs documented at a previous visit/contact and defined as not recovered/not resolved or 
recovering/resolving will be reviewed at subsequent visits/contacts until 30 days after the 
last study intervention administration. 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.6.3.2. Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information to GSK on a 
previously reported SAE using an electronic Expedited Adverse Events Report. The 
investigator is obliged to perform or arrange for the conduct of supplemental clinical 
examinations/tests and/or evaluations to elucidate the nature and/or causality of the SAE 
as fully as possible. 
10.3.6.4. 
Updating of SAE information after removal of write access to the 
participant’s eCRF 
When additional SAE information is received after write access to the participant’s eCRF 
is removed, new or updated information should be recorded on the appropriate paper 
report, with all changes signed and dated by the investigator. The updated report should 
be faxed to the Study contact for reporting SAEs (refer to Section 8.3.3.1 or to GSK 
Global Safety department within the defined reporting timeframes specified in the Table 
12). 
10.3.7. 
Assessment of intensity and causality 
10.3.7.1. 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 18 
Intensity scales to be used by the parent(s)/LAR(s) for solicited 
symptoms during the solicited follow-up period 
Infant 
Adverse Event 
Intensity grade 
Parameter 
Fever* 
Record temperature in °C  
Diarrhea $ 
Record the number of looser than normal stools/day 
Vomiting § 
Record the number of episodes of vomiting/day 
Loss of appetite 
0 
Appetite as usual 
1 
Eating less than usual/no effect on normal activity 
2 
Eating less than usual/interferes with normal activity 
3 
Not eating at all 
Irritability/Fussiness 
0 
Behavior as usual 
1 
Crying more than usual/no effect on normal activity 
2 
Crying more than usual/interferes with normal activity 
3 
Crying that cannot be comforted/prevents normal activity 

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Infant 
Adverse Event 
Intensity grade 
Parameter 
Cough/runny nose 
0 
Normal 
1 
Cough/runny nose which is easily tolerated 
2 
Cough/runny nose which interferes with daily activity 
3 
Cough/runny nose which prevents daily activity 
*Refer to the SoA for the definition of fever and the preferred location for temperature measurement. 
$ Diarrhea is defined as passage of 3 or more looser than normal stools within a day. 
§ Vomiting is defined as 1 or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after 
feeding within a day. 
Table 19 
Intensity scales for diarrhea, vomiting and fever in infants  
Infant 
Event  
Intensity grade 
Parameter 
Diarrhea 
0 
Normal (0-2 looser than normal stools/day) 
1 
3 looser than normal stools/day 
2 
4-5 looser than normal stools/day 
3 
 6 looser than normal stools/day 
Vomiting 
0 
Normal (no emesis) 
1 
1 episode of vomiting/day 
2 
2 episodes of vomiting/day 
3 
3 episodes of vomiting/day 
Fever+ 
0 
Normal (< 37.5°C) 
1 
37.5°C – < 38.0°C 
2 
38.0°C – < 39.5°C 
3 
≥39.5°C 
4 
≥39.5°C, lasts more than 5 consecutive days 
+ The intensity of fever using the grading scale as defined by Chinese authorities [NMPA, 2019b]. 
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgment. 
The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the participant, causing 
minimal discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities (in a young 
child, such an AE would, for example, prevent attendance at 
school/kindergarten/a day-care center and would cause the 
parent(s)/LAR(s) to seek medical advice). 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. Grade 3 
is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets 1 of the predefined 
outcomes as described in the Section 10.3.2. 

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10.3.7.2. 
Assessment of causality 
The investigator must assess the relationship between study intervention and the 
occurrence of each AE/SAE using clinical judgment. Where several different 
interventions were administered, the investigator should specify, when possible, if the 
AE/SAE could be causally related to a specific intervention. When a causal relationship 
to a specific study intervention cannot be determined, the investigator should indicate the 
AE/SAE to be related to all interventions. 
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The investigator will also consult 
the IB and/or PI for marketed products while making their assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the AE may have been caused by the study 
intervention? 
YES 
: 
There is a reasonable possibility that the study intervention 
contributed to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to 
the administration of the study intervention. There are other, more 
likely causes and administration of the study intervention is not 
suspected to have contributed to the AE. 
If an event meets the criteria to be determined ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible 
contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the study intervention, if applicable. 
• 
An error in study intervention administration. 
• 
Other cause (specify).  
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Expedited 
Adverse Events Report to GSK.  

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The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. The investigator(s) may change their opinion of causality after receiving 
additional information and update the SAE information accordingly. 
10.3.7.3. 
Medically attended visits 
For each solicited (post administration of Dose 1 and Dose 2 of Rotarix and IPV) and 
unsolicited symptom (post Rotarix administration) the participant experiences, the 
participant’s parent(s)/LAR(s) will be asked if the participant received medical attention 
defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel 
for any reason, including emergency room visits. This information will be recorded in the 
eCRF.  
Medical attention received for SAEs will have to be reported using the normal AE 
reporting process in the eCRF. 
10.3.7.4. 
Assessment of outcomes 
The investigator will assess the outcome of all serious (post Rotarix and IPV 
administration) and nonserious unsolicited AEs (post Rotarix administration) recorded 
during the study as: 
• 
Recovered/resolved 
• 
Recovering/resolving 
• 
Not recovered/not resolved 
• 
Recovered with sequelae/resolved with sequelae 
• 
Fatal (SAEs only). 
10.3.8. 
Reporting of SAEs and other events 
10.3.8.1. 
Events requiring expedited reporting to GSK 
Once an investigator becomes aware that an SAE has occurred in enrolled participant, the 
investigator (or designee) must complete information in the electronic Expedited AEs 
Report WITHIN 24 HOURS, even if the investigator does not have complete information 
on the SAE. It must be completed as thoroughly as possible, with all available details of 
the event. 
The SAE report must be updated WITHIN 24 HOURS of the receipt of updated 
information on the SAE. The investigator will always provide an assessment of causality 
at the time of the initial report. Refer to the Table 12 for the details on timeframes for 
reporting of SAEs. 

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10.3.8.2. 
Back up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designee) must fax 
or email a completed, dated and signed paper Expedited AEs Report to the study contact 
for reporting SAEs (refer to Sponsor Information) or to GSK Global Safety department 
within 24 hours of becoming aware of the SAE.  
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
within 24 hours after the electronic reporting system is working again. The information 
reported through the electronic SAE reporting system will be considered valid for 
regulatory reporting purposes. 
10.4. 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
This section is not applicable. 
10.5. 
Appendix 5: Genetics 
This section is not applicable. 
10.6. 
Appendix 6: Definition of medical device AE, adverse device 
effect (ADE), serious adverse device effect (SADE) and 
unanticipated SADE (USADE) 
10.6.1. 
Definition of medical device AE and ADE  
• 
Medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether considered related to a medical device or not. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a medical device. This definition includes events related to the medical device 
or comparator and events related to the procedures involved. 
• 
An ADE is an AE related to the use of a medical device. This definition includes any 
AE resulting from: 
− 
insufficient or inadequate instructions for use (i.e., user error), or 
− 
any malfunction of a medical device, or 
− 
intentional misuse of the medical device. 

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10.6.2. 
Definition of medical device SAE, SADE and USADE  
A medical device SAE is any serious adverse event that: 
a. 
Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
− 
A life-threatening illness or injury. The term ‘life-threatening' in the definition 
of ‘serious' refers to an event in which the participant was at risk of death at 
the time of the event. It does not refer to an event, which hypothetically might 
have caused death, if it were more severe. 
− 
A permanent impairment of a body structure or a body function. 
− 
Inpatient or prolonged hospitalization. Planned hospitalization for a pre-
existing condition, or a procedure required by the protocol, without serious 
deterioration in health, is not considered an SAE. 
− 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
− 
Chronic disease (MDR 2017/745). 
c. 
Is a suspected transmission of any infectious agent via a medicinal product 
SADE definition 
• 
A SADE is defined as an ADE that has resulted in any of the consequences 
characteristic of an SAE. 
• 
Any device deficiency that might have led to an SAE if appropriate action had not 
been taken, intervention had not occurred, or circumstances had been less 
fortunate. 
Unanticipated SADE (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a 
serious adverse device effect that by its nature, incidence, severity, or outcome has 
not been identified in the current version of the IB. 
10.6.3. 
Recording and reporting of medical device AE, ADEs, SADEs and 
USADE  
• 
Any device deficiency must be reported to GSK within 24 hours after the 
investigator determines that the event meets the definition of a device deficiency. 
• 
Refer to paper ‘Medical device or combination product with device 
deficiency/incident report form’ for details on transmission of this information to the 
sponsor. 
• 
GSK will review all device deficiencies, determine, and document in writing whether 
they could have led to an SAE. These device deficiencies will be reported to the 
regulatory authorities and IRBs/IECs as required by national regulations. 

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• 
If required or in case of any issues refer to the general safety contacts for SAE/AE 
reporting in Section 8.3.3.1. 
10.6.4. 
Reporting of Medical Device Deficiencies for Associated Person  
• 
If an Associated Person (i.e., e.g., spouse, caregiver, site staff) experiences a device 
deficiency, the medical device deficiency information, and any associated AE/SAE 
information will be reported to GSK. The associated person will be provided with 
the safety reporting information and authorization to contact physician letter. 
• 
If follow-up information is required, authorization to contact physician (or other 
licensed medical practitioner) must be signed to obtain consent. 
• 
Medical device deficiencies should be reported using the medical device deficiency 
report form. 
• 
GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported to 
the regulatory authorities and IRBs/IECs as required by national regulations. 
• 
Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 
10.7. Appendix 7: Country-specific requirements 
This section is not applicable. 
10.8. 
Appendix 8: Abbreviations and glossary of terms 
10.8.1. 
List of abbreviations 
Ab 
Antibody 
ADE 
Adverse Device Effect 
AE 
Adverse event 
ANOVA 
Analysis of variance 
CDC 
Centers for Disease Control and Prevention 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical 
Sciences 
CoP 
Correlate of protection 
COVID-19 
Coronavirus disease 2019 

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CSR 
Clinical study report 
eCRF 
electronic Case Report Form 
EEA 
European Economic Area 
ELISA 
Enzyme linked immunosorbent assay 
EMA 
European Medicines Agency 
EoS 
End of study 
ES 
Exposed set 
EU SmPC 
European Union Summary of Product Characteristics 
FSFV 
First subject first visit 
GCP 
Good Clinical Practice 
GE 
Gastroenteritis 
GMC 
Geometric mean antibody concentration 
GMT 
Geometric mean titer 
GSK 
GlaxoSmithKline Biologicals SA 
HRV 
Human rotavirus 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IPV 
Inactivated poliovirus vaccine 
IRB 
Institutional Review Board 
IS 
Intussusception 
Kg 
Kilogram 

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LAR 
Legally acceptable representative 
LML 
Local medical lead 
LSLV 
Last subject last visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
NIP 
National immunization programme 
OPV 
Oral poliovirus vaccine 
PCD 
Primary Completion Date 
PCV 
Porcine circovirus 
PI 
Prescribing Information 
PPS 
Per Protocol set 
QTL 
Quality tolerance limit 
RV 
Rotavirus 
RVGE 
Rotavirus gastroenteritis 
SADE 
Serious Adverse Device Effect 
SAE 
Serious adverse event 
SBIR 
Source data Base for Internet Randomization 
SoA 
Schedule of activities 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
UK 
United Kingdom 
US 
United States 
USADE or UADE 
 Unanticipated Serious Adverse Device Effect 
WHO 
World Health Organization 

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10.8.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product.  
An adverse event (AE) can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal 
product. For marketed medicinal products, this also 
includes failure to produce expected benefits (i.e., lack 
of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the study are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
study, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a serious adverse 
event  
In an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned. 
Caregiver: 
A ‘caregiver’ is someone who 
− 
lives in the close surroundings of a participant 
and has a continuous caring role or 
− 
has substantial periods of contact with a 
participant and is engaged in their daily health 
care (e.g., a relative of the participant, a nurse 
who helps with daily activities in case of 
residence in a nursing home).  
In the context of a clinical study, a caregiver could 
include an individual appointed to oversee and support 
the participant's compliance with protocol specified 
procedures. 
Child in care: 
A child who has been placed under the control or 
protection of an agency, organization, institution or 
entity by the courts, the government or a government 
body, acting in accordance with powers conferred on 
them by law or regulation. The definition of a child in 
care can include a child cared for by foster parents or 

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living in a care home or institution, provided that the 
arrangement falls within the definition above. The 
definition of a child in care does not include a child who 
is adopted or has an appointed legal guardian. 
Combination product: 
Combination product comprises any combination of  
− 
drug  
− 
device  
− 
biological product  
Each drug, device, and biological product included in a 
combination product is a constituent part.  
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolment: 
The process of registering a participant into a clinical 
study by assigning participant identification number 
after signing the ICF. 
Essential documents: 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced. 
eTrack: 
GSK’s tracking tool for clinical studies. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis. 
Immunological correlate 
of protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intervention: 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Invasive medical device: 
EEC directive 93/42/EEC defines an invasive medical 
device as ‘A device which, in whole or in part, 
penetrates inside the body, either through a body orifice 
or through the surface of the body’.  

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Investigator: 
A person responsible for the conduct of the clinical 
study at a study site. If a study is conducted by a team of 
individuals at a study site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate study-related duties and 
functions conducted at the study site to qualified 
individual or party to perform those study-related duties 
and functions 
Legally acceptable 
representative: 
An individual, judicial or other body authorized under 
applicable law to consent on behalf of a prospective 
participant to the participant's participation in the 
clinical study. 
The terms legal representative or legally authorized 
representative are used in some settings. 
Medical device deficiency: A device deficiency is an inadequacy of a medical 
device with respect to its identity, quality, durability, 
reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors and information 
supplied by the manufacturer. 
Participant: 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject 
Participant number: 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Primary completion date: 
The date that the final participant was examined or 
received an intervention for the purpose of final 
collection of data for all primary outcomes, whether the 
clinical trial was concluded according to the pre-
specified protocol or was terminated. 
Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  

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Protocol amendment: 
The International Council on Harmonization (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK further details this to include a change to an 
approved protocol that affects the safety of participants, 
scope of the investigation, study design, or scientific 
integrity of the study. 
Randomization: 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Solicited event: 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified follow-up period following study 
intervention administration. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical study necessary for the 
reconstruction and evaluation of the study. Source data 
are contained in source documents (original records or 
certified copies). 
Source documents: 
Original legible documents, data, and records (e.g., 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participants' diaries or evaluation 
checklists, pharmacy dispensing records, recorded data 
from automated instruments, copies or transcriptions 
certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, participant files, and records 
kept at the pharmacy, laboratories and at medico-
technical departments involved in the clinical study). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Study monitor: 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event. 

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10.9. 
Appendix 9: Protocol Amendment change history 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
11. 
REFERENCES 
Atherly D, Dreibelbis R, Parashar U D, et al. Rotavirus Vaccination: Cost-Effectiveness 
and Impact on Child Mortality in Developing Countries. J Infect Dis. 2009; 200: S28–38. 
Baker JM, Tate JE, Leon J, et al. Postvaccination Serum Antirotavirus Immunoglobulin 
A as a Correlate of Protection Against Rotavirus Gastroenteritis Across Settings. J Infect 
Dis 2020. doi: 10.1093/infdis/jiaa068. 
Bányai K, Estes MK, Martella V, et al. Viral gastroenteritis. Lancet. 2018; 
392(10142):175-186. doi: 10.1016/S0140-6736(18)31128-0. 
Cheuvart B, Neuzil KM, Steele AD, et al. Association of serum anti-rotavirus 
immunoglobulin A antibody seropositivity and protection against severe rotavirus 
gastroenteritis: analysis of clinical trials of human rotavirus vaccine. Hum Vaccin 
Immunother. 2014;10(2):505-11. 
Dennehy PH., Rotavirus Vaccines: an Overview. Clin Microbiol Rev. 2008; 21(1):198–
208. 
Fu C, Dong Z, Shen J, et al. Rotavirus Gastroenteritis Infection Among Children 
Vaccinated and Unvaccinated With Rotavirus Vaccine in Southern China. JAMA Netw 
Open. 2018, 1(4):e181382. 
Inactivated Poliomyelitis Vaccine Made From Sabin Strains (Vero Cells) package insert. 
Beijing Biological Products Institute Co.,Ltd. January, 2019. 
NMPA Technical Guidelines for Clinical Comparability Research of Preventive Vaccines 
(No. 94, 2019), 18 December 2019 (a). www.nmpa.gov.cn/WS04/CL2182/372828.html. 
Accessed 08 May 2020. 
NMPA Guiding Principle of Adverse Event Grading Standards for Clinical Trials of 
Preventive Vaccines, 26 December 2019 (b). 
www.nmpa.gov.cn/WS04/CL2182/373037.html. Accessed 08 May 2020 
Tate JE, Burton AH, Boschi-Pinto C, et al. Global, Regional, and National Estimates of 
Rotavirus Mortality in Children <5 Years of Age, 2000-2013. Clin Infect Dis. 2016: S96-
S105. 
WHO position paper. Standard procedure for determining immunity to poliovirus using 
single microneutralization test. WHO/EPI/Gen 93.3 1993:1. 
WHO position paper – July 2021. Rotavirus vaccines: Weekly Epidemiological Record 
2021;28:301-319. 

Signature Page for  218485 TMF-17049861 v1.0
Signature Page for TMF-17049861 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 25-Oct-2023 14:51:16 GMT+0000
PPD