A Phase III, Observer-blind, Randomized, Multicenter Study to Evaluate Immunogenicity, Reactogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Rotarix Porcine Circovirus (PCV)-Free Liquid as Compared to GSK's Rotarix Liquid, Given in 2-doses in Healthy Chinese Infants Starting at Age 6-16 Weeks
Phase: PHASE3
Conditions: Gastroenteritis
Sponsor: GlaxoSmithKline

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212692 (ROTA-097) 
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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Rue de l’Institut, 89 
1330 Rixensart, Belgium 
Primary study intervention 
and number 
Porcine circovirus (PCV)-free liquid formulation of 
GlaxoSmithKline Biologicals SA (GSK) oral live 
attenuated human rotavirus (HRV) vaccine (444563) 
Other study intervention 
GSK’s liquid oral live attenuated HRV vaccine 
(Rotarix) 
eTrack study number and 
abbreviated title 
212692 (ROTA-097) 
EudraCT number 
2020-000972-38 
Date of protocol 
Final: 13 May 2022  
Date of protocol amendment 
Amendment 1 Final: 18 Dec 2023 
Title 
A Phase III, observer-blind, randomized, 
multicenter study to evaluate immunogenicity, 
reactogenicity and safety of GlaxoSmithKline 
(GSK) Biologicals’ Rotarix Porcine circovirus 
(PCV)-free liquid as compared to GSK’s Rotarix 
liquid, given in 2-doses in healthy Chinese infants 
starting at age 6-16 weeks. 
Brief title 
Immunogenicity, reactogenicity and safety of 
GlaxoSmithKline (GSK) Biologicals’ Rotarix 
Porcine circovirus (PCV)-free liquid compared to 
Rotarix liquid given in 2-doses in healthy Chinese 
infants starting at age 6-16 weeks. 
Based on GSK Biologicals’ Protocol WS v17.0 
© 2023 GSK group of companies or its licensor. 

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Protocol Amendment 1 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
212692 (ROTA-097) 
EudraCT number 
2020-000972-38 
Date of protocol 
Final: 13 May 2022  
Date of protocol amendment 
Amendment 1 Final: 18 Dec 2023 
Title  
A Phase III, observer-blind, randomized, multicenter 
study to evaluate immunogenicity, reactogenicity 
and safety of GlaxoSmithKline (GSK) Biologicals’ 
Rotarix Porcine circovirus (PCV)-free liquid as 
compared to GSK’s Rotarix liquid, given in 2-doses 
in healthy Chinese infants starting at age 6-16 
weeks. 
Sponsor signatory 
 
Md Ahsan Habib, Clinical and Epidemiology 
Project Lead, Live viral vaccines 
 
 
Signature 
 
 
 
Date 
 
 
 
Note: Not applicable if an alternative signature process (e.g., electronic signature or 
email approval) is used to get the sponsor approval. 

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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 Biologicals SA. 
• 
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 interventions and other study-related duties and functions as 
described in the protocol. 
• 
To supervise any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site. 
• 
To ensure that any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site are qualified to perform those trial-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 representatives 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 trial. 
• 
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 interventions, 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 
212692 (ROTA-097) 
EudraCT number 
2020-000972-38 
Date of protocol 
Final: 13 May 2022  
Date of protocol amendment 
Amendment 1 Final: 18 Dec 2023 
Title 
A Phase III, observer-blind, randomized, multicenter 
study to evaluate immunogenicity, reactogenicity 
and safety of GlaxoSmithKline (GSK) Biologicals’ 
Rotarix Porcine circovirus (PCV)-free liquid as 
compared to GSK’s Rotarix liquid, given in 2-doses 
in healthy Chinese infants starting at age 6-16 
weeks. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 

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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA 
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 a Serious Adverse Event 
GSK Central Back-up Study Contact for Reporting SAEs: refer to the protocol section 
8.3.3.1. 
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
5. GSK Biologicals’ Helpdesk for Emergency Unblinding 
Refer to the protocol section 6.3.4.1. 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 1 
18 Dec 2023 
Original Protocol 
13 May 2022 
Amendment 1 (18 Dec 2023) 
Overall rationale for the current Amendment: The protocol is being amended in order 
to align with the requirements of the corresponding CDMS version 21 R2 being used. 
The original protocol became effective on 13 May 2022, while the new protocol template 
came into effect on 26 October 2022. The CDMS has no “reviewed” box to tick, in line 
with the new protocol template. Therefore, the following statement is not required in this 
protocol: “The investigator will be required to confirm the review of the SAE causality 
by ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 
72 hours of submission of the SAE”. 
List of main changes in the protocol and their rationale: 
Section # and 
title 
Description of change 
Brief rationale 
Section 10.3.8.1: 
Events requiring 
expedited 
reporting to GSK 
Deletion of the text “The investigator 
will be required to confirm the review of 
the SAE causality by ticking the 
‘reviewed’ box in the electronic 
Expedited Adverse Events Report 
within 72 hours of submission of the 
SAE.” 
To align with the requirements of 
the corresponding CDMS version 
21 R2 being used. This CDMS 
version is based on the current 
protocol template (effective 
26 Oct 2022) and therefore, it 
does not have a “reviewed” box to 
tick. 
 

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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
List of main changes in the protocol and their rationale: ........................................... 7 
1. 
PROTOCOL SUMMARY ........................................................................................ 14 
1.1. 
Synopsis ..................................................................................................... 14 
1.2. 
Schema ...................................................................................................... 14 
1.3. 
Schedule of Activities (SoA) ........................................................................ 15 
2. 
INTRODUCTION .................................................................................................... 18 
2.1. 
Study rationale ............................................................................................ 18 
2.2. 
Background ................................................................................................ 19 
2.3. 
Benefit/Risk assessment ............................................................................. 19 
2.3.1. 
Risk Assessment ......................................................................... 20 
2.3.2. 
Benefit Assessment ..................................................................... 20 
2.3.3. 
Overall Benefit/Risk Conclusion ................................................... 20 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 21 
4. 
STUDY DESIGN .................................................................................................... 22 
4.1. 
Overall design ............................................................................................. 22 
4.2. 
Scientific rationale for study design ............................................................. 23 
4.2.1. 
Rationale for study blinding .......................................................... 23 
4.3. 
Justification for dose ................................................................................... 23 
4.4. 
End of Study (EoS) definition ...................................................................... 23 
5. 
STUDY POPULATION ........................................................................................... 24 
5.1. 
Inclusion criteria for enrolment .................................................................... 24 
5.2. 
Exclusion criteria for enrolment ................................................................... 24 
5.2.1. 
Medical conditions ....................................................................... 24 
5.2.2. 
Prior/Concomitant therapy ........................................................... 25 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 25 
5.2.4. 
Other exclusions .......................................................................... 25 
5.3. 
Lifestyle considerations ............................................................................... 26 
5.4. 
Screening failures ....................................................................................... 26 
6. 
STUDY INTERVENTION ........................................................................................ 26 
6.1. 
Study interventions administered ................................................................ 26 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 27 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 27 
6.3.1. 
Participant identification ............................................................... 27 
6.3.2. 
Randomization to study intervention ............................................ 27 
6.3.3. 
Intervention allocation to the participant ....................................... 27 
6.3.4. 
Blinding and unblinding ................................................................ 28 
6.3.4.1. 
Emergency unblinding ................................................ 28 
6.3.4.2. 
Emergency unblinding prior to regulatory 
reporting of SAEs ....................................................... 29 
6.4. 
Study intervention compliance .................................................................... 29 

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6.5. 
Concomitant therapy ................................................................................... 29 
6.6. 
Dose modification ....................................................................................... 30 
6.7. 
Intervention after the end of the study ......................................................... 30 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 30 
7.1. 
Discontinuation of study intervention ........................................................... 30 
7.1.1. 
Criteria for temporary delay for enrolment and/or study 
intervention administration ........................................................... 31 
7.1.2. 
Contraindications to subsequent study intervention(s) 
administration .............................................................................. 31 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 31 
7.3. 
Lost to follow-up .......................................................................................... 32 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 32 
8.1. 
Immunogenicity assessments ..................................................................... 33 
8.1.1. 
Biological samples ....................................................................... 34 
8.1.2. 
Laboratory assays ....................................................................... 34 
8.1.3. 
Immunological read-outs .............................................................. 34 
8.1.4. 
Immunological correlates of protection ......................................... 35 
8.2. 
Safety Assessments ................................................................................... 35 
8.2.1. 
Procedures prior to study intervention administration ................... 35 
8.2.1.1. 
Collection of demographic data .................................. 35 
8.2.1.2. 
Medical and vaccination history .................................. 35 
8.2.1.3. 
Physical examination .................................................. 35 
8.3. 
AEs, SAEs and other events of interest ...................................................... 36 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information ............................................................... 36 
8.3.2. 
Method of detecting AEs and SAEs ............................................. 37 
8.3.3. 
Regulatory reporting requirements for SAEs, and other 
events .......................................................................................... 37 
8.3.3.1. 
Contact information for reporting of SAEs ................... 38 
8.3.4. 
Treatment of adverse events ....................................................... 38 
8.3.5. 
Participant card ............................................................................ 38 
8.3.6. 
Medical device deficiencies.......................................................... 38 
8.3.6.1. 
Detection, follow-up, and prompt reporting of 
medical device deficiency ........................................... 39 
8.3.6.2. 
Regulatory reporting of medical device 
deficiency when used as combination product ............ 39 
8.4. 
Treatment of overdose ................................................................................ 39 
8.5. 
Pharmacokinetics ....................................................................................... 39 
8.6. 
Pharmacodynamics .................................................................................... 39 
8.7. 
Genetics ..................................................................................................... 40 
8.8. 
Biomarkers ................................................................................................. 40 
8.9. 
Health outcomes ......................................................................................... 40 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 40 
9.1. 
Statistical hypotheses ................................................................................. 40 
9.2. 
Sample size determination .......................................................................... 40 
9.2.1. 
Power for non-inferiority in seroconversion .................................. 40 
9.2.2. 
Power for non-inferiority in GMC .................................................. 41 

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9.2.3. 
Power for non-inferiority in the percentage of participants 
with serum anti-RV IgA antibody concentrations greater or 
equal to 90 U/mL 1 month post Dose 2 ........................................ 41 
9.3. 
Populations for analyses ............................................................................. 42 
9.4. 
Statistical analyses ..................................................................................... 42 
9.4.1. 
General considerations ................................................................ 42 
9.4.1.1. 
Immunogenicity .......................................................... 42 
9.4.1.2. 
Reactogenicity/Safety ................................................. 43 
9.4.2. 
Participant disposition .................................................................. 43 
9.4.3. 
Analysis of immunogenicity .......................................................... 43 
9.4.3.1. 
Within groups assessment .......................................... 43 
9.4.3.2. 
Between groups assessment ...................................... 43 
9.4.4. 
Analysis of safety ......................................................................... 44 
9.4.4.1. 
Within groups assessment .......................................... 44 
9.4.5. 
Other analyses............................................................................. 44 
9.4.5.1. 
Demography and baseline characteristics 
analyses ..................................................................... 44 
9.5. 
Interim analyses .......................................................................................... 45 
9.5.1. 
Sequence of analyses .................................................................. 45 
9.6. 
Data Monitoring Committee ........................................................................ 45 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 46 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 46 
10.1.1. 
Regulatory and ethical considerations ......................................... 46 
10.1.2. 
Financial disclosure ..................................................................... 46 
10.1.3. 
Informed consent process ............................................................ 47 
10.1.4. 
Data protection ............................................................................ 47 
10.1.5. 
Dissemination of clinical study data ............................................. 48 
10.1.6. 
Data quality assurance ................................................................ 48 
10.1.7. 
Source documents ....................................................................... 49 
10.1.8. 
Study and site start and closure ................................................... 49 
10.1.9. 
Publication policy ......................................................................... 50 
10.2. 
Appendix 2: Tests ....................................................................................... 50 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 51 
10.3.1. 
Definition of an Adverse Event (AE) ............................................. 51 
10.3.1.1. Events Meeting the AE Definition ............................... 51 
10.3.1.2. Events NOT Meeting the AE Definition ....................... 52 
10.3.2. 
Definition of a Serious Adverse Event (SAE) ............................... 52 
10.3.3. 
Solicited events ............................................................................ 53 
10.3.4. 
Unsolicited adverse events .......................................................... 53 
10.3.5. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 54 
10.3.6. 
Recording and follow-up of AEs, SAEs ........................................ 54 
10.3.6.1. Time period for collecting and recording AEs, 
and SAEs ................................................................... 55 
10.3.6.2. Follow-up of AEs, SAEs or any other events of 
interest ....................................................................... 55 
10.3.6.2.1. Follow-up during the study ...................... 55 

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10.3.6.2.2. Follow-up after the participant is 
discharged from the study....................... 55 
10.3.6.3. Updating of SAE information after removal of 
write access to the participant’s eCRF ........................ 55 
10.3.7. 
Assessment of intensity and toxicity ............................................. 56 
10.3.7.1. Assessment of intensity .............................................. 56 
10.3.7.2. Assessment of causality ............................................. 57 
10.3.7.3. Medically attended visits ............................................. 58 
10.3.7.4. Assessment of outcomes ............................................ 58 
10.3.8. 
Reporting of SAEs and other events ............................................ 59 
10.3.8.1. Events requiring expedited reporting to GSK .............. 59 
10.3.8.2. Back-up system in case facsimile or electronic 
reporting system does not work .................................. 59 
10.4. 
Appendix 4: Definition of medical device AE, adverse device effect 
(ADE), serious adverse device effect (SADE) and unanticipated 
SADE (USADE) .......................................................................................... 60 
10.4.1. 
Definition of medical device AE and adverse device effect 
(ADE) ........................................................................................... 60 
10.4.2. 
Definition of medical device SAE, SADE and USADE .................. 60 
10.4.3. 
Recording and reporting of medical device AE, ADEs, 
SADEs and USADE ..................................................................... 61 
10.4.4. 
Reporting of Medical Device Deficiencies for Associated 
Person) ........................................................................................ 61 
10.5. 
Appendix 5: Abbreviations and glossary of terms ........................................ 62 
10.5.1. 
List of abbreviations ..................................................................... 62 
10.5.2. 
Glossary of terms ......................................................................... 64 
10.6. 
Appendix 6: Protocol Amendment change history ....................................... 68 
11. REFERENCES ....................................................................................................... 68 
 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities ............................................................................. 15 
Table 2 
Intervals between study visits ................................................................. 18 
Table 3 
Study objectives and endpoints .............................................................. 21 
Table 4 
Study groups, intervention and blinding foreseen in the study ................ 23 
Table 5 
Study interventions administered ........................................................... 26 
Table 6 
Contact information for emergency unblinding ....................................... 28 
Table 7 
Biological samples ................................................................................. 34 
Table 8 
Laboratory assays .................................................................................. 34 
Table 9 
Immunological read-outs ........................................................................ 34 
Table 10 
Timeframes for collecting and reporting of safety information ................. 36 
Table 11 
Timeframes for submitting SAE and other events reports to GSK .......... 38 
Table 12 
Contact information for reporting of SAEs .............................................. 38 
Table 13 
Probability that the lower limit of the 95% CI around group 
difference in seroconversion rate (Rotarix PCV-free minus 
Rotarix), 1 month after Dose 2 of Rotarix, is greater or equal to -
10% ........................................................................................................ 41 
Table 14 
Probability that the lower limit of the 95% CI around the anti-RV 
IgA Ab GMC ratio (Rotarix PCV-free / Rotarix), 1 month after 
Dose 2 of Rotarix, is greater or equal to 0.67 ......................................... 41 
Table 15 
Probability that the lower limit of the 95% CI around group 
difference in the percentage of participants with serum anti-RV 
IgA antibody concentrations greater or equal to 90 U/mL (Rotarix 
PCV-free minus Rotarix), 1 month after Dose 2 of Rotarix, is 
greater or equal to -10% ......................................................................... 41 
Table 16 
Populations for analyses ........................................................................ 42 
Table 17 
Solicited systemic events ....................................................................... 53 
Table 18 
Intensity scales to be used by the parent(s)/LAR(s) for solicited 
symptoms during the solicited follow-up period ...................................... 56 
Table 19 
Intensity scales for diarrhea, vomiting and fever in infants ...................... 56 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 22 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale:  
Study ROTA-097 is designed to support licensure of the Rotarix Porcine circovirus 
(PCV)-free (no detection of PCV-1 and PCV-2 according to the limit of detection of the 
tests used) liquid vaccine in China. The objective of study ROTA-097 is to evaluate, in 
the Chinese population, the immunogenicity, reactogenicity and safety of GSK’s Rotarix 
PCV-free liquid, compared to Rotarix liquid, for which vaccine efficacy was 
demonstrated in the ROTA-075 study conducted in China.  
Objectives and Endpoints: See Table 3 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 
Schedule of Activities 
Age at enrolment 
6-16 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 
Extended 
Safety 
Follow-up 
Time points 
Day 1 
Month 1 
Month 2 
Month 7 
Informed consent by parent(s)/LAR(s) 
● 
 
 
 
See Section 10.1.3 for details  
Check inclusion/exclusion criteria 
● 
 
 
 
Recheck clinical status before randomization 
and/or 1st dose of study intervention. See 
Sections 5.1 and 5.2 for Inclusion and Exclusion 
criteria 
Collect demographic data including gestational age 
● 
 
 
 
See Section 8.2.1 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 to study intervention administration 
● 
● 
 
 
See Section 7.1.2 for more information 
Randomization 
● 
 
 
 
See Section 6.3 for more information 
Allocation of treatment number for subsequent dose 
 
● 
 
 
See Section 6.3.3 for more information 
Check criteria for temporary delay for enrolment and study 
intervention administration 
○ 
○ 
 
 
See Section 7.1.1 for more information 
Study group and intervention number allocation 
○ 
 
 
 
See Sections 6.3.2 and 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 
● 
● 
 
 
See Section 6.1 for more information 
Recording of administered intervention number 
● 
● 
 
 
 
Recording of regurgitation/vomiting 
● 
● 
 
 
 

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Age at enrolment 
6-16 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 
Extended 
Safety 
Follow-up 
Time points 
Day 1 
Month 1 
Month 2 
Month 7 
Replacement of study intervention administration in case of 
regurgitation/vomiting 
● 
● 
 
 
If regurgitation or vomiting, which may impair the 
study intervention take, occurs within 30 minutes 
after study intervention administration, a single 
replacement dose may be given at the same 
study intervention administration visit at the 
discretion of the investigator. This information 
should be recorded in the eCRF. The participant 
should continue to participate in the study. 
Distribution of diary cards 
○ 
○ 
 
 
 
Laboratory Assessment  
 
Blood sampling for antibody determination (2 mL) 
● 
 
● 
 
Blood sampling to be done before study 
intervention (Rotarix and Rotarix PCV-free) 
administration. 
See Section 8.1.1 for more information 
Safety assessments 
 
Recording of any concomitant medications/vaccinations 
● 
● 
● 
 
See Section 6.5 for more information 
Recording of solicited events after each dose of study intervention 
(Days 1-14*) 
● 
● 
 
 
See Sections 10.3.3 and 10.3.6 for more 
information 
Recording of unsolicited AEs after each dose of study intervention 
(Days 1-31) 
● 
● 
 
 
See Sections 10.3.4 and 10.3.6 for more 
information 
Recording of AEs/SAEs leading to withdrawal from study  
● 
● 
● 
● 
See Section 10.3.6 for more information 
Recording of SAEs 
● 
● 
● 
● 
See Section 10.3.6 for more information 
Return of diary cards  
 
○ 
○ 
 
 
Diary card transcription by investigator or designee 
 
● 
● 
 
 
Recording of SAEs related to study participation, or to a concurrent 
GSK medication/vaccine 
● 
● 
● 
● 
See Section 10.3.6 for more information 
Contact for safety follow-up  
 
 
 
● 
A safety follow-up contact will be done by a 
telephone call or any other convenient 
procedure to collect information on SAEs and 
medication taken for treatment of SAEs 

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Age at enrolment 
6-16 weeks 
Notes 
Type of contact 
Visit 1 
Visit 2 
Visit 3 
Extended 
Safety 
Follow-up 
Time points 
Day 1 
Month 1 
Month 2 
Month 7 
Analysis on data collected up to Visit 3 
 
 
○ 
 
See Section 9.5.1 for more information 
Study Conclusion 
 
 
 
● 
See Section 4.4 for more information 
LAR = Legally Acceptable Representative; AE = Adverse Event; SAE = Serious Adverse Event; mL= milliliter.  
● is used to indicate a study procedure that requires documentation in the individual eCRF 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Notes: All participants are allowed to receive routine childhood vaccinations according to the local immunization practice. 
The double-line border following Visit 3 indicates the analyses which will be performed on all data (i.e., data that are as clean as possible) obtained up to Visit 3. 
*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 
Intervals between study visits 
Interval 
Optimal length of interval1  
Allowed interval 
Visit 1→Visit 2 
30-48 days 
28-48† days after Dose 1 
Visit 2→Visit 3 
30-48 days 
28-48† days after Dose 2 
Visit 2→ESFU contact‡ 
6 months 
180-210 days after Dose 2  
1 Whenever possible the investigator should arrange study visits within this interval. 
† Participants will not be eligible for inclusion in the Per-Protocol Set for immunogenicity if they make the study visit 
outside this interval. 
‡An extended safety follow-up (ESFU) contact (by telephone call or any other convenient procedure) to collect 
information on serious adverse events and medication taken for treatment of the same. 
2. 
INTRODUCTION 
2.1. 
Study rationale 
Study ROTA-097 is designed to support licensure of the Rotarix PCV-free (no detection 
of PCV-1 and PCV-2 according to the limit of detection of the tests used) liquid vaccine 
(hereafter referred as Rotarix PCV-free) in China. The objective of the study is to 
evaluate, in the Chinese population the immunogenicity, reactogenicity and safety of 
GSK’s Rotarix PCV-free, compared to Rotarix liquid (hereafter referred as Rotarix), for 
which vaccine efficacy was demonstrated in the ROTA-075 study conducted in China. 
In 2010, PCV-1 deoxyribonucleic acid fragments were identified in Rotarix and in its 
starting materials, as well as low levels of PCV-1 viral particles during production 
process and in the final container [Dubin, 2013]. PCV-1 is not known to cause disease in 
either animals or humans [Hattermann, 2004a; Hattermann, 2004b] and there is no 
evidence that the presence of PCV-1 in Rotarix poses a safety risk to vaccinated 
participants. The presence of PCV-1 in Rotarix is, therefore, a manufacturing quality 
issue [Dubin, 2013; Han, 2017]. GSK has replaced the cell bank and virus seeds used as 
the base production material for Rotarix.  
To support worldwide licensure of Rotarix PCV-free, GSK conducted the global clinical 
study ROTA-081. The study demonstrated lot-to-lot consistency of 3 production lots of 
the Rotarix PCV-free and its non-inferiority compared to Rotarix lyophilized in terms of 
immunogenicity. No safety concerns were raised, and the study showed that Rotarix 
PCV-free and Rotarix lyophilized have a similar reactogenicity and safety profile. The 
European Medicines Agency (EMA) approved the use of new cell banks and virus seeds 
to render Rotarix PCV-free based on a comparability package that included the results of 
study ROTA-081 on 13 February 2020. 
Rotarix showed high vaccine efficacy against severe rotavirus gastroenteritis (RVGE) 
and an acceptable safety profile in several global efficacy studies and in the efficacy 
study ROTA-075 conducted in China [Li, 2013; Li, 2014; Li, 2016]. The current study is 
conducted to evaluate, in the Chinese population, the immunogenicity, reactogenicity and 
safety of GSK’s Rotarix PCV-free compared to Rotarix. 
Though no recognized immunological correlate of protection (CoP) has been established 
for human rotavirus (HRV) vaccines, anti-rotavirus (RV) serum immunoglobulin A (IgA) 

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antibody (Ab) concentration is considered as the best correlate of efficacy 
[Velazquez,  2000; Franco, 2006; Patel, 2013; Cheuvart, 2014; Baker, 2020]. Analyses on 
GSK sponsored efficacy studies conducted by GSK [Cheuvart, 2014] and by independent 
research groups [Baker, 2020] showed that a post-vaccination anti-RV IgA antibody 
concentration of  20 U/mL measured by the GSK anti-RV IgA Enzyme linked 
Immunosorbent Assay (ELISA) is a correlate of efficacy against RVGE for Rotarix 
clinical trials. The analysis conducted by Baker et al, 2020 included the Phase III efficacy 
study ROTA-075 conducted in China [Baker, 2020].  
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, 2013; 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, 2013].  
GSK HRV vaccine (Rotarix) is registered in around 130 countries worldwide and the 
Rotarix liquid formulation is pre-qualified by WHO. More than 716 million doses of the 
vaccine (lyophilized and liquid formulations) are estimated to have been distributed 
worldwide from its launch until July 2021. 
Please refer to the current investigator’s brochure (IB) for information regarding the pre-
clinical and clinical studies and the epidemiological information of Rotarix and Rotarix 
PCV-free vaccines.  
2.3. 
Benefit/Risk assessment 
Detailed information about the known and expected benefits and risks and expected 
adverse events (AEs) of Rotarix and Rotarix PCV-free can be found in the current IB.  

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2.3.1. 
Risk Assessment 
Participants will be observed for at least 30 minutes after study intervention 
administration, with medical attention available in case of anaphylaxis. 
In addition to risks related to the study intervention, there may be risks related to the 
blood sampling planned in the study:  
• 
Pain and bruising may occur at the site where blood is drawn; as a mitigation 
strategy, a topical analgesic may be applied to the site where blood will be taken. 
For details of study procedures, refer to Section 1.3.  
2.3.2. 
Benefit Assessment  
By receiving the HRV vaccines the participants may have the benefit of being protected 
against RV disease. In addition, the participants will undergo a physical examination at 
the first study visit. In case the study doctor discovers any medical condition, the 
participant will be referred to the local healthcare system. 
2.3.3. 
Overall Benefit/Risk Conclusion 
Taking into account the measures taken to minimize the risk for participants taking part 
in this study, the potential or identified risks in association with live attenuated human 
(RIX4414 strain) RV vaccine are justified by the potential benefits (prevention/treatment) 
that may be afforded to participants receiving the study intervention for the prevention of 
GE due to RV infection. 

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3. 
OBJECTIVES AND ENDPOINTS 
Table 3 
Study objectives and endpoints 
Objectives 
Endpoints 
Primary  
• 
To demonstrate the immunological non-inferiority of 
Rotarix PCV-free as compared to Rotarix in terms 
of seroconversion rates 1 month post Dose 2. 
- 
Non-inferiority will be demonstrated if the 
lower limit of the two-sided asymptotic 
standardized 95% CI for the difference in 
seroconversion rate between the Rotarix 
PCV-free and Rotarix is greater than or equal 
to -10%. 
• 
To demonstrate the non-inferiority of the Rotarix 
PCV-free as compared to Rotarix in terms of serum 
anti-RV IgA Ab concentrations 1 month post Dose 
2.  
- 
Non-inferiority will be demonstrated if the 
lower limit of the two-sided 95% CI for the 
ratio of anti-RV IgA Ab geometric mean 
concentration (GMC) 1 month post Dose 2 
between the Rotarix PCV-free and Rotarix is 
greater than or equal to 0.67. 
Evaluation of immunogenicity in terms of anti-RV 
antibody concentrations. 
• 
Anti-RV IgA Ab seroconversion rate* 1 month 
post Dose 2 in the Rotarix PCV-free and 
Rotarix groups. 
• 
Serum anti-RV IgA Ab concentrations 
expressed as GMCs 1 month post Dose 2 in 
the Rotarix PCV-free and Rotarix groups. 
*Seroconversion rate 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 Visit 3 (1 month 
post Dose 2). 
Secondary 
• 
To assess the immunological non-inferiority of 
Rotarix PCV-free as compared to Rotarix in terms 
of percentage of participants with anti-RV IgA 
antibody concentrations  90 U/mL 1 month post 
Dose 2. 
− 
Non-inferiority will be demonstrated if the 
lower limit of the two-sided asymptotic 
standardized 95% CI for the difference in the 
percentage between the Rotarix PCV-free 
and Rotarix is greater than or equal to -10%. 
Evaluation of immunogenicity in terms of anti-RV 
antibody concentrations. 
• 
Percentage of participants with serum anti-RV 
IgA antibody concentrations  90 U/mL 
1 month post Dose 2 in Rotarix PCV-free and 
Rotarix groups. 
• 
To evaluate the reactogenicity of Rotarix PCV-free 
and Rotarix in terms of solicited systemic events.  
• 
To assess the safety of Rotarix PCV-free and 
Rotarix in terms of unsolicited AEs and serious 
adverse events (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 each study 
intervention administration. 
• 
Unsolicited AEs 
− 
Percentage of participants reporting the 
occurrence of unsolicited AEs within 31 
days (Day 1- Day 31) after each study 
intervention administration, according to 
the Medical Dictionary for Regulatory 
Activities (MedDRA) classification.  
• 
SAEs 
− 
Percentage of participants reporting the 
occurrence of SAEs from Dose 1 of the 
study intervention up to study end. 
Ab = Antibody; AE = Adverse event; CI = Confidence Interval; IgA = Immunoglobulin A; GMC = Geometric mean Ab 
concentration; MedDRA = Medical Dictionary for Regulatory Activities; PCV = Porcine circovirus; SAE = Serious 
adverse event; RV = Rotavirus; U = Unit; mL = milliliter 

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4. 
STUDY DESIGN 
4.1. 
Overall design 
Figure 1 
Study design overview 
 
N = number of participants; AE = adverse event; SAE = serious adverse event; EoS: end of study; ESFU: extended 
safety follow-up; HRV: Human Rotavirus; PCV-free = No detection of PCV-1 and PCV-2 according to the limit of 
detection of the tests used. 
* An ESFU contact (by telephone call or any convenient procedure) 6 months post Dose 2. 
+ Refer to Section 9.5.1 for detailed information about sequence of analysis. 
• 
Experimental design: Phase III, self-contained, observer-blind, randomized, 
multicenter study with 2 parallel groups (see Figure 1). 
• 
Duration of the study: The total duration of the study, per participant, will be 
approximately 7 months including the 6 months of extended safety follow-up 
(ESFU) period after the last dose of study intervention. 
• 
Primary completion date: Visit 3 (Month 2). 
• 
Control: Active control, GSK’s HRV liquid vaccine (Rotarix). 
• 
Blinding: Observer-blind. 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.  
• 
Study groups: Refer to Figure 1 and Table 4 for an overview of the study groups. 

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Table 4 
Study groups, intervention and blinding foreseen in the study 
Study 
Groups 
Number of 
participants 
Age 
(Min-Max) 
Study 
intervention(s) 
Blinding 
Visit 1→Visit 2 
(Observer-blind) 
Visit 2→Visit 3 
(Observer-blind) 
Visit 3→ 
ESFU 
contact 
(Observer-
blind)* 
HRV 
1000 
6 – 16 
weeks 
HRV RIX4414 
live attenuated 
≥106.0CCID50 
X 
X 
X 
HRV 
PCV-free 
1000 
6 – 16 
weeks 
HRV PCV-free 
RIX4414 live 
attenuated 
≥106.0CCID50 
X 
X 
X 
*Observer-blind except for a limited number of GSK personnel. For unblinding after Visit 3, refer to Section 4.2.1. 
ESFU: extended safety follow-up 
4.2. 
Scientific rationale for study design 
The study is designed as a Phase III study in healthy Chinese infants aged 6-16 weeks at 
the time of the first dose. 
Refer to Section 4.3 for information about justification for dose. 
4.2.1. 
Rationale for study blinding 
The study will be conducted in an observer-blind manner because of the different 
presentations of the study interventions. For more details regarding the blinding of study 
refer to Section 6.3.4. 
The final analysis (Visit 3) will be performed by GSK. Access to the individual treatment 
codes during the final analysis will be limited to the statistician and the database 
administrator. The study personnel involved in the clinical evaluation of the participants 
and the participants’ parents/LARs will remain blinded during the ESFU. This will allow 
unbiased evaluation of the study interventions. 
4.3. 
Justification for dose 
Two oral doses of the study interventions will be administered at approximately 1 month 
interval to participants, according to the immunization schedule of Rotarix licensed 
outside of China.  
4.4. 
End of Study (EoS) definition 
A participant is considered to have completed the study if he/she is available for contact 
(Month 7) as described in the protocol. 
EoS is defined as last subject last contact (Month 7). 

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5. 
STUDY POPULATION 
5.1. 
Inclusion criteria for enrolment 
Adherence to these criteria as specified in the protocol is essential. Inclusion criteria 
deviations are not allowed because they can jeopardize the scientific integrity or 
regulatory acceptability of the study or participant safety.  
All participants must satisfy ALL of the following criteria at study entry: 
• 
Participants’ parent(s)/ LAR(s), who, in the opinion of the investigator, can and will 
comply with the requirements of the protocol (e.g., completion of the diary cards, 
return for follow-up visits). 
• 
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.  
• 
A male or female with Chinese origin, between, and including, 6 and 16 weeks (42-
112 days) of age at the time of the first study intervention administration. 
• 
Healthy participants as established by medical history and clinical examination 
before entering into the study. 
• 
Born after a gestation period of 36 to 42 weeks inclusive.  
5.2. 
Exclusion criteria for enrolment 
Adherence to criteria specified in the protocol is essential. Exclusion criteria deviations 
are not allowed because they can potentially jeopardize the scientific integrity or 
regulatory acceptability of the study or safety of the participant. 
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 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required). 
• 
History of severe combined immunodeficiency.  
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study intervention. 
• 
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. 

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• 
Major congenital defects, or serious chronic illness as assessed by the investigator. 
• 
Previous confirmed occurrence of RVGE. 
• 
Participants with confirmed or suspected Coronavirus Disease 2019 (COVID-19). 
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 second dose of study intervention 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 organized by public health authorities outside the routine immunization 
programme, the time period described above can be reduced if, necessary for that 
mass vaccination vaccine, provided it is licensed and used according to its Product 
Information. 
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
from birth or planned administration during the study period. 
• 
Administration of long-acting immune-modifying drugs from birth or planned 
administration at any time during the study period (e.g., infliximab). 
• 
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 and topical steroids are allowed. 
• 
Previous vaccination against RV. 
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 vaccine/product (drug or medical device). 
5.2.4. 
Other exclusions 
• 
Child in care 
Please refer to the glossary of terms for the definition of child in care.  

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5.3. 
Lifestyle considerations 
This section is not applicable. 
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. 
6. 
STUDY INTERVENTION 
A ‘study intervention’ is defined as a set of investigational or marketed product(s) or 
placebo intended to be administered to a participant during the study. 
Refer to the Study Procedures Manual (SPM) for additional details. 
6.1. 
Study interventions administered 
Table 5 
Study interventions administered 
Study intervention name 
HRV (Rotarix) 
HRV PCV-free (Rotarix PCV-free) 
Presentation 
Study interventions formulation 
Human Rotavirus, Live Attenuated, 
RIX4414 strain ( 106.0 CCID50); 
Sucrose (1.073 g); Di-sodium 
adipate; DMEM; Sterile water q.s. 
1.5 mL 
Human Rotavirus, Live Attenuated, 
RIX4414 strain ( 106.0 CCID50); 
Sucrose (1.073 g); Di-sodium 
adipate; DMEM; Sterile water q.s. 
1.5 mL 
Type  
Control 
Study 
Product category 
Combination Product* 
Combination Product* 
Route of administration  
Oral use 
Oral use 
Number of doses to be 
administered 
2 
2 
Volume to be administered 
1.5 mL 
1.5 mL 
Packaging, labelling and TM 
Refer to SPM for more details 
Refer to SPM for more details 
Manufacturer 
GSK 
GSK 
Refer to Section 4.1 for schedule of study intervention administration; mL: milliliter; qs: quantum satis 
*Combining a biological product and device 
The 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 and/or syncope. 
CCI

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6.2. 
Preparation/Handling/Storage/Accountability 
The study interventions must be stored in a safe, locked place at the temperature specified 
on the study intervention’s label. The storage temperature should be continuously 
monitored with calibrated (if not validated) temperature monitoring device(s) and 
recorded.  
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 section on Study Supplies in the SPM 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 2000 eligible participants will be randomly assigned (1:1) to the 2 study 
groups (HRV and HRV PCV-free). 
The numbering of HRV vaccine 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 at 
individual centers in this multi-center 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.  
Upon providing the participant identification number, the randomization system will 
determine the study group and will provide the intervention number to be used for the 
first study intervention administration. The intervention number(s) to be used for 
subsequent dose administration(s) will be provided by the same automated Internet-based 
system. 
When source data base for internet randomization (SBIR) is not available, please refer to 
the SBIR user guide or SPM for specific instructions. 
Refer to the SPM for additional information relative to the intervention number 
allocation. 

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6.3.4. 
Blinding and unblinding 
The study will be conducted in an observer-blind manner with respect to Rotarix PCV-
free and Rotarix. To do so, study interventions will be prepared and administered by 
qualified study personnel who will not participate in data collection, evaluation, review, 
or the entry of any study endpoint.  
The parents/LARs of the participants will be unaware of the study intervention 
administered throughout the study. The site and sponsor personnel involved in the 
clinical evaluation of the participants will also be unaware of the study intervention, 
while other study personnel may be aware of the treatment assignment. 
The laboratory in charge of the sample testing will be blinded to the intervention 
assignment. Codes will be used to link the participant and study (without any link to the 
intervention attributed to the participant) to each sample. 
The study will be unblinded for a limited number of people at GSK at the final analysis 
(Visit 3). The study personnel involved in the clinical evaluation of the participants and 
parents/LARs of the participants will be kept blinded throughout the conduct of the study. 
6.3.4.1. 
Emergency unblinding 
Unblinding a participant’s individual intervention number should occur ONLY in case of 
a medical emergency when knowledge of the intervention is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate, and direct access to the participant’s individual study intervention via an 
automated internet-based system (SBIR).  
As back up process, the investigator has the option of contacting a GSK Biologicals’ 
Helpdesk (refer to the Table 6) if he/she needs help performing the unblinding (i.e., 
he/she cannot access the SBIR). 
A non-investigator physician (e.g., physician from emergency room) or participant/care 
giver/family member may also request emergency unblinding either via the investigator 
(preferred option) or via the GSK Biologicals’ Helpdesk (back up process). The 
patient/participant card lists contact information for both the investigator and GSK 
Biologicals’ Helpdesk. 
Table 6 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Phone: +32 2 656 68 04, 4008423236 
Fax: +32 2 401 25 75 
Email: rix.ugrdehelpdesk@gsk.com 

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6.3.4.2. 
Emergency unblinding prior to regulatory reporting of SAEs 
GSK policy (which incorporates International Council on Harmonization [ICH] E2A 
guidance, the European Union Clinical Trial Directive and United States Federal 
Regulations) is to unblind the report of any unexpected SAE and which is 
attributable/suspected to be attributable to the study interventions, prior to regulatory 
reporting. Vaccines Clinical Safety and Pharmacovigilance (VCSP) is responsible for 
unblinding the intervention assignment in accordance with the specified timeframes for 
expedited reporting of SAEs (refer to the Section 10.3.8.1).  
In addition, GSK VCSP staff may unblind the intervention assignment for any participant 
with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or a SAE that is fatal 
or life threatening. If the SAE requires an expedited regulatory report be sent to 1 or more 
regulatory agencies, a copy of the report, identifying the participant’s intervention 
assignment, may be sent to investigators in accordance with local regulations and/or GSK 
policy. 
6.4. 
Study intervention compliance 
Study intervention administration will be performed under medical supervision on Day 1 
and Month 1 (refer to the Section 4.1). The date of each dose administered in the study 
center will be recorded in the source documents and in the eCRF.  
6.5. 
Concomitant therapy 
At each study visit/contact, the investigator or delegate should question the participant’s 
parent(s)/LAR(s) about any 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 intervention (Day 1 to Day 31). 
• 
All concomitant vaccinations from Visit 1 up to the Visit 3 (blood sample visit). 
• 
Any concomitant medications/products/vaccines leading to the withdrawal or non-
eligibility of the participant from the study (Please refer to the Section 5.2.2 for 
further details). 
• 
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].  

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• 
Any concomitant medications/products/vaccines relevant to an SAE to be reported as 
per protocol or administered at any time during the study period for the treatment of 
an SAE. Concomitant medications relevant to SAEs must be recorded on the 
Expedited Adverse Event report. 
The Local Medical Lead should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.6. 
Dose modification 
This section is not applicable. 
6.7. 
Intervention after the end of the study 
The immunological assay results will be shared with investigators after the end of the 
study. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
‘Discontinuation’ of study interventions means any participant who has not received all 
planned doses of study interventions. A participant who discontinued study interventions 
may, if deemed appropriate by the investigator, continue other study procedures (e.g., 
safety or immunogenicity) if planned in the study protocol.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF based on the following: 
• 
Adverse event requiring expedited reporting to GSK 
• 
Unsolicited non-serious adverse event  
• 
Solicited adverse event 
• 
Protocol deviation 
• 
Not willing to be vaccinated 
• 
Migrated/moved from study area 
• 
Other (specify). 

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7.1.1. 
Criteria for temporary delay for enrolment and/or study 
intervention administration 
Enrolment/study intervention administration may be postponed within the 
permitted time interval until transient circumstances 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 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. 
7.1.2. 
Contraindications to subsequent study intervention(s) 
administration 
Participants must be evaluated to confirm they are eligible for subsequent study 
intervention administration before administering each additional study dose.  
Participants who meet any of the criteria listed below or criteria listed in Sections 5.2.1, 
5.2.2, 5.2.3 and 5.2.4 should not receive additional study intervention administrations. 
However, these participants should be encouraged to continue other study procedures at 
the discretion of the investigator (Section 10.3.6.2). The relevant criteria for 
discontinuing study intervention administration must be recorded in the eCRF.  
• 
Participants who experience any SAE judged to be possibly or probably related to 
study intervention, including hypersensitivity reactions. 
• 
Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participant if he/she continues to 
participate in the study. 
• 
Anaphylaxis following the administration of study intervention(s). 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this participant from the date of withdrawal/last contact. 
From an analysis perspective, a ‘withdrawal’ from the study refers to any participant who 
was not available for the concluding contact foreseen in the protocol.  
Investigators will attempt to contact those participants who do not return for scheduled 
visits or follow-up. 

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All data and samples collected until the date of withdrawal/last contact of the participant 
will be used for the analysis. 
The primary reason for study withdrawal will be documented in the eCRF based on the 
list below: 
• 
AEs requiring expedited reporting to GSK (please refer to Section 10.3.8.1 for the 
details). 
• 
Unsolicited non-serious AE. 
• 
Solicited AE. 
• 
Protocol deviation.  
• 
Withdrawal by participant, not due to an AE*. 
• 
Migrated/Moved from the study area. 
• 
Lost to follow-up. 
• 
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 provided the reason for its withdrawal, the investigator must 
document this reason in the eCRF. 
Participants who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigators will 
follow participants who are withdrawn from the study as result of an SAE/AE until the 
event is resolved (see Section 10.3.6.2). 
7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if participant’s parent(s)/LAR(s) fails 
to return for scheduled visits and is unable to be contacted by the study site.  
Please refer to the SPM for a description of the actions to be taken before considering the 
participant as 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).  

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Adherence to the protocol is required for study conduct. 
The investigator is not allowed to do testing on samples outside of what has been agreed 
upon by the Institutional Review Board/ Independent Ethics Committee (IRB/IEC). 
The investigator will maintain a screening 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.  
The SPM provides the investigator and site personnel with administrative and detailed 
technical information that does not impact participant safety. 
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:  
• 
ESFU may be made by a telephone call, other means of virtual contact or home visit, 
if appropriate. 
• 
Diary cards may be transmitted from and to the site by electronic means and or 
conventional mail. 
• 
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 (see Table 2), then the interval may be extended 
up to a maximum length of 60 days.  
• 
If despite best efforts it is not possible to administer the 2nd dose of study 
intervention as defined in the protocol (see Table 2), a maximum age of 24 weeks 
may be used. 
* It is the investigator’s responsibility to identify an alternate location. The investigator 
should ensure that this alternate location meets 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 2, 27 March, 2020) for more details. 
8.1. 
Immunogenicity assessments 
Collected biological samples will be used for protocol mandated research and purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol.  

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Sample testing will be done in accordance with the recorded consent of the individual 
participant’s parent(s)/LAR(s).  
Collected samples will be stored for a maximum of 20 years. This storage period begins 
when the last participant performed the last study visit, unless local rules, regulations or 
guidelines require different timeframes or procedures, which would then be in line with 
participant consent. These extra requirements need to be communicated formally to and 
discussed and agreed with GSK. 
8.1.1. 
Biological samples 
An overall volume of approximately 4 mL will be collected during the entire study 
period. Refer to Table 7 and SoA for details of volumes collected for different 
assessments. 
Table 7 
Biological samples 
Sample type 
Quantity 
Unit 
Time point 
Blood 
~2 
mL 
Visit 1 (Day 1 [pre-study intervention administration]) 
~2 
mL 
Visit 3 (Month 2) 
mL = milliliter 
8.1.2. 
Laboratory assays 
The serological assay (anti-RV IgA ELISA) will be transferred to and performed at 
laboratories in China designated by GSK and using validated GSK’s procedures. 
Table 8 
Laboratory assays  
Assay type 
System 
Component 
Method 
Laboratory* 
Humoral Immunity 
(Ab determination) 
SERUM 
Rotavirus Ab, IgA 
ELISA 
GSK designated lab in 
China 
*Refer to the list of clinical laboratories for details. 
Ab = Antibody; IgA = Immunoglobulin A; ELISA = Enzyme Linked Immunosorbent Assay 
Please refer to the Section 10.2 for a brief description of the assay performed in the 
study. 
The addresses of clinical laboratory (ies) used for sample analysis are provided in a 
separate document accompanying this study protocol. 
8.1.3. 
Immunological read-outs 
Table 9 
Immunological read-outs 
Blood sampling timepoint 
No. participants 
Component 
Components priority 
rank  
 
Type of contact and 
timepoint 
Sampling 
timepoint 
Visit 1 (Day 1) 
Pre-Dose 1 
2000 
Rotavirus Ab.IgA 
Not applicable 
Visit 3 (Month 2) 
Post-Dose 2 
2000 
Rotavirus Ab.IgA 
Not applicable 
Ab = Antibody; IgA = Immunoglobulin A; Dose = study intervention administration 

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8.1.4. 
Immunological correlates of protection 
No recognized immunological CoP has been established for the antigen used as part of 
the HRV vaccines. However, an analysis by Cheuvart et al. in 2014 showed that 
post-vaccination anti-RV IgA seropositivity (Ab concentration ≥ 20 U/mL) 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]. 
The immunological assay results will be communicated to the investigator after the end 
of the study.  
8.2. 
Safety Assessments 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and any 
designees remain responsible for following up AEs that are serious, considered related to 
the study intervention or the study, or that caused the participant to discontinue the study 
intervention or the study. 
8.2.1. 
Procedures prior to study intervention administration 
8.2.1.1. 
Collection of demographic data 
Record demographic data such as date of birth including gestational age, sex, and race in 
the participants’ eCRF. 
8.2.1.2. 
Medical and 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 participant 
conditions, signs and/or symptoms present, and any vaccination received prior to the first 
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 administration of study intervention visit will be rescheduled within 
the allowed interval for this visit (see Table 2).  
*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℃. 

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• 
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. 
8.3. 
AEs, SAEs and other events of interest 
8.3.1. 
Time period and frequency for collecting AE, SAE and other 
safety information 
An overview of the protocol-required reporting periods for AEs and SAEs is given in 
Table 10 and Table 11. 
Table 10 
Timeframes for collecting and reporting of safety information 
Event 
V1+ 
Dose 1 
 
 
 
V2+ 
Dose 2 
 
 
V3 
ESFU 
contact 
D1 
D14 D31 
M1 
M1+13 
days 
M1+30 
days 
M2 
M 7 
Systemic solicited events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-V1: pre -visit 1; V: Visit; D: Day; M: Month; AE: adverse event; SAE: serious adverse event; ESFU: extended 
safety follow-up; +Refer to Section 1.3 for information about optimal interval. 

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The investigator or designee will record and immediately report all SAEs to the sponsor 
or designee via the Expedited AE Reporting Form. This 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 10. Investigators are not obligated to actively seek AEs 
or SAEs in 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 
he/she considers the event to be reasonably related to the study interventions, the 
investigator will promptly notify the Study Contact for Reporting SAEs mentioned in the 
Table 12. 
8.3.2. 
Method of detecting AEs and SAEs 
Methods of detecting and recording AE/SAE are detailed in the Section 10.3.6. The 
assessment of AE/SAE intensity, causality and outcome are provided in the Section 
10.3.7.  
Open-ended and non-leading verbal questioning of the 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, and other events 
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE, he/she must report it to GSK using the required documentation, and 
within the timeframes, mentioned in the Table 11. This is essential for meeting legal 
obligations and ethical responsibilities for participant safety and the safety of a study 
intervention under clinical investigation. 
For SAEs, the investigator will 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 the preparation of an investigator 
safety report for SUSAR must be followed. These reports will be forwarded to 
investigators as necessary. 
The sponsor has a legal responsibility to notify local authorities and other regulatory 
agencies about the safety of a study intervention under clinical investigation. 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. 

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Table 11 
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. 
8.3.3.1. 
Contact information for reporting of SAEs 
Table 12 
Contact information for reporting of 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 Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: ogm28723@gsk.com 
8.3.4. 
Treatment of adverse events 
Any medication administered for the treatment of an SAE should be recorded in the 
Expedited Adverse Event Report of the participant’s eCRF screen (refer to the 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 keep the participant card in his/her/their 
possession at all times throughout the study. In an emergency, this card serves to inform 
the responsible attending physician/LAR/care giver/family member that the participant is 
in a clinical study and that relevant information may be obtained by contacting the 
investigator. 
8.3.6. 
Medical device deficiencies 
Both study groups have study interventions that are a combination product constituted of 
a device (e.g., 
) and biologic product. Refer to the 
Glossary of terms for the definition of combination product and medical device 
deficiency.  
CCI

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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 10.4 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.  
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 10.4.3 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. 
Treatment of overdose 
This section is not applicable. 
8.5. 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 

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8.7. 
Genetics 
This section is not applicable. 
8.8. 
Biomarkers 
This section is not applicable. 
8.9. 
Health outcomes 
This section is not applicable. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
This section is not applicable 
9.2. 
Sample size determination 
A maximum of 2000 participants (1000 per arm) will be randomized such that 
approximately 1500 evaluable participants complete the study, considering that 25% of 
the participants will not be evaluable for the analysis of the primary endpoint leading to 
750 evaluable participants per arm. 
To control the type 1 error for the primary objectives and first secondary objective a 
hierarchical procedure will be used. Namely the primary objective on ratio of anti-RV 
IgA Ab GMCs will be conclusive if the success criterion is reached and the first primary 
objective is met. The first secondary objective will be conclusive if the success criterion 
is reached and the 2 primary objectives are met. 
The sample size provides at least 90% power to reach the first primary endpoint (see 
Table 13) and at least 80.7% power to reach the second primary endpoint. 80.7% is a 
very conservative power estimate and is obtained as 100% minus the sum of type II 
errors for the 2 primary objectives, see Table 13 and Table 14. Using the same approach, 
the power to meet the first secondary objectives will be at least 67% power.  
9.2.1. 
Power for non-inferiority in seroconversion 
The power presented in Table 13 is based on PASS 2019 (one-sided Non-Inferiority 
Tests for the Difference Between Two Proportions), under the alternative of a 70% and 
67.8% seroconversion rate for Rotarix and Rotarix PCV-free, respectively, Miettinen and 
Nurminen’s Likelihood Score Test of the Difference).  

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Table 13 
Probability that the lower limit of the 95% CI around group difference 
in seroconversion rate (Rotarix PCV-free minus Rotarix), 1 month 
after Dose 2 of Rotarix, is greater or equal to -10% 
Expected Seroconversion rate 
(Rotarix / Rotarix PCV-free) 
N evaluable 
(each Rotarix 
 group) 
Power 
Alpha 
70%* / 67.8% 
750 
90% 
0.025 
* = Reference from Rota-075  
9.2.2. 
Power for non-inferiority in GMC 
The power presented in Table 14 is based on PASS 2019 (one-sided non-inferiority test 
for 2 independent means, under the alternative of equal variance & alpha=2.5%). 
Table 14 
Probability that the lower limit of the 95% CI around the anti-RV IgA 
Ab GMC ratio (Rotarix PCV-free / Rotarix), 1 month after Dose 2 of 
Rotarix, is greater or equal to 0.67 
Endpoint 
True group GMC 
ratio 
Standard 
deviation 
[Log10 (titer)] 
N evaluable 
(each Rotarix 
group) 
Power 
Alpha 
Anti-RV IgA Ab 
concentration 
1 
0.797* 
750 
99.0% 
0.025 
Anti-RV IgA Ab 
concentration 
0.91 
0.797* 
750 
90.7% 
0.025 
* = Reference from Rota-075 
9.2.3. 
Power for non-inferiority in the percentage of participants with 
serum anti-RV IgA antibody concentrations greater or equal to 90 
U/mL 1 month post Dose 2 
The power presented in Table 15 is based on PASS 2019 (one-sided Non-Inferiority 
Tests for the Difference Between Two Proportions), under the alternative of a 45.7% and 
43.5% percentage for Rotarix and Rotarix PCV-free, respectively, Miettinen and 
Nurminen’s Likelihood Score Test of the Difference).  
Table 15 
Probability that the lower limit of the 95% CI around group difference 
in the percentage of participants with serum anti-RV IgA antibody 
concentrations greater or equal to 90 U/mL (Rotarix PCV-free minus 
Rotarix), 1 month after Dose 2 of Rotarix, is greater or equal to -10% 
Expected rate (Rotarix / Rotarix 
PCV-free) 
N evaluable 
(each Rotarix 
 group) 
Power 
Alpha 
45.7%* / 43.5% 
750 
86.2% 
0.025 
* = Reference from Rota-075  

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9.3. 
Populations for analyses 
Table 16 
Populations for analyses 
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 Analysis set as they did not enter the 
study.  
Exposed Set (ES) 
All participants with at least 1 dose of the study intervention documented. The 
allocation in a group is done in function of the administered intervention. The ES 
analysis will be performed per treatment actually administered at Dose 1. 
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 2). 
Note that in case regurgitation or vomiting occurs within 30 minutes after 
study intervention administration and impairs up-take of the intervention, a 
single replacement dose should be used for the participant to be part of the 
PPS, 
• 
who were not unblinded, 
• 
who did not receive a vaccine not specified or forbidden in the protocol up to 
Visit 3 blood sampling, 
• 
who did not receive medication forbidden by the protocol up to Visit 3 blood 
sampling, 
• 
who had anti-RV concentration below 20 U/mL before study intervention 
administration and who had anti-RV results from the Visit 3 blood sampling, 
• 
who complied with the blood sampling schedule for Visit 3 (see Table 2), 
• 
who had no concomitant infection up to Visit 3 blood sample, which may 
influence the immune system. 
9.4. 
Statistical analyses 
9.4.1. 
General considerations 
9.4.1.1. 
Immunogenicity 
Ab concentrations below the assay cut-off will be given an arbitrary value of half the 
assay cut-off for the purpose of GMC calculation. 
• 
The GMC calculations will be performed by taking the anti-log of the mean of the 
log concentration transformations. Ab concentrations below the cut-off of the assay 
will be given an arbitrary value of half the cut-off for the purpose of GMC 
calculation.  
• 
For a given participant and a given immunogenicity measurement time point, 
missing or non-evaluable measurements will not be replaced. 

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9.4.1.2. 
Reactogenicity/Safety 
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). 
9.4.2. 
Participant disposition 
Number of enrolled, vaccinated participants and reason for withdrawal will be described.  
The distribution of participants enrolled in each site will be tabulated across and per study 
group.  
Number of participants excluded from PPS analyses will be tabulated for the total 
population and for each group based on the reason for exclusion. 
9.4.3. 
Analysis of immunogenicity 
The immunogenicity analysis will be based on the PPS for analysis of immunogenicity. 
If, in any study intervention group, the percentage of vaccinated participants with 
serological results excluded from the PPS for analysis of immunogenicity is 5% or more, 
a second analysis based on the ES will be performed to complement the PPS analysis. 
9.4.3.1. 
Within groups assessment 
The following calculations will be performed. 
• 
For each group, at Visit 1 and Visit 3 time point, 
− 
Seropositivity/seroconversion rates and their exact 95% CI will be computed, 
− 
Percentage of participants with anti-RV IgA antibody concentrations ≥ 90 U/mL 
and their exact 95% CI will be computed. 
− 
GMCs and their exact 95% CIs will be computed, 
− 
The distribution of anti-RV IgA Ab concentrations at Visit 3 will be displayed 
using reverse cumulative curves. 
9.4.3.2. 
Between groups assessment 
• 
The asymptotic standardized 95% CI for the difference in seroconversion rate at 
Visit 3 between Rotarix PCV-free minus Rotarix will be computed. 
• 
The 95% CI for the ratio of anti-RV IgA Ab GMCs at Visit 3 between Rotarix 
PCV-free over Rotarix will be computed.  
• 
The asymptotic standardized 95% CI for the difference in the percentage of 
participants with anti-RV IgA antibody concentrations ≥ 90 U/mL at Visit 3 between 
Rotarix PCV-free minus Rotarix will be computed. 

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9.4.4. 
Analysis of safety 
Safety analysis will be performed on the ES. 
9.4.4.1. 
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 drop outs due to AEs will be described in detail.  
9.4.5. 
Other analyses 
9.4.5.1. 
Demography and baseline characteristics analyses 
The median, mean, range and standard deviation of age (in weeks) for each dose of 
Rotarix 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.  

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Summary of co-administered vaccinations (i.e., vaccinations given on the day of each 
Rotarix dose) and intercurrent vaccinations (i.e., vaccinations other than Rotarix 
administered from birth up to Visit 3, excluding vaccination given on the day of Rotarix 
administration) will be summarized by group for the ES. 
9.5. 
Interim analyses  
9.5.1. 
Sequence of analyses 
Final analysis will be conducted once anti-RV IgA ELISA testing at Visit 3 (1 month 
after Dose 2) is completed and all the immunogenicity data are available. This final 
analysis will include immunogenicity and safety data up to Visit 3 and a clinical study 
report (CSR) will be written.  
An EoS analysis with all data including the data obtained during ESFU period will be 
performed and an integrated CSR will be written and made available to the investigators 
and submitted to regulatory authorities as appropriate. 
Note: If there is a delay in availability of the immunogenicity data, leading to a window 
between the 2 analyses shorter than what is planned at the time of protocol writing, only 
1 statistical analysis including all immunogenicity and safety data will be performed and 
1 study report will be developed. 
9.6. 
Data Monitoring Committee 
This section is not applicable. 

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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 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 IRB/IEC 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. 
• 
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/EC. 
− 
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 financial interest information prior initiation 
of the center and at the end of the study. Investigators are responsible for providing a 

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Financial Disclosure update if their financial interests change at any point during their 
participation in a study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
The investigator or his/her representative will explain the nature of the study to the 
participants’ parent(s) or his/her LAR(s) and answer all questions regarding the study.  
Participants’ parent(s)/LAR(s) must be informed that the participant’s involvement 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 informed consent form must meet the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
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 to the most current version of the ICF(s) or an ICF 
addendum during their participation in the study.  
A copy of the ICF(s) must be provided to the participants’ parent(s)/LAR(s).  
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 sponsor. Any participant records 
or datasets that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred.  
The participants’ parent(s)/LAR(s) must be informed that his/her child’s/ward’s personal 
study-related data will be used by the sponsor in accordance with local data protection 
law.  
The participants’ parent(s)/LAR(s) must be informed of his/her child’s/ward’s rights 
regarding the use of their personal data in accordance with the data privacy Section of the 
ICF. 

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The participants’ parent(s)/LAR(s) must be informed that his/her child’s/ward’s medical 
records 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. 
GSK will also ensure protection of the personal data of the investigator and site staff 
which will be collected within the framework and for the purpose of the study in 
accordance with the Data Privacy Notice that will be sent to the site staff.  
10.1.5. 
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 the 
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 trial 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. 
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 trial 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 trial 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.6. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents including source documents. The storage system used during the trial and for 
archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g., source documents), the copy should fulfil the 
requirements for certified copies.  

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All participant data relating 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 trial records 
that include all pertinent observations on each of the site’s trial 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.  
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 
into the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data should be traceable, should not 
obscure the original entry, and should be explained if necessary (e.g., via an audit trail). 
The safety and rights of participants must be protected and study be conducted in 
accordance with the currently approved protocol and any other study agreements, ICH 
GCP, and all applicable regulatory requirements.  
Trial records and source documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the investigator for 15 years from the Report Complete 
date entered in eTrack. 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.  
10.1.7. 
Source documents 
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Investigator should maintain a record of the location(s) 
of their source documents.  
Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the 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. 
Definition of what constitutes source data and source documents can be found in the 
Glossary of terms. 
10.1.8. 
Study and site start and closure 
First act of recruitment 
The start of study is defined as FSFV. 

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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 the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure 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 sufficient notice is given 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 
• 
Discontinuation of further study intervention development 
10.1.9. 
Publication policy 
GSK aims to submit for publication the results of the study in searchable, peer reviewed 
scientific literature within 18 months from last subject last visit for interventional studies 
and follows the guidance from the International Committee of Medical Journal Editors. 
10.2. 
Appendix 2: Tests 
Anti-RV IgA Ab Determination 
The anti-RV Ab concentrations are determined by a validated anti-RV IgA ELISA. 
Microtiter plates (96-well) are coated with an anti-RV monoclonal Ab. 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 Abs. 
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. 

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10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting  
10.3.1. 
Definition of an Adverse Event (AE)  
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of 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 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 study intervention(s) administration 
even though they may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention(s) or a concurrent medication (overdose per se should not be reported 
as an AE/SAE). 
• 
Signs or symptoms temporally associated with study intervention(s) 
administration. 
• 
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 the Section 10.3.3. All other 
AEs 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 fulfil 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 prior to 
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 prior to informed consent signature) that did not worsen from baseline. 
• 
Clinically significant abnormal laboratory findings or other abnormal assessments 
that are associated with the disease being studied, unless judged by the investigator 
as more severe than expected for the participant’s condition, or that are present or 
detected at the start of the study and do not worsen. 
10.3.2. 
Definition of a Serious Adverse Event (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 at 
the hospital or emergency ward for observation and/or treatment that would not 
have been appropriate in the physician’s office or in an out-patient setting. 
Complications that occur during hospitalization are also considered as AEs. If a 
complication prolongs hospitalization or fulfils any other serious criteria, the event 
will also be considered serious. When in doubt as to whether ‘hospitalization’ 
occurred, or was necessary, the AE should be considered serious. 
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 judgement should be exercised in deciding whether reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These should also 
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 or convulsions that do not result in hospitalization. 
10.3.3. 
Solicited events 
The following systemic 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 adverse events 
An unsolicited adverse event is an adverse event that was not solicited using a Participant 
Diary and that was spontaneously communicated by a participant’s parent(s)/LAR(s) who 
has signed the informed consent. Unsolicited AEs include serious and non-serious AEs. 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or emergency room visit, or visit to/by a health care 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/ parental /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 
participant’s parent(s)/LAR(s) will be collected during interview with the participant’s 
parent(s)/LAR(s) and by review of available medical records at the next visit. 

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10.3.5. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs  
In the absence of a diagnosis, abnormal laboratory findings (e.g., clinical chemistry, 
hematology, urinalysis) or other abnormal assessments 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 the Sections 10.3.1 and 10.3.2).  
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 
10.3.6. 
Recording and follow-up of AEs, SAEs 
The participants’ parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should the participants manifest any signs or symptoms they perceive as 
serious.  
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
participant’s medical records to GSK instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all participant identifiers will be blinded on the copies 
of the medical records prior to submission to GSK. 
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 and not the 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) on Visit 2 and Visit 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.  

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10.3.6.1. 
Time period for collecting and recording AEs, and SAEs 
All AEs that occur during 30 days following administration of each dose of study 
intervention(s) (Day 1 to Day 31) must be recorded into the appropriate section of the 
eCRF, irrespective of intensity or whether or not they are considered related to the study 
intervention. 
10.3.6.2. 
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 non-serious AEs must be followed until 30 days after the last study intervention 
administration or until the participant is lost to follow-up. 
10.3.6.2.1. 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 participant dies during participation in the study or during a recognized follow-up 
period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.6.2.2. Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information on previously 
reported SAE to GSK using a paper/electronic Expedited Adverse Events Report as 
applicable. 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 AE or SAE as fully as possible.   
10.3.6.3. 
Updating of SAE information after removal of write access to the 
participant’s eCRF 
When additional SAE information is received after removal of write access to the 
participant’s eCRF, 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 or emailed to the Study Contact for Reporting SAEs (refer to the Section 
8.3.3.1 or to GSK Clinical Safety and Pharmacovigilance department within the defined 
reporting time frames specified in the Table 11). 

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10.3.7. 
Assessment of intensity and toxicity 
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 
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 judgement. 

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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 pre-defined 
outcomes as described in the Section 10.3.2. 
10.3.7.2. 
Assessment of causality 
All solicited systemic events will be considered causally related to study intervention 
administration. The complete list of these events is provided in the Table 17. 
The investigator must assess the relationship between study intervention(s) and the 
occurrence of each unsolicited AE/SAE using clinical judgement. Where several different 
vaccines/products were administered, the investigator should specify, when possible, if 
the unsolicited AE/SAE could be causally related to a specific vaccine/product (i.e., 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine(s) cannot be determined, the investigator should indicate the 
unsolicited AE/SAE to be related to all products. 
Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention(s) will be considered and investigated. The investigator will also 
consult the IB determine his/her assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study intervention? 
YES 
: 
There is a reasonable possibility that the study intervention(s) 
contributed to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study intervention(s). There are other, more likely 
causes and administration of the study intervention(s) is not suspected 
to have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible 
contributing factors for each SAE. 

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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(s), if applicable. 
• 
Erroneous 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.  
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. The investigator may change his/her opinion of causality after receiving 
additional information and update the SAE information accordingly. 
10.3.7.3. 
Medically attended visits 
For each solicited and unsolicited symptom 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.  
10.3.7.4. 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 

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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 a study participant, the 
investigator (or designee) must complete information in the electronic Expedited Adverse 
Events Report WITHIN 24 HOURS. The report will always be completed as thoroughly 
as possible with all available details of the event.  
Even if the investigator does not have all information regarding an SAE, the report 
should still be completed within 24 hours. Once additional relevant information is 
received, the report should be updated WITHIN 24 HOURS. The investigator will always 
provide an assessment of causality at the time of the initial report. 
Refer to the Table 11 for the details on timeframes for reporting of SAEs. 
Refer to the Section 10.3.8.2 for the back-up system in case the electronic reporting 
system does not work. 
10.3.8.2. 
Back-up system in case facsimile or electronic reporting system does 
not work 
In rare circumstances if the electronic reporting system does not work, the investigator 
(or designee) must fax or email the completed, dated and signed paper Expedited Adverse 
Events Report to the Study Contact for Reporting SAEs (refer to the Sponsor 
Information) or to GSK Clinical Safety and Pharmacovigilance department within 24 
hours (refer to Section 8.3.3.1 for contact information).  
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
within 24 hours upon electronic reporting system is resumed. The information reported 
through the electronic SAE reporting system will be considered valid for regulatory 
reporting purposes. 

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10.4. 
Appendix 4: Definition of medical device AE, adverse device 
effect (ADE), serious adverse device effect (SADE) and 
unanticipated SADE (USADE) 
10.4.1. 
Definition of medical device AE and adverse device effect (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 adverse device effect (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. 
10.4.2. 
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 
c. 
Is a suspected transmission of any infectious agent via a medicinal product 

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Serious Adverse Device Effect (SADE) definition 
• 
A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
• 
Any device deficiency that might have led to an SAE if appropriate action had not 
been taken 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. 
10.4.3. 
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. 
• 
If required or in case of any issues refer to the general safety contacts for SAE/AE 
reporting in Section 8.3.3.1. 
10.4.4. 
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. 

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10.5. 
Appendix 5: Abbreviations and glossary of terms 
10.5.1. 
List of abbreviations  
Ab 
Antibody 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CI 
Confidence Interval 
CoP 
Correlate of Protection 
COVID-19 
Coronavirus Disease 2019 
CSR 
Clinical Study Report 
eCRF 
electronic Case Report Form 
ELISA 
Enzyme Linked Immunosorbent Assay 
EMA 
European Medicines Agency 
EoS 
End of Study 
ES 
Exposed Set 
ESFU 
Extended Safety Follow-Up 
GCP 
Good Clinical Practice 
GE 
Gastroenteritis 
GMC 
Geometric Mean Antibody Concentration 
GSK 
GlaxoSmithKline 
HRV 
Human Rotavirus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonization 
IgA 
Immunoglobulin A 
IRB/IEC 
Institutional Review Board/ Independent Ethics Committee 

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IS 
Intussusception 
Kg 
Kilogram 
LAR 
Legally Acceptable Representative 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
PCV 
Porcine Circovirus 
PP 
Per Protocol 
PPS 
Per Protocol Set 
RV 
Rotavirus 
RVGE 
Rotavirus Gastroenteritis 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SBIR 
Source data Base for Internet Randomization  
SmPC 
Summary of Product Characteristics 
SoA 
Schedule of Activities 
SPM 
Study Procedures Manual 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
U 
Unit 
USADE or UADE 
Unanticipated Serious Adverse Device Effect 
VCSP 
Vaccines Clinical Safety and Pharmacovigilance 
WHO 
World Health Organization 

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10.5.2. 
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 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 trial 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 
trial, 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 observer-blind study, the participant, the site 
and sponsor personnel involved in the clinical evaluation 
of the participants are blinded while other study 
personnel may be aware of the treatment assignment.  
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 his/her 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 
living in a care home or institution, provided that the 
arrangement falls within the definition above. The 

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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. 
Enrolled: 
‘Enrolled’ means a participant’s/parent’s/LAR’s 
agreement to participate in a clinical study following 
completion of the informed consent process. Potential 
participants who are screened for the purpose of 
determining eligibility for the study, but do not 
participate in the study, are not considered enrolled, 
unless otherwise specified by the protocol. Refer to the 
Section 9.3 for the definition of ‘enrolled’ applicable to 
the study. 
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 trials. 
Evaluable:  
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis (see Section 9.3 for 
details on criteria for evaluability). 
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’.  
Investigational vaccine: 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorization when used in a way different 

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from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use.  
Synonym: Investigational Medicinal Product 
Investigator: 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
and functions 
Legally acceptable 
representative: 
An individual or juridical or other body authorized under 
applicable law to consent, on behalf of a prospective 
participant, to the participant's participation in the 
clinical trial. 
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 
participates in the clinical study, either as a recipient of 
the study intervention(s) or as a 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 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 Biologicals 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. 

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Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  
Randomization: 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
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 trial necessary for the 
reconstruction and evaluation of the trial. 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, at the laboratories and at medico-
technical departments involved in the clinical trial). 
Study intervention 
/product: 
Any investigational intervention /product being tested 
and/or any authorized use of an intervention 
/product/placebo as a reference or administered 
concomitantly, in a clinical trial that evaluates the use of 
an investigational intervention /product. 
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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10.6. 
Appendix 6: Protocol Amendment change history 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents. 
11. 
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