A Phase III, Randomized, Partially Double- Blind, Active Control Study to Compare the Immunogenicity and Safety of a Liquid Formulation of ROTAVIN With the Currently Licensed Frozen Formulation of the Vaccine (ROTAVIN-M1), in Healthy Vietnamese Infants
Phase: PHASE3
Conditions: Diarrhea, Diarrhea Rotavirus
Sponsor: Center for Research and Production of Vaccines and Biologicals, Vietnam

RESEARCH PROTOCOL OF VACCINE CLINICAL TRIAL
A PHASE III, RANDOMIZED, PARTIALLY DOUBLE- BLIND, ACTIVE CONTROL 
STUDY TO COMPARE THE IMMUNOGENICITY AND SAFETY OF A LIQUID 
FORMULATION OF ROTAVIN WITH THE CURRENTLY LICENSED FROZEN 
FORMULATION OF THE VACCINE (ROTAVIN-M1), IN HEALTHY VIETNAMESE 
INFANTS.
Protocol Number:&9,$
Version Number:
Date:-XQH
Vietnam MOH Reference:9;
Trial Registration Reference:1&7&OLQLFDO7ULDOVJRY 
SUMMARY NAME: Phase III Bridging Study of Liquid Formulation of ROTAVIN
Principal Investigator: 
 NIHE
Co- Principal Investigator:
 NIHE
Investigator’s Institution: National Institute of Hygiene and Epidemiology, Vietnam
Sponsor: Center for Research and Production of Vaccines and Biologicals (POLYVAC),
Vietnam
In Collaboration with: PATH, USA 
Manufacturer: Center for Research and Production of Vaccines and Biologicals
(POLYVAC), Vietnam
Authority Agency: Ministry of Health, Vietnam
Planned time: 4th quarter 2018
Total budget: From Government budget for Science and Technology: 0 VND
From PATH: Approximately 8.5 billion VND
Confidentiality Statement
This document is confidential and is to be distributed for review only to investigators, 
potential investigators, consultants, study staff, and applicable independent ethics 
committees or institutional review boards.  The contents of this document shall not be 
disclosed to others without written authorization from PATH (or others, as applicable), 
unless it is necessary to obtain informed consent from potential study participants.

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Hanoi, Vietnam 
Co- Principal Investigator
Head, Center for Clinical Trials , NIHE
Principal Investigator
Prof. and Director, NIHE.
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TABLE OF CONTENTS
STATEMENT OF COMPLIANCE ....................................................................................................................... 2 
TABLE OF CONTENTS ....................................................................................................................................... 3 
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PROTOCOL SUMMARY
Title:
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Description of 
Study Design:
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Study Objectives 
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Primary Objectives
Immunogenicity
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Safety
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Secondary Objective
Immunogenicity

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Study Endpoints
Primary Endpoint: 
Immunogenicity 
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Secondary Endpoint:
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Description of 
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Table 1: Trial Schema- Schedule of Events
Visit
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Time point (Day)
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2
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE
2.1
Overview of Rotavirus Diarrhea Disease 
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Summary Results of Related Preclinical Studies
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Table 2.4: Weight and body temperature of Monkey during the study
Vaccine
Weight (kg)
Temperature (oC)
Pre injection
Post injection
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Table 2.5: Results of safety study on Macaca mulatta monkey 6 – 17 months old
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Total number of rabbits
40
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Table 2.7: Average food consumption per week per rabbit
Study group
Week
Average food consumption (g)
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Figure 2.2: Chart of average weight gain of rabbit groups
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Figure 2.4: Solicited adverse events within 7 days after each vaccine dose.
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Table 2.9: Proportion of children with RV-IgA antibody prior to administration of 
vaccine/placebo
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Table 2.10: Conversion rate of IgA antibody at 1 month after the second oral dose
Site
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Table 2.11: IgA Geometric Mean Concentration (GMC) before and after the 
administration of vaccine/placebo at study sites
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Table 2.12: Comparison of IgG antibody concentration levels of children before 
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Table 2.13: IgG Geometric Mean Concentration (GMC) at examination times
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Table 2.14: RV-IgA antibody concentrations in ROTAVIN-M1 and Rotarix group at 
different time points (prior to study enrollment – M0, 3 and 12 months after the first dose 
(M2 and M3)
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Table 2.15: Rate of participants with Rota IgA antibody positive one year after the first 
dose
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STUDY ENROLLMENT AND WITHDRAWAL
5.1
Description of Participants, Source of Participants
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6
STUDY PRODUCTS
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Study Product Descriptions
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Dosage, Preparation, and Administration of Study Products
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STUDY SCHEDULE; DESCRIPTION OF VISITS
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Final Study Visit (Day 85; + 14) 
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Unscheduled Visits
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End of Trial According to the Protocol
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STUDY EVALUATIONS
8.1
Clinical Evaluations
Definition and Categorization of AEs
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10 MONITORING
10.1
Monitoring Plan
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Routine Monitoring Visits
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11 AUDITS AND INSPECTIONS
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12 STATISTICAL CONSIDERATIONS
12.1
Overview and General Considerations
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Table 12.1: Power to detect at least a ratio > 0.5 of anti-rotavirus IgA GMCs between 
ROTAVIN liquid formulation and ROTAVIN-M1 groups 28 days after the second dose, 
based on various group sizes and different assumed SD of log10 IgA antibody concentrations
Assumed SD of log10 
IgA antibody 
concentrations
Number of evaluable 
participants SHU
group (ROTAVIN 
liquid formulation vs. 
ROTAVIN-M1)
Power to detect at least a 0.5 ratio of
anti-rotavirus IgA GMCs between 
ROTAVIN liquid formulation and 
ROTAVIN-M1
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Table 12.2: The minimum difference in percentage of participants with solicited post-
vaccination reaction after each vaccination between ROTAVIN liquid formulation and 
ROTAVIN-M1 groups can be detected with 90% power
Expected percentage of 
participants with a solicited 
post-vaccination reaction in 
ROTAVIN-M1 group
Number of vaccinated 
participants per group 
(ROTAVIN liquid 
formulation vs. ROTAVIN-
M1)
Minimum difference in 
percentage of participants
with a solicited post-
vaccination reaction
between the groups which 
can be detected with 90% 
power
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12.3
Analysis Populations 
12.3.1 Enrolled Population 
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Analytical Methodology
12.4.1 Analysis of demographics and other baseline characteristics
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12.4.2 Analysis of primary objectives
Analysis of primary immunogenicity objective
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12.4.3 12.4.3 Analysis of secondary objectives
Analysis of secondary immunogenicity objectives
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13 DATA MANAGEMENT
13.1
Case Report Form (CRF)
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Participant Confidentiality
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15.10 Sharing of Study Result
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APPENDIX A-DECLARATION OF HELSINKI
Ethical Principles for Medical Research Involving Human Subjects
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