Immunogenicity and Safety of a Single Dose of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Children, Adolescents, and Adults 2 to 55 Years of Age
Phase: PHASE3
Conditions: Meningococcal Immunisation (Healthy Volunteers)
Sponsor: Sanofi

Any and all information presented in this document shall be treated as confidential and shall remain the exclusive property of Sanofi (or any of its 
affiliated companies). The use of such confidential information must be restricted to the recipient for the agreed purpose and must not be 
disclosed, published or otherwise communicated to any unauthorized persons, for any reason, in any form whatsoever without the prior written 
consent of Sanofi (or the concerned affiliated company); ‘affiliated company’ means any corporation, partnership or other entity which at the date 
of communication or afterwards (i) controls directly or indirectly Sanofi, (ii) is directly or indirectly controlled by Sanofi, with ‘control’ meaning 
direct or indirect ownership of more than 50% of the capital stock or the voting rights in such corporation, partnership or other entity
According to template: CJPN-SD-000042 VERSION N°2.0 (15-AUG-2019) 
Page 1 
AMENDED CLINICAL STUDY PROTOCOL 01 
Immunogenicity and Safety of a Single Dose of an Investigational Quadrivalent 
Meningococcal Conjugate Vaccine in Children, Adolescents, and Adults 2 to 55 
Years of Age 
Phase III, modified double-blind, randomized, parallel-group, active-controlled, multi-center study to evaluate the immune 
non-inferiority of MenACYW conjugate vaccine versus Menactra®, and describe the safety and additional immunogenicity of study 
vaccines in children, adolescents and adults 2 to 55 years of age in Japan 
Product Code / Study Number: 
SP0047 / EFC16335_MEQ00068 
Development Phase:  
Phase III 
Sponsor: 
Sanofi K.K. 
3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
Investigational Product: 
MenACYW conjugate vaccine: Meningococcal Polysaccharide 
(Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate 
Vaccine 
Form / Route: 
Liquid solution / Intramuscular 
Indication For This Study: 
MenACYW conjugate vaccine as a single dose in children, 
adolescents and adults 2 to 55 years of age 
Manufacturer: 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, USA 
Version Number: 1.0 
EudraCT: 
Not applicable 
IND Number(s): 
Not applicable 
WHO universal trial number: 
U1111-1241-8382 
Date: 
10-Mar-2020
Total number of pages: 
86 
NCT04368429

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NAMES AND ADDRESSES OF 
INVESTIGATORS 
Name: 
Address: 
Tel: 
Fax: 
E-mail: 
This is a multi-center study with multiple 
Investigators. Investigators and study sites are 
listed in the list of Investigators and centers 
involved in the study. 
 
MONITORING TEAM’S 
REPRESENTATIVE 
Name: 
Address: 
 
Tel: 
Fax: 
E-mail: 
 
GLOBAL STUDY 
MANAGER 
Name: 
Address: 
 
Tel: 
Fax: 
E-mail: 
 
STUDY MEDICAL 
MANAGER  
Name: 
Address: 
 
Tel: 
Fax: 
E-mail 
 
OTHER EMERGENCY 
TELEPHONE NUMBERS 
Company: 
 
Address: 
 
Tel: 
Emergency Scientific & Medical Services 
International 
Mary Sheridan House, Guy's Hospital, 13 St 
Thomas Street, London, SE1 9RY, UK 
0120-276-700 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES  
 
DOCUMENT HISTORY 
Document 
Country/Countries 
impacted by amendement 
Date, version 
Clinical Study Protocol 
 
05-Dec-2019, version 1.0 (electronic 1.0) 
 
OVERALL RATIONALE FOR THE AMENDMENT 
The revisions made are owing to the PMDA requests or requirements as summarized below. 
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3.2 Potential Risks to 
Subjects 
Added induration as injection site reaction 
As requested by PMDA 
Section 5.2.5 Exclusion Criteria 
Added the explanation of the contraception 
methods 
As requested by PMDA 
Section 6.7 Concomitant 
Medication and Other 
Therapies  
Deleted the description that medications will 
not be coded 
Medication will be coded for the PMDA 
requirements on electronic study data 
submission 
Section 9.2.2.3.2 
Reactogenicity (Solicited 
Reactions From Day 0 to Day 7 
After Vaccination) 
Added the terminology, definitions, and 
intensity scales for Injection site induration 
on Table 1 and Table 2 
As requested by PMDA 

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TABLE OF CONTENTS 
AMENDED CLINICAL STUDY PROTOCOL 01 ............................................................................................. 1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................................................................... 3 
TABLE OF CONTENTS .................................................................................................................................. 4 
LIST OF TABLES ............................................................................................................................................ 9 
SYNOPSIS .................................................................................................................................................... 10 
TABLE OF STUDY PROCEDURES ............................................................................................................. 17 
LIST OF ABBREVIATIONS .......................................................................................................................... 18 
1 
INTRODUCTION ............................................................................................................................ 20 
1.1 
BACKGROUND ............................................................................................................................. 20 
1.2 
BACKGROUND OF THE INVESTIGATIONAL PRODUCT ........................................................... 21 
1.2.1 
Non-clinical Safety ......................................................................................................................... 21 
1.2.2 
Clinical ............................................................................................................................................ 22 
1.2.2.1 
Study MET35 (Phase III) ................................................................................................................ 22 
1.2.2.2 
Study MET43 (Phase III) ................................................................................................................ 24 
1.2.2.3 
Study MET49 (Phase III) ................................................................................................................ 26 
1.3 
POTENTIAL BENEFITS AND RISKS ............................................................................................ 27 
1.3.1 
Potential Benefits to Subjects ........................................................................................................ 27 
1.3.2 
Potential Risks to Subjects ............................................................................................................ 28 
1.4 
RATIONALE FOR THE STUDY ..................................................................................................... 29 
2 
STUDY OBJECTIVES ................................................................................................................... 31 
2.1 
PRIMARY OBJECTIVE(S) ............................................................................................................. 31 
2.2 
SECONDARY OBJECTIVE(S) ...................................................................................................... 31 
3 
INVESTIGATORS AND STUDY ORGANIZATION ....................................................................... 32 
4 
INSTITUTIONAL REVIEW BOARD / INDEPENDENT ETHICS COMMITTEE (IRB/IEC) ........... 33 
5 
INVESTIGATIONAL PLAN ........................................................................................................... 34 
5.1 
DESCRIPTION OF THE OVERALL STUDY DESIGN AND PLAN ............................................... 34 
5.1.1 
Study Design .................................................................................................................................. 34 
5.1.2 
Justification of the Study Design .................................................................................................... 34 

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5.1.3 
Study Plan ...................................................................................................................................... 35 
5.1.4 
Visit Procedures ............................................................................................................................. 35 
5.1.5 
Planned Study Calendar ................................................................................................................ 38 
5.2 
ENROLLMENT AND RETENTION OF STUDY POPULATION .................................................... 38 
5.2.1 
Recruitment Procedures ................................................................................................................ 38 
5.2.2 
Informed Consent Procedures ....................................................................................................... 38 
5.2.3 
Screening Criteria .......................................................................................................................... 39 
5.2.4 
Inclusion Criteria ............................................................................................................................ 39 
5.2.5 
Exclusion Criteria ........................................................................................................................... 39 
5.2.6 
Medical History ............................................................................................................................... 41 
5.2.7 
Contraindications for Subsequent Vaccinations ............................................................................ 42 
5.2.8 
Contraindications for Visit 2 Blood Samples .................................................................................. 42 
5.2.9 
Conditions for Withdrawal .............................................................................................................. 42 
5.2.10 
Lost to Follow-up Procedures ........................................................................................................ 42 
5.2.11 
Classification of Subjects Who Discontinue the Study .................................................................. 43 
5.2.12 
Follow-up of Discontinuations ........................................................................................................ 43 
5.2.13 
Follow-up and Reporting of Pregnancies ....................................................................................... 43 
5.3 
SAFETY EMERGENCY CALL ....................................................................................................... 44 
5.4 
INTERRUPTION OF THE STUDY ................................................................................................. 44 
5.5 
PREMATURE CLOSE-OUT OF A SITE ........................................................................................ 45 
5.5.1 
By the sponsor ............................................................................................................................... 45 
5.5.2 
By the Investigator ......................................................................................................................... 45 
6 
PRODUCTS ADMINISTERED ...................................................................................................... 46 
6.1 
IDENTITY OF THE INVESTIGATIONAL PRODUCT(S) ............................................................... 46 
6.1.1 
Identity of Study Product(s) ............................................................................................................ 46 
6.1.1.1 
Composition ................................................................................................................................... 46 
6.1.1.2 
Preparation and Administration ...................................................................................................... 46 
6.1.1.3 
Dose Selection and Timing ............................................................................................................ 47 
6.1.2 
Identity of Control Product(s) ......................................................................................................... 47 
6.1.2.1 
Composition ................................................................................................................................... 47 
6.1.2.2 
Preparation and Administration ...................................................................................................... 48 
6.1.2.3 
Dose Selection and Timing ............................................................................................................ 48 
6.2 
IDENTITY OF OTHER PRODUCT(S) ........................................................................................... 48 
6.3 
PRODUCT LOGISTICS ................................................................................................................. 48 
6.3.1 
Labeling and Packaging ................................................................................................................. 48 

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6.3.2 
Product Shipment, Storage, and Accountability ............................................................................ 48 
6.3.2.1 
Product Shipment ........................................................................................................................... 48 
6.3.2.2 
Product Storage ............................................................................................................................. 48 
6.3.2.3 
Product Accountability ................................................................................................................... 49 
6.3.3 
Replacement Doses ....................................................................................................................... 49 
6.3.4 
Disposal of Unused Products ......................................................................................................... 49 
6.3.5 
Recall of Products .......................................................................................................................... 49 
6.4 
BLINDING AND CODE-BREAKING PROCEDURES .................................................................... 49 
6.5 
RANDOMIZATION AND ALLOCATION PROCEDURES .............................................................. 50 
6.6 
TREATMENT COMPLIANCE ........................................................................................................ 51 
6.7 
CONCOMITANT MEDICATION AND OTHER THERAPIES ......................................................... 51 
7 
MANAGEMENT OF SAMPLES .................................................................................................... 53 
7.1 
SAMPLE COLLECTION ................................................................................................................ 53 
7.2 
SAMPLE PREPARATION .............................................................................................................. 53 
7.3 
SAMPLE STORAGE AND SHIPMENT.......................................................................................... 53 
7.4 
FUTURE USE OF STORED BIOLOGICAL SAMPLES FOR RESEARCH ................................... 54 
8 
CLINICAL SUPPLIES.................................................................................................................... 55 
9 
ENDPOINTS AND ASSESSMENT METHODS ............................................................................ 56 
9.1 
PRIMARY ENDPOINTS AND ASSESSMENT METHODS ........................................................... 56 
9.1.1 
Immunogenicity .............................................................................................................................. 56 
9.1.1.1 
Immunogenicity Endpoints ............................................................................................................. 56 
9.1.1.2 
Immunogenicity Assessment Methods .......................................................................................... 56 
9.1.2 
Safety ............................................................................................................................................. 56 
9.1.3 
Efficacy ........................................................................................................................................... 56 
9.2 
SECONDARY ENDPOINTS AND ASSESSMENT METHODS ..................................................... 57 
9.2.1 
Immunogenicity .............................................................................................................................. 57 
9.2.1.1 
Immunogenicity Endpoints ............................................................................................................. 57 
9.2.1.2 
Immunogenicity Assessment Methods .......................................................................................... 57 
9.2.2 
Safety ............................................................................................................................................. 57 
9.2.2.1 
Safety Definitions ........................................................................................................................... 57 
9.2.2.2 
Safety Endpoints ............................................................................................................................ 60 
9.2.2.3 
Safety Assessment Methods ......................................................................................................... 60 
9.2.3 
Efficacy ........................................................................................................................................... 67 
9.3 
OBSERVATIONAL ENDPOINTS AND ASSESSMENT METHODS ............................................. 67 

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10 
REPORTING OF SERIOUS ADVERSE EVENTS ........................................................................ 68 
10.1 
REPORTING BY THE INVESTIGATOR ........................................................................................ 68 
10.2 
REPORTING OF SAES OCCURRING AFTER A SUBJECT HAS COMPLETED THE 
STUDY ........................................................................................................................................... 69 
10.3 
ASSESSMENT OF CAUSALITY ................................................................................................... 69 
10.4 
REPORTING SAES TO HEALTH AUTHORITIES AND IRBS/IECS ............................................. 69 
11 
DATA COLLECTION AND MANAGEMENT................................................................................. 70 
11.1 
DATA COLLECTION AND CRB COMPLETION ........................................................................... 70 
11.2 
DATA MANAGEMENT ................................................................................................................... 71 
11.3 
DATA REVIEW .............................................................................................................................. 71 
12 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ..................................... 72 
12.1 
STATISTICAL METHODS ............................................................................................................. 72 
12.1.1 
Hypotheses and Statistical Methods for Primary Objective ........................................................... 72 
12.1.1.1 Primary Objective ........................................................................................................................... 72 
12.1.2 
Hypotheses and Statistical Methods for Secondary Objective ...................................................... 73 
12.1.2.1 Secondary Objective ...................................................................................................................... 73 
12.2 
ANALYSIS SETS ........................................................................................................................... 73 
12.2.1 
Full Analysis Set ............................................................................................................................. 74 
12.2.2 
Safety Analysis Set ........................................................................................................................ 74 
12.2.3 
Per-Protocol Analysis Set .............................................................................................................. 74 
12.2.4 
Populations Used in Analyses ....................................................................................................... 74 
12.3 
HANDLING OF MISSING DATA AND OUTLIERS ........................................................................ 75 
12.3.1 
Safety ............................................................................................................................................. 75 
12.3.2 
Immunogenicity .............................................................................................................................. 75 
12.3.3 
Efficacy ........................................................................................................................................... 75 
12.4 
INTERIM/PRELIMINARY ANALYSIS ............................................................................................ 75 
12.5 
DETERMINATION OF SAMPLE SIZE AND POWER CALCULATION ......................................... 76 
13 
ETHICAL AND LEGAL ISSUES AND INVESTIGATOR/SPONSOR RESPONSIBILITIES ........ 77 
13.1 
ETHICAL CONDUCT OF THE STUDY / GOOD CLINICAL PRACTICE ....................................... 77 
13.2 
SOURCE DATA AND SOURCE DOCUMENTS ............................................................................ 77 
13.3 
CONFIDENTIALITY OF DATA, DATA PROTECTION, AND ACCESS TO SUBJECT 
RECORDS ..................................................................................................................................... 77 

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13.4 
MONITORING, AUDITING, AND ARCHIVING .............................................................................. 78 
13.4.1 
Monitoring ...................................................................................................................................... 78 
13.4.2 
Audits and Inspections ................................................................................................................... 79 
13.4.3 
Archiving ........................................................................................................................................ 80 
13.4.4 
Responsibilities of Investigator(s) .................................................................................................. 80 
13.4.5 
Responsibilities of the Sponsor ...................................................................................................... 81 
13.5 
CONFIDENTIALITY ....................................................................................................................... 81 
13.6 
PROPERTY RIGHTS ..................................................................................................................... 81 
13.7 
INSURANCE COMPENSATION .................................................................................................... 82 
13.8 
STIPENDS FOR PARTICIPATION ................................................................................................ 82 
13.9 
PUBLICATION POLICY ................................................................................................................. 82 
14 
REFERENCES LIST ...................................................................................................................... 83 

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LIST OF TABLES  
Table 1 - Solicited injection site reactions for Children (2 to 9 years of age): terminology, definitions, and 
intensity scales .............................................................................................................................................. 62 
Table 2 - Solicited injection site reactions for Adolescents (10 to 17 years of age) or Adults (18 to 55 years 
of age): terminology, definitions, and intensity scales ................................................................................... 63 
Table 3 - Solicited systemic reactions for Children, Adolescents or Adults (2 to 55 years of age): 
terminology, definitions, and intensity scales ................................................................................................ 64 
Table 4 - Power of the study based on the primary objective of non-inferiority with 171 evaluable subjects 
per group ....................................................................................................................................................... 76 
 

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SYNOPSIS  
Company: 
Sanofi K.K. 
Investigational Product: 
MenACYW conjugate vaccine 
Active Substance: 
Capsular polysaccharide from meningococcal serogroups A, C, Y, and W conjugated to 
tetanus toxoid 
Title of the Study: 
Immunogenicity and Safety of a Single Dose of an Investigational Quadrivalent 
Meningococcal Conjugate Vaccine in Children, Adolescents and Adults 2 to 55 Years of 
Age  
Development Phase: 
Phase III 
Coordinating Investigator: 
Not applicable 
Study Sites: 
This will be a multi-center study conducted at approximately 5 sites in Japan.  
Investigators and sites are listed in the list of Investigators and centers Involved in the 
study. 
Planned Study Period: 
22 May 2020 to 16 December 2020 
Study Design, Schedule of 
Study Procedures, and 
Methodology: 
This will be a Phase III, modified double-blind, randomized, parallel-group, 
active-controlled, multi-center study to evaluate immune non-inferiority of MenACYW 
conjugate vaccine versus Menactra® and describe the safety and additional 
immunogenicity of the study vaccines in children (2-9 years of age), adolescents (10-17 
years of age) and adults (18-55 years of age) in Japan. Approximately 360 healthy 
children, adolescents and adults will be stratified and randomly assigned in a 1:1 ratio to 
the following groups: 
 
Group 1 (investigational): MenACYW conjugate vaccine (180 subjects) 
 
Group 2 (control): Menactra® (180 subjects) 
All subjects will provide blood samples for immunogenicity assessment at baseline 
(pre-vaccination) and at 30 days post-vaccination. Solicited injection site and systemic 
reactions will be collected for 7 days after vaccination, unsolicited adverse events (AEs) 
will be collected from Visit 1 (Day [D] 0) to Visit 2 (D30 [+14 days]), and serious adverse 
events (SAEs) will be collected from signing of the informed consent at D0 through D30 
(+14 days) after vaccination. 
Vaccination 
All subjects will receive a single intramuscular (IM) dose of either MenACYW conjugate 
vaccine or Menactra® on D0. 
Blood sampling 
All subjects will provide a pre-vaccination blood sample at Visit 1 (D0) and a 
post-vaccination sample at Visit 2 (D30 [+14 days] after the vaccination at Visit 1). 
Collection of safety data 
 
All subjects will be observed for 30 minutes after vaccination, and any unsolicited 
systemic AEs occurring during that time will be recorded as immediate 
unsolicited systemic AEs in the case report form (CRF). 
 
The subject or the subject’s parent / legally acceptable representative will record 
information in a diary card about solicited reactions from D0 to D07 after 
vaccination and unsolicited AEs from Visit 1 (D0) to Visit 2 (D30 [+14 days]). 
SAEs will be reported throughout the duration of the study from the signing of the 

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informed consent form (ICF) or the assent form. 
 
In addition, the subject or subject’s parent / legally acceptable representative will 
be asked to notify the site immediately about any potential SAEs at any time 
during the study. 
 
Study site staff will contact the subject or the subject’s parent / legally acceptable 
representative by telephone on D8 (+2 days) to identify the occurrence of any 
SAE not yet reported and to remind them to complete the diary card up to Visit 2 
and to bring it back at Visit 2. 
 
The completed diary card will be reviewed with the subject and/or the subject’s 
parent / legally acceptable representative at Visit 2. 
Interruption of the Study 
The study may be discontinued if new data about the investigational product resulting from 
this study or any other studies become available; or for administrative reasons; or on 
advice of the Sponsor, the Investigators, the IRBs, or the governing regulatory authority in 
Japan where the study is taking place. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IRBs, the regulatory authority, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the study 
subjects or subjects’ parents / legally acceptable representatives and should assure 
appropriate subject therapy and/or follow-up. 
Primary Objective: 
To demonstrate the non-inferiority of the antibody responses to meningococcal 
serogroups A, C, Y, and W following the administration of a single dose of MenACYW 
conjugate vaccine compared with those observed following the administration of a single 
dose of Menactra® 
Primary Endpoint: 
Vaccine seroresponse of meningococcal serogroups A, C, Y, and W measured by serum 
bactericidal assay using human complement (hSBA) assessed at baseline (Visit 1, D0, 
before vaccination) and at Visit 2 (D30 [+14 days]) after vaccination for immune 
non-inferiority between MenACYW conjugate vaccine and Menactra® (Group 1 versus 
Group 2) 
Secondary Objectives: 
Immunogenicity  
To describe the antibody responses to the meningococcal serogroups A, C, Y, and W 
before and 30 days (+14 days) after vaccination with MenACYW conjugate vaccine or 
Menactra® 
Safety 
To describe the safety profile of MenACYW conjugate vaccine and that of Menactra® 
Secondary Endpoints:  
Immunogenicity 
Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA 
assessed at baseline (D0, before vaccination) and after vaccination at D30 (+14 days) for 
all groups 
 
hSBA vaccine seroresponse 
 
Proportion of subjects with hSBA titer ≥1:4 and ≥1:8 
 
hSBA geometric mean titer (GMT) 
 
hSBA titer distribution and reverse cumulative distribution curve (RCDC) 
 
Proportion of subjects with hSBA titer ≥4-fold rise from baseline (Visit 1, D0, 
before vaccination) to after vaccination (Visit 2, D30 [+14 days]) 
Safety 
 
Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] 
preferred term), duration, intensity, and relationship to vaccination, of any 

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unsolicited systemic AEs reported in the 30 minutes after vaccination. 
 
Occurrence, time to onset, number of days of occurrence, intensity, action 
taken, and whether the reaction led to early termination from the study, of 
solicited (prelisted in the subject’s diary card and CRF) injection site reactions 
occurring up to 7 days after vaccination. 
 
Occurrence, time to onset, number of days of occurrence, intensity, action 
taken, and whether the reaction led to early termination from the study, of 
solicited (prelisted in the subject’s diary card and CRF) systemic reactions 
occurring up to 7 days after vaccination. 
 
Occurrence, nature (MedDRA preferred term), time to onset, duration, intensity, 
action taken, relationship to vaccination (for systemic AEs only), and whether 
the event led to early termination from the study, of unsolicited AEs up to Visit 2 
after vaccination. 
 
Occurrence, nature (MedDRA preferred term), time to onset, duration, 
seriousness criteria, relationship to vaccination, outcome, and whether the SAE 
led to early termination from the study, of SAEs throughout the study from Visit 
1 (D0) to Visit 2 (D30 [+14 days]) after vaccination. 
Planned Sample Size: 
A total of 360 subjects are planned to be enrolled: 
 
Group 1 (investigational): MenACYW conjugate vaccine (n=180) 
 
Group 2 (control): Menactra® (n=180) 
 
 
 
Duration of Participation 
in the Study: 
The duration of each subject’s participation in the study will be approximately 30 to 
44 days. 
Investigational Product: 
MenACYW conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and 
W) Tetanus Toxoid Conjugate Vaccine 
 Form: 
Liquid Solution 
 Composition: 
Each 0.5 mL dose of MenACYW conjugate vaccine is formulated in sodium acetate 
buffered saline solution to contain the following ingredients: 
Meningococcal capsular polysaccharides: 
Serogroup A………………………………………………………………….10 µg 
Serogroup C………………………………………………………………….10 µg 
Serogroup Y………………………………………………………………….10 µg 
Serogroup W…………………………………………………………………10 µg 
Tetanus toxoid protein carrier………………………….……..approximately 55 µg 
 Route: 
IM 
 Batch Number: 
To be determined 
Control Product: 
Menactra®: Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria 
Toxoid Conjugate Vaccine 
 Form: 
Liquid solution for injection 

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 Composition: 
Each 0.5 mL dose of vaccine is formulated in sodium phosphate buffered isotonic sodium 
chloride solution to contain as active ingredients the following meningococcal capsular 
polysaccharides conjugated to approximately 48 µg of diphtheria toxoid protein: 
Serogroup A……………………………………………………………………….4 µg 
Serogroup C……………………………………………………………………….4 µg 
Serogroup Y……………………………………………………………………….4 µg 
Serogroup W-135…………………………………………..…………………….4 µg 
Diphtheria toxoid protein carrier…………………………...…approximately 48 µg 
 Route: 
IM 
 Batch Number: 
To be determined 
Inclusion Criteria: 
An individual must fulfill all of the following criteria to be eligible for study enrollment:  
I 01. 
Aged 2 to 55 years on the day of inclusion 
I 02. 
Informed consent form has been signed and dated by the subjects or subjects’ 
parents / legally acceptable representatives as applicable 
In addition:  
Subjects 7 to 19 years will provide written assent 
I 03. 
Subjects (and subjects’ parents / legally acceptable representatives for the 2 to 
19 years age groups) are able to attend all scheduled visits and to comply with 
all study procedures 
Exclusion Criteria: 
An individual fulfilling any of the following criteria is to be excluded from study enrollment: 
E 01. 
Subject is pregnant, or lactating, or of childbearing potential (to be considered of 
non-childbearing potential, a female must be pre-menarche or post-menopausal 
for at least 1 year, surgically sterile, or using an effective method of 
contraception or abstinence from at least 4 weeks prior to vaccination until at 
least 4 weeks after vaccination) 
E 02. 
Participation in the 4 weeks preceding the study vaccination or planned 
participation during the present study period in another clinical study 
investigating a vaccine, drug, medical device, or medical procedure  
E 03. 
Receipt of any vaccine in the 4 weeks preceding the study vaccination or 
planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, 
which may be received at least 2 weeks before or after the study investigational 
vaccines. This exception includes monovalent pandemic influenza vaccines 
and multivalent influenza vaccines 
E 04. 
Previous vaccination against meningococcal disease with either the study 
vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or 
conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or 
meningococcal B vaccine) 
E 05. 
Receipt of immune globulins, blood or blood-derived products in the past 
3 months 
E 06. 
Known or suspected congenital or acquired immunodeficiency; or receipt of 
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation 
therapy, within the preceding 6 months; or long-term systemic corticosteroid 
therapy (prednisone or equivalent for more than 2 consecutive weeks within the 
past 3 months) 
E 07. 
History of meningococcal infection, confirmed either clinically, serologically, or 
microbiologically 
E 08. 
At high risk for meningococcal infection during the study (specifically, but not 
limited to, subjects with persistent complement deficiency, with anatomic or 
functional asplenia, or subjects traveling to countries with high endemic or 
epidemic disease) 

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E 09. 
Known systemic hypersensitivity to any of the vaccine components, or history of 
a life-threatening reaction to the vaccines used in the study or to a vaccine 
containing any of the same substances 
E 10. 
Laboratory confirmed / self-reported thrombocytopenia, contraindicating 
intramuscular vaccination in the Investigator’s judgment 
E 11. 
Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding 
inclusion, contraindicating intramuscular vaccination in the Investigator’s 
judgement 
E 12. 
History of Guillain-Barre syndrome (GBS) 
E 13. 
History of convulsions 
E 14. 
History of an Arthus-like reaction after vaccination with a tetanus 
toxoid-containing vaccine and a diphtheria toxoid-containing vaccine within 
10 years of the proposed study vaccination 
E 15. 
Deprived of freedom by an administrative or court order, or in an emergency 
setting, or hospitalized involuntarily 
E 16. 
Current alcohol abuse or drug addiction  
E 17. 
Chronic illness that, in the opinion of the Investigator, is at a stage where it 
might interfere with study conduct or completion 
E 18. 
Moderate or severe acute illness/infection (according to Investigator judgment) 
or febrile illness (temperature ≥99.5°F or ≥37.5°C) on the day of vaccination. A 
prospective subject should not be included in the study until the condition has 
resolved or the febrile event has subsided 
E 19. 
Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first 
blood draw  
E 20. 
Identified as an Investigator or employee of the Investigator or study center with 
direct involvement in the proposed study, or identified as an immediate family 
member (i.e., parent, spouse, natural or adopted child) of the Investigator or 
employee with direct involvement in the proposed study  
Statistical Methods: 
All immunogenicity analyses will be performed on the Per-Protocol Analysis Set (PPAS). 
Additional immunogenicity analyses will be performed for exploratory purposes on the Full 
Analysis Set (FAS) according to randomization group. All safety analyses will be 
performed on the Safety Analysis Set (SafAS). 
Primary Objective  
Non-inferiority of MenACYW conjugate vaccine compared to Menactra® in terms of hSBA 
vaccine seroresponse. 
Thirty days after the administration of MenACYW conjugate vaccine or Menactra®, the 
percentage of subjects who achieve an hSBA vaccine seroresponse* for meningococcal 
serogroups A, C, Y, and W in Group 1 are non-inferior to the corresponding percentages 
in Group 2. 
Null hypothesis (H0): p(G1) − p(G2) ≤−10% 
Alternative hypothesis (H1): p(G1) − p(G2) >−10% 
where p(G1) and p(G2) are the percentages of subjects who achieve an hSBA vaccine 
seroresponse in Group 1 and Group 2, respectively. Each of the serogroups A, C, Y, and 
W will be tested separately. If the lower limit of the 2-sided 95% confidence interval (CI) of 
the difference between the 2 proportions is >−10%, the inferiority assumption will be 
rejected. 
* Vaccine seroresponse for serogroups A, C, Y, and W is defined as post-vaccination 
hSBA titers ≥1:16 for subjects with pre-vaccination hSBA titers <1:8 or at least a 4-fold 
increase in hSBA titers from pre- to post-vaccination for subjects with pre-vaccination 
hSBA titers ≥1:8. 

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Secondary Objectives 
Immunogenicity 
Descriptive statistics will be provided for the antibody titers against meningococcal 
serogroups contained in each lot of MenACYW conjugate vaccine and Menactra®.  
In general, categorical variables will be summarized and presented by frequency counts, 
percentages, and CIs. The 95% CIs of point estimates will be calculated using the normal 
approximation for quantitative data and the exact binomial distribution (Clopper-Pearson 
method) for percentages. For GMTs, 95% CIs of point estimates will be calculated using 
normal approximation assuming they are log-normally distributed. RCDC figures will be 
provided for the antibody titers against meningococcal serogroups. 
In summary, descriptive analyses on A, C, Y, and W serogroups will include but not be 
limited to: 
 
hSBA vaccine seroresponse rate and 95% CI 
 
Proportion of subjects with hSBA titer ≥1:4 and ≥1:8 and 95% CI 
 
hSBA GMT and 95% CI 
 
hSBA titer distribution and RCDCs 
 
Proportion of subjects with hSBA titer ≥4-fold rise from baseline (Visit 1, D0, 
before vaccination) to after vaccination (Visit 2, D30 [+14 days]) and 95% CI 
Safety 
Safety results will be described for subjects in both study groups. The main parameters 
for the safety endpoints will be described by 95% CIs (based on the Clopper-Pearson 
method). 
Calculations of Sample Size 
A total of 360 subjects (180 subjects per group) will be enrolled and randomly assigned to 
treatment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 

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Power of the study based on the primary objective of non-inferiority with 
evaluable subjects per group 
Serogroup 
Estimateda 
MenACYW 
conjugate 
vaccine 
Estimatedb 
Menactra® 
Non-inferiority 
margin 
Power 
 
 
 
 
 
 
 
 
 

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TABLE OF STUDY PROCEDURES  
 
Phase III Study, 2 Visits, 1 Vaccination, 2 Blood Samples, 1 Telephone Call, 30 to 44 Days Duration Per Subject 
Visit / Contact 
Visit 1 
Telephone Call 1 
Visit 2 
Study timelines (days) 
Day 0 
Day 8 
Day 30 
Time windows (days) 
-- 
+2 days 
+14 days 
Informed consent form / assent form (if applicable) 
X 
 
 
Inclusion / exclusion criteria 
X 
 
 
Collection of demographic data 
X 
 
 
Urine pregnancy test (if applicable) 
X 
 
 
Medical history 
X 
 
 
Physical examinationa 
X 
 
 
Review of temporary contraindications for blood 
samplingb 
 
 
X 
Contact interactive response technology (IRT) 
X 
 
X 
Randomization / allocation 
X 
 
 
Blood sampling (BL), 5 mL 
BL0001c 
 
BL0002 
Vaccinationd 
X 
 
 
Immediate surveillance (30 min) 
X 
 
 
Diary card provided 
X 
 
 
Telephone call 
 
Xe 
 
Recording of solicited injection site & systemic reactions 
D0 to D07 
 
 
Recording of unsolicited AEs 
D0 to Visit 2 
Diary card reviewed and collected 
 
 
X 
Reporting of SAEs 
To be reported at any time during the study 
Collection of reportable concomitant medications 
X 
 
X 
Termination of study 
 
 
X 
a Physical examination can be done in accordance with medical practice at each site and for each age range. Body temperature (preferably 
axillary temperature) will be measured and recorded in source documents. 
b Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the second blood draw, the Investigator will postpone 
that blood draw until it has been 3 days since the subject last received oral or injectable antibiotic therapy. Postponement must still be 
within the timeframe for blood draw (30 to 44 days after vaccination at D0), when possible. 
c Blood sample at Visit 1 will be drawn before administration of vaccine. 
d Subjects will receive 1 dose of MenACYW conjugate vaccine or Menactra®. 
e This call is made 8 to 10 days after the vaccination at Visit 1. If D08 (+2 days) falls on a weekend or holiday, the telephone call may be 
made on the following business day. During this telephone call, the study site staff will find out whether the subject experienced any SAE 
not yet reported, and will remind the subject or subject’s parent / legally acceptable representative to continue using the diary card up to 
Visit 2, to bring the diary card to the study center at Visit 2, and confirm the date and time of Visit 2. 

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LIST OF ABBREVIATIONS  
 
AE 
adverse event 
AR 
adverse reaction 
BL 
blood sampling 
CDM 
Clinical Data Management 
CI 
confidence interval 
CRB 
(electronic) case report book [all the case report forms for a subject] 
CRF 
case report form 
D 
day 
EDC 
electronic data capture 
FAS 
Full Analysis Set 
FVFS 
first visit, first subject 
FVLS 
first visit, last subject 
GBS 
Guillain-Barre syndrome 
GCI 
Global Clinical Immunology 
GCP 
Good Clinical Practice 
GDPR 
Global Data Protection Regulation 
GMT 
geometric mean titer  
GMTR 
geometric mean titer ratio 
GPV 
Global Pharmacovigilance 
hSBA 
serum bactericidal assay using human complement 
IASR 
Infectious Agents Surveillance Report 
IATA 
International Air Transport Association 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G 
IM 
intramuscular 
IMD 
invasive meningococcal disease 
IME 
important medical event 
IOM 
Institute of Medicine 
IP 
investigational product 
IRB 
Institutional Review Board 

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IRT 
interactive response technology 
LCLS 
last contact, last subject 
LLOQ 
lower limit of quantification 
LLT 
lowest level term 
MedDRA 
Medical Dictionary for Regulatory Activities 
μg 
micrograms 
mL 
milliliter 
N. 
Neisseria 
NSAID 
non-steroidal anti-inflammatory drug 
PPAS 
Per-Protocol Analysis Set 
RCDC 
reverse cumulative distribution curve 
PMDA 
Pharmaceuticals and Medical Device Agency 
rSBA 
serum bactericidal assay using baby rabbit complement 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SMM 
Study Medical Manager 
SafAS 
Safety Analysis Set 
ULOQ 
upper limit of quantitation 
USA 
United States of America 
 

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1 
INTRODUCTION  
1.1 
BACKGROUND  
This trial will evaluate the immune non-inferiority of MenACYW conjugate vaccine versus 
Menactra®, and will describe the safety and immunogenicity of MenACYW conjugate vaccine 
and Menactra® in children, adolescents, and adults 2 to 55 years of age in Japan. 
Invasive meningococcal disease (IMD) is a serious illness caused by the bacterium Neisseria (N.) 
meningitidis, a Gram-negative diplococcus found exclusively in humans. Symptoms may include 
intense headache, fever, nausea, vomiting, photophobia, stiff neck, lethargy, myalgia, and a 
characteristic petechial rash (1). At least 12 distinct meningococcal serogroups have been 
classified based on the immunochemistry of the capsular polysaccharides. Some strains are more 
likely than others to cause infection (1) (2) (3). Worldwide, most cases of meningococcal disease 
are caused by serogroups A, B, C, X, Y, and W (2) (3) (4). Serogroup B is responsible for 
endemic disease and some outbreaks, while serogroup C is responsible for large outbreaks (5). 
Serogroup A is the main cause of epidemics in the world, and is especially dominant in Africa and 
Asia. Serogroup W has been seen in Africa, as well as in the United Kingdom in residents who 
participated in the Hajj pilgrimage to the Kingdom of Saudi Arabia (5) (6) (7) and more recently 
in Chile (8), Turkey (9) (10), China (11), Argentina (12), and Brazil (13) (14), and in other parts 
of the world. Serogroup X causes substantial meningococcal disease in parts of Africa but rarely 
causes disease in other parts of the world (9) (15). Serogroup Y has not been associated with 
outbreaks, but its frequency as a cause of sporadic cases has gradually increased in the United 
States of America (USA) and more recently in Canada and Europe (16) (17) (18). This serogroup 
is commonly associated with meningococcal pneumonia, particularly in older adults >65 years of 
age (19). Outbreaks of serogroup B meningococcal disease have also been reported on college 
campuses in the USA: A prolonged outbreak of serogroup B on a university campus in Ohio from 
2008-2010, and 2 universities in New Jersey and California in 2013 (20) (21). 
The epidemiology of N. meningitidis can be described as complex, unpredictable, geographically 
variable, and changing over time. Meningococcal disease occurs worldwide in both endemic and 
epidemic forms with seasonal variation. In Europe, the incidence rate of IMD has remained stable 
over the last 5 to 10 years, with the highest peak occurring in the population less than 4 years of 
age and a smaller peak in the 15 to 19-year-old group. The highest incidence rate in Europe is 
caused by serogroup B, followed by C (22).The highest proportion of meningococcal cases was 
due to serogroup B in the population under 5 years of age. The highest proportion of serogroup C 
cases was observed in the population 25 to 44 years of age while the proportion of serogroup Y 
cases was highest in the population age 65 years and above. 
Surveillance data from England and Wales showed an increase in endemic meningococcal 
serogroup W disease across all age groups, accounting for 15% of all IMD cases in 2013-2014 
compared with an average of 1% to 2% of all IMD cases in earlier years (23). A gradual increase 
in serogroup Y IMD has also been recently reported in Sweden during 2005-2012 (24) (25). 
Nearly 50% of all IMD was caused by serogroup Y in 2012 (24). Similarly, an increase in the 

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proportion of IMD caused by serogroup Y has been observed in other Scandinavian countries, 
accounting for 31% in Norway in 2009-2010 and 38% in Finland in 2010 (26). 
In the USA, the incidence rate of IMD was 0.14 per 100 000 in all ages; 0.83 per 100 000 in 
infants less than 1 year; 0.62 per 100 000 in toddlers 1 year of age; 0.27 per 100 000 in children 2 
to 4 years of age; and 0.02 per 100 000 in children 5 to 17 years of age in 2013. The age-specific 
incidence rate per 100 000 was 0.08 in adults 50 to 64 years of age, 0.03 in adults 65 to 74 years 
of age, 0.14 in adults 75 to 84 years of age, and 0.43 in adults 85 years of age and older in 2013 
(27). 
The epidemiological trend of IMD in Japan is described below based on Infectious Agents 
Surveillance Report (IASR) published by Infectious Disease Surveillance Center, National 
Institute of Infectious Diseases in January 2018 (28). 
Invasive meningococcal infection in Japan: A total of 160 cases were notified in Japan from April 
2013 to October 2017 as epidemiological trend.  
Gender and age distribution: Among the 160 cases reported from April 2013 to October 2017, the 
male-to-female ratio was about 3:2, and many cases were those aged 0-4 years, 15-19 years, and 
those in their 40s to early 70s. Among invasive meningococcal infection cases, reported as such 
since 2013, the case-fatality rate at the time of notification was 15.0% (24/160). Based on the 
information at the time of notification, two thirds of the reported deaths were among those aged in 
their 10s to 50s. 
Serogroup distribution: From April 2013 to October 2017, there were 160 reported cases of 
invasive meningococcal infection, and among them, serogroup information was obtained from 
116 (72.5%) cases. Serogroup Y was the most frequent serogroup (75 cases), followed by 
serogroup B (15 cases), serogroup C (13 cases) and serogroup W (5 cases). In addition, there were 
4 cases that could not be distinguished between serogroup Y and W and 4 non-typable strain cases. 
In the past, serogroup B was considered to be predominant but recently serogroup Y is dominant 
in Japan. Indeed, it occurs in 20 to 40 people, and Y is the largest as serogroup. 
The goal for MenACYW conjugate vaccine is to provide broad protection against IMD caused by 
serogroups A, C, Y, and W in all target age groups. 
1.2 
BACKGROUND OF THE INVESTIGATIONAL PRODUCT  
1.2.1 Non-clinical Safety  
MenACYW conjugate vaccine has been evaluated for toxicity in rats and for the ability to elicit 
polysaccharide-specific antibody (total and bactericidal antibodies) responses in mice and rats. 
These species generate only marginal antibody responses to polysaccharides alone but strong 
responses to polysaccharides conjugated to a carrier protein. 
MenACYW conjugate vaccine was well tolerated in rats administered 4 intramuscular (IM) 
injections of MenACYW conjugate vaccine at 10 micrograms (μg) per serogroup, which 

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corresponds to the human dose level. The non-clinical safety data for MenACYW conjugate 
vaccine showed no major safety concerns and support the use of MenACYW conjugate vaccine in 
future clinical trials with the same formulation. 
1.2.2 Clinical  
MenACYW conjugate vaccine formulation was finalized based on data provided by 2 studies: 
MET28, a Phase I study in infants, toddlers, and adults 18 to 39 years of age; and MET32, a Phase 
I/II study in toddlers. 
Based on the information from 12 completed clinical trials, overall, a total of 11,538 participants 
have been enrolled and vaccinated, of which approximately 7613 have received MenACYW 
conjugate vaccine (different formulations). Subjects received single (n=7006; 92.0%) or multiple 
doses (n=607; 8.0%) of MenACYW conjugate vaccine given alone (n=6026; 79.2%) or with at 
least one concomitant vaccine (n=1587; 20.8%). 
MenACYW conjugate vaccine was found to be well tolerated and no unanticipated or new 
significant safety concerns have been identified in the clinical trials completed to date. 
1.2.2.1 Study MET35 (Phase III)  
MET35 was a Phase III, modified double-blind, randomized, parallel-group, active-controlled, 
multi-center trial to evaluate the immunogenicity and describe the safety of MenACYW conjugate 
vaccine compared to a licensed quadrivalent meningococcal conjugate vaccine in healthy children 
2 to 9 years of age in the USA and Puerto Rico.  
A total of 1000 meningococcal-vaccine naïve children were randomized to the following groups:  
 Group 1: MenACYW conjugate vaccine 
 Group 2: MENVEO® 
Immunogenicity 
Non-Inferiority of MenACYW Conjugate Vaccine to MENVEO® 
The immune response following administration of MenACYW conjugate vaccine was non 
inferior to the immune response following administration of MENVEO® for all 4 serogroups as 
measured by serum bactericidal assay using human complement (hSBA) vaccine seroresponse. 
For each serogroup, the lower limit of the 2-sided 95% confidence interval (CI) of the difference 
was greater than -10%.  
hSBA Vaccine titers ≥1:8 at Day (D) 30 
Thirty days after vaccination, the percentages of subjects with hSBA titers ≥1:8 were increased 
from baseline for all serogroups and both groups. Percentages of subjects with hSBA titers ≥1:8 
were numerically higher in Group 1 (86.4%) than in Group 2 (79.3%), with overlapping CIs, for 

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serogroup A, and were higher in Group 1 than in Group 2, with non-overlapping CIs for 
serogroups C, Y, and W. 
Antibody Responses (hSBA geometric mean titers [GMTs]) at D30 
At D30, the Group 1 / Group 2 GMT ratios ranged from 1.09 to 14.0 for all serogroups. 
Antibody Responses (hSBA GMTs) at D30 by Age Group 
At D30, the Group 1 / Group 2 geometric mean titer ratios (GMTRs) ranged from 1.14 to 17.4 in 
subjects aged 2 to 5 years and from 1.06 to 11.5 in subjects aged 6 to 9 years for all serogroups.  
In subjects aged 2 to 5 years, at D30, the GMTs in Group 1 were numerically higher than in 
Group 2 for serogroups A and Y (21.6 and 49.8 in Group 1 and 18.9 and 36.1 in Group 2, 
respectively) with overlapping 95% CIs, and the GMTRs for serogroups A and Y were 1.14 and 
1.38, respectively. The GMTs were higher in Group 1 than in Group 2 for serogroups C and W 
(208 and 28.8 in Group 1 and 11.9 and 20.1 in Group 2, respectively) with non-overlapping 95% 
CIs; and the GMTRs for serogroups C and W were 17.4 and 1.43, respectively. 
In subjects aged 6 to 9 years, at D30, the GMTs were numerically higher in Group 1 (28.4) than in 
Group 2 (26.8) for serogroup A with overlapping 95% CIs, and the GMTR was 1.06. The GMTs 
were higher in Group 1 than in Group 2 with non-overlapping 95% CIs for serogroups C, Y, and 
W ranging from 48.9 to 272 in Group 1 and from 23.7 to 51.8 in Group 2, and GMTRs ranging 
from 1.45 to 11.5.  
Safety 
The safety objective of the study was to describe the safety profile of MenACYW conjugate 
vaccine compared to that of the licensed Menveo®. Overall, vaccination with MenACYW 
conjugate vaccine among children aged 2 to 9 years was found to be safe, with no safety concerns 
identified. The safety profile was comparable in subjects from the age subgroup 2 to 5 years and 
subjects from the age subgroup 6 to 9 years between both treatment groups (Group 1 and 
Group 2). The MenACYW conjugate vaccine was well tolerated with no immediate 
hypersensitivity reactions, no discontinuations due to a serious adverse event (SAE) or other 
adverse event (AE), and no related SAEs. 
The majority of reactions at the MenACYW conjugate vaccine or MENVEO® injection sites were 
of Grade 1 or 2 intensity, started between D0 and D03, and lasted 1 to 3 days. Grade 3 Erythema 
and swelling were reported at a lower frequency in MenACYW conjugate vaccine Group (3.1% 
and 1.4%, respectively) than in Menactra® Group (9.9% and 5.6%, respectively). Overall, most 
solicited systemic reactions were of Grade 1 or Grade 2 intensity, started between D0 and D30, 
and lasted 1 to 3 days. 
Three subjects experienced SAEs within the first 30 days after vaccination. Seven subjects (5 in 
Group 1 and 2 in Group 2) experienced a total of 9 SAEs after D30 through the 6-month 
follow-up. None of the SAEs were considered as related to the vaccine by the Investigator and 

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none led to discontinuation from the study. No cases of death were reported during the study. No 
pregnancies were reported during the study. 
Overall, the safety profile of MenACYW conjugate vaccine was comparable to that of the 
licensed vaccine, Menveo®. 
1.2.2.2 Study MET43 (Phase III)  
MET43 was a Phase III, modified double-blind, randomized, parallel-group, active-controlled, 
multi-center study to evaluate immune lot consistency of MenACYW conjugate vaccine, evaluate 
the immune non-inferiority versus Menactra®, and describe the safety and additional 
immunogenicity of these study vaccines in adolescents and adults aged 10 to 55 years in the USA.  
A total of 3344 healthy, meningococcal-vaccine naïve adolescents and adults were randomized in 
a 3:3:3:2 ratio to the following groups:  
 Group 1: MenACYW conjugate vaccine (Lot 1) 
- 
Group 1a: 400 subjects 10 to 17 years of age 
- 
Group 1b: 500 subjects 18 to 55 years of age 
 Group 2: MenACYW conjugate vaccine (Lot 2) 
- 
Group 2a: 400 subjects 10 to 17 years of age 
- 
Group 2b: 500 subjects 18 to 55 years of age 
 Group 3: MenACYW conjugate vaccine (Lot 3) 
- 
Group 3a: 400 subjects 10 to 17 years of age 
- 
Group 3b: 500 subjects 18 to 55 years of age 
 Group 4: Menactra® 
- 
Group 4a: 300 subjects 10 to 17 years of age 
- 
Group 4b: 300 subjects 18 to 55 years of age 
Immunogenicity 
Equivalence of 3 MenACYW conjugate vaccine lots in terms of GMTs 
Immune equivalence was demonstrated across the 3 lots in that the 2-sided 95% CI of the ratio of 
the GMTs was between >1/2 and <2 for each pair of lots and each serogroup. 
Non-Inferiority of MenACYW Conjugate Vaccine to Menactra® 
Non-inferiority of immune response was demonstrated between MenACYW conjugate vaccine 
and Menactra® based on percentage of subjects achieving hSBA vaccine seroresponse. For each 
serogroup, the lower limit of the 2-sided 95% CI of the difference was >−10%. The percentage of 
subjects with an hSBA vaccine seroresponse was numerically higher in Groups 1-3 pooled than in 

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Group 4 for all serogroups: ranging from 73.8% (1846/2503) to 91.4% (2290/2505) in Groups 1-3 
pooled and from 47.9% (284/593) to 73.4% (435/593) in Group 4. 
Antibody Responses (hSBA Titers ≥1:8) at D30 
Thirty days after vaccination, the percentages of subjects with hSBA titers ≥1:8 were increased 
from baseline for all serogroups and all groups. Percentages of subjects with hSBA titers ≥1:8 
after MenACYW conjugate vaccine were similar in Group 1, Group 2 and Group 3. In Groups 1-3 
pooled, the percentages ranged from 94.7% to 98.8%. In Group 4, the percentages of subjects with 
hSBA titers ≥1:8 after Menactra® tended to be numerically lower ranging from 76.2% to 88.5%.  
Antibody Responses (hSBA GMTs) at D30 
At D30, the Group 1-3 pooled / Group 4 GMT ratios ranged from 1.90 to 8.05 for all serogroups. 
Antibody Responses (serum bactericidal assay using baby rabbit complement [rSBA] GMTs and 
seroresponse) at D30 
At D30, meningococcal rSBA GMTs for all serogroups were higher after MenACYW conjugate 
vaccine than after Menactra® for all serogroups. The percentages of subjects with an rSBA 
vaccine seroresponse was comparable in all groups for serogroups A and W but were numerically 
higher after vaccination with MenACYW conjugate vaccine than after vaccination with 
Menactra® for serogroups C and Y. 
Safety 
The safety objective of the study was to describe the safety profile of MenACYW conjugate 
vaccine compared to that of the licensed Menactra®. 
Vaccination with MenACYW conjugate vaccine among adolescents and adults aged 10 to 
55 years was found to be safe, with no safety concerns identified, and no discontinuations due to 
an SAE or other AE, and no related SAEs. 
The majority of reactions at the MenACYW conjugate vaccine or Menactra® injection sites were 
of Grade 1 or Grade 2 intensity, started between D0 and D03, and most lasted 1 to 3 days. The 
injection site reactions were reported at similar frequencies in all groups with pain being the most 
frequently reported injection site reaction. Overall, most solicited systemic reactions were of 
Grade 1 or Grade 2 intensity, started between D0 and D03, and most lasted 1 to 3 days. 
Few subjects reported immediate unsolicited AEs: 0.3% (3/895) of subjects in Group 1, 0.5% 
(4/883) of subjects in Group 2, 0.3% (3/898) of subjects in Group 3, 0.4% (10/2676) of subjects in 
Groups 1-3 pooled, and 0.5% (3/635) of subjects in Group 4. There were no immediate SAEs, 
including any anaphylactic or life-threatening events. Most unsolicited non-serious AEs within 
30 days of vaccine injection were of Grade 1 or Grade 2 intensity. 
Five subjects experienced SAEs within the first 30 days after vaccination. Twenty-eight subjects 
experienced a total of 34 SAEs after D30 through the 6-month follow-up. None of the SAEs were 
considered as related to the vaccine by the Investigator and none led to discontinuation from the 

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study. No cases of death were reported during the study. There were 13 reported pregnancies 
during the study: 5 in Group 1, 5 in Group 2, 1 in Group 3, and 2 in Group 4. Of these pregnancies, 
1 was classified as exposed and pregnant at time of vaccination with MenACWY conjugate 
vaccine whereas urine pregnancy test was negative on vaccination day, 8 were classified as 
unexposed, and 4 as exposed but not yet pregnant. The pregnancy outcome was known for the 
11 subjects who were administered MenACYW conjugate vaccine and 1 of the 2 subjects that 
were administered Menactra®. Ten subjects gave birth to healthy babies, 2 reports were of 
spontaneous abortion (subjects had received MenACYW conjugate vaccine; both pregnancies 
were classified as unexposed; and none were considered as related to the vaccine by the 
Investigator), and 1 pregnancy was lost to follow-up. 
Overall, the safety profile of MenACYW conjugate vaccine was comparable to that of the 
licensed vaccine, Menactra®. 
1.2.2.3 Study MET49 (Phase III)  
MET49 was a Phase III, modified double-blind, randomized, parallel-group, active-controlled, 
multi-center trial to compare the immunogenicity and safety of MenACYW conjugate vaccine to 
Menomune® – A/C/Y/W-135 in adults ≥56 years of age in the USA. 
Approximately 900 healthy adults were randomized in a 1:1 ratio to the following groups: 
 Group 1: MenACYW conjugate vaccine 
 Group 2: Menomune® − A/C/Y/W-135 
Immunogenicity 
Non-Inferiority of MenACYW Conjugate Vaccine to Menumone® 
The immune response following administration of a single dose of MenACYW conjugate vaccine 
was non-inferior to the immune response following administration of a single dose of 
Menomune® − A/C/Y/W-135 for all 4 serogroups as measured by hSBA vaccine seroresponse. 
For each serogroup, the lower limit of the 2-sided 95% CI of the difference was more than −10%. 
Antibody Responses (hSBA Titers ≥1:8) at D30 
Thirty days after vaccination, the percentages of subjects with hSBA titers ≥1:8 increased from 
baseline for all serogroups and in both groups. The percentages were comparable for serogroup A 
between Group 1 (89.4%) and Group 2 (84.2%). For serogroups C, Y, and W, the percentages 
were higher in Group 1 than Group 2 with non-overlapping 95% CIs (90.1% vs 71.0%, 91.7% vs 
67.7%, and 77.4% vs 63.1%, in Group 1 vs Group 2 respectively). 
Antibody Responses (hSBA GMTs) at D30 
At D30, the Group 1 / Group 2 GMT ratios ranged from 1.75 to 4.10 for all serogroups. 

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Antibody Responses (rSBA GMTs and seroresponse) at D30 
At D30, meningococcal rSBA GMTs for all serogroups were higher after MenACYW conjugate 
vaccine than after Menomune®. The percentages of subjects with an rSBA vaccine seroresponse 
after vaccination with MenACYW conjugate vaccine were numerically higher than the 
percentages after Menomune®. 
Safety 
The safety objective of the study was to describe the safety profile of MenACYW conjugated 
vaccine compared to that of the licensed Menomune® – A/C/Y/W-135 after a single 
administration. 
Overall, vaccination with MenACYW conjugate vaccine was found to be safe, with no safety 
concerns identified. The MenACYW conjugate vaccine was well tolerated with no 
discontinuations due to an SAE or other AE. 
The majority of reactions at the MenACYW conjugate vaccine or Menomune® − A/C/Y/W-135 
injection sites were of Grade 1 or 2 intensity, started between D0 and D03, and lasted 1 to 3 days. 
Erythema and swelling were reported at higher frequency in the MenACYW conjugate vaccine 
(5.2% and 4.5% respectively) than in the Menomune® − A/C/Y/W-135 (no subjects reported 
erythema or swelling). Overall, most solicited systemic reactions in both groups were of Grade 1 
or 2 intensity, started between D0 and D03, and lasted 1 to 3 days. 
One subject (0.2%) in Group 1 and no subjects (0.0%) in Group 2 reported 1 immediate 
unsolicited AE. Most unsolicited non-serious AEs within 30 days of vaccine injection were of 
Grade 1 or Grade 2 intensity. 
Six subjects (3 subjects in each group) experienced at least one SAE within the first 30 days after 
vaccination on D0. Twenty-five subjects (12 in Group 1 and 13 in Group 2) experienced at least 
one SAE through the 6-month follow-up, for a total of 33 SAEs after: 12 subjects (2.7%) in Group 
1 experienced 16 SAEs and 13 subjects (2.9%) in Group 2 experienced 17 SAEs. None of the 
SAEs were considered as related to the vaccine by both the Investigator and the Sponsor. There 
were 2 deaths reported during the study. Both subjects had been vaccinated with Menomune® − 
A/C/Y/W-135. None of the deaths were considered related to vaccination. No pregnancies were 
reported during the study.  
No new clinically important findings were identified with administration of MenACYW 
conjugate vaccine. 
1.3 
POTENTIAL BENEFITS AND RISKS  
1.3.1 Potential Benefits to Subjects  
MenACYW conjugate vaccine is an investigational vaccine that is undergoing active clinical 
investigation. There may be no direct benefit from receiving MenACYW conjugate vaccine. 

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However, based on the data generated from previous studies, the immunogenicity profile of 
MenACYW conjugate vaccine in different age groups shows that the majority of subjects 
developed seroprotective levels of antibodies after vaccination. The safety evaluation indicates 
that the vaccine is well-tolerated, and no safety issues have been detected to date. In all, the data 
support further evaluation of MenACYW conjugate vaccine in humans. 
Subjects who receive Menactra® will likely be protected against meningococcal disease caused by 
N. meningitidis serogroups A, C, Y, and W. 
As with any vaccine, MenACYW conjugate vaccine and Menactra® may not protect 100% of 
individuals against the diseases they are designed to prevent. 
1.3.2 Potential Risks to Subjects  
Like other vaccines, vaccination with MenACYW conjugate vaccine or Menactra® may cause 
injection site reactions such as pain, swelling, induration, and erythema, or certain systemic events 
such as fever, headache, malaise, or myalgia.  
Other common reactions after Menactra® in the studied age group include injection site induration, 
fatigue, arthralgia, appetite lost, and diarrhea. 
There may be a rare possibility of an allergic reaction which could be severe. Prior to any vaccine 
injection, all known precautions should be taken to prevent hypersensitivity reactions. This 
includes a review of the subject’s prior vaccination history with respect to possible 
hypersensitivity to the vaccine or similar vaccines. Epinephrine injection (1:1000) and other 
appropriate agents used for the control of immediate allergic reactions must be available to treat 
unexpected reactions (e.g., anaphylaxis). 
There may also be a risk of febrile convulsion in some children who experience high fever. 
There may be other risks for MenACYW conjugate vaccine which are not yet known. 
The following additional adverse events have been very rarely reported during post-approval use 
of Menactra®: Guillain-Barré syndrome (GBS), transverse myelitis, acute disseminated 
encephalomyelitis, vasovagal syncope, facial palsy, dizziness, paraesthesia, convulsion, and 
hypersensitivity reactions such as anaphylactic / anaphylactoid reaction, wheezing, difficulty 
breathing, upper airway swelling, urticaria, erythema, pruritus, and hypotension. Because these 
events were reported voluntarily from a population of uncertain size, it is not possible to reliably 
estimate their frequency or to establish a causal relationship to Menactra® exposure. 
GBS has been reported mostly in persons aged 11 to 19 years who had symptom onset within 
6 weeks of administration of Menactra® (29). A retrospective cohort study carried out in the USA 
using healthcare claims data found no evidence of increased GBS risk following Menactra® 
vaccination. The study was able to exclude all but relatively small incremental risks (30). 
A review by the Institute of Medicine (IOM) found inadequate evidence to accept or reject a 
causal relationship between tetanus toxoid-containing vaccines and GBS (31). The IOM found 

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evidence for a causal relation between tetanus toxoid-containing vaccines and brachial neuritis 
(32). Arthus reactions are rarely reported after vaccination and can occur after tetanus 
toxoid-containing vaccines (33). 
No occurrences of GBS, brachial neuritis, or Arthus reaction have been reported with the use of 
MenACYW conjugate vaccine in the completed clinical trials. 
 
 
 
 
 
 
 
 
The risk of vasovagal syncope exists after any vaccination in the adolescent age group. A few 
cases of immediate vasovagal-like response or syncope have been observed in adolescent subjects 
who had received MenACYW conjugate vaccine. Syncope has been reported following 
vaccination with Menactra®. Procedures should be in place to prevent falling injury and manage 
syncopal reactions. 
The potential risks associated with blood drawing include local pain, bruising, and, rarely, fainting. 
The potential risk listed here are not exhaustive. Refer to the package insert of Menactra® (34) and 
the Investigator’s brochure (IB) for the investigational vaccine for additional information 
regarding the potential risks. 
1.4 
RATIONALE FOR THE STUDY  
MenACYW conjugate vaccine is designed for the immunization of individuals of all ages (infants 
6 weeks of age and older through and including older adults ≥56 years of age) against IMD. The 
purpose of the vaccine is to provide broad coverage against circulating meningococcal strains 
from serogroups A, C, Y, and W. Compared to a previous Sanofi Pasteur meningococcal 
conjugate vaccine, Menactra®, MenACYW conjugate vaccine is prepared using tetanus toxoid as 
the carrier protein. Conjugation of polysaccharide antigens to a protein carrier can induce T-cell 
dependent immune responses, which are anticipated to give rise to higher antibody titers, longer 
duration of the immune response, and enhanced immunologic memory that allows for a booster 
response. 
Meningococcal polysaccharide vaccines have two important limitations: a) the antibody response 
is age-dependent, with infants giving the poorest response; and b) polysaccharides alone are T-cell 
independent immunogens, and therefore no anamnestic response is seen. The immunogenicity of 
polysaccharide vaccines in infants and children has been shown to be improved by conjugating 
the polysaccharides to protein carriers. Among the key advantages expected of the tetanus carrier 

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is improved immunogenicity in infants and older adults. Pre-clinical studies using a mouse model 
and investigating different carriers, showed significant levels of polysaccharide-specific total 
immunoglobulin G (IgG) and bactericidal responses in response to the formulations with tetanus 
toxoid as a carrier. Early Phase I/II trials including those with the final formulation (MET28 and 
MET32) showed the potential of the candidate vaccine as a very good immunogen in all age 
groups, including young infants and older adults. MenACYW conjugate vaccine was found to be 
immunogenic and well tolerated; it did not raise any safety concerns in the above trials using the 
final formulation or in the earlier trials. 
The purpose of this trial is to evaluate the immune non-inferiority of MenACYW conjugate 
vaccine versus Menactra®, and describe the safety and additional immunogenicity of MenACYW 
conjugate vaccine and Menactra® in children, adolescents, and adults 2 to 55 years of age in Japan. 

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2 
STUDY OBJECTIVES  
2.1 
PRIMARY OBJECTIVE(S)  
To demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, 
Y, and W following the administration of a single dose of MenACYW conjugate vaccine 
compared with those observed following the administration of a single dose of Menactra®. 
The endpoint for the primary objective is presented in Section 9.1. 
2.2 
SECONDARY OBJECTIVE(S)  
Immunogenicity  
To describe the antibody responses to the meningococcal serogroups A, C, Y, and W before and 
30 days (+14 days) after vaccination with MenACYW conjugate vaccine or Menactra®. 
Safety 
To describe the safety profile of MenACYW conjugate vaccine and that of Menactra®. 
The endpoints for the secondary objectives are presented in Section 9.2. 

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3 
INVESTIGATORS AND STUDY ORGANIZATION  
This study will be conducted in approximately 5 centers in Japan. Details of the study centers, the 
Investigators at each center are provided in the list of Investigators and centers involved in the 
study. 
Sanofi Pasteur’s laboratory (Global Clinical Immunology [GCI], Swiftwater, PA, USA) or an 
external testing laboratory under GCI responsibility will be used for the assessment of all 
immunogenicity endpoints. 
The Sponsor’s Study Medical Manager (the SMM, the person authorized to sign this protocol and 
any amendments on behalf of the Sponsor) is 
 
. 

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4 
INSTITUTIONAL REVIEW BOARD / INDEPENDENT ETHICS 
COMMITTEE (IRB/IEC)  
As required by local regulation, the Sponsor must submit this clinical study protocol to the Health 
Authorities (Competent Regulatory Authority) and the appropriate Institutional Review Board 
(IRB) / Independent Ethics Committee (IEC), and is required to forward to the respective other 
party a copy of the written and dated approval / favorable opinion signed by the chairman with 
IRB/IEC composition. 
The clinical study (study number, clinical study protocol title and version number), the documents 
reviewed (clinical study protocol, informed consent form [ICF], IB, Investigator’s curriculum 
vitae etc.) and the date of the review should be clearly stated on the written IRB/IEC approval / 
favorable opinion. 
The investigational product (IP) will not be released at the study site and the Investigator will not 
start the study before the written and dated approval / favorable opinion is received by the 
Investigator and the Sponsor. 
During the clinical study, any amendment or modification to the clinical study protocol should be 
submitted to the Health Authorities (Competent Regulatory Authority), as required by local 
regulation, in addition to the IRB/IEC before implementation, unless the change is necessary to 
eliminate an immediate hazard to the subjects, in which case the Health Authorities (Competent 
Regulatory Authority) and the IRB/IEC should be informed as soon as possible. They should also 
be informed of any event likely to affect the safety of subjects or the continued conduct of the 
clinical study, in particular any change in safety. All updates to the IB will be sent to the IRB/IEC 
and to Health Authorities (Competent Regulatory Authority), as required by local regulation. 
A progress report is sent to the IRB/IEC at least annually and a summary of the study’s outcome 
at the end of the clinical study. 

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5 
INVESTIGATIONAL PLAN  
5.1 
DESCRIPTION OF THE OVERALL STUDY DESIGN AND PLAN  
5.1.1 Study Design  
This will be a Phase III, modified double-blind, randomized, parallel-group, active-controlled, 
multi-center study to evaluate immune non-inferiority of MenACYW conjugate vaccine versus 
Menactra® and describe the safety and additional immunogenicity of the study vaccines in 
children (2-9 years of age), adolescents (10-17 years of age) and adults (18-55 years of age) in 
Japan. Approximately 360 healthy children, adolescents and adults will be stratified and randomly 
assigned in a 1:1 ratio to the following groups: 
 Group 1 (investigational): MenACYW conjugate vaccine (180 subjects) 
 Group 2 (control): Menactra® (180 subjects) 
All subjects will provide blood samples for immunogenicity assessment at baseline 
(pre-vaccination) and at 30 days post-vaccination.  
Solicited injection site and systemic reactions will be collected for 7 days after vaccination, 
unsolicited AEs will be collected from Visit 1 (D0) to Visit 2 (D30 [+14 days]), and SAEs will be 
collected from signing of the informed consent at D0 through D30 (+14 days) after vaccination. 
5.1.2 Justification of the Study Design  
This trial is part of the ongoing development program that focuses on demonstrating that 
MenACYW conjugate vaccine is non-inferior to the licensed quadrivalent meningococcal 
conjugate vaccine in direct comparison trials. This is a study that will be conducted as part of the 
Phase III development of MenACYW conjugate vaccine in which the vaccine candidate will be 
evaluated in children, adolescents, and adults 2 to 55 years of age in Japan. 
This trial is designed to evaluate the immune non-inferiority of MenACYW conjugate vaccine 
versus Menactra®, and will describe the safety and immunogenicity of MenACYW conjugate 
vaccine and Menactra® in children, adolescents, and adults 2 to 55 years of age in Japan. 
This trial will be conducted in a modified double-blind method, in which only designated staff 
members at each study site will know which vaccine has been administered to the subjects. The 
subjects and the Investigator in charge of the safety assessment will be blinded in order to 
decrease the potential bias in safety assessments. The vaccines are prepared by the unblinded site 
staff member (a designated administrator such as a subinvestigator, a nurse, or a designated 
pharmacist) and administered by the administrator without the presence of any other site staff 
members who may be an assessor for safety in subsequent visits. The subjects and subjects’ 
parents / legally acceptable representatives will also remain blinded to study product. Furthermore, 

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the Sponsor and laboratory personnel performing the serology testing will also remain blinded to 
treatment assignments throughout the trial until database lock. 
5.1.3 Study Plan  
A schedule of assessments and study vaccinations is provided in the Table of Study Procedures. 
Vaccination 
All subjects will receive a single IM dose of either MenACYW conjugate vaccine or Menactra® 
on D0. 
Blood sampling 
All subjects will provide a pre-vaccination blood sample at Visit 1 D0 and a post-vaccination 
sample at Visit 2 (D30 [+14 days] after the vaccination at Visit 1). 
Collection of safety data 
 All subjects will be observed for 30 minutes after vaccination, and any unsolicited 
systemic AEs occurring during that time will be recorded as immediate unsolicited 
systemic AEs in the case report form (CRF). 
 The subject or the subject’s parent / legally acceptable representative will record 
information in a diary card about solicited reactions from D0 to D07 after vaccination and 
unsolicited AEs from Visit 1 (D0) to Visit 2 (D30 [+14 days]). SAEs will be reported 
throughout the duration of the study from the signing of the ICF or the assent form. 
 In addition, the subject or subject’s parent / legally acceptable representative will be asked 
to notify the site immediately about any potential SAEs at any time during the study. 
 Study site staff will contact the subject or the subject’s parent / legally acceptable 
representative by telephone on D8 (+2 days) to identify the occurrence of any SAE not yet 
reported and to remind them to complete the diary card up to Visit 2 and to bring it back at 
Visit 2. 
 The completed diary card will be reviewed with the subject and/or the subject’s parent / 
legally acceptable representative at Visit 2. 
5.1.4 Visit Procedures  
Medical procedures (examinations, injections, etc.) must be conducted by appropriately licensed 
or credentialed study site staff working within the scope of their license/credentials. 
Visit 1 (D0): Inclusion, Randomization, Blood Sample, and Vaccination  
1. Give the subject and/or the subject’s parent / legally acceptable representative information 
about the study, answer any questions, obtain written informed consent and assent (as 
applicable) and give the subject or subject’s parent / legally acceptable representative a 
signed copy of the ICF and a signed copy of the assent form (as applicable). 

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- 
Subjects 2 to 6 years of age: ICF signed by the subject’s parent / legally acceptable 
representative 
- 
Subjects 7 to 19 years of age: assent form signed by the subject and ICF signed by the 
subject’s parent / legally acceptable representative 
- 
Subjects 20 to 55 years of age: ICF signed by the subject 
2. Check inclusion and exclusion criteria for eligibility (see Section 5.2.4 and Section 5.2.5, 
respectively). 
3. Collect relevant demographic information. 
4. Perform urine pregnancy test (if applicable). 
5. Obtain verbal medical history about the subject. 
6. Conduct a history-directed physical examination, including temperature (preferably 
axillary temperature). A physical examination conducted during the same day as part of 
routine clinical care may be used for this purpose. 
7. Contact the interactive response technology (IRT) for subject identification number and 
vaccine dose number (see Section 6.5 for instructions). 
8. Obtain the first blood sample (5 milliliter [mL]) (see Section 7 for detailed instructions 
regarding the handling of blood samples). If attempts to obtain the first blood draw are 
unsuccessful (no more than 3 attempts), then Visit 1 can be rescheduled to a later date at 
which point informed consent and inclusion/exclusion criteria must be re-validated. If the 
first blood draw cannot be obtained, the subject will be withdrawn from the study without 
being vaccinated. 
9. Administer the appropriate study vaccine to the subject in the deltoid muscle. The vaccine 
must be administered on the side opposite to that of the blood sampling. 
Note: The study product is prepared by an unblinded study site staff (a designated 
administrator such as a Sub-investigator or nurse, or a designated pharmacist) and 
administered by the administrator without the presence of any other study site staffs who 
may be an assessor for safety in subsequent visits. The subjects and subjects’ parents / 
legally acceptable representatives are blinded with eye mask or other appropriate methods 
during administration. 
10. Observe the subject for 30 minutes, and record any AE in the source document. 
11. Give the subject or the subject’s parent / legally acceptable representative a diary card, a 
thermometer, and a ruler, and go over the instructions for their use. 
12. Remind the subject or the subject’s parent / legally acceptable representative to expect a 
telephone call 8 days (+2 days) after Visit 1 and to bring back the diary card when they 
return for Visit 2 at a specified date and time. 
13. Remind the subject or the subject’s parent / legally acceptable representative to notify the 
site in case of an SAE. 
14. Complete the relevant CRF pages for this visit. 

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Telephone Call 1 (D8 [+2 days] after Visit 1) 
Note: If D8 falls on a weekend or a holiday, the telephone call may be made on the following 
business day. If the subject or the subject’s parent / legally acceptable representative is not 
available, the study site staff should document the attempts to make contact. 
1. Record relevant information concerning the subject’s health status on the telephone 
contact form. If an SAE occurred, follow the instructions in Section 10 for reporting it. 
2. Remind the subject or the subject’s parent / legally acceptable representative to do the 
following: 
- 
Complete the D0 to D7 pages of the diary card. 
- 
Complete the remaining pages of the diary card, and bring them to Visit 2. 
- 
Notify the site in case of an SAE. 
Visit 2 (D30 [+14 days] after Visit 1): Collection of Safety Information and Blood Sample 
1. Review the pages of the diary card with the subject or the subject’s parent / legally 
acceptable representative, including any AEs, medications, or therapy that occurred since 
vaccination. 
2. Review the temporary contraindications for blood sampling (see Section 5.2.8). 
3. Obtain the second blood sample (see Section 7 for detailed instructions regarding the 
handling of blood samples). 
4. Complete the termination record of the CRF. 
5. If the subject does not return for Visit 2, and the diary card is not received at the site, study 
site staffs will contact the subject or the subject’s parent / legally acceptable representative 
by telephone. During the telephone call, the subject or the subject’s parent / legally 
acceptable representative will be reminded to return the diary card to the study site. 
Telephone calls will be documented on the telephone/interview record. If the study site 
staffs are unable to contact the subject or the subject’s parent / legally acceptable 
representative with 3 attempts, the study site staffs will follow instructions given in 
Section 5.2.11. 
6. Contact the IRT to inform the subject's status. 
Follow-up of subjects with Related AEs or with AEs That Led to Study Discontinuation: 
Unless a subject or subject’s parent / legally acceptable representative refuses further contact, 
each subject who experiences an AE (whether serious or non-serious) during the study must be 
followed until the condition resolves, becomes stable, or becomes chronic (even after the end of 
the subject’s participation in the study) if either of the following is true:   
 The AE is considered by the Investigator to be related to the product administered. 
 The AE caused the discontinuation of the subject from the study. 

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5.1.5 Planned Study Calendar  
The following dates are approximate. The actual dates may differ as, for example, the study will 
not start until all the appropriate regulatory and ethical approvals have been obtained. 
Planned study period - FVFS (first visit, first subject) to LCLS (last contact, last subject): 22 May 
2020 to 16 December 2020 
Planned inclusion period - FVFS to FVLS (first visit, last subject): 22 May 2020 to 11 November 
2020 
Planned vaccination period: 22 May 2020 to 11 November 2020 
Planned end of study (LCLS): 16 December 2020 
Planned date of final clinical study report: 26 Jun 2021 
5.2 
ENROLLMENT AND RETENTION OF STUDY POPULATION  
5.2.1 Recruitment Procedures  
Before the start of the study, the Investigator and/or study site staff may contact the subjects or the 
subjects’ parents / legally acceptable representatives of an appropriate pool of potential subjects 
and invite them to participate in the study. The site will ensure that any advertisements used to 
recruit subjects (e.g., letters, pamphlets, and posters) are submitted to Sponsor for review prior to 
submission to the IRB/IEC for approval. 
In addition, a potential subject who comes to a study site for a routine visit may be invited to 
enroll in the study, or a parent who brings a child to the study site for a routine visit may be 
invited to enroll the child in the study, if eligible. Subjects may also be recruited from the general 
population. 
5.2.2 Informed Consent Procedures  
The Investigator (according to applicable regulatory requirements), or a person designated by the 
Investigator and under the Investigator’s responsibility, should fully inform the subject and/or 
subject’s parent / legally acceptable representative of all pertinent aspects of the clinical study 
including the written information giving approval / favorable opinion by the ethics committee 
(IRB/IEC). All participants should be informed to the fullest extent possible about the study, in 
language and terms they are able to understand. 
Prior to a subject’s participation in the clinical study, the written ICF (and assent form) should be 
signed, name filled in, and personally dated by the subject and/or by subject’s parent / legally 
acceptable representative, and by the person who conducted the informed consent discussion. A 
copy of the signed and dated written ICF (and assent form) will be provided to the subject or 
subject’s parent / legally acceptable representative. 

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The ICF (and assent form) used by the Investigator for obtaining the informed consent of the 
subject or subject’s parent / legally acceptable representative must be reviewed and approved by 
the Sponsor prior to submission to the appropriate ethics committee (IRB/IEC) for approval / 
favorable opinion. 
The written ICF and any other written information to be provided to subjects or subjects’ parents / 
legally acceptable representatives should be revised whenever important new information 
becomes available that may be relevant to the consent of the subject or subject’s parent / legally 
acceptable representative. Any revised written ICF and assent form, and written information 
should receive the IRB/IEC’s approval / favorable opinion in advance of use. The subject and/or 
subject’s parent / legally acceptable representative should be informed in a timely manner if new 
information becomes available that may be relevant to the willingness of the subject or subject’s 
parent / legally acceptable representative to continue participation in the study. The 
communication of this information should be documented. In case of study suspension due to 
safety concerns, subjects and/or subjects’ parents / legally acceptable representatives will be 
informed of this study suspension and the reason for it. Once it is confirmed that it is safe for the 
study to continue, subjects and/or subjects’ parents / legally acceptable representatives will be 
asked to confirm their agreement to continue the study. 
5.2.3 Screening Criteria  
There are no screening criteria other than the inclusion and exclusion criteria. 
5.2.4 Inclusion Criteria  
An individual must fulfill all of the following criteria to be eligible for study enrollment: 
I 01. Aged 2 to 55 years on the day of inclusion 
I 02. Informed consent form has been signed and dated by the subjects or subjects’ parents / 
legally acceptable representatives as applicable 
In addition:  
Subjects 7 to 19 years will provide written assent 
I 03. Subjects (and subjects’ parents / legally acceptable representatives for the 2 to 19 years age 
groups) are able to attend all scheduled visits and to comply with all study procedures 
5.2.5 Exclusion Criteria  
An individual fulfilling any of the following criteria is to be excluded from study enrollment: 
E 01. Subject is pregnant, or lactating, or of childbearing potential (to be considered of 
non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 

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1 year, surgically sterile, or using an effective method of contraception1 or abstinence from 
at least 4 weeks prior to vaccination until at least 4 weeks after vaccination) 
E 02. Participation in the 4 weeks preceding the study vaccination or planned participation 
during the present study period in another clinical study investigating a vaccine, drug, 
medical device, or medical procedure  
E 03. Receipt of any vaccine in the 4 weeks preceding the study vaccination or planned receipt 
of any vaccine prior to Visit 2 except for influenza vaccination, which may be received at 
least 2 weeks before or after the study investigational vaccines. This exception includes 
monovalent pandemic influenza vaccines and multivalent influenza vaccines 
E 04. Previous vaccination against meningococcal disease with either the study vaccine or 
another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal 
vaccine containing serogroups A, C, Y, or W; or meningococcal B vaccine) 
E 05. Receipt of immune globulins, blood or blood-derived products in the past 3 months 
E 06. Known or suspected congenital or acquired immunodeficiency; or receipt of 
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within 
the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or 
equivalent for more than 2 consecutive weeks within the past 3 months) 
E 07. History of meningococcal infection, confirmed either clinically, serologically, or 
microbiologically 
E 08. At high risk for meningococcal infection during the study (specifically, but not limited to, 
subjects with persistent complement deficiency, with anatomic or functional asplenia, or 
subjects traveling to countries with high endemic or epidemic disease) 
E 09. Known systemic hypersensitivity to any of the vaccine components, or history of a 
life-threatening reaction to the vaccines used in the study or to a vaccine containing any of 
the same substances 
E 10. Laboratory confirmed / self-reported thrombocytopenia, contraindicating intramuscular 
vaccination in the Investigator’s judgment 
E 11. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating intramuscular vaccination in the Investigator’s judgement 
E 12. History of GBS 
E 13. History of convulsions 
                                                 
1 Effective methods of contraception include oral contraception (pill), intrauterine device, or condoms used 
with spermicide. 

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E 14. History of an Arthus-like reaction after vaccination with a tetanus toxoid-containing 
vaccine and a diphtheria toxoid-containing vaccine within 10 years of the proposed study 
vaccination 
E 15. Deprived of freedom by an administrative or court order, or in an emergency setting, or 
hospitalized involuntarily 
E 16. Current alcohol abuse or drug addiction  
E 17. Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere 
with study conduct or completion 
E 18. Moderate or severe acute illness/infection (according to Investigator judgment) or febrile 
illness (temperature ≥99.5°F or ≥37.5°C) on the day of vaccination. A prospective subject 
should not be included in the study until the condition has resolved or the febrile event has 
subsided 
E 19. Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw  
E 20.  Identified as an Investigator or employee of the Investigator or study center with direct 
involvement in the proposed study, or identified as an immediate family member (i.e., 
parent, spouse, natural or adopted child) of the Investigator or employee with direct 
involvement in the proposed study 
If the subject has a primary physician who is not the Investigator, the site should contact this 
physician with the consent of the subject or subject’s parent / legally acceptable representative to 
inform him/her of the subject’s participation in the study. In addition, the site should ask this 
primary physician to verify exclusion criteria relating to previous therapies, such as receipt of 
blood products or previous vaccines. 
5.2.6 Medical History  
Prior to enrollment, subjects will be assessed for pre-existing conditions and illnesses, both past 
and ongoing. Any such conditions will be documented in the source document. Significant 
(clinically relevant) medical history (reported as diagnosis) including conditions/illnesses for 
which the subject is or has been followed by a physician or conditions/illnesses that could resume 
during the course of the study or lead to an SAE or to a repetitive outpatient care will be collected 
in the case report book (CRB). The significant medical history section of the CRB contains a core 
list of body systems and disorders that could be used to prompt comprehensive reporting, as well 
as space for the reporting of specific conditions and illnesses. 
For each condition, the data collected will be limited to: 
 Diagnosis (this is preferable to reporting signs and symptoms) 
 Presence or absence of the condition at enrollment 
The reporting of signs and symptoms in lieu of a diagnosis is strongly discouraged. 

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Dates, medications, and body systems are not to be recorded, and the information collected will 
not be coded. Its purpose is to assist in the later interpretation of safety data collected during the 
study. 
5.2.7 Contraindications for Subsequent Vaccinations  
Not applicable. 
5.2.8 Contraindications for Visit 2 Blood Samples  
Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the second 
blood draw, the Investigator will postpone that blood draw until it has been 3 days (72 hours) 
since the subject last received oral or injectable antibiotic therapy. Postponement must still be 
within the timeframe for blood draw (30 to 44 days after vaccination at D0). If postponement 
would result in the sample collection falling outside of this timeframe, the blood sample should be 
collected without postponement, and it should be documented appropriately that the sample was 
taken less than 3 days after stopping antibiotic treatment. 
5.2.9 Conditions for Withdrawal  
Subjects and/or subjects’ parents / legally acceptable representatives will be informed that they 
have the right to withdraw from the study at any time. A subject may be withdrawn from the 
study: 
 At the discretion of the Investigator or Sponsor due to safety concerns or significant 
non-compliance with the protocol (based on the Investigator’s judgment), without the 
subject’s or subject’s parent’s / legally acceptable representative’s permission 
(withdrawal) 
 At the request of the subject or subject’s parent / legally acceptable representative 
(dropout)  
The reason for a withdrawal or dropout should be clearly documented in the source documents 
and in the CRB.  
The Investigator must determine whether voluntary withdrawal is due to safety concerns (in 
which case, the reason for discontinuation will be noted as “Adverse Event”) or for another 
reason. 
Withdrawn subjects will not be replaced. 
5.2.10 Lost to Follow-up Procedures  
In the case of subjects who fail to return for Visit 2, documented reasonable effort (i.e., 
documented telephone calls and certified mail) should be undertaken to locate or recall them, or at 
least to determine their health status while fully respecting their rights. These efforts should be 
documented in the source documents. 

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5.2.11 Classification of Subjects Who Discontinue the Study  
For any subject who discontinues the study prior to completion, the most significant reason for 
early termination will be checked in the CRB. Reasons are listed below from the most significant 
to the least significant (refer to the CRF completion instructions for additional details and 
examples): 
Adverse Event 
To be used when the subject is permanently terminated from the study because of an AE 
(including an SAE), as defined in Section 9.2.2.1. 
Lost to Follow-up 
To be used when the subject cannot be found or contacted in spite of efforts to locate him/her 
before the date of his/her planned last visit, as outlined in Section 5.2.10. The certified letter was 
sent by the Investigator and returned unsigned, and the subject or subject’s parent / legally 
acceptable representative did not give any other news and did not come to any following visit. 
Protocol Deviation 
To be used: 
 
In case of significant noncompliance with the protocol (e.g., deviation of the 
Inclusion/Exclusion criteria, non-compliance with time windows, blood sampling or 
vaccination refusal, missed injection/treatment, or error in the vaccine/treatment 
administration). 
 
The subject or the subject’s parent / legally acceptable representative signed the certified 
letter sent by the Investigator but did not give any other news and did not come to any 
following visit. 
Withdrawal by Subject or 
Subject’s Parent / Legally 
Acceptable Representative 
To be used: 
 
When the subject or subject’s parent / legally acceptable representative indicated 
unwillingness to continue in the study 
 
When the subject or subject’s parent / legally acceptable representative made the decision to 
discontinue participation in the study for any personal reason other than an SAE/AE (e.g., 
subject is relocating, inform consent withdrawal, etc.) 
5.2.12 Follow-up of Discontinuations  
The site should complete all scheduled safety follow-ups and contact any subject who has 
prematurely terminated the study because of an AE or a protocol deviation.  
For subjects where the reason for early termination was lost to follow-up or if the subject or 
subject’s parent / legally acceptable representative withdrew informed consent and specified that 
they do not want to be contacted again and it is documented in the source document, the site will 
not attempt to obtain further safety information. 
5.2.13 Follow-up and Reporting of Pregnancies  
Pregnancy is an exclusion criterion for enrollment in this study, but a subject could potentially 
become pregnant during her participation. In case of pregnancy and if the study vaccine has been 
administered, the subject will not be discontinued from the study and will be followed for safety 
assessment (and may be followed for immunogenicity assessment, if applicable). 
All pregnancy cases should be reported if they occurred during the study. To report the pregnancy 
case, the Investigator must fill out Pregnancy Reporting Forms in the electronic data capture 
(EDC) system and inform the Sponsor within 1 month of identifying a pregnancy case.  

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If the EDC system is not available, the Investigator must fill out a paper Pregnancy Reporting 
Form (provided by the Sponsor at the start of the study) and inform the Sponsor within 1 month of 
identifying a pregnancy case. 
Study site staff must then maintain contact with the subject to obtain information about the 
outcome (i.e., details about the delivery and the newborn, or about pregnancy termination) and 
must update the Pregnancy Reporting forms even after the end of the study. This information 
should be provided to the Sponsor within 1 month of delivery. 
Pregnancy itself is not considered an AE, but any complications during pregnancy are to be 
considered as AEs, and in some cases could be considered SAEs. Spontaneous abortions, blighted 
ovum, fetal death, stillbirth, and congenital anomalies reported in the baby are always considered 
as SAEs, and the information should be provided to the Sponsor regardless of when the SAE 
occurs (e.g., even after the end of the study). 
5.3 
SAFETY EMERGENCY CALL  
If, as per the Investigator's judgment, a subject experiences a medical emergency, the Investigator 
may contact the Sponsor for advice on how to address any study related medical question or 
problem. If the Sponsor is not available, then the Investigator may contact the Call Center —
available 24 hours a day, 7 days a week—that will forward all safety emergency calls to the 
appropriate primary or back-up Sponsor’s contact, as needed. The toll-free contact information for 
the Call Center is provided in the clinical study protocol (see Names and Addresses). 
This process does not replace the need to report an SAE. The Investigator is still required to 
follow the protocol-defined process for reporting SAEs to the Sponsor (see Section 10). 
In case of emergency code-breaking, the Investigator is required to follow the code-breaking 
procedures described in Section 6.4. 
5.4 
INTERRUPTION OF THE STUDY  
The study may be discontinued if new data about the investigational product resulting from this 
study or any other studies become available; or for administrative reasons; or on advice of the 
Sponsor, the Investigators, the IRBs, or the governing regulatory authority in Japan where the 
study is taking place. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IRBs, the regulatory authority, and any contract research organization(s) used in 
the study of the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The Investigator shall promptly inform the study subjects or subjects’ parents / 
legally acceptable representatives and should assure appropriate subject therapy and/or follow-up. 

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5.5 
PREMATURE CLOSE-OUT OF A SITE  
5.5.1 By the sponsor  
The sponsor has the right to terminate the participation of an individual site at any time, for any 
reason, including but not limited to the following: 
 The Investigator has received from the Sponsor all IP, means, and information necessary 
to perform the clinical study and has not included any subject after a reasonable period of 
time mutually agreed upon 
 Non-compliance of the Investigator or Sub-investigator, delegated site staff with any 
provision of the clinical study protocol, and breach of the applicable laws and regulations 
or breach of the ICH GCP 
In any case, the Sponsor will notify the Investigator of its decision by written notice. 
5.5.2 By the Investigator  
The Investigator may terminate his/her participation upon thirty (30) days' prior written notice if 
the study site or the Investigator for any reason becomes unable to perform or complete the 
clinical study.  
In the event of premature close-out of a site, for any reason whatsoever, the appropriate IRB/IEC 
and regulatory authority should be informed according to applicable regulatory requirements. 
 

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6 
PRODUCTS ADMINISTERED  
6.1 
IDENTITY OF THE INVESTIGATIONAL PRODUCT(S)  
6.1.1 Identity of Study Product(s)  
MenACYW conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) 
Tetanus Toxoid Conjugate Vaccine  
Form: Liquid solution 
Dose: 0.5 mL 
Route: IM 
Batch number: To be determined 
6.1.1.1 Composition  
Each 0.5 mL dose of MenACYW conjugate vaccine is formulated in sodium acetate buffered 
saline solution to contain the following ingredients: 
Meningococcal capsular polysaccharides: 
Serogroup A………………………………………………………………………...10 µg 
Serogroup C………………………………………………………………………...10 µg 
Serogroup Y………………………………………………………………………...10 µg 
Serogroup W………………………………………………………………………..10 µg 
Tetanus toxoid protein carrier…………………………………………approximately 55 µg 
6.1.1.2 Preparation and Administration  
MenACYW conjugate vaccine is supplied in single-dose (0.5 mL) vials. 
The study product is prepared by an unblinded study site staff (a designated administrator such as 
a Sub-investigator or nurse, or a designated pharmacist) and administered by the administrator 
without the presence of any other study site staffs who may be an assessor for safety in 
subsequent visits. The subjects and subjects’ parents / legally acceptable representatives are 
blinded with eye mask or other appropriate methods during administration. 
Prior to administration, all study products must be inspected visually for cracks, broken seals, 
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whenever solution and container permit. If any of these conditions exists, the vaccine must not be 
administered. A replacement dose is to be used, and the event is to be reported to the Sponsor.  
The rubber stopper should not be removed from any of the vaccine vials. 
The site of IM injection should be prepared with a suitable antiseptic prior to administration of 
one dose (0.5 mL) of MenACYW conjugate vaccine in the deltoid muscle of the arm. After 
vaccine administration, the used syringe and needle will be disposed of in accordance with 
currently established guidelines. 
Subjects must be kept under observation for 30 minutes after vaccination to ensure their safety, 
and any reactions during this period will be documented in the CRB. Appropriate medical 
equipment and emergency medications, including epinephrine (1:1000), must be available on site 
in the event of an anaphylactic, vasovagal, or other immediate allergic reaction. 
6.1.1.3 Dose Selection and Timing  
All subjects in Group 1 will receive 1 dose of MenACYW conjugate vaccine on D0. 
6.1.2 Identity of Control Product(s)  
Menactra®: Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid 
Conjugate Vaccine  
Form: Liquid solution for injection 
Dose: 0.5 mL 
Route: IM 
Batch number: To be determined 
6.1.2.1 Composition  
Each 0.5 mL dose of vaccine is formulated in sodium phosphate buffered isotonic sodium 
chloride solution to contain as active ingredients the following meningococcal capsular 
polysaccharides conjugated to approximately 48µg of diphtheria toxoid protein: 
Serogroup A………………………………………………………………………........ 4 µg 
Serogroup C………………………………………………………………………........ 4 µg 
Serogroup Y………………………………………………………………………........ 4 µg 
Serogroup W-135……………………………………………………………………… 4 µg 
Diphtheria toxoid protein carrier...........................................................approximately 48 µg 

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6.1.2.2 Preparation and Administration  
Menactra® is supplied in single-dose (0.5 mL) vials.  
See the Menactra® package insert (34). The procedures for preparing and administering the 
control product are the same as those described for the study product in Section 6.1.1.2. 
6.1.2.3 Dose Selection and Timing  
All subjects in Group 2 will receive 1 dose of Menactra® on D0. 
6.2 
IDENTITY OF OTHER PRODUCT(S)  
Not applicable. 
6.3 
PRODUCT LOGISTICS  
6.3.1 Labeling and Packaging  
MenACYW conjugate vaccine and a commercial lot of Menactra® will be supplied in single-dose 
vials, labeled and packaged according to national regulations. 
6.3.2 Product Shipment, Storage, and Accountability  
6.3.2.1 Product Shipment  
The Sponsor’s monitoring staff will contact the Investigator or a designee to determine the dates 
and times of delivery of products. 
Each vaccine shipment will include a temperature-monitoring device to verify maintenance of the 
cold chain during transit. On delivery of the product to the site, the person in charge of product 
receipt will follow the instructions given in the procedures for the product management, including 
checking that the cold chain was maintained during shipment (i.e., verification of the temperature 
recorders). If there is an indication that the cold chain was broken, this person should immediately 
quarantine the product, alert the Sponsor representative, and request authorization from the 
Sponsor to use the product. 
6.3.2.2 Product Storage  
The Investigator will be personally responsible for product management or will designate a study 
site staff to assume this responsibility. 
At the site, products must be kept in a secure place with restricted access. Vaccines will be stored 
in a refrigerator at a temperature ranging from +2°C to +8°C. The vaccines must not be frozen. 
The temperature must be monitored and documented (see the procedures for the product 

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management) for the entire time that the vaccine is at the study site. In case of accidental freezing 
or disruption of the cold chain, vaccines must not be administered and must be quarantined, and 
the Investigator or authorized designee should contact the Sponsor for further instructions. 
6.3.2.3 Product Accountability  
The person in charge of product management at the site will maintain records of product delivery 
to the study site, product inventory at the site, the dose given to each subject, and the disposal of 
or return to the Sponsor of unused doses. 
The necessary information on the product labels is to be entered into the source document and the 
CRB.  
The Sponsor’s monitoring staff will verify the study site’s product accountability records against 
the record in the CRBs and the communication from the IRT (if applicable). 
In case of any expected or potential shortage of product during the study, the Investigator or an 
authorized designee should alert the Sponsor representative as soon as possible, so that a shipment 
of extra doses can be arranged. 
6.3.3 Replacement Doses  
If a replacement dose is required (e.g., because the vial broke or particulate matter was observed 
in the vial), the site personnel must either contact the IRT to receive the new dose allocation, or 
follow the instructions given in the procedures for the product management. 
6.3.4 Disposal of Unused Products  
Unused or wasted products will be returned to the Sponsor in accordance with the instructions in 
the procedures for the product management. Product accountability will be verified throughout the 
study period. 
6.3.5 Recall of Products  
If the Sponsor makes a decision to launch a retrieval procedure, the Investigators will be informed 
of what needs to be done. 
6.4 
BLINDING AND CODE-BREAKING PROCEDURES  
This study will be conducted in a modified double-blind method, in which only designated staffs 
at each study site will know which vaccine has been administered to the subjects. The subjects, 
the subjects’ parents / legally acceptable representatives and the Investigator in charge of the 
safety assessment will be blinded in order to decrease the potential bias in safety assessments. 
Furthermore, the Sponsor and laboratory personnel performing the serology testing will also 
remain blinded to treatment assignments throughout the study until database lock. 

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The code may be broken in the event of an AE only when the identification of the vaccine 
received could influence the treatment of the subject. Code-breaking should be limited to the 
subject(s) experiencing the AE. 
The blind can be broken by the Investigator or a delegate through the IRT system, as explained in 
the code-breaking procedures described in the IRT operation manuals. Once the emergency has 
been addressed by the site, the Investigator or a delegate must notify the Sponsor if a subject’s 
code was broken. All contact attempts with the Sponsor prior to unblinding are to be documented 
in the source documents, and the code breaking CRF is to be completed. 
A request for the code to be broken may also be made: 
 by the Sponsor through an internal system for reporting to Health authorities in the case of 
an SAE as described in ICH E2A. In this case, the code will be broken only for the 
subject(s) in question. The information resulting from code-breaking (i.e., the subject’s 
vaccine or group assignment) will not be communicated to either the Investigator or the 
immediate team working on the study, except for the Global Pharmacovigilance (GPV) 
representative.  
The IRB/IEC must be notified of the code-breaking. All documentation pertaining to the event 
must be retained in the site’s study records and in the Sponsor’s files. Any intentional or 
unintentional code-breaking must be reported, documented, and explained, and the name of the 
person who requested it must be provided to the Sponsor. 
6.5 
RANDOMIZATION AND ALLOCATION PROCEDURES  
On the day of enrollment, subjects who meet the inclusion/exclusion criteria and sign the ICF 
(subjects 20 to 55 years of age) or sign the assent form (subjects 7 to 19 years of age) and whose 
parent / legally acceptable representative signs the ICF (subjects 2 to 19 years of age) will be 
randomly assigned to Group 1 or Group 2 in a 1:1 ratio, stratified according to age (children, 
adolescents and adults) such that each of Groups 1 and 2 will have approximately 180 subjects. 
Study site staff will connect to the IRT, enter the identification and security information, and 
confirm a minimal amount of data in response to IRT prompts. The IRT will then provide the 
vaccine dose number and have the study site staff confirm it. The full detailed procedures for 
group allocation are described in the IRT operation manuals. If the subject is not eligible to 
participate in the study, then the information will only be recorded on the screening/enrollment 
log. 
Subject numbers that are assigned by the IRT will consist of a 12-digit string (a 3-digit country 
identifier, a 4-digit study center identifier, and a 5-digit subject identifier). For example, 
Subject 392000100005 is the fifth subject enrolled in Center Number 1 in Japan (392 being the 
Japan country code). 
Subject numbers should not be reassigned for any reason. The randomization codes will be kept 
securely in the IRT and an internal system. 

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6.6 
TREATMENT COMPLIANCE  
The following measures will ensure that the vaccine doses administered comply with those 
planned, and that any non-compliance is documented so that it can be accounted for in the data 
analyses: 
 All vaccinations will be administered by qualified study personnel 
 The person in charge of product management at the site will maintain accountability 
records of product delivery to the study site, product inventory at the site, dose(s) given to 
each subject, and the disposal of unused or wasted doses 
6.7 
CONCOMITANT MEDICATION AND OTHER THERAPIES  
At the time of enrollment, ongoing medications and other therapies (e.g., blood products) should 
be recorded in the source document as well as new medications prescribed for new medical 
conditions / AEs during study participation. 
Documentation in the CRB of ongoing concomitant medication(s) will be limited to specific 
categories of medication(s) of interest beginning on the day of vaccination. This may include 
medications of interest that were started prior to the day of vaccination.  
Reportable medications will be collected in the CRB from the day of vaccination to the end of the 
study (D30 [+14 days]). 
Reportable medications include medications that impact or may impact the consistency of the 
safety information collected after vaccination and/or the response to vaccination. Three standard 
categories of reportable medications are defined: 
 Category 1: antipyretics, analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), 
corticosteroids, and other immune modulators. 
Note: inhaled and topical steroids should not be captured. 
 Category 2: Reportable medications used to define the Per-Protocol Analysis Set (PPAS). 
For example: 
- 
Influenza and other non-study vaccines: Influenza vaccine in the 2 weeks preceding 
the study vaccination up to the subject’s termination from the study and any other 
vaccines (other than the study vaccine) in the 4 weeks preceding the study vaccination 
up to the subject’s termination from the study 
- 
Immune globulins, blood or blood-derived products: used in the 3 months preceding 
the first blood draw and up to the last blood draw 
- 
Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy: 
used in the 6 months preceding the study vaccination and the 4 weeks following the 
study vaccination 
 Category 3: Oral or injectable antibiotics, which may interfere with bioassays used for 
antibody testing when taken before a blood draw. 

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- 
The period of collection should be within 3 days before the first blood draw and up to 
the last scheduled blood draw. 
Note: Inhaled and topical antibiotics (drops, creams, or ointments) should not be captured. 
The information reported in the CRB for each reported medication will be limited to: 
 Trade name or generic name 
 Origin of prescription: prophylaxis Yes/No. Medication(s) prescribed for AE prophylaxis 
will be recorded in the Action Taken of the AE collection tables 
 Medication category (1, 2, or 3) 
 Start and stop dates 
Dosage and administration route will not be recorded. Homeopathic medication will not be 
recorded. Topical treatment will not be recorded. 
Medications given in response to an AE will be captured in the “Action Taken” section of the AE 
CRF only. No details will be recorded in the concomitant medication CRF unless the 
medication(s) received belongs to one of the prelisted categories. 
Restricted treatments during the study period 
 Influenza and other non-study vaccines  
 Immune globulins, blood or blood-derived products 
 Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or 
long-term systemic corticosteroid therapy (prednisone or equivalent for more than 
2 consecutive weeks) 
 Oral or injectable antibiotics 

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7 
MANAGEMENT OF SAMPLES  
Blood samples for the assessment of antibody responses will be collected at Visit 1 and 2. See the 
Table of Study Procedures and Section 5.1.3 for details of the sampling schedule. 
7.1 
SAMPLE COLLECTION  
At Visit 1 and 2, 5 mL of blood will be collected in tubes provided by or recommended by the 
Sponsor. Immediately prior to the blood draw, the study site staff performing the procedure will 
verify the subject’s identity as well as the assigned subject’s number and sampling stage on the 
pre-printed label, and will attach the label to the tube. Blood is to be taken from the limb opposite 
to the one that will be used for vaccination, if possible. 
7.2 
SAMPLE PREPARATION  
Detailed instructions on how to prepare blood samples for assessment of immune response are 
contained in the sample handling procedures provided to the site. An overview of the procedures 
is provided here. 
Following the blood draw, the tubes are to be left undisturbed, positioned vertically and not 
shaken, for a minimum of 1 hour and a maximum of 24 hours to allow the blood to clot. Samples 
can be stored at room temperature for up to 2 hours; beyond 2 hours, they must be refrigerated at a 
temperature of +2°C to +8°C after the period of clotting at room temperature and must be 
centrifuged within a maximum of 24 hours. 
The samples are then centrifuged, and the serum is transferred to the appropriate number of 
aliquoting tubes. These tubes are pre-labeled with adhesive labels that identify the study code, the 
subject’s number and the sampling stage or visit number. 
The subject’s number and the date of sampling, the number of aliquots obtained, the date and time 
of preparation, and the consent of the subject or subject’s parent / legally acceptable 
representative for future use of subject’s samples are to be specified on a sample identification list 
and recorded in the source document. Space is provided on this list for comments on the quality of 
samples. 
7.3 
SAMPLE STORAGE AND SHIPMENT  
During storage, serum tubes are to be kept in a freezer whose temperature is set and maintained at 
−20°C or below. The temperature will be monitored and documented on the appropriate form 
during the entire study. If it rises above −10°C for any period of time, the Sponsor’s monitoring 
staff must be notified. See the sample handling procedures for further details. 

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Sample collection by a logistics vendor will be made only after appropriate monitoring, and 
following notification of the Sponsor’s monitoring staff. Sera will be shipped frozen, using dry ice 
to maintain them in a frozen state, in the packaging container provided by the logistics vendor. 
Again, temperatures will be monitored. Shipments must be compliant with the United Nations 
Class 6.2 specifications and the International Air Transport Association (IATA) 602 packaging 
instructions. 
Samples will be shipped to GCI at Sanofi Pasteur. The address is provided in the sample handling 
procedures. 
7.4 
FUTURE USE OF STORED BIOLOGICAL SAMPLES FOR RESEARCH  
Any unused part of the serum samples will be securely stored at the Sanofi Pasteur serology 
laboratory (GCI) for at least 25 years after the end of the study. These samples are being retained 
in long-term storage to support answers to regulatory questions related to the product’s licensure 
and the potential revalidation of the study results. 
In addition, subjects or subjects’ parents / legally acceptable representatives will be asked to 
indicate in the ICF whether they will permit the future use of any unused stored serum samples for 
other tests. If they refuse permission, the samples will not be used for any testing other than that 
directly related to this study. If they agree to this use, they will not be paid for giving permission. 
Anonymity of samples will be ensured. The aim of any possible future research is unknown today, 
and may not be related to this particular study. It may be to improve the knowledge of vaccines or 
infectious diseases, or to improve existing tests or develop new tests to assess vaccines. Human 
genetic tests will never be performed on these samples without specific individual informed 
consent.  

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8 
CLINICAL SUPPLIES  
The Sponsor will supply the study sites with protocols, ICFs, CRBs, SAE reporting forms, diary 
cards, and other study documents, as well as with the following study materials: all study 
vaccines, blood collection tubes, cryotubes, cryotube storage boxes, cryotube labels, temperature 
recorders, shipping containers, rulers, and digital thermometers. 
The means for performing EDC will be defined by the Sponsor. If a computer is provided by the 
Sponsor, it will be retrieved at the end of the study. 
The Investigator will supply all vaccination supplies, phlebotomy, and centrifugation equipment, 
including biohazard and/or safety supplies. The biohazard and safety supplies include needles and 
syringes, examination gloves, laboratory coats, sharps disposal containers, and absorbent 
countertop paper. The site will ensure that all biohazard wastes are autoclaved and disposed of in 
accordance with local practices. The Investigator will also supply appropriate space in a 
temperature-monitored refrigerator for the storage of the products and for the blood samples, and 
appropriate space in a temperature-monitored freezer for serum aliquots. 
In the event that additional supplies are required, study site staff must contact the Sponsor, 
indicating the quantity required. Contact information is provided in the clinical study protocol 
(See Names and Addresses).  

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9 
ENDPOINTS AND ASSESSMENT METHODS  
9.1 
PRIMARY ENDPOINTS AND ASSESSMENT METHODS  
9.1.1 Immunogenicity  
9.1.1.1 Immunogenicity Endpoints  
The primary endpoint(s) for the evaluation of immunogenicity is: 
Vaccine seroresponse (see Section 12.1.1.1) of meningococcal serogroups A, C, Y, and W 
measured by hSBA assessed at baseline (Visit 1, D0, before vaccination) and at Visit 2 (D30 
[+14 days]) after vaccination for immune non-inferiority between MenACYW conjugate vaccine 
and Menactra® (Group 1 versus Group 2). 
9.1.1.2 Immunogenicity Assessment Methods  
The assay method to be used is summarized below. Laboratory technicians conducting the 
immunogenicity assays will be blinded to the group to which each subject was assigned. 
Antibodies to meningococcal antigens (hSBA Method) 
Functional meningococcal antibody activity against serogroups A, C, Y, and W will be measured 
in a serum bactericidal assay utilizing human complement. Two-fold dilutions of test sera are 
prepared in sterile 96-well microtiter plates. Serogroup-specific meningococcal bacteria along 
with human complement are added to the serum dilutions and allowed to incubate. After this 
incubation period, an agar overlay medium is added to the serum/complement/bacteria mixture, 
allowed to harden, and then incubated overnight at 37°C with 5% CO2. Bacterial colonies present 
in the wells are then counted. The endpoint titer is determined by the reciprocal serum dilution 
yielding ≥50% killing as compared to the mean of the complement control wells. The lower limit 
of quantitation (LLOQ) of the hSBA assay is a titer of 1:4. 
This method will be performed on all blood samples (blood sampling [BL] 0001 and BL0002). 
The hSBA testing will be performed at GCI, Sanofi Pasteur, Swiftwater, PA. 
9.1.2 Safety  
There are no primary objectives for safety. 
9.1.3 Efficacy  
No clinical efficacy data will be obtained in the study. 

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9.2 
SECONDARY ENDPOINTS AND ASSESSMENT METHODS  
9.2.1 Immunogenicity  
9.2.1.1 Immunogenicity Endpoints  
The secondary endpoint for immunogenicity is:  
Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA assessed at 
baseline (D0, before vaccination) and after vaccination at D30 (+14 days) for all groups. 
 hSBA vaccine seroresponse 
 Proportion of subjects with hSBA titer ≥1:4 and ≥1:8 
 hSBA GMT 
 hSBA titer distribution and reverse cumulative distribution curve (RCDC) 
 Proportion of subjects with hSBA titer ≥4-fold rise from baseline (Visit 1, D0, before 
vaccination) to after vaccination (Visit 2, D30 [+14 days]) 
9.2.1.2 Immunogenicity Assessment Methods  
The immunogenicity assessment methods for the secondary endpoints are the same as those 
presented in Section 9.1.1.2. 
9.2.2 Safety  
9.2.2.1 Safety Definitions  
The following definitions are taken from the ICH E2A Guideline for Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting. 
Adverse Event (AE): 
An AE is any untoward medical occurrence in a patient or in a clinical investigation subject 
administered a medicinal product and which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom or disease temporally associated with the use 
of a medicinal product, whether or not considered related to the medicinal product.   
Therefore an AE may be: 
 A new illness 
 The worsening of a pre-existing condition 
 An effect of the vaccination, including the comparator 
 A combination of the above 

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All AEs include serious and non-serious AEs. 
Surgical procedures are not AEs; they are the actions taken to treat a medical condition. It is the 
condition leading to the action taken that is the AE (if it occurs during the study period). 
Pre-existing medical conditions are not to be reported as AEs. However, if a pre-existing medical 
condition worsens following study interventions in frequency or intensity, or if according to the 
Investigator there is a change in its clinical significance, this change should be reported as an AE 
(exacerbation). This applies equally to recurring episodes of pre-existing conditions (e.g., asthma) 
if the frequency or intensity increases post-vaccination. 
Serious Adverse Event (SAE): 
Serious and severe are not synonymous. The term severe is often used to describe the intensity of 
a specific event as corresponding to Grade 3. This is not the same as serious which is based on 
subject/event outcome or action criteria usually associated with events that pose a threat to a 
subject’s life or functioning. Seriousness, not severity, serves as a guide for defining regulatory 
reporting obligations. 
An SAE is any untoward medical occurrence that at any dose  
 Results in death 
 Is life-threatening2 
 Requires inpatient hospitalization or prolongation of existing hospitalization3 
 Results in persistent or significant disability/incapacity4 
 Is a congenital anomaly / birth defect 
 Is an important medical event (IME) 
Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in other situations, such as IMEs that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the health of the 
subject or may require intervention to prevent one of the other outcomes listed in the 
definition above. These IMEs should also usually be considered serious. Examples of such 
events include allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse, new-onset diabetes, or autoimmune 
disease.  
                                                 
2 The term “life-threatening” refers to an event in which the subject was at risk of death at the time of the 
event; it does not refer to an event which hypothetically might have caused death if it were more severe. 
3 All medical events leading to hospitalizations will be recorded and reported as SAEs, with the exception 
of: hospitalization planned before inclusion into the study or outpatient treatment with no hospitalization. 
4 “Persistent or significant disability or incapacity” means that there is a substantial disruption of a person’s 
ability to carry out normal life functions. 

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Adverse Reaction: 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered adverse reactions (AR). 
(The phrase “responses to a medicinal product” means that a causal relationship between a 
medicinal product and an AE is at least a reasonable possibility.) 
The following additional definitions are used by the Sponsor: 
Immediate Event/Reaction: 
Immediate events are recorded to capture medically relevant unsolicited systemic AEs (including 
those related to the product administered) that occur within the first 30 minutes after vaccination. 
Solicited Reaction: 
A solicited reaction is an “expected” adverse reaction (sign or symptom) observed and reported 
under the conditions (nature and onset) prelisted in the protocol and CRB (e.g., injection site pain 
or headache occurring between D0 and D7 post-vaccination). 
By definition, solicited reactions are to be considered as being related to the product administered. 
For injectable vaccines, solicited reactions can either be solicited injection site reactions or 
solicited systemic reactions. 
Unsolicited AE/AR: 
An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the CRB in 
terms of diagnosis and/or onset window post-vaccination. For example, if headache between D0 
and D7 is a solicited reaction (i.e., prelisted in the protocol and CRB), then a headache starting on 
D7 is a solicited reaction, whereas headache starting on D8 post-vaccination is an unsolicited AE. 
Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. 
Injection Site Reaction: 
An injection site reaction is an AR at and around the injection site. Injection site reactions are 
commonly inflammatory reactions. They are considered to be related to the product administered.  
Systemic AE: 
Systemic AEs are all AEs that are not injection or administration site reactions. They therefore 
include systemic manifestations such as headache, fever, as well as localized or topical 
manifestations that are not associated with the vaccination or administration site (e.g., erythema 
that is localized but that is not occurring at the injection site). 

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9.2.2.2 Safety Endpoints  
The secondary endpoints for the evaluation of safety are: 
 Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred 
term), duration, intensity, and relationship to vaccination, of any unsolicited systemic AEs 
reported in the 30 minutes after vaccination. 
 Occurrence, time to onset, number of days of occurrence, intensity, action taken, and 
whether the reaction led to early termination from the study, of solicited (prelisted in the 
subject’s diary card and CRF) injection site reactions occurring up to 7 days after 
vaccination. 
 Occurrence, time to onset, number of days of occurrence, intensity, action taken, and 
whether the reaction led to early termination from the study, of solicited (prelisted in the 
subject’s diary card and CRF) systemic reactions occurring up to 7 days after vaccination. 
 Occurrence, nature (MedDRA preferred term), time to onset, duration, intensity, action 
taken, relationship to vaccination (for systemic AEs only), and whether the event led to 
early termination from the study, of unsolicited AEs up to Visit 2 after vaccination. 
 Occurrence, nature (MedDRA preferred term), time to onset, duration, seriousness criteria, 
relationship to vaccination, outcome, and whether the SAE led to early termination from 
the study, of SAEs throughout the study from Visit 1 (D0) to Visit 2 (D30 [+14 days]) 
after vaccination. 
9.2.2.3 Safety Assessment Methods  
At Visit 2, the Investigator or a delegate will ask the subject or subject’s parent / legally 
acceptable representative about any solicited reactions and unsolicited AEs recorded in the diary 
card, as well as about any other AEs that may have occurred since the previous visit. All relevant 
data will be transcribed into the CRB according to the instructions provided by the Sponsor. 
9.2.2.3.1 Immediate Post-vaccination Observation Period  
Subjects will be kept under observation for 30 minutes after vaccination to ensure their safety. 
The post-vaccination observation should be documented in the source document. Any AE that 
occurs during this period will be noted on the source document and recorded in the CRB, as 
follows: 
 Unsolicited systemic AEs will be recorded as immediate AEs in the CRB (presence 
marked as “yes” and details collected). 
 Solicited and unsolicited injection site reactions and solicited systemic reactions will be 
recorded in the CRB in the same way as any reactions starting on the day of vaccination.  
 SAEs will be recorded in the CRB and reported to the Sponsor in the same way as any 
other SAEs, according to the procedures described in Section 10. 

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9.2.2.3.2 Reactogenicity (Solicited Reactions From Day 0 to Day 7 After Vaccination)  
After vaccination, subjects or subjects’ parents / legally acceptable representatives will be 
provided with a diary card, a digital thermometer, and a flexible ruler, and will be instructed how 
to use them. The following items will be recorded by the subjects or subjects’ parents / legally 
acceptable representatives in the diary card on the day of vaccination and for the next 7 days (i.e., 
D0 through D7) until resolution: 
 Daily temperature, with the route by which it was taken 
 Daily measurement or intensity grade of all other solicited injection site and systemic 
reactions 
 Action taken for each event (e.g., medication) 
The action(s) taken by the subject or subject’s parent / legally acceptable representative to 
treat and/or manage any solicited reactions will be classified in the CRB using the following 
list (all applicable items should be checked): 
- 
None 
- 
Medication 
- 
Health care provider contact 
- 
Hospitalized 
Subjects or subjects’ parents / legally acceptable representatives will be contacted by telephone 
8 days (+2 days) after vaccination to remind them to record all safety information in the diary 
card. 
If the timing of the telephone call should fall on a weekend or a holiday, the call should be made 
on the next business day. If contact is not made on the designated day, study site staff will 
continue calling until contact is made. Every telephone attempt and its outcome will be 
documented in the source document. 
Table 1, Table 2 and Table 3 present, respectively, the injection site reactions and systemic 
reactions that are prelisted in the diary cards and CRB, together with the intensity scales. 
 

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Table 1 - Solicited injection site reactions for Children (2 to 9 years of age): terminology, definitions, and intensity scales  
CRB term 
(MedDRA 
lowest level 
term [LLT]) 
Injection site pain 
Injection site erythema 
Injection site swelling  
Injection site induration 
Diary card 
term 
Pain 
Redness 
Swelling 
Hardening 
Definition 
Pain either present spontaneously or 
when the injection site is touched or 
injected limb is mobilized 
Presence of a redness including the 
approximate point of needle entry 
Swelling at or near the injection site. 
Swelling or edema is caused by a fluid 
infiltration in tissue or cavity and, 
depending on the space available for the 
fluid to disperse, swelling may be either 
soft (typically) or firm (less typical) to 
touch and thus can be best described by 
looking at the size of the swelling. 
Hardening at or near the injection site. 
Hardening is caused by a slow diffusion 
of the product in the tissue leading to a 
thick or hard area to touch at or near the 
injection site and thus can be best 
described by looking at the size of the 
hardening. 
Intensity 
scalea 
Grade 1: Easily tolerated 
Grade 2: Sufficiently discomforting to 
interfere with normal behavior or 
activities 
Grade 3: Incapacitating, unable to 
perform usual activities 
Grade 1: >0 to <25 mm 
Grade 2: ≥25 to <50 mm 
Grade 3: ≥50 mm 
Grade 1: >0 to <25 mm 
Grade 2: ≥25 to <50 mm 
Grade 3: ≥50 mm 
Grade 1: >0 to <25 mm 
Grade 2: ≥25 to <50 mm 
Grade 3: ≥50 mm 
a For the subjective reaction of pain, subjects or subjects’ parents / legally acceptable representatives will record the intensity level (Grade 1, 2, or 3) in the diary card. For the measurable reactions of redness, 
swelling and hardening, they will record just the size of the reaction, and the classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis. 

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Table 2 - Solicited injection site reactions for Adolescents (10 to 17 years of age) or Adults (18 to 55 years of age): terminology, definitions, and 
intensity scales  
CRB term 
(MedDRA LLT) 
Injection site pain 
Injection site erythema 
Injection site swelling  
Injection site induration 
Diary card 
term 
Pain 
Redness 
Swelling 
Hardening 
Definition 
Pain either present spontaneously or 
when the injection site is touched or 
injected limb is mobilized 
Presence of a redness including the 
approximate point of needle entry 
Swelling at or near the injection site. 
Swelling or edema is caused by a fluid 
infiltration in tissue or cavity and, 
depending on the space available for the 
fluid to disperse, swelling may be either 
soft (typically) or firm (less typical) to 
touch and thus can be best described by 
looking at the size of the swelling. 
Hardening at or near the injection site. 
Hardening is caused by a slow diffusion 
of the product in the tissue leading to a 
thick or hard area to touch at or near the 
injection site and thus can be best 
described by looking at the size of the 
hardening. 
Intensity 
scalea 
 
Grade 1: A type of adverse event that is 
usually transient and may require only 
minimal treatment or therapeutic 
intervention. The event does not 
generally interfere with usual activities of 
daily living. 
Grade 2: A type of adverse event that is 
usually alleviated with additional 
therapeutic intervention. The event 
interferes with usual activities of daily 
living, causing discomfort but poses no 
significant or permanent risk of harm to 
the research participant. 
Grade 3: A type of adverse event that 
interrupts usual activities of daily living, 
or significantly affects clinical status, or 
may require intensive therapeutic 
intervention. 
Grade 1: ≥25 to ≤50 mm 
Grade 2: ≥51 to ≤100 mm 
Grade 3: >100 mm 
Grade 1: ≥25 to ≤50 mm 
Grade 2: ≥51 to ≤100 mm 
Grade 3: >100 mm 
Grade 1: ≥25 to ≤50 mm 
Grade 2: ≥51 to ≤100 mm 
Grade 3: >100 mm 
a For the subjective reaction of pain, subjects or subjects’ parents / legally acceptable representatives will record the intensity level (Grade 1, 2, or 3) in the diary card. For the measurable reactions of redness, 
swelling and hardening, they will record just the size of the reaction, and the classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis 

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Table 3 - Solicited systemic reactions for Children, Adolescents or Adults (2 to 55 years of age): terminology, definitions, and intensity scales  
CRB term 
(MedDRA LLT) 
Fever 
Headache 
Malaise 
Myalgia 
Diary card term 
Temperature 
Headache 
Feeling unwell 
Muscle aches and pains 
Definition 
Elevation of temperature to ≥38.0°C 
(≥100.4°F) 
Pain or discomfort in the head or 
scalp.  
Does not include migraine. 
General ill feeling. 
Malaise is a generalized feeling of 
discomfort, illness, or lack of well-
being that can be associated with a 
disease state. It can be accompanied 
by a sensation of exhaustion or 
inadequate energy to accomplish 
usual activities. 
Muscle aches and pains are common 
and can involve more than one muscle 
at the same time. Muscle pain can also 
involve the soft tissues that surround 
muscles. These structures, which are 
often referred to as connective tissues, 
include ligaments, tendons, and fascia 
(thick bands of tendons). 
Does not apply to muscle pain at the 
injection site which should be reported 
as injection site pain. 
Intensity scalea 
Grade 1: ≥38.0°C to ≤38.4°C, 
or ≥100.4°F to ≤101.1°F 
Grade 1: A type of adverse event that 
is usually transient and may require 
only minimal treatment or therapeutic 
intervention. The event does not 
generally interfere with usual activities 
of daily living. 
Grade 1: A type of adverse event that 
is usually transient and may require 
only minimal treatment or therapeutic 
intervention. The event does not 
generally interfere with usual activities 
of daily living. 
Grade 1: A type of adverse event that 
is usually transient and may require 
only minimal treatment or therapeutic 
intervention. The event does not 
generally interfere with usual activities 
of daily living. 
 
Grade 2: ≥38.5°C to ≤38.9°C, 
or ≥101.2°F to ≤102.0°F 
Grade 2: A type of adverse event that 
is usually alleviated with additional 
therapeutic intervention. The event 
interferes with usual activities of daily 
living, causing discomfort but poses no 
significant or permanent risk of harm to 
the research participant. 
Grade 2: A type of adverse event that 
is usually alleviated with additional 
therapeutic intervention. The event 
interferes with usual activities of daily 
living, causing discomfort but poses no 
significant or permanent risk of harm to 
the research participant. 
Grade 2: A type of adverse event that 
is usually alleviated with additional 
therapeutic intervention. The event 
interferes with usual activities of daily 
living, causing discomfort but poses no 
significant or permanent risk of harm to 
the research participant. 
 
Grade 3: ≥39.0°C 
or ≥102.1°F 
Grade 3: A type of adverse event that 
interrupts usual activities of daily living, 
or significantly affects clinical status, or 
may require intensive therapeutic 
intervention. 
Grade 3: A type of adverse event that 
interrupts usual activities of daily living, 
or significantly affects clinical status, or 
may require intensive therapeutic 
intervention. 
Grade 3: A type of adverse event that 
interrupts usual activities of daily living, 
or significantly affects clinical status, or 
may require intensive therapeutic 
intervention. 
a For all reactions but fever, subjects or subjects’ parents / legally acceptable representatives will record the intensity level (Grade 1, 2, or 3) in the diary card. For fever, they will record the body temperature, and the 
classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis based on the unit used to measure the temperature and the intensity scale. 

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Important notes for the accurate assessment of temperature: 
Subjects or subjects’ parents / legally acceptable representatives are to measure subjects’ body 
temperature once per day, preferably always at the same time. The optimal time for measurement 
is the evening, when body temperature is the highest. Temperature is also to be measured at the 
time of any apparent fever. The observed daily temperature and the route of measurement are to 
be recorded in the diary card, and the highest temperature will be recorded by the site in the CRB. 
The preferred route for this study is axillary. Pre-vaccination temperature is also systematically 
collected by the Investigator on the source document. Tympanic thermometers must not be used. 
9.2.2.3.3 Unsolicited Adverse Events  
In addition to recording solicited reactions, subjects or subjects’ parents / legally acceptable 
representatives will be instructed to record any other medical events that may occur during the 
30-day (+14-day) period after vaccination. Space will be provided in the diary card for this 
purpose. Information on SAEs will be collected and assessed throughout the study, from inclusion 
until 30 days (+14 days) after vaccination. Any SAE occurring at any time during the study will 
be reported by the Investigator in the CRB according to the completion instructions provided by 
the Sponsor; this includes checking the “Serious” box on the AE CRF and completing the 
appropriate Safety Complementary Information CRFs. All information concerning the SAE is to 
be reported either as part of the initial reporting or during follow-up reporting if relevant 
information became available later (e.g., outcome, medical history, results of investigations, copy 
of hospitalization reports). In case a subject experiences febrile convulsion (neurological event 
associating fever and seizure), the assessment will be performed according to the “Guideline for 
definition and collection of cases of febrile convulsion”, and this event will be considered an 
SAE. See Section 10 for further details on SAE reporting. 
For each unsolicited AE (whether serious or non-serious), the following information is to be 
recorded: 
 Start and stop dates5 
 Intensity of the event: 
For measurable unsolicited AEs that are part of the list of solicited reactions, the size of 
the AE as well as the temperature for fever will be collected and analyzed based on the 
corresponding scale used for solicited reactions (see Table 1, Table 2 and Table 3). 
All other unsolicited AEs will be classified according to the following intensity scale: 
- 
Grade 1: A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 
                                                 
5 The stop date of all related AEs will be actively solicited. For other events, the Investigator will provide 
the stop date when it becomes available. AEs for which no stop date was obtained during the course of 
the study will be considered as ongoing at the end of the study. 

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- 
Grade 2: A type of AE that is usually alleviated with additional therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
- 
Grade 3: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. 
 Whether the AE was related to the investigational product (for unsolicited systemic AEs) 
The Investigator will assess the causal relationship between the AE and the investigational 
product as either “Not related” or “Related”, as described in Section 9.2.2.3.4. 
 Action taken for each AE (e.g., medication) 
The action(s) taken by the subject or subject’s parent / legally acceptable representative to 
treat and/or manage any unsolicited AEs will be classified in the CRB using the following 
list (all applicable items should be checked): 
- 
None 
- 
Medication 
- 
Health care provider contact 
- 
Hospitalized 
 Whether the AE was serious 
For each SAE, the Investigator will complete all seriousness criteria that apply (outcome, 
elapsed time, and relationship to study procedures). 
 Whether the AE caused study discontinuation 
9.2.2.3.4 Assessment of Causality  
The Investigator will assess the causal relationship between each unsolicited systemic AE and the 
product administered as either not related or related, based on the following definitions: 
Not related – The AE is clearly / most probably caused by other etiologies such as an 
underlying condition, therapeutic intervention, or concomitant therapy; or the delay 
between vaccination and the onset of the AE is incompatible with a causal relationship; or 
the AE started before the vaccination (screening phase, if applicable) 
Related – There is a “reasonable possibility” that the AE was caused by the product 
administered, meaning that there is evidence or arguments to suggest a causal relationship 
Note: By convention, all AEs reported at the injection site (whether solicited or unsolicited) and 
all solicited systemic AEs are considered to be related to the administered product and therefore 
are referred to as reactions and do not require the Investigator’s opinion on relatedness. 

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Adverse events likely to be related to the product, whether serious or not, that persist at the end of 
the study will be followed up by the Investigator until their complete disappearance or the 
stabilization of the subject’s condition. The Investigator will inform the Sponsor of the date of 
final disappearance of the event or the date of “chronicity” establishment. 
9.2.3 Efficacy  
No clinical efficacy data will be obtained in the study. 
9.3 
OBSERVATIONAL ENDPOINTS AND ASSESSMENT METHODS  
There are no observational objectives in this study. 

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10 
REPORTING OF SERIOUS ADVERSE EVENTS  
To comply with current regulations on SAE reporting to health authorities, the Investigator must 
document all SAEs regardless of causal relationship, and notify the Sponsor within the 
notification timelines stated in the following sections. The Investigator will give access and 
provide the Sponsor with all necessary information to allow the Sponsor to conduct a detailed 
analysis of the safety of the IP. It is the responsibility of the Investigator to request all necessary 
documentation (e.g., medical records, discharge summary) in order to provide comprehensive 
safety information. All relevant information must then be transcribed onto the AE CRF and the 
appropriate Safety Complementary Information CRFs.  
10.1 
REPORTING BY THE INVESTIGATOR  
In the case of a SAE, the Investigator must immediately: 
 ENTER (within 24 hours) all the information related to the SAE in the appropriate screens 
of the CRB; the system will automatically send the notification to the Sponsor after 
approval by the Investigator within the CRB or after a standard delay. 
 All further data updates should be recorded in the CRB as appropriate, and further 
documentation as well as additional information (for laboratory data, concomitant 
medication, subject status, etc.) should be sent (by fax or e-mail) to the monitoring team 
within 24 hours of knowledge. In addition, any effort should be made to further document 
within the week (7 days) following initial notification any SAE that is fatal or life 
threatening. 
 A back-up plan is used (using paper flow) when the CRB system does not work. 
Back-up plan 
 SEND (within 24 hours, preferably by fax or e-mail) the signed and dated corresponding 
page(s) in the CRB to the representative of the monitoring team whose name, fax number, 
and e-mail address appear on the clinical study protocol. 
 All further documentation should be sent to the monitoring team within 24 hours of 
knowledge. In addition, every effort should be made to further document within the week 
(7 days) following initial notification any SAE that is fatal or life threatening.  
There may be instances when photocopies of medical records for certain cases are requested by 
the Sponsor. In this case, the Investigator should ensure that the subject's identity is protected and 
the subject's identifiers in the clinical study are properly mentioned on any photocopy of source 
document provided to the Sponsor. 
Any SAE brought to the attention of the Investigator at any time after the end of the study for the 
subject and considered by the Investigator to be caused by the IP with a reasonable possibility, 
should be reported to the monitoring team. 

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10.2 
REPORTING OF SAES OCCURRING AFTER A SUBJECT HAS COMPLETED THE 
STUDY  
Any SAE that occurs after a subject has completed the study but that is likely to be related to the 
IP, other products (e.g., a benefit vaccine), or to the experiment must also be reported as soon as 
possible. In such a case, the reporting procedure to be followed is identical to that described in 
Section 10.1. 
10.3 
ASSESSMENT OF CAUSALITY  
The causal relationship between the SAE and the product administered will be evaluated by the 
Investigator as described in Section 9.2.2.3.4. 
Following this, the Global Safety Officer of Sanofi Pasteur will also assess the causal relationship 
to the product, based on the available information and current medical knowledge. 
The causal relationship to study procedures will be also assessed in the CRB. 
The decision to modify or discontinue the study may be made after mutual agreement between the 
Sponsor and the Investigator(s). 
10.4 
REPORTING SAES TO HEALTH AUTHORITIES AND IRBS/IECS  
The Sponsor will inform the relevant health authorities of any reportable SAEs according to the 
local regulatory requirements. Reporting to the health authorities will be according to the 
Sponsor’s standard operating procedures. 
The Sponsor will notify the Investigators in writing of the occurrence of any reportable SAEs. The 
Sponsor will be responsible for informing the IRBs or IECs that reviewed the study protocol.  

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11 
DATA COLLECTION AND MANAGEMENT  
11.1 
DATA COLLECTION AND CRB COMPLETION  
Individual diary cards, specifically designed for this study by the Sponsor and provided to the 
study sites, will be given to study participants for the recording of daily safety information as 
described in Section 9.2.2.3. These diary cards will include prelisted terms and intensity scales 
(see Table 1, Table 2 and Table 3) as well as areas for free text to capture additional safety 
information or other relevant details. Subjects or subjects’ parents / legally acceptable 
representatives will also be provided with rulers for measuring the size of injection site reactions, 
and with standard digital thermometers for measuring daily temperatures. To ensure consistency 
of reporting, the study sites will instruct subjects or subjects’ parents / legally acceptable 
representatives on how to correctly use these tools. 
At specified intervals, the Investigator or an authorized designee will interview the subjects or 
subjects’ parents / legally acceptable representatives to collect the information recorded in the 
diary card, and will attempt to clarify anything that is incomplete or unclear. All clinical study 
information gathered by the study site will be reported electronically by the Investigator or 
authorized designee using a web-based CRB. (Any information that was not documented in the 
diary card will first be captured in the source document and then reported electronically. The CRB 
has been designed specifically for this study under the responsibility of the Sponsor, using a 
validated Electronic Records / Electronic Signature-compliant platform (21 CFR Part 11). 
To ensure the correct and consistent completion of the CRBs, the Sponsor or authorized 
representative will provide all necessary tools, instructions, and training to all study site staff 
involved in data entry prior to study start. Additional instructional documents such as training 
manuals and completion instructions will be provided to assist with data entry during the course 
of the study. 
Upon completion of training, each user requiring access to the EDC system will be issued a 
unique username and password. In the event of a change in study personnel, each newly assigned 
individual will receive a unique username and password; the username and password of a 
previous user may not be reissued. If any study personnel leaves the study, the Investigator is 
responsible for informing the Sponsor immediately so that their access is deactivated. An audit 
trail will be initiated in the EDC system at the time of the first data entry to track all modifications 
and ensure database integrity. 
The Investigator is responsible for the timeliness, completeness, and accuracy of the information 
in the CRBs; must provide explanations for all missing information; and must sign the CRB using 
an e-signature. 

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11.2 
DATA MANAGEMENT  
Management of SAE and Pregnancy Data 
During the study, SAE data (reported on the AE, Death, and Safety Complementary Information 
CRFs) and pregnancy data (reported by the Investigator on ePregnancy Forms) will be integrated 
into the Sponsor’s centralized GPV database upon receipt of these forms and after a duplicate 
check. Each case will be assigned a case identification number. Each case will be assessed by the 
case management platform or its delegate before being reported to the relevant authorities as 
necessary. The assessment of related cases will be done in collaboration with the Global Safety 
Officer of Sanofi Pasteur, and SMM of Sanofi Pasteur and Sanofi.K.K. Follow-up information 
concerning a completed case will be entered into the GPV database, and a new version of the case 
will be created. 
The information from the GPV database cases will be reconciled with that in the clinical database. 
Management of Clinical and Laboratory Data 
Clinical data, defined as all data reported in the CRB, and laboratory data will be handled by the 
Sponsor’s Clinical Data Management (CDM) platform or authorized representative. 
During the study, clinical data reported in the CRBs will be integrated into the clinical database 
under the responsibility of the Sponsor CDM platform. Data monitoring at the sites and quality 
control in the form of computerized logic and/or consistency checks will be systematically applied 
to detect errors or omissions. In addition, data reviews may be performed several times by the 
Sponsor’s staff in the course of the study. Any questions pertaining to the reported clinical data 
will be submitted to the Investigator for resolution using the EDC system. Each step of this 
process will be monitored through the implementation of individual passwords to maintain 
appropriate database access and to ensure database integrity. 
The validation of the immunogenicity data will be performed at the laboratory level following the 
laboratory’s procedures. Information from the laboratory will be checked for consistency before 
integration into the clinical Datawarehouse. 
After integration of all corrections in the complete set of data, and after the SAE information 
available from CDM and the GPV Department has been reconciled, the database will be released 
for statistical analysis.  
11.3 
DATA REVIEW  
A blind review of the data is anticipated through the data review process led by CDM before 
database lock.  
The safety of the investigational product will be continuously monitored by the Sponsor. 

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12 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE  
12.1 
STATISTICAL METHODS  
Clinical data will be analyzed under the responsibility of the Biostatistics Platform of the Sponsor. 
A statistical analysis plan (SAP) will be written and peer reviewed before any analyses. In 
accordance with the protocol, the SAP will describe all analyses to be performed under the 
responsibility of the Sponsor and all the conventions to be taken. 
12.1.1 Hypotheses and Statistical Methods for Primary Objective  
12.1.1.1 Primary Objective  
Non-inferiority of MenACYW conjugate vaccine compared to Menactra® in terms of hSBA 
vaccine seroresponse. 
Thirty days after the administration of MenACYW conjugate vaccine or Menactra® vaccine, the 
percentage of subjects who achieve an hSBA vaccine seroresponse* for meningococcal 
serogroups A, C, Y, and W in Group 1 are non-inferior to the corresponding percentages in 
Group 2. 
Null hypothesis (H0): p(G1) - p(G2) ≤−10% 
Alternative hypothesis (H1): p(G1) - p(G2) >−10% 
where p(G1) and p(G2) are the percentages of subjects who achieve an hSBA vaccine seroresponse 
in Group 1 and Group 2, respectively. Each of the serogroups A, C, Y, and W will be tested 
separately. If the lower limit of the 2-sided 95% CI of the difference between the 2 proportions 
is >−10%, the inferiority assumption will be rejected. 
*Vaccine seroresponse for serogroups A, C, Y, and W is defined as post-vaccination hSBA titers 
≥1:16 for subjects with pre-vaccination hSBA titers <1:8 or at least a 4-fold increase in hSBA 
titers from pre- to post-vaccination for subjects with pre-vaccination hSBA titers ≥1:8. 
For the 4 non-inferiority hypothesis using the seroresponse rates, the CI of the difference in 
proportions will be computed using the Wilson Score method without continuity correction (35). 
The overall non-inferiority of this objective will be demonstrated if all 4 individual null 
hypotheses are rejected. 

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12.1.2 Hypotheses and Statistical Methods for Secondary Objective  
12.1.2.1 Secondary Objective  
Immunogenicity 
Descriptive statistics will be provided for the antibody titers against meningococcal serogroups 
contained in each lot of MenACYW conjugate vaccine and Menactra®.  
In general, categorical variables will be summarized and presented by frequency counts, 
percentages, and CIs. The 95% CIs of point estimates will be calculated using the normal 
approximation for quantitative data and the exact binomial distribution (Clopper-Pearson method) 
for percentages (36). For GMTs, 95% CIs of point estimates will be calculated using normal 
approximation assuming they are log-normally distributed. RCDC figures will be provided for the 
antibody titers against meningococcal serogroups. 
In summary, descriptive analyses on A, C, Y, and W serogroups will include but not be limited to: 
 hSBA vaccine seroresponse rate and 95% CI 
 Proportion of subjects with hSBA titer ≥1:4 and ≥1:8 and 95% CI 
 hSBA GMT and 95% CI 
 hSBA titer distribution and RCDCs 
 Proportion of subjects with hSBA titer ≥4-fold rise from baseline (Visit 1, D0, before 
vaccination) to after vaccination (Visit 2, D30 [+14 days]) and 95% CI 
Safety 
Safety results will be described for subjects in both study groups. The main parameters for the 
safety endpoints will be described by 95% CIs (based on the Clopper-Pearson method).  
The frequency and percentage of subjects who had solicited injection site and systemic reactions 
and their 95% CIs will be provided. These events will be tabulated by type of reactions and 
intensity for each study group, as well as by other categories specified in the endpoints.  
Unsolicited AEs will be collected, coded, and summarized by MedDRA system organ class and 
preferred term. For each unsolicited AE, the number of subjects with at least one instance of that 
event will be reported. Unsolicited AEs will also be tabulated by other categories specified in the 
endpoints. 
12.2 
ANALYSIS SETS  
Three analysis sets will be used: the Full Analysis Set (FAS), the PPAS, and the Safety Analysis 
Set (SafAS). 

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12.2.1 Full Analysis Set  
The FAS is defined as the subset of subjects who received at least one dose of the study vaccine 
and had a valid post-vaccination blood sample result. All subjects will be analyzed according to 
the vaccine group to which they were randomized. 
12.2.2 Safety Analysis Set  
The SafAS is defined as those subjects who have received at least one dose of the study vaccine 
and have any safety data available. All subjects will have their safety analyzed according to the 
vaccine they actually received. 
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.3 Per-Protocol Analysis Set  
The PPAS is a subset of the FAS. The subjects presenting with at least one of the following 
relevant protocol deviations will be excluded from the PPAS: 
 Subject did not meet all protocol-specified inclusion criteria or met at least one of the 
protocol-specified exclusion criteria 
 Subject did not receive vaccine 
 Subject received a vaccine other than the one that he/she was randomized to receive 
 Preparation and/or administration of vaccine was not done as per-protocol 
 Subject did not receive vaccine in the proper time window 
 Subject did not provide post-dose serology sample in the proper time window or a 
post-dose serology sample was not drawn. 
 Subject received a protocol-prohibited Category 2 or Category 3 
therapy/medication/vaccine 
 Subject’s serology sample did not produce a valid test result 
 Subject had other protocol violations that affected the subject’s immune response, as 
determined by the clinical team before locking the database. 
12.2.4 Populations Used in Analyses  
The primary immunogenicity analyses will be performed on the PPAS, and will be confirmed on 
the FAS. In the FAS, subjects will be analyzed by the vaccine group to which they were 
randomized. 
All safety analyses will be performed on the SafAS. Subjects will be analyzed according to the 
vaccine they actually received. 

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12.3 
HANDLING OF MISSING DATA AND OUTLIERS  
12.3.1 Safety  
No replacement will be done.  However, missing relationship will be considered as related at the 
time of statistical analysis. Details will be described in the SAP. 
12.3.2 Immunogenicity  
Missing data will not be imputed. No test or search for outliers will be performed. 
In order to appropriately manage extreme values (undetectable responses <LLOQ and ≥upper 
limit of quantitation [ULOQ]), the following computational rule is applied to the values provided 
in the clinical database for each blood sample drawn for analysis purposes: 
 If a value is <LLOQ, then use the computed value LLOQ/2 
 If a value is between ≥LLOQ and <ULOQ, then use the value 
 If a value is ≥ULOQ, then use the computed value ULOQ 
The derived endpoint of fold-rise is computed as follows for extreme values, to minimize the 
numerator and maximizes the denominator: 
 If the baseline computed value is <LLOQ and the post-baseline computed value is <LLOQ 
then the fold-rise is 1 fold for the baseline 
 If the baseline computed value is ≥LLOQ and the post-baseline computed value is ≥LLOQ 
then the fold-rise is post-baseline computed value / baseline computed value 
 If the baseline computed value is ≥LLOQ and the post-baseline computed value is <LLOQ 
then the fold-rise is (LLOQ/2) / baseline computed value 
 If the baseline computed value is <LLOQ and the post-baseline computed value is ≥LLOQ 
then the fold-rise is post-baseline computed value / LLOQ 
12.3.3 Efficacy  
Not applicable. 
12.4 
INTERIM/PRELIMINARY ANALYSIS  
No interim/preliminary analyses are planned. 

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12.5 
DETERMINATION OF SAMPLE SIZE AND POWER CALCULATION  
Approximately 360 healthy children, adolescents and adults (180 subjects per group) will be 
randomly assigned in a 1:1 ratio to the following vaccine groups: 
 Group 1 (investigational): MenACYW conjugate vaccine (180 subjects) 
 Group 2 (control): Menactra® (180 subjects) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
Table 4 - Power of the study based on the primary objective of non-inferiority with 
 
evaluable subjects per group  
Serogroup 
Estimateda MenACYW 
conjugate vaccine 
Estimatedb 
Menactra® 
Non-inferiority 
margin 
Power 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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13 
ETHICAL AND LEGAL ISSUES AND INVESTIGATOR/SPONSOR 
RESPONSIBILITIES  
13.1 
ETHICAL CONDUCT OF THE STUDY / GOOD CLINICAL PRACTICE  
The conduct of this study will be consistent with the standards established by the Declaration of 
Helsinki and compliant with the ICH guidelines for GCP as well as with all local and/or national 
regulations and directives. 
13.2 
SOURCE DATA AND SOURCE DOCUMENTS  
“Source data” are the data contained in source documents. Source documents are original 
documents or certified copies, and include, but are not limited to, diary cards, medical and 
hospital records, screening/enrollment logs, informed consent / assent forms, telephone contact 
logs, and worksheets. The purpose of study source documents is to document the existence of 
subjects and to substantiate the integrity of the study data collected. Investigators must maintain 
source documents so that they are accurate, complete, legible, and up to date. 
For missing or discrepant data on a diary card, the Investigator or study coordinator will obtain 
verbal clarification from the subject or subject’s parent / legally acceptable representative, enter 
the response into the “Investigator’s comment” page of the diary card or source document, and 
transfer the information to the CRB. 
The Investigator must print6 any electronic records on an ongoing basis, sign and date them 
immediately after creation, and keep the printouts on file as source documents that can be verified 
by the Sponsor or an inspector against the electronic records. Any subsequent changes of an 
electronic record require the record to be re-printed, dated (with an indication of the date of 
change), and signed. Such records must also be kept together with the original printed copy. 
Good Documentation Practice should be followed by the Investigator and the study site staff 
managing source documents. 
13.3 
CONFIDENTIALITY OF DATA, DATA PROTECTION, AND ACCESS TO SUBJECT 
RECORDS  
Prior to initiation of the study, the Investigator will sign a fully executed confidentiality 
agreement with the Sponsor. In the event a subject’s medical records are not at the investigational 
site, it is the responsibility of the Investigator to obtain those records if needed. 
                                                 
6 Unless the electronic medical records are determined to be appropriate at site selection, in which case 
they are acceptable on their own. 

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All personal data collected related to subjects, Investigators, or any person involved in the study, 
which may be included in the Sponsor’s databases, shall be treated in compliance with all 
applicable laws and regulations including the GDPR (Global Data Protection Regulation). Data 
collected must be adequate, relevant and not excessive, in relation to the purposes for which they 
are collected. Each category of data must be properly justified and in line with the study objective. 
The race and ethnicity of each subject will be collected in this study because these data are 
required for submissions for licensure in countries which require an analysis of results by race and 
ethnicity.  
Subjects will be assigned a unique identifier by the Sponsor. Any subject records or datasets that 
are transferred to the Sponsor will contain the identifier only; subject names or any information 
that would make the subject identifiable will not be transferred. 
The subject or subject’s parent / legally acceptable representative must be informed that subject’s 
personal study-related data will be used by the Sponsor in accordance with local data protection 
law. The level of disclosure must also be explained to the subject or subject’s parent / legally 
acceptable representative. 
The subject or subject’s parent / legally acceptable representative must be informed that subject’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. 
When archiving or processing personal data pertaining to the Investigator and/or to the subjects, 
the Sponsor shall take all appropriate measures to safeguard and prevent access to this data by any 
unauthorized third party. 
13.4 
MONITORING, AUDITING, AND ARCHIVING  
13.4.1 Monitoring  
Before the start of the study (i.e., before the inclusion of the first subject in the first center), the 
Investigators and the Sponsor’s staff or a representative will meet at the site-initiation visit to 
discuss the study protocol and the detailed study procedures. Emphasis will be placed on inclusion 
and exclusion criteria, visit timing, safety procedures, informed consent procedures, SAE 
reporting procedures, CRB completion, and the handling of samples and products. The Sponsor’s 
monitoring staff or a representative will ensure and document that all material to be used during 
the study has been received at the site; and that the study investigator team and local Sponsor / 
delegate staff have been properly informed about the study, GCP and regulatory requirements, 
and the Sponsor’s procedures. Specific training sessions for the study investigator team and the 
Sponsor’s monitoring staff on these topics may be performed as necessary, and should be 
documented. 

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The following instruction manuals will be provided: the CRF Completion Instructions for entering 
data into the CRB, and the guidelines for detailed study procedures such as the product 
management, sample-handling procedures and IRT operation manuals. 
After the start of the study, the Sponsor’s staff or a representative will be in regular contact with 
the investigational team through telephone calls and regular follow-up visits. The Investigator or 
delegate must be available for these visits, and must allow the Sponsor / delegate staff direct 
access to subject medical files and CRBs. During these visits, the Sponsor / delegate staff will: 
 Evaluate the quality of the study progress (adherence to protocol and any study-specific 
guidelines, quality of data collection and document completion, signature of consent forms, 
occurrence of SAEs, sample and product management, cold-chain monitoring, archiving). 
 Source-verify completed CRBs and any corresponding answered queries. 
 Determine the number of complete or ongoing issues identified at monitoring visits (e.g., 
protocol deviations, SAEs). Any identified problems will be discussed with the 
Investigator, and corrective or preventive actions will be determined, as appropriate. 
 After all protocol procedures have been completed and the data have been entered into the 
CRB, the Investigator must still be available to answer any queries forwarded by the 
Sponsor. All data-related queries must be completed prior to database lock. 
At the end of the study, a close-out visit will be performed to ensure that: 
 The center has all the documents necessary for archiving 
 All samples have been shipped to the appropriate laboratories 
 All unused materials and products have been either destroyed or returned to the Sponsor 
13.4.2 Audits and Inspections  
For the purpose of ensuring compliance with the clinical study protocol, GCP and applicable 
regulatory requirements, the Investigator should permit auditing by or on behalf of the Sponsor 
and inspection by regulatory authorities. 
The Investigator agrees to allow the auditors/inspectors to have direct access to his/her study 
records for review, being understood that these personnel is bound by professional secrecy, and as 
such will not disclose any personal identity or personal medical information. 
The Investigator will make every effort to help with the performance of the audits and inspections, 
giving access to all necessary facilities, data, and documents. 
As soon as the Investigator is notified of a planned inspection by the authorities, he/she will 
inform the Sponsor and authorize the Sponsor to participate in this inspection. 
The confidentiality of the data verified, and the protection of the subjects should be respected 
during these inspections. 

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Any result and information arising from the inspections by the regulatory authorities will be 
immediately communicated by the Investigator to the Sponsor. 
The Investigator shall take appropriate measures required by the Sponsor to take corrective 
actions for all problems found during the audit or inspections. 
13.4.3 Archiving  
The Investigator must maintain confidential all study documentation, and take measures to 
prevent accidental or premature destruction of these documents. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for at least 25 years after the end of the clinical study unless local 
regulations or institutional policies require a longer retention period.  
The Investigator must notify the Sponsor prior to destroying any study essential documents 
following the clinical study completion or discontinuation. 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.  
If the Investigator's personal situation is such that archiving can no longer be ensured by him/her, 
the Investigator shall inform the Sponsor and the relevant records shall be transferred to a 
mutually agreed upon designee. 
13.4.4 Responsibilities of Investigator(s)  
The Investigator is required to ensure compliance with all procedures required by the clinical 
study protocol and with all study procedures provided by the Sponsor (including security rules). 
The Investigator agrees to provide reliable data and all information requested by the clinical study 
protocol (with the help of the CRF, discrepancy resolution form, or other appropriate instrument) 
in an accurate and legible manner according to the instructions provided and to ensure direct 
access to source documents to the Sponsor representatives. 
If any circuit includes transfer of data, particular attention should be paid to the confidentiality of 
the subject’s data to be transferred. 
The Investigator may appoint such other individuals as he/she may deem appropriate as 
Sub-investigators to assist in the conduct of the clinical study in accordance with the clinical study 
protocol. All Sub-investigators shall be appointed and listed in a timely manner. The 
Sub-investigators will be supervised by and work under the responsibility of the Investigator. The 
Investigator will provide them with a copy of the clinical study protocol and all necessary 
information. 

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13.4.5 Responsibilities of the Sponsor  
The Sponsor of this clinical study is responsible to regulatory authorities for taking all reasonable 
steps to ensure the proper conduct of the clinical study as regards ethics, clinical study protocol 
compliance, and integrity and validity of the data recorded on the CRFs. Thus, the main duty of 
the monitoring team is to help the Investigator and the Sponsor maintain a high level of ethical, 
scientific, technical and regulatory quality in all aspects of the clinical study. 
At regular intervals during the clinical study, the site will be contacted, through monitoring visits, 
letters or telephone calls, by a representative of the monitoring team to review study progress, 
Investigator and subject compliance with clinical study protocol requirements, and any emergent 
problems. These monitoring visits will include but not be limited to review of the following 
aspects: subject and/or subject’s parent / legally acceptable representative informed consent (and 
assent), subject recruitment and follow-up, SAE documentation and reporting, AE documentation, 
IP allocation, IP accountability, concomitant therapy use, and quality of data. 
13.5 
CONFIDENTIALITY  
All information disclosed or provided by the Sponsor (or any company/institution acting on their 
behalf), or produced during the clinical study, including, but not limited to, the clinical study 
protocol, personal data in relation to the subjects, the CRFs, the IB, and the results obtained 
during the course of the clinical study, is confidential, prior to the publication of results. The 
Investigator and any person under his/her authority agree to undertake to keep confidential and 
not to disclose the information to any third party without the prior written approval of the 
Sponsor. 
However, the submission of this clinical study protocol and other necessary documentation to the 
IRB/IEC is expressly permitted, the IRB/IEC members having the same obligation of 
confidentiality. 
The Sub-investigators shall be bound by the same obligation as the Investigator. The Investigator 
shall inform the Sub-investigators of the confidential nature of the clinical study. 
The Investigator and the Sub-investigators shall use the information solely for the purposes of the 
clinical study, to the exclusion of any use for their own or for a third party’s account. 
13.6 
PROPERTY RIGHTS  
All information, documents and IP provided by the Sponsor or its designee are and remain the 
sole property of the Sponsor. 
The Investigator shall not and shall cause the delegated study site staff / Sub-investigator not to 
mention any information or the Product in any application for a patent or for any other intellectual 
property rights. 

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All the results, data, documents and inventions, which arise directly or indirectly from the clinical 
study in any form, shall be the immediate and exclusive property of the Sponsor. 
The Sponsor may use or exploit all the results at its own discretion, without any limitation to its 
property right (territory, field, continuance). The Sponsor shall be under no obligation to patent, 
develop, market or otherwise use the results of the clinical study. 
As the case may be, the Investigator and/or the Sub-investigators shall provide all assistance 
required by the Sponsor, at the Sponsor’s expense, for obtaining and defending any patent, 
including signature of legal documents. 
13.7 
INSURANCE COMPENSATION  
The Sponsor certifies that it has taken out a liability insurance policy covering all clinical studies 
under its sponsorship. This insurance policy is in accordance with local laws and requirements. 
The insurance of the Sponsor does not relieve the Investigator and the collaborators from any 
obligation to maintain their own liability insurance policy. An insurance certificate will be 
provided to the IRB/IEC or regulatory authorities in countries requiring this document. 
13.8 
STIPENDS FOR PARTICIPATION  
Subjects may be provided with a stipend according to local practice to compensate for the time 
and travel required for study visits and procedures. 
13.9 
PUBLICATION POLICY  
Data derived from this study are the exclusive property of the Sponsor and Sanofi Pasteur. Any 
publication or presentation related to the study must be submitted to the Sponsor and Sanofi 
Pasteur for review before submission of the manuscript. After publication of the results of the 
study, any participating center may publish or otherwise use its own data provided that any 
publication of data from the study gives recognition to the study group. In addition, the Sponsor 
and Sanofi Pasteur shall be offered an association with all such publications, it being understood 
that the Sponsor and Sanofi Pasteur is entitled to refuse the association. 
The Sponsor and Sanofi Pasteur must have the opportunity to review all proposed abstracts, 
manuscripts, or presentations regarding this study at least 90 days prior to submission for 
publication/presentation. Any information identified by the Sponsor and Sanofi Pasteur as 
confidential must be deleted prior to submission, it being understood that the results of this study 
are not to be considered confidential. 
The Sponsor’s and Sanofi Pasteur’s reviews can be expedited to meet publication guidelines. 

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14 
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