Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in Europe
Phase: PHASE3
Conditions: Meningococcal Infections
Sponsor: Sanofi Pasteur, a Sanofi Company

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Immunogenicity and Safety Study of an Investigational 
Quadrivalent Meningococcal Conjugate Vaccine when 
Administered Concomitantly with Routine Pediatric Vaccines in 
Healthy Infants and Toddlers in Europe 
Phase III, partially modified double-blind, randomized, parallel-group, active-controlled, multi-
center study to compare the immunogenicity and describe the safety of MenACYW conjugate 
vaccine and Nimenrix® when administered as a 3-dose series concomitantly with routine 
pediatric vaccines to healthy infants and toddlers in Europe 
Clinical Study Protocol, Amendment 5 
Health Authority File Number: 
EudraCT #: 
2017-004731-36 
WHO Universal Trial Number 
(UTN): 
U1111-1183-6653 
Study Code: 
MET58 
Development Phase: 
Phase III 
Sponsor: 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, USA 
Investigational Product: 
MenACYW conjugate vaccine: Meningococcal Polysaccharide (Serogroups 
A, C, W, and Y) Tetanus Toxoid Conjugate Vaccine 
Form / Route: 
Liquid solution / Intramuscular (IM) 
Indication For This Study: 
MenACYW conjugate vaccine administered to healthy infants and toddlers 
Manufacturer: 
Same as Sponsor 
Coordinating Investigator  
This is a multi-center trial with multiple investigators. Investigators and 
study sites are listed in the “List of Investigators and Centers Involved in 
the Trial” document.  
Sponsor’s Responsible Medical 
Officer: 
NCT number: NCT03547271

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Pharmacovigilance Global Safety 
Officer: 
 
 
Clinical Trial Managers: 
 
 
 
 
Version and Date of the Protocol: 
Version 7.0 dated 03 February 2022 
 
Information contained in this publication is the property of Sanofi Pasteur and is confidential. This information may not be 
disclosed to third parties without written authorization from Sanofi Pasteur. This document may not be reproduced, stored in a 
retrieval system, or transmitted in any form or by any means–electronic, mechanical recording, or otherwise–without prior 
authorization from Sanofi Pasteur. This document must be returned to Sanofi Pasteur upon request. 

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History of Protocol Versions  
Previous versions of the protocol 
Version 
Date 
Comments 
1.0 
29 March 2018 
Protocol updated in response to comments provided by the 
Health Authorities  
2.0 
09 July 2018 
Original version of the protocol approved by Health 
Authorities and Ethics Committees 
3.0 
25 June 2019 
Protocol Amendment 1 – Version approved by Health 
Authorities and Ethics Committees 
4.0 
22 January 2020 
Protocol Amendment 2 - Version approved by Health 
Authorities and Ethics Committees 
5.0 
14 April 2020 
Protocol Amendment 3 - Version approved by Health 
Authorities and Ethics Committees 
6.0 
18 June 2021 
Protocol Amendment 4 - Version approved by Health 
Authorities and Ethics Committees 
*Version in bold font have been approved by the Independent Ethics Committee(s) (IEC[s]) / Institutional Review 
Board(s) (IRB[s]) and used in the study. 

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Table of Contents  
History of Protocol Versions ........................................................................................................... 3 
List of Tables .................................................................................................................................... 9 
Synopsis .......................................................................................................................................... 10 
Table of Study Procedures - Groups 1, 2, and 3 ......................................................................... 26 
Table of Study Procedures - Group 4 .......................................................................................... 29 
List of Abbreviations ..................................................................................................................... 33 
1 
Introduction ..................................................................................................................... 36 
1.1 
Background ..................................................................................................................... 36 
1.2 
Background of the Investigational Product ..................................................................... 37 
1.2.1 
Clinical .......................................................................................................................... 37 
1.2.1.1 
Study MET39 (Phase II) ............................................................................................ 37 
1.2.1.2 
Study MET54 (Phase II) ............................................................................................ 39 
1.3 
Potential Benefits and Risks ........................................................................................... 40 
1.3.1 
Potential Benefits to Subjects ....................................................................................... 40 
1.3.2 
Potential Risks to Subjects ........................................................................................... 40 
1.4 
Rationale for the Study ................................................................................................... 41 
2 
Study Objectives .............................................................................................................. 42 
2.1 
Primary Objective ........................................................................................................... 42 
2.2 
Secondary Objectives ...................................................................................................... 42 
2.3 
Observational Objectives ................................................................................................ 43 
3 
Investigators and Study Organization ........................................................................... 43 
4 
Independent Ethics Committee / Institutional Review Board .................................... 44 
5 
Investigational Plan ......................................................................................................... 44 
5.1 
Description of the Overall Study Design and Plan ......................................................... 44 
5.1.1 
Study Design ................................................................................................................. 44 
5.1.2 
Justification of the Study Design .................................................................................. 45 
5.1.3 
Study Plan ..................................................................................................................... 47 
5.1.4 
Visit Procedures ............................................................................................................ 53 
5.1.5 
Planned Study Calendar ................................................................................................ 63 

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5.2 
Enrollment and Retention of Study Population .............................................................. 63 
5.2.1 
Recruitment Procedures ................................................................................................ 63 
5.2.2 
Informed Consent Procedures ...................................................................................... 63 
5.2.3 
Screening Criteria ......................................................................................................... 64 
5.2.4 
Inclusion Criteria .......................................................................................................... 64 
5.2.5 
Exclusion Criteria ......................................................................................................... 64 
5.2.6 
Medical History ............................................................................................................ 66 
5.2.7 
Contraindications for Subsequent Vaccinations ........................................................... 67 
5.2.7.1 
Temporary Contraindications ..................................................................................... 67 
5.2.7.2 
Definitive Contraindications ...................................................................................... 67 
5.2.7.3 
Warnings and Precautions to Vaccination ................................................................. 69 
5.2.8 
Contraindications for Subsequent Blood Draw ............................................................ 69 
5.2.9 
Conditions for Withdrawal ........................................................................................... 69 
5.2.10 
Lost to Follow-up Procedures ....................................................................................... 70 
5.2.11 
Classification of Subjects Who Discontinue the Study ................................................ 70 
5.2.12 
Follow-up of Discontinuations ..................................................................................... 70 
5.3 
Safety Emergency Call ................................................................................................... 71 
5.4 
Modification of the Study and Protocol .......................................................................... 71 
5.5 
Interruption of the Study ................................................................................................. 71 
6 
Vaccines Administered ................................................................................................... 72 
6.1 
Identity of the Investigational Product ............................................................................ 72 
6.1.1 
Identity of Study Product .............................................................................................. 72 
6.1.1.1 
Composition ............................................................................................................... 72 
6.1.1.2 
Preparation and Administration ................................................................................. 72 
6.1.1.3 
Dose Selection and Timing ........................................................................................ 73 
6.1.2 
Identity of Control Product ........................................................................................... 73 
6.1.2.1 
Composition ............................................................................................................... 73 
6.1.2.2 
Preparation and Administration ................................................................................. 73 
6.1.2.3 
Dose Selection and Timing ........................................................................................ 74 
6.2 
Identity of Other Products ............................................................................................... 74 
6.2.1 
Identity of Other Product 1 ........................................................................................... 74 
6.2.1.1 
Composition ............................................................................................................... 74 
6.2.1.2 
Preparation and Administration ................................................................................. 75 
6.2.1.3 
Dose Selection and Timing ........................................................................................ 75 
6.2.2 
Identity of Other Product 2 ........................................................................................... 75 
6.2.2.1 
Composition ............................................................................................................... 76 
6.2.2.2 
Preparation and Administration ................................................................................. 76 
6.2.2.3 
Dose Selection and Timing ........................................................................................ 76 
6.2.3 
Identity of Other Product 3 ........................................................................................... 76 
6.2.3.1 
Composition ............................................................................................................... 77 

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6.2.3.2 
Preparation and Administration ................................................................................. 77 
6.2.3.3 
Dose Selection and Timing ........................................................................................ 77 
6.2.4 
Identity of Other Product 4 ........................................................................................... 77 
6.2.4.1 
Composition ............................................................................................................... 78 
6.2.4.2 
Preparation and Administration ................................................................................. 78 
6.2.4.3 
Dose Selection and Timing ........................................................................................ 78 
6.3 
Product Logistics ............................................................................................................ 79 
6.3.1 
Labeling and Packaging ................................................................................................ 79 
6.3.2 
Product Shipment, Storage, and Accountability ........................................................... 79 
6.3.2.1 
Product Shipment ....................................................................................................... 79 
6.3.2.2 
Product Storage .......................................................................................................... 79 
6.3.2.3 
Product Accountability ............................................................................................... 80 
6.3.3 
Replacement Doses ....................................................................................................... 80 
6.3.4 
Disposal of Unused Products ........................................................................................ 80 
6.3.5 
Recall of Products ......................................................................................................... 80 
6.4 
Blinding and Code-breaking Procedures ........................................................................ 80 
6.5 
Randomization and Allocation Procedures ..................................................................... 81 
6.6 
Treatment Compliance .................................................................................................... 82 
6.7 
Concomitant Medications and Other Therapies.............................................................. 82 
7 
Management of Samples ................................................................................................. 85 
7.1 
Sample Collection ........................................................................................................... 85 
7.2 
Sample Preparation ......................................................................................................... 86 
7.3 
Sample Storage and Shipment ........................................................................................ 86 
7.4 
Future Use of Stored Serum Samples for Research ........................................................ 87 
8 
Clinical Supplies .............................................................................................................. 87 
9 
Endpoints and Assessment Methods ............................................................................. 87 
9.1 
Primary Endpoints and Assessment Methods ................................................................. 87 
9.1.1 
Safety ............................................................................................................................ 87 
9.1.2 
Immunogenicity ............................................................................................................ 88 
9.1.2.1 
Immunogenicity Endpoint .......................................................................................... 88 
9.1.2.2 
Immunogenicity Assessment Methods....................................................................... 88 
9.1.3 
Efficacy ......................................................................................................................... 88 
9.2 
Secondary Endpoints and Assessment Methods ............................................................. 88 
9.2.1 
Safety ............................................................................................................................ 88 
9.2.2 
Immunogenicity ............................................................................................................ 88 
9.2.2.1 
Immunogenicity Endpoints ........................................................................................ 88 
9.2.2.2 
Immunogenicity Assessment Methods....................................................................... 92 

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9.2.3 
Efficacy ......................................................................................................................... 98 
9.3 
Observational Endpoints and Assessment Methods ....................................................... 99 
9.3.1 
Immunogenicity ............................................................................................................ 99 
9.3.1.1 
Immunogenicity Endpoints ........................................................................................ 99 
9.3.1.2 
Immunogenicity Assessment Methods....................................................................... 99 
9.3.2 
Safety .......................................................................................................................... 100 
9.3.2.1 
Safety Definitions ..................................................................................................... 100 
9.3.2.2 
Safety Endpoints ...................................................................................................... 102 
9.3.2.3 
Safety Assessment Methods ..................................................................................... 103 
9.3.2.3.1 
Immediate Post-vaccination Observation Period ................................................... 103 
9.3.2.3.2 
Reactogenicity (Solicited Reactions from Day 0 to Day 7 after Each 
Vaccination) ........................................................................................................... 103 
9.3.2.3.3 
Unsolicited Adverse Events ................................................................................... 106 
9.3.2.3.4 
Adverse Events of Special Interest ........................................................................ 107 
9.3.2.3.5 
Assessment of Causality ........................................................................................ 108 
9.3.3 
Efficacy ....................................................................................................................... 108 
10 
Reporting of Serious Adverse Events .......................................................................... 108 
10.1 
Initial Reporting by the Investigator ............................................................................. 109 
10.2 
Follow-up Reporting by the Investigator ...................................................................... 109 
10.3 
Reporting of SAEs Occurring After a Subject Has Completed the Study .................... 110 
10.4 
Assessment of Causality ............................................................................................... 110 
10.5 
Reporting SAEs to Health Authorities and IECs / IRBs ............................................... 110 
11 
Data Collection and Management ............................................................................... 111 
11.1 
Data Collection and CRB Completion .......................................................................... 111 
11.2 
Data Management ......................................................................................................... 111 
11.3 
Data Review .................................................................................................................. 112 
12 
Statistical Methods and Determination of Sample Size ............................................. 112 
12.1 
Statistical Methods ........................................................................................................ 112 
12.1.1 
Hypotheses and Statistical Methods for Primary Objective ....................................... 113 
12.1.1.1 
Hypotheses ............................................................................................................... 113 
12.1.1.2 
Statistical Methods ................................................................................................... 113 
12.1.2 
Hypotheses and Statistical Methods for Secondary Objectives ................................. 113 
12.1.2.1 
Hypotheses for Secondary Objective 1 .................................................................... 113 
12.1.2.2 
Statistical Methods for Secondary Objective 1 ........................................................ 114 
12.1.2.3 
Hypotheses for Secondary Objectives 2, 3, 4, 5, 6 and 7 ......................................... 114 
12.1.2.4 
Statistical Methods for Secondary Objectives 2, 3, 4, 5, 6 and 7 ............................. 114 

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12.1.3 
Statistical Methods for Observational Objectives ...................................................... 114 
12.1.4 
Sensitivity analysis due to COVID-19 pandemic ....................................................... 115 
12.2 
Analysis Sets ................................................................................................................. 115 
12.2.1 
Full Analysis Set ......................................................................................................... 115 
12.2.2 
Safety Analysis Set ..................................................................................................... 115 
12.2.3 
Overall Safety Analysis Set for Any Dose ................................................................. 116 
12.2.4 
Safety Analysis Set for Vaccination at 2 Months of Age ........................................... 116 
12.2.5 
Safety Analysis Set for Vaccination at 4 Months of Age ........................................... 116 
12.2.6 
Safety Analysis Set for Vaccination at 6 Months of Age (Group 4) .......................... 116 
12.2.7 
Safety Analysis Set for Vaccination at 12 to 18 Months of Age ................................ 116 
12.2.8 
Per-Protocol Analysis Set ........................................................................................... 116 
12.2.8.1 
Per-Protocol Analysis Set for Primary Series (PPAS1) ........................................... 117 
12.2.8.2 
Per-Protocol Analysis Set for Booster Series (PPAS2) ........................................... 117 
12.2.9 
Populations Used in Analyses .................................................................................... 118 
12.3 
Handling of Missing Data and Outliers ........................................................................ 118 
12.3.1 
Safety .......................................................................................................................... 118 
12.3.2 
Immunogenicity .......................................................................................................... 118 
12.4 
Interim / Preliminary Analysis ...................................................................................... 119 
12.5 
Determination of Sample Size and Power Calculation ................................................. 119 
13 
Ethical and Legal Issues and Investigator / Sponsor Responsibilities ...................... 121 
13.1 
Ethical Conduct of the Study / Good Clinical Practice ................................................. 121 
13.2 
Source Data and Source Documents ............................................................................. 121 
13.3 
Confidentiality of Data, Data Protection and Access to Subject Records .................... 121 
13.4 
Monitoring, Auditing, and Archiving ........................................................................... 122 
13.4.1 
Monitoring .................................................................................................................. 122 
13.4.2 
Audits and Inspections ................................................................................................ 123 
13.4.3 
Archiving .................................................................................................................... 123 
13.5 
Financial Contract and Insurance Coverage ................................................................. 124 
13.6 
Stipends for Participation .............................................................................................. 124 
13.7 
Publication Policy ......................................................................................................... 124 
14 
Reference List ................................................................................................................ 125 
15 
Signature Page ............................................................................................................... 130 
 

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List of Tables  
Table 5.1: Vaccination and blood sampling schedule in Groups 1, 2, and 3 ................................. 49 
Table 5.2: Vaccination and blood sampling schedule in Group 4 .................................................. 50 
Table 5.3: Vaccinations and route of administration ...................................................................... 54 
Table 9.1: Blood sampling schedule and testing plan in Groups 1 and 2 ...................................... 93 
Table 9.2: Blood sampling schedule and testing plan in Group 3 .................................................. 94 
Table 9.3: Blood sampling schedule and testing plan in Group 4 .................................................. 95 
Table 9.4: Solicited injection site reactions: terminology, definitions, and intensity scales ........ 104 
Table 9.5: Solicited systemic reactions: terminology, definitions, and intensity scales .............. 105 
Table 12.1: Power of the study based on the primary objective .................................................. 119 
Table 12.2: Power of the study for the secondary objective ........................................................ 120 
 

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Synopsis  
Company: 
Sanofi Pasteur 
Investigational Product: 
MenACYW conjugate vaccine 
Active Substances: 
Capsular polysaccharide from meningococcal serogroups A, C, Y, and W conjugated 
to tetanus toxoid 
 
 
Title of the Study: 
Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal 
Conjugate Vaccine when Administered Concomitantly with Routine Pediatric 
Vaccines in Healthy Infants and Toddlers in Europe  
Development Phase: 
Phase III 
Coordinating Investigator: This is a multi-center trial with multiple investigators. 
Study Sites: 
This will be a multi-center, multinational study with approximately 50 sites in Europe.  
Investigators and sites are listed in the “List of Investigators and Centers Involved in 
the Trial” document. 
Planned Study Period: 
Q4 2018 to Q4 2023 
Study Design, Schedule of 
Study Procedures, and 
Methodology: 
A Phase III, partially modified double-blind (open-label for some of the vaccines / 
study groups), randomized, parallel-group, active-controlled, multi-center study to 
compare the immunogenicity and describe the safety of MenACYW conjugate vaccine 
and Nimenrix® (Meningococcal group A, C, W-135, and Y conjugate vaccine) when 
administered as a 3-dose series concomitantly with routine pediatric vaccines to 
healthy infants and toddlers in Europe. Licensed pediatric vaccines administered 
concomitantly with the study vaccines will be the following: 
• 
DTaP-IPV-HB-Hib (combined Diphtheria, Tetanus, acellular Pertussis, Hepatitis 
B, Inactivated Poliovirus and Haemophilus influenzae type b conjugate vaccine; 
hexavalent vaccine) 
• 
Prevenar 13® (pneumococcal 13-valent conjugate vaccine; PCV13) 
• 
Synflorix® (pneumococcal 10-valent conjugate vaccine; PCV10) 
• 
M-M-RVAXPRO® (measles, mumps, rubella vaccine; MMR vaccine) 
Vaccinations 
Approximately 1652 healthy infants aged 2 months* at enrollment will be randomized 
as follows depending on the pneumococcal vaccines that will be administered in the 
respective countries. 
* “2 months” refers to infants aged 6 to 12 weeks (≥ 42 to ≤ 89 days) at enrollment. 
Countries where the pneumococcal vaccination administered will be PCV10 
(Czech Republic, Romania, Sweden, Finland, and Poland): 1432 subjects will be 
randomized in a 1:1 ratio to one of the following 2 groups: 
• 
Group 1: MenACYW conjugate vaccine (2+1 regimen) + PCV10 + Hexavalent 
vaccine + MMR vaccine (n=716)  
• 
Group 2: Nimenrix® (2+1 regimen) + PCV10 + Hexavalent vaccine + MMR 
vaccine (n=716)  

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Countries where the pneumococcal vaccination administered will be PCV13 (Italy 
and Spain): 220 subjects will be randomized in a 1:1 ratio to one of the following 2 
groups: 
• 
Group 3: MenACYW conjugate vaccine (2+1 regimen) + PCV13 + Hexavalent 
vaccine + MMR vaccine (n=110)  
• 
Group 4: MenACYW conjugate vaccine (3+1 regimen) + PCV13 + Hexavalent 
vaccine + MMR vaccine (n=110)  
Subjects in Groups 1, 2, and 3 will receive either 3 doses of MenACYW conjugate 
vaccine or 3 doses of Nimenrix® administered concomitantly with routine vaccines at 
2 months of age (Visit 1), 4 months of age (Visit 2), and 12 to 18 months of age 
(Visit 4). The hexavalent vaccines and the pneumococcal vaccines (PCV10 or PCV13) 
will be administered in a 2+1 regimen (ie, 2 doses in infancy and 1 final dose in the 
second year of life).  
 
Subjects in Group 4 will receive 4 doses of MenACYW conjugate vaccine with 
routine pediatric vaccines at 2 months of age (Visit 1), 4 months of age (Visit 2), 
6 months of age (Visit 3; MenACYW conjugate vaccine only), and 12 to 18 months of 
age (Visit 5; MenACYW conjugate vaccine and routine vaccines). The hexavalent 
vaccine and PCV13 will be administered in a 2+1 regimen, concomitantly with the 1st 
and 2nd doses in infancy and the 4th dose of MenACYW conjugate vaccine. The 3rd 
dose of MenACYW conjugate vaccine will be administered alone, without any other 
routine pediatric vaccines. 
 
In all 4 vaccine groups, the MMR vaccine may be preferably administered 
concomitantly with the other vaccines at 12 to 18 months of age. If not, the subject 
will receive a licensed Measles, Mumps and Rubella vaccine with a gap of at least 4 
weeks before any study vaccines or after the end of the study (ie, after the subject will 
have completed the last study procedure at the last study visit). When administered 
outside the study visit, the licensed Measles, Mumps and Rubella vaccine will be 
sourced by the health care system, according to the national immunization program. 
Subjects in Finland, Sweden or Poland may receive the licensed rotavirus vaccine 
concomitantly with study vaccines at study vaccination visits Visit 1 and Visit 2. If 
not, the rotavirus vaccine can be administered with a time interval of at least 2 weeks 
before or 2 weeks after Visit 1 and/or Visit 2. The rotavirus vaccines will be sourced 
by the study sites and administered as per local standard practices. Safety data will be 
collected after its administration when done concomitantly with the study vaccine. No 
immunogenicity data will be evaluated after its administration. 
Subjects in Spain, Czech Republic, and Poland will be offered 2 doses of the 
Meningococcal B vaccine (Bexsero®) when parents are willing to vaccinate their child 
within the second year of life. This vaccine is a non-study vaccine to be administered 
as per local standard practices at additional optional visits after the end of the trial (ie, 
after the subject will have completed the last study procedure at the last study visit). 
This vaccine will be outside the scope of the study evaluations. No immunogenicity 
and safety data will be collected after its administration. The Meningococcal B 
vaccine (Bexsero®) will be reimbursed by the Sponsor. 

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Note: To perform an appropriate description of the safety of MenACYW conjugate 
vaccine and Nimenrix® in Groups 1 and 2, MenACYW conjugate vaccine and 
Nimenrix® will be administered in a modified double-blind manner in these 2 groups. 
The MenACYW conjugate vaccine in Groups 3 and 4 and all other concomitant 
vaccines in all vaccine groups will be administered in an open-label manner. 
Given that the meningococcal vaccines in Groups 3 and 4 have different vaccination 
schedules in the number of vaccines administered and timing of their administration, 
these vaccines will be administered in an open-label manner. 
Other concomitant vaccines in all groups will be administered in an open-label manner 
to ensure the subjects received appropriate vaccines as per local standard of care. 
 
Blood sampling 
All subjects will provide 4 blood samples. 
Subjects in Groups 1, 2, and 3 will provide blood samples for immunogenicity 
assessment as follows: 
• 
at baseline (pre-primary vaccination 1, Day 0) 
• 
30 days (+21 days) after the 2nd dose of MenACYW conjugate vaccine / 
Nimenrix® 
• 
prior to the 3rd dose (toddler dose) of MenACYW conjugate vaccine/ Nimenrix® 
• 
30 days (+21 days) after the 3rd dose (toddler dose) of MenACYW conjugate 
vaccine / Nimenrix® 
 
Subjects in Group 4 will provide blood samples for immunogenicity assessment as 
follows:  
• 
at baseline (pre-primary vaccination 1, Day 0) 
• 
30 days (+21 days) after the 3rd dose of MenACYW conjugate vaccine 
• 
prior to the 4th dose (toddler dose) of MenACYW conjugate vaccine 
• 
30 days (+21 days) after the 4th dose (toddler dose) of MenACYW conjugate 
vaccine  
 
Collection of safety data 
 
• 
All subjects will be followed for safety from Day 0 to the last study visit. 
 
• 
All subjects will be observed for 30 minutes after each vaccination and any 
unsolicited systemic adverse events (AEs) occurring during that time will be 
recorded as immediate unsolicited systemic AEs in the electronic case report 
book (CRB). 
 
• 
The subject’s parent / legally acceptable representative will record information in 
a diary card about solicited reactions from Day 0 to Day 7 after each vaccination 
and unsolicited AEs will be recorded from Day 0 to Day 30 after each 
vaccination. 
 
• 
Serious adverse events (SAEs, including adverse events of special interest 
[AESIs]) will be recorded in a diary card throughout the study. The 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 subjects’ parent / legally acceptable representative by 
telephone on 8 days (+2 days) after each vaccination visit to identify the 
occurrence of any SAEs not yet reported and to remind them to complete the 
diary card after each vaccination visit and bring it back to the subsequent visit so 
that it can be reviewed at the study site. 

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• 
Staff will also contact subjects’ parent / legally acceptable representative by 
telephone 5 months after the last visit in infancy and at least 14 days before 
Visit 4 (Groups 1, 2, and 3) or Visit 5 (Group 4). This contact is to identify the 
occurrence of any SAEs not yet reported, but also to remind them that routine 
vaccinations will be provided in the context of this study and that they should 
bring back the diary card to the subsequent visit so that it can be reviewed at the 
study site. If the subject does not want to continue in the study, the information 
recorded on the diary card will be reviewed during this call, and the diary card 
will be retrieved by the site. 
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 independent ethics committees (IECs) / 
institutional review boards (IRBs), or the governing regulatory authorities in the 
countries where the study is taking place.  
There will be an internal team at the level of the Sponsor (Safety Management Team 
[SMT]), which will review the data being generated from all ongoing studies with 
MenACYW conjugate vaccine at regular intervals for any new safety signals or safety 
concerns. The SMT is empowered to recommend a pause in both recruitment and/ or 
further vaccination while it investigates any potential signal or concern. 
 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform 
the Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as 
specified by the applicable regulatory requirements. The Investigator shall promptly 
inform the 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 response against meningococcal 
serogroups A, C, W, and Y following the administration of a 3-dose series of 
MenACYW conjugate vaccine compared to a 3-dose series of Nimenrix® when each 
vaccine is administered concomitantly with routine pediatric vaccines (PCV10 and 
hexavalent vaccine) to infants and toddlers from 6 weeks to 18 months old (Group 1 
versus Group 2) 
Primary Endpoint: 
Antibody titers (geometric mean titers [GMTs]) against meningococcal serogroups A, 
C, W, and Y measured by serum bactericidal assay using human complement (hSBA) 
in Groups 1 and 2, 30 days after the booster dose (third dose/toddler dose) of 
MenACYW conjugate vaccine or Nimenrix® when administered concomitantly with 
routine pediatric vaccines (PCV10 and hexavalent vaccine) to infants and toddlers 
from 6 weeks to 18 months of age (Group 1 versus Group 2) 
Secondary Objectives: 
1) 
To demonstrate the non-inferiority of the antibody response against 
meningococcal serogroups A, C, W, and Y following the administration of 
2 doses in infancy of MenACYW conjugate vaccine compared to 2 doses in 
infancy of Nimenrix® when each vaccine is administered concomitantly with 
routine pediatric vaccines (PCV10 and hexavalent vaccine) (Group 1 versus 
Group 2) 
 
2) 
To describe the antibody responses against meningococcal serogroups A, C, W, 
and Y when MenACYW conjugate vaccine is administered in a 3-dose series 
concomitantly with the routine pediatric vaccines (Group 3) 
 
3) 
To describe the antibody responses against the antigens of the routine pediatric 
vaccines administered in a 3-dose series concomitantly with MenACYW 
conjugate vaccine or Nimenrix® (Groups 1, 2, and 3) 

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4) 
To describe the antibody responses against meningococcal serogroups A, C, W, 
and Y measured by hSBA when MenACYW conjugate vaccine or Nimenrix® is 
administered in a 3-dose series concomitantly with PCV10 and other routine 
pediatric vaccines (Groups 1 and 2) 
 
5) 
To describe the antibody responses against meningococcal serogroups A, C, W, 
and Y measured by hSBA when MenACYW conjugate vaccine is administered 
in a 4-dose series concomitantly with PCV13 and other routine pediatric 
vaccines (Group 4) 
 
6) 
To describe the antibody responses against the antigens of the routine pediatric 
vaccines administered with MenACYW conjugate vaccine administered in a 
4-dose series concomitantly (Group 4) 
Secondary Endpoints: 
Secondary immunogenicity endpoints will include at least the following: 
1) 
Antibody titers ≥ 1:8 against meningococcal serogroups A, C, W, and Y 
assessed at 30 days after Dose 2 of MenACYW conjugate vaccine or Nimenrix® 
measured by hSBA, when administered concomitantly with routine pediatric 
vaccines (Group 1 versus Group 2)   
 
2) 
Antibody titers (GMTs) against meningococcal serogroups A, C, W, and Y 
measured by hSBA in Group 3 at the following time points: 
• 
Day 0 (before Dose 1 of MenACYW conjugate vaccine) 
In addition, the following endpoints will be assessed: 
- 
Antibody titers ≥ 1:4 and titers ≥ 1:8 
• 
30 days after Dose 2 of MenACYW conjugate vaccine in infancy, and before 
and 30 days after the booster dose (Dose 3) 
In addition, the following endpoints will be assessed: 
- 
Antibody titers ≥ 1:4 and titers ≥ 1:8 
 
- 
Post-vaccination titers ≥ 4 times the latest pre vaccination titers 
- 
hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
▪ For a subject with a pre vaccination titer < 1:8, the post-vaccination 
titer must be ≥ 1:16; 
▪ For a subject with a pre vaccination titer ≥ 1:8, the post-vaccination 
titer must be at least 4-fold greater than the pre vaccination titer. 
 
3) 
Antibody titers or concentrations against the antigens of hexavalent vaccine 
(DTaP-IPV-HB-Hib) in Groups 1, 2, and 3 at the following time points: 
• 
Day 0 (before Dose 1) 
- 
Anti-pertussis antibody concentrations (pertussis toxin [PT], filamentous 
hemagglutinin [FHA]) 
• 
30 days after Dose 2 in infancy 
- 
Antibody concentrations/titers for all antigens 
- 
Anti-tetanus antibody concentrations ≥ 0.01 international units  
(IU)/ milliliter (mL) and ≥ 0.1 IU/mL 
- 
Anti-diphtheria antibody concentrations ≥ 0.01 IU/mL and ≥ 0.1 IU/mL 
- 
Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8  
- 
Anti-polyribosyl-ribitol phosphate (PRP) antibody concentrations 
≥ 0.15 µg/mL 

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- 
Pertussis vaccine seroresponse for anti-PT and anti-FHA, defined as: 
▪ If the pre-primary vaccination concentration is < 4 × lower level of 
quantitation (LLOQ), post-primary vaccination concentration 
≥ 4 × LLOQ 
▪ If the pre-primary vaccination concentration is ≥ 4 × LLOQ, post-
primary vaccination concentration ≥ pre-primary vaccination 
concentration 
- 
Anti-hepatitis B surface antigen (HBsAg) antibody concentrations 
≥ 10 milli International units (mIU)/mL and ≥ 100 mIU/mL 
 
• 
Before and 30 days after the booster dose (Dose 3): 
- 
Antibody concentrations/titers for all antigens 
- 
Anti-tetanus antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- 
Anti-diphtheria antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- 
Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8  
- 
Anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL 
 
- 
Pertussis vaccine seroresponse for anti-PT and anti-FHA, defined as: 
▪ 
If the pre-booster vaccination concentration is < 4 × LLOQ, 
post-booster vaccination concentration ≥ 4 × pre-booster 
concentration  
▪ 
If the pre-booster vaccination concentration is ≥ 4 × LLOQ, 
post-booster vaccination concentration ≥ 2 × pre-booster 
concentration 
- 
Anti-HBsAg antibody concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL 
 
Antibody concentrations against the antigens of PCV10 in Groups 1 and 2, 
30 days after Dose 2 in infancy and 30 days after the booster dose (Dose 3): 
- 
Anti-pneumococcal antibody concentrations for serotypes 1, 4, 5, 6B, 
7F, 9V, 14, 18C, 19F, and 23F 
- 
Anti-pneumococcal antibody concentrations ≥ 0.35 μg/mL for serotypes 
1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F  
 
Antibody concentrations against the antigens of PCV13 in Group 3, 30 days after 
Dose 2 in infancy and 30 days after the booster dose (Dose 3): 
- 
Anti-pneumococcal antibody concentrations for serotypes 1, 3, 4, 5, 6A, 
6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F 
- 
Anti-pneumococcal antibody concentrations ≥ 0.35 μg/mL for serotypes 
1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F  
 
Antibody concentrations against the antigens of MMR vaccine 30 days after the 
MMR vaccine injection* 
- 
Antibody concentrations for all antigens 
- 
Anti-measles antibody concentrations (serostatus cutoff: 255 mIU/mL)  
- 
Anti-mumps antibody concentrations (serostatus cutoff: 10 Mumps Ab 
units/mL)  
- 
Anti-rubella antibody concentrations (serostatus cutoff:  10 IU/mL) 
*when the MMR vaccine has been administered concomitantly with the study vaccines 
 
4) 
Antibody titers against meningococcal serogroups A, C, W, and Y measured by 
hSBA in Groups 1 and 2, as detailed for the Secondary Endpoints 2 (similar time 
points and endpoints) 
 

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5) 
Antibody titers (GMTs) against meningococcal serogroups A, C, W, and Y 
measured by hSBA in Group 4 on Day 0 (before Dose 1 of MenACYW conjugate 
vaccine), 30 days after Dose 3 in infancy, and before and 30 days after the booster 
dose (Dose 4) at the following timepoints: 
• Day 0 (before Dose 1 of MenACYW conjugate vaccine) 
In addition, the following endpoints will be assessed: 
- 
Antibody titers ≥ 1:4 and titers ≥ 1:8 
• 30 days after Dose 3 of MenACYW conjugate vaccine in infancy, and before  
and 30 days after the booster dose (Dose 4) 
In addition, the following endpoints will be assessed: 
- 
Antibody titers ≥ 1:4 and titers ≥ 1:8 
- 
Post-vaccination titers ≥ 4 times the latest pre vaccination titers 
- 
hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
▪ 
For a subject with a pre vaccination titer < 1:8, the post-vaccination 
titer must be ≥ 1:16 
▪ 
For a subject with a pre vaccination titer ≥ 1:8, the post-vaccination 
titer must be at least 4-fold greater than the pre vaccination titer 
 
6) 
For Group 4, antibody titers or concentrations against the antigens of DTaP-IPV-
HB-Hib vaccine before and 30 days after the booster dose (Dose 4), antibody 
concentrations against the antigens of PCV13 vaccine 30 days after the booster 
dose (Dose 4), and antibody concentrations against the antigens of MMR vaccine 
30 days after vaccination* 
*when the MMR vaccine has been administered concomitantly with the study vaccines 
The timepoints are: 
Antibody titers or concentrations against the antigens of hexavalent vaccine 
(DTaP-IPV-HB-Hib): 
• 
Pre-booster dose 
- 
Anti-pertussis antibody concentrations anti-PT, anti-FHA 
• 
30 days after the booster dose (Dose 4): 
- Antibody concentrations/titers for all antigens 
- Anti-tetanus antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- Anti-diphtheria antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8 
- Anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL 
- Pertussis vaccine seroresponse for anti-PT and anti-FHA, defined as: 
▪ 
If the pre-booster vaccination concentration is < 4 × LLOQ,  
post-booster vaccination concentration ≥ 4 × pre-booster 
concentration 
▪ 
If the pre-booster vaccination concentration is ≥ 4 × LLOQ, 
post-booster vaccination concentration ≥ 2 × pre-booster 
concentration 

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Anti-HBsAg antibody concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL 
Antibody concentrations against the antigens of PCV13 in Group 4, 30 days after 
the booster dose (Dose 4): 
- 
Anti-pneumococcal antibody concentrations for serotypes 1, 3, 4, 5, 6A, 
6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F 
- 
Anti-pneumococcal antibody concentrations ≥ 0.35 μg/mL for serotypes 
1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F 
Antibody concentrations against the antigens of MMR vaccine 30 days after the 
MMR vaccine injection† 
- 
Antibody concentrations for all antigens 
- 
Anti-measles antibody concentrations (serostatus cutoff: 255 mIU/mL) 
- 
Anti-mumps antibody concentrations (serostatus cutoff: 10 Mumps Ab  
units/mL) 
- 
Anti-rubella antibody concentrations (serostatus cutoff: 10 IU/mL) 
†when the MMR vaccine has been administered concomitantly with the study vaccines 
Observational Objectives: 
Immunogenicity 
To describe the antibody responses against meningococcal serogroups A, C, W, and Y 
measured by serum bactericidal assay using rabbit complement (rSBA) in a subset of 
subjects when MenACYW conjugate vaccine or Nimenrix® is administered 
concomitantly with routine pediatric vaccines (all groups) 
Safety 
To describe the safety profile of MenACYW conjugate vaccine and Nimenrix® when 
administered concomitantly with routine pediatric vaccines in healthy infants and 
toddlers 
Observational Endpoints: 
Immunogenicity 
• 
Antibody titers (GMTs) against meningococcal serogroups A, C, W, and Y 
measured by rSBA in a subset of subjects in all groups‡ at Day 0 (before Dose 1) 
(all groups), 30 days after Dose 2 (Groups 1, 2, and 3) or 30 days after Dose 3 
(Group 4) in infancy, and before and 30 days after the booster dose (in all 
groups) 
 
In addition, the following endpoints will be assessed for all groups: 
- 
Antibody titers ≥ 1:8, and titers ≥ 1:128 
- 
Post-vaccination titers ≥ 4 times the latest pre vaccination titers 
- 
rSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
▪ a post-vaccination rSBA titer ≥ 1:32 for subjects with pre vaccination 
rSBA titer < 1:8, or 
▪ a post-vaccination titer ≥ 4 times the pre vaccination titer for subjects 
with pre vaccination rSBA titer ≥ 1:8  
 
(‡) The rSBA subset will comprise: 
- 
Group 1 and Group 2: 100 subjects in each group  
- 
Group 3 and Group 4: 50 subjects in each group 
The rSBA subset will include subjects from all countries except Poland.  

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The following endpoints will be used for all subjects for the evaluation of safety: 
• 
Unsolicited systemic AEs reported in the 30 minutes after each vaccination, 
including occurrence, nature (Medical Dictionary for Regulatory Activities 
[MedDRA] preferred term), duration, intensity, action taken, relationship to the 
product administered, and whether the event caused termination from the 
study. 
 
• 
Solicited (prelisted in the subject’s diary card and CRB) injection site and 
systemic reactions starting any time from Day 0 (day of vaccination) through 
Day 7 after each vaccination, including occurrence, time of onset, number of 
days of occurrence, intensity, action taken, and whether the reaction caused 
termination from the study. 
 
• 
Unsolicited non-serious AEs reported up to 30 days after each vaccination, 
including occurrence, nature (MedDRA preferred term), time of onset, 
duration, intensity, action taken, relationship to the product administered, and 
whether the event caused termination from the study. 
 
• 
SAEs (including AESIs) reported throughout the study, ie, from Visit 1 (first 
vaccination) to the last study visit (Visit 5 for Groups 1, 2, and 3 and Visit 6 
for Group 4, occurring 30 days [+21 days] after the last vaccination), including 
occurrence, nature (MedDRA preferred term), time of onset, duration, 
intensity, action taken, relationship to the product administered, whether the 
event caused termination from the study, outcome, elapsed time from last 
administration (if less than 24 hours), relationship to study procedures, and 
seriousness criterion. 
Planned Sample Size: 
Approximately a total of 1652 subjects are planned to be enrolled (with an estimated 
dropout rate from the Per-Protocol Analysis Set [PPAS] of 26.2%): 
• 
Group 1: n=716 enrolled, 528 evaluable 
• 
Group 2: n=716 enrolled, 528 evaluable 
• 
Group 3: n=110 enrolled, 88 evaluable 
• 
Group 4: n=110 enrolled, 88 evaluable 
Approximately 20% of subjects 6 to 8 weeks of age (≥ 42 to ≤ 59 days) should be 
enrolled in Groups 1 and 2 to provide safety and immunogenicity data for this 
population of age, as described below:  
• 
Group 1 and Group 2: approximately 144 subjects in each group  
• 
Group 3 and Group 4: approximately 22 subjects in each group 
Duration of Participation 
in the Study: 
The duration of each subject’s participation in the study will be approximately 11 to 
17 months. 
Investigational Product: 
MenACYW conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, W, 
and Y) Tetanus Toxoid Conjugate Vaccine (Sanofi Pasteur Inc., Swiftwater, PA, USA) 
 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 micrograms (µg) 
Serogroup C.................................................................................................... 10 µg 
Serogroup Y ................................................................................................... 10 µg 
Serogroup W .................................................................................................. 10 µg 
Tetanus toxoid protein carrier .................................................... approximately 55 µg* 
* Tetanus toxoid protein quantity is approximate and dependent on the polysaccharide-
to-protein ratio for the conjugates used in each formulation.  

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 Route: 
Intramuscular (IM) 
 Batch Number: 
To be determined 
Control Product: 
Nimenrix®: Meningococcal group A, C, W-135, and Y conjugate vaccine (Pfizer 
Limited, Sandwich, United Kingdom) 
 Form: 
Powder and solvent for solution for injection in a pre-filled syringe 
 Composition: 
After reconstitution, each 0.5 mL dose contains: 
 
Neisseria meningitidis group A polysaccharide* ................................................... 5 µg 
Neisseria meningitidis group C polysaccharide* ................................................... 5 µg 
Neisseria meningitidis group W-135 polysaccharide* ........................................... 5 µg 
Neisseria meningitidis group Y polysaccharide* ................................................... 5 µg 
*conjugated to tetanus toxoid protein carrier ....................................................... 44 µg 
The vaccine also contains the excipients: sucrose, trometamol, sodium chloride, water 
for injections 
 Route: 
IM 
 Batch Number: 
To be determined 
Other Product 1: 
DTaP-IPV-HB-Hib: Diphtheria, tetanus, pertussis (acellular, component), hepatitis B 
(rDNA), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate 
vaccine (adsorbed) (Sanofi Pasteur SA, Marcy L’Etoile, France) (licensed products: 
Hexyon®, Hexacima®), referred to as hexavalent vaccine in the protocol 
 Form: 
Suspension for injection 
 Composition: 
Each 0.5 mL dose* is formulated to contain the following components: 
 
Diphtheria Toxoid .......................................................................... not less than 20 IU† 
Tetanus Toxoid .............................................................................. not less than 40 IU† 
 
Bordetella pertussis antigens 
Pertussis Toxoid................................................................................................... 25 µg 
Filamentous Haemagglutinin ............................................................................... 25 µg 
 
Poliovirus (Inactivated)‡ 
Type 1 (Mahoney) ......................................................................... 40 D-antigen units§ 
Type 2 (MEF-1) ............................................................................... 8 D-antigen units§ 
Type 3 (Saukett) ............................................................................ 32 D-antigen units§ 
 
Hepatitis B surface antigen** .............................................................................. 10 µg 
Haemophilus influenzae type b polysaccharide ................................................... 12 µg 
 
(Polyribosylribitol phosphate) 
conjugated to tetanus protein .......................................................................... 22-36 µg 
 
*Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
†As lower confidence limit (p=0.95) 
‡Produced on Vero cells 
§Or equivalent antigenic quantity determined by a suitable immunochemical method 
**Produced in yeast Hansenula polymorpha cells by recombinant deoxyribonucleic 
acid (DNA) technology 
The vaccine also contains the excipients: disodium hydrogen phosphate, potassium 
dihydrogen phosphate, trometamol, saccharose, essential amino acids including  
L-phenylalanine, water for injections. 
The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, 
streptomycin, and polymyxin B, which are used during the manufacturing process. 
 Route: 
IM 
 Batch Number: 
To be determined 

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Other Product 2: 
Synflorix®: Pneumococcal polysaccharide conjugate vaccine (adsorbed) 
(GlaxoSmithKline Biologicals SA, Rixensart, Belgium), referred to as PCV10 
 Form: 
Suspension for injection 
 Composition: 
Each 0.5 mL dose is formulated to contain the following: 
 
Pneumococcal polysaccharide serotype 1*† .......................................................... 1 µg 
Pneumococcal polysaccharide serotype 4*† .......................................................... 3 µg 
Pneumococcal polysaccharide serotype 5*† .......................................................... 1 µg 
Pneumococcal polysaccharide serotype 6B*† ........................................................ 1 µg 
Pneumococcal polysaccharide serotype 7F*† ........................................................ 1 µg 
Pneumococcal polysaccharide serotype 9V*†........................................................ 1 µg 
Pneumococcal polysaccharide serotype 14*† ........................................................ 1 µg 
Pneumococcal polysaccharide serotype 18C*‡ ...................................................... 3 µg 
Pneumococcal polysaccharide serotype 19F*§ ...................................................... 3 µg 
Pneumococcal polysaccharide serotype 23F*† ...................................................... 1 µg 
* adsorbed on aluminum phosphate  ......................................................... 0.5 mg Al3+ 
† conjugated to protein D (derived from non-typable Haemophilus influenzae)             
carrier protein .................................................................................................... 9-16 µg 
‡ conjugated to tetanus toxoid carrier protein ................................................... 5-10 µg 
§ conjugated to diphtheria toxoid carrier protein ................................................ 3-6 µg 
 
The vaccine also contains the excipients: sodium chloride, water for injections. 
 Route: 
IM 
 Batch Number: 
To be determined 
Other Product 3: 
Prevenar 13®: Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) 
(Pfizer Limited, Sandwich, United Kingdom), referred to as PCV13 
 Form: 
Suspension for injection 
 Composition: 
Each 0.5 mL vaccine dose is formulated to contain the following: 
 
Pneumococcal polysaccharide serotype 1 ........................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 3 ........................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 4 ........................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 5 ........................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 6A ........................................................ 2.2 µg 
Pneumococcal polysaccharide serotype 6B ......................................................... 4.4 µg 
Pneumococcal polysaccharide serotype 7F ......................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 9V ........................................................ 2.2 µg 
Pneumococcal polysaccharide serotype 14 ......................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 18C ....................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 19A ...................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 19F ....................................................... 2.2 µg 
Pneumococcal polysaccharide serotype 23F ....................................................... 2.2 µg 
The pneumococcal polysaccharides are conjugated to CRM197 carrier protein and 
adsorbed on aluminum phosphate (0.125 mg aluminum). 
 
The vaccine also contains the excipients: sodium chloride, succinic acid, 
Polysorbate 80, water for injections. 
 Route: 
IM 
 Batch Number: 
To be determined 

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Other Product 4: 
M-M-RVAXPRO®: Measles, mumps, and rubella vaccine (live) (Merck Sharp & 
Dohme B.V., Haarlem, The Netherlands), referred to as MMR vaccine  
 Form: 
Powder and solvent for suspension for injection 
 Composition: 
Each 0.5 mL dose is formulated to contain the following: 
 
Measles virus* Enders’ Edmonston strain (live, attenuated) 
 .................................... not less than 1x103 cell culture infection dose 50% (CCID50)† 
Mumps virus* Jeryl Lynn™ [Level B] strain (live, attenuated) 
 .................................................................................... not less than 12.5x103 CCID50† 
Rubella virus‡ Wistar RA 27/3 strain (live attenuated) 
 ......................................................................................... not less than 1x103 CCID50† 
 
* produced in chick embryo cells 
†50% cell culture infectious dose 
‡ produced in WI-38 human diploid lung fibroblasts  
 
The vaccine contains the following excipients: sorbitol, sodium phosphate, potassium 
phosphate, sucrose, hydrolyzed gelatin, Medium 199 with Hank’s salts, Minimum 
Essential Medium Eagle, monosodium L-glutamate, neomycin, phenol red, sodium 
bicarbonate, hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH), water 
for injections. The vaccine may also contain traces of recombinant human albumin. 
 Route: 
IM  
 Batch Number: 
To be determined 
Inclusion Criteria: 
An individual must fulfill all of the following criteria to be eligible for study 
enrollment: 
 
1) 
Aged ≥ 42 to ≤ 89 days on the day of the first study visit 
 
2) 
Healthy infants as determined by medical history, physical examination and 
judgment of the Investigator 
 
3) 
Informed consent form has been signed and dated by the parent(s) or other legally 
acceptable representative  
 
4) 
Subject and parent/legally acceptable representative are able to attend all 
scheduled visits and to comply with all study procedures 
 
5) 
Covered by health insurance according to local regulations 
Exclusion Criteria: 
An individual fulfilling any of the following criteria is to be excluded from study 
enrollment: 
 
1) 
Participation at the time of study enrollment (or in the 4 weeks preceding the first 
study vaccination) or planned participation during the present study period in 
another clinical study investigating a vaccine, drug, medical device, or medical 
procedure 
 
2) Receipt of any vaccine in the 4 weeks preceding the first study vaccination or 
planned receipt of any vaccine in the 4 weeks before and/or following any study 
vaccination except for influenza vaccination and rotavirus vaccination, which may 
be received at a gap of at least 2 weeks before or 2 weeks after any study vaccines. 
This exception includes monovalent pandemic influenza vaccines and multivalent 
influenza vaccines. This exclusion criterion does not apply to subjects in Finland, 
Sweden or Poland who plan to receive the licensed rotavirus vaccine 
concomitantly with study vaccines at study vaccination visits V1 and V2 
 
3) 
Receipt or planned receipt during the study period vaccination against 
meningococcal disease with either the study vaccine or another vaccine (ie, mono- 
or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing 
serogroups A, C, W or Y; or meningococcal B serogroup-containing vaccine) 

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4) 
Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus 
influenzae type b (Hib), poliovirus, Streptococcus pneumoniae, measles, mumps, 
or rubella. Previous vaccination against hepatitis B when administered to risk 
groups, as per local recommendation.  
 
5) 
Receipt of immune globulins, blood or blood-derived products since birth 
 
6) 
Known or suspected congenital or acquired immunodeficiency; or receipt of 
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) since birth 
 
7) 
Family history of congenital or hereditary immunodeficiency, unless the immune 
competence of the potential vaccine recipient is demonstrated 
 
8) 
Individuals with blood dyscrasias, leukemia, lymphoma of any type, or other 
malignant neoplasms affecting the bone marrow or lymphatic systems 
 
9) 
Individuals with active tuberculosis 
 
10) History of Neisseria meningitidis infection, confirmed either clinically, 
serologically, or microbiologically 
 
11) History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, measles, 
mumps, rubella, and of Haemophilus influenzae type b, and / or Streptococcus 
pneumoniae infection or disease. 
 
12) 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) 
 
13) Individuals with underlying conditions predisposing them to invasive 
pneumococcal disease (specifically, but not limited to, subjects with sickle cell 
disease or human immunodeficiency virus [HIV] infection) 
 
14) History of any neurologic disorders, including seizures and progressive 
neurologic disorders 
 
15) History of Guillain-Barré syndrome 
 
16) Known systemic hypersensitivity to any of the vaccine components, or history of 
a severe allergic reaction (eg, anaphylaxis) to the vaccine(s) used in the study or 
to a vaccine containing any of the same substances including neomycin, 
streptomycin, polymyxin B, glutaraldehyde, formaldehyde, and gelatin 
 
17) Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in 
the investigator’s opinion 
 
18) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating intramuscular vaccination in the investigator’s opinion 
 
19) Chronic illness (including, but not limited to, cardiac disorders, congenital heart 
disease, chronic lung disease, renal disorders, auto-immune disorders, diabetes, 
psychomotor diseases, and known congenital or genetic diseases) that, in the 
opinion of the investigator, is at a stage where it might interfere with study 
conduct or completion 
 
20) Any condition which, in the opinion of the investigator, might interfere with the 
evaluation of the study objectives 
 
21) Moderate or severe acute illness/infection (according to investigator judgment) on 
the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective 
subject should not be included in the study until the condition has resolved or the 
febrile event has subsided. 

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22) Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first 
blood draw 
 
23) Identified as a natural or adopted child of the Investigator or employee with direct 
involvement in the proposed study 
24) Infants born preterm (by less than 37 weeks of gestation) requiring specific 
immunization schedule for routine childhood vaccines and/or specific care at the 
time of vaccination, as per national recommendations 
Statistical Methods: 
Main immunogenicity analyses will be performed on the PPAS. Additional 
immunogenicity analyses will be performed 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 (Group 1) compared to Nimenrix® 
(Group 2) in terms of hSBA antibody titers after a 3-dose series to infants and toddlers 
will be tested.  
For each of the 4 serogroups (A, C, W, and Y), GMTs 30 days after a 3-dose series 
vaccination will be used to compare Group 1 and Group 2 with the following individual 
hypotheses: 
 
H0 (Null hypothesis):  
• 
GMT MenACYW / GMT Nimenrix ≤ 1/1.5 (or GMT Nimenrix / GMT MenACYW ≥ 1.5) 
H1 (Alternative hypothesis):  
• 
GMT MenACYW / GMT Nimenrix > 1/1.5 (or GMT Nimenrix / GMT MenACYW < 1.5) 
The statistical methodology will be based on the use of the 2-sided 95% confidence 
interval (CI) of the ratio of post-vaccination GMTs between Group 1 and Group 2. 
The CI will be calculated using a normal approximation of log-transformed titers. 
 
Non-inferiority will be demonstrated if all 4 individual null hypotheses (4 serogroups) 
are rejected. For each serogroup, the 2-sided 95% CI of the GMT ratio Group 1 
(MenACYW) / Group 2 (Nimenrix) should lie above 1/1.5.  
 
The PPAS will be used as the main analysis. 
 
Secondary Objectives 
If the primary objective is met, non-inferiority of MenACYW conjugate vaccine (Group 
1) compared to Nimenrix® (Group 2) in terms of hSBA antibody titers ≥ 1:8 after a 2-
dose series in infants will be tested (Secondary Objective 1). 
 
For each of the 4 serogroups (A, C, W, and Y), the percentages of subjects who achieve 
an hSBA titer ≥ 1:8 30 days after the 2 dose administered in infancy will be used to 
compare responses between Group 1 and Group 2 with the following individual 
hypotheses: 
• 
H0 (Null hypothesis): p(MenACYW) - p(Nimenrix) ≤ -10% 
• 
H1 (Alternative hypothesis): p(MenACYW) - p(Nimenrix) > -10% 
 
where p(MenACYW) and p(Nimenrix) are the percentages of subjects who achieve an hSBA 
titer ≥ 1:8 in the MenACYW conjugate vaccine group and the Nimenrix® group, 
respectively.  

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Non-inferiority will be demonstrated if all 4 individual null hypotheses (4 serogroups) 
are rejected. If the lower limit of the 2-sided 95% CI of the difference between the 
2 percentages is > -10%, the non-inferiority will be demonstrated. The CI of the 
difference in percentages will be computed using the Wilson score method without 
continuity correction. 
The PPAS will be used as the main analysis. 
The statistical analyses for the Secondary Objectives 2, 3, 4, 5, 6 and 7 will be 
descriptive. 
 
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 proportions. For GMTs and geometric mean 
concentrations (GMCs), 95% CIs of point estimates will be calculated using a normal 
approximation assuming they are log-normally distributed.  
 
Observational Objectives 
 
Safety 
Safety results will be described for subjects in all study groups. The main parameters for 
the safety endpoints will be described by 95% CIs (based on the Clopper-Pearson 
method). 
 
Calculation of Sample Size: 
 
Approximately a total of 1652 subjects will be enrolled.  
 
For the Primary Objective 
With 716 enrolled subjects in Group 1 and in Group 2, the study will have 96.2% power 
to declare the non-inferiority of Group 1 versus Group 2 based on A, C, W, Y hSBA 
antibody titers (ratio of GMTs in the 2 groups) after a 3-dose series to infants and 
toddlers 6 weeks to 18 months old, assuming: 
 
• 
An estimated 26.2% dropout rate from the PPAS (528 subjects evaluable by group), 
• 
a 1-sided alpha level of 2.5%,  
• 
a non-inferiority margin of 1.5 (GMT ratio), 
• 
a standard deviation (SD) of log10-transformed titers of 0.7 for serogroups A and 
C, 0.5 for serogroup Y, and 0.6 for serogroup W.  
 
Table S1 Power of the study based on the primary objective 
Antigen 
MenACYW Standard 
Deviation* 
Non-inferiority 
Margin 
Power 
A 
0.7 
1.5 
98.3% 
C 
0.7 
1.5 
98.3% 
Y 
0.5 
1.5 
> 99.9% 
W 
0.6 
1.5  
99.7% 
Overall 
 
 
96.2% 
Since the hypothesis needs to be met for all serogroups, no alpha adjustment for 
multiple comparisons is necessary in these calculations. 
* SDs are based on the results of the MET39 (NCT01049035) MenACYW 2/4/12 months 
schedule (Group 3) after booster results. For the power computation, the same SD in the control 
group (Nimenrix®) is assumed. 

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395 – MenACYW Conjugate Vaccine 
Protocol Version 7.0 
 
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For the Secondary Objective 
With 716 enrolled subjects in Group 1 and in Group 2, the study will have a > 90% 
power (Farrington and Manning formula) to declare the non-inferiority of Group 1 
versus Group 2 based on A, C, W, Y hSBA antibody titers ≥ 1:8 (difference in the 
percentage of seroprotected subjects in the 2 groups) after 2 doses in infancy at 
2 months and 4 months of age, assuming: 
• 
An estimated 26.2% dropout rate from the PPAS (528 subjects evaluable per 
group) 
• 
A 1-sided alpha level of 2.5%, 
• 
A non-inferiority margin of 10% (percentage difference) 
 
Table S2: Power of the study for the secondary objective 
Antigen 
Estimated Percentage 
of hSBA Titer ≥ 1:8  
Nimenrix®* 
Non-inferiority 
margin† 
Power 
A 
76% 
10% 
96.7% 
C 
94% 
10% 
> 99.9% 
Y 
71% 
10% 
94.7% 
W 
82% 
10% 
98.7% 
Overall 
 
 
90% 
Since the hypothesis needs to be met for all serogroups, and the secondary objective is 
to be tested only if the primary objective succeeds, no alpha adjustment for multiple 
comparisons is necessary in these calculations. 
* Percentages of subjects with an hSBA titer ≥ 1:8 are based on the MET39 (NCT01049035) 
MenACYW 2/4/12 months schedule (Group 3) post dose 2 results using estimates 2% lower than 
in the MenACYW group. The power is calculated with the assumption that the estimates from the 
investigational group equal that of the control group corresponding to the estimated percentages 
in the Nimenrix® group described above. 
† A non-inferiority margin of 10% has been widely used in previous studies evaluating the same 
antigens and in a competitor’s study of the same type. Also taking into account the level of the 
reference rate taken in the Nimenrix® group, it is reasonable to use 10%. 
 
The sample size has been arbitrarily set to 110 subjects in Group 3 and Group 4 as these 
data are not intended to be used for any hypothesis testing. No formal sample size 
calculations were performed. In each group, there is more than 95% probability to 
observe an event with an incidence of 2.7%. 
In case of unexpected situation or any study hold resulting in an unexpected number of 
unevaluable subjects, total sample size may be increased to replace withdrawn, or 
unevaluable subjects. 

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Table of Study Procedures - Groups 1, 2, and 3  
Phase III study, 5 visits, 3 vaccination visits, 4 telephone calls, 10 vaccine injections, 4 blood collections per subject,  
11- to 17-month duration per subject 
Visit/Contact 
Visit 1 
Telephone 
Call (TC) 1 
Visit 2 
TC2 
Visit 3 
TC3 
Visit 4 
TC4 
Visit 5 
Age of Subject 
2 months 
(42 to 89 days) 
 
 
 
 
 
12-18 
months* 
 
 
Study timelines (days) 
Day 0 
Visit 1 +  
8 days 
Visit 1 + 
60 days 
Visit 2 + 
8 days 
Visit 2 + 
30 days 
Visit 3 + 
5 months 
AND  
Visit 4 – at 
least 
14 days† 
Visit 2 + at 
least 180 
days 
Visit 4 + 
8 days 
Visit 4 + 
30 days 
Time windows (days) 
 
+2 days 
+14 days 
+2 days 
+21 days 
 
 
+2 days 
+21 days 
Informed consent form signed and dated 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
Collection of demographic data 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Physical examination (including temperature)‡§ 
X 
 
 
 
 
 
X 
 
 
Temperature measurement§ 
 
 
X 
 
 
 
 
 
 
Contact interactive response technology (IRT) system for 
vaccine group randomization 
X 
 
X 
 
 
 
X 
 
 
Review of temporary contraindications for blood 
sampling** 
X 
 
 
 
X 
 
X 
 
X 
Blood sampling (BL)††  
BL0001 (2 or 
3 mL)‡‡ 
 
 
 
BL0002 (3 or 
4 mL) ‡‡ 
 
BL0003 (5 or 
6 mL)‡‡ 
 
BL0004 (5 or 
6 mL) 
Review warnings and precautions to vaccinations 
X 
 
X 
 
 
 
X 
 
 
Review of contraindications to subsequent vaccinations 
 
 
X 
 
 
 
X 
 
 

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Visit/Contact 
Visit 1 
Telephone 
Call (TC) 1 
Visit 2 
TC2 
Visit 3 
TC3 
Visit 4 
TC4 
Visit 5 
Age of Subject 
2 months 
(42 to 89 days) 
 
 
 
 
 
12-18 
months* 
 
 
Study timelines (days) 
Day 0 
Visit 1 +  
8 days 
Visit 1 + 
60 days 
Visit 2 + 
8 days 
Visit 2 + 
30 days 
Visit 3 + 
5 months 
AND  
Visit 4 – at 
least 
14 days† 
Visit 2 + at 
least 180 
days 
Visit 4 + 
8 days 
Visit 4 + 
30 days 
Time windows (days) 
 
+2 days 
+14 days 
+2 days 
+21 days 
 
 
+2 days 
+21 days 
Vaccination with MenACYW conjugate vaccine or 
Nimenrix® 
X 
 
X 
 
 
 
X 
 
 
Vaccination with routine pediatric vaccines§§ 
X 
 
X 
 
 
 
X 
 
 
Immediate surveillance (30 minutes) 
X 
 
X 
 
 
 
X 
 
 
Diary card (DC) provided 
DC1 
 
DC2 
 
DC3 
 
DC4 
 
 
Telephone call 
 
X*** 
 
X*** 
 
X††† 
 
X*** 
 
Diary card reviewed and collected 
 
 
DC1 
 
DC2 
 
DC3 
 
DC4 
Recording of solicited injection site and systemic 
reactions‡‡‡ 
X 
 
X§§§ 
 
X§§§ 
 
 
 
X§§§ 
Recording of unsolicited adverse events (AEs) 
Day 0 to Day 30 after each vaccination visit 
Reporting of serious adverse events (SAEs, including 
adverse events of special interest [AESIs])**** 
To be reported throughout the study period 
Collection of reportable concomitant medications 
X 
 
X 
 
X 
 
X 
 
X 
Study termination record (Completion at End of study) 
 
 
 
 
 
 
 
 
X 
* Visit 4 may occur anytime from the day the subject turns 12 months to the day before the subject turns 19 months of age as long as there is an interval of at least 180 days since Visit 2. 
†Staff will contact subjects’ parent / legally acceptable representative by telephone 5 months after the last visit in infancy and at least 14 days before Visit 4. 
‡ Physical examination should be performed as per standard of care. If a routine examination had been performed within the last week by the Investigator, a sub-investigator, or a licensed nurse 
practitioner, it does not need to be repeated unless there were some changes in health status, in which case it may be limited to the affected area. 

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§Temperature needs to be measured before each vaccination and recorded in the source documents. The route for this study is rectal, oral, or axillary according to local practices, with the rectal route 
preferred for infants and the axillary route preferred for toddlers. 
** Should a subject receive oral or injectable antibiotic therapy within 3 days prior to any 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. 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 appropriately documented that the sample was taken less than 3 days after stopping antibiotic treatment. 
†† At Visits 1 and 3, the blood sample volume indicated will be taken from all subjects including those subjects in a subset to assess the antibody response to meningococcal serogroups (A, C, W, and Y) 
measured by rSBA assay in addition to hSBA assay. At Visits 4 and 5, blood sample volume of 5 mL will be taken from all subjects, except subjects included in the rSBA subset. Blood sample 
volume of 6 mL will be taken from subjects included in the rSBA subset. 
‡‡ Blood sample at Visit 1 and Visit 4 will be drawn before administration of the vaccines. 2 or 3 mL of blood at Visit 1, and 3 or 4 mL of blood at Visit 3 are collected depending on the weight at the 
study visit 
§§ Routine pediatric vaccines: Hexavalent vaccine and PCV10 (Group 1 and Group 2) or PCV13 (Group 3) at Visits 1, 2, and 4. The MMR vaccine may be administered preferably at Visit 4. Subjects in 
Finland, Sweden or Poland may receive the licensed rotavirus vaccine concomitantly with study vaccines at Visit 1 and Visit 2.  
*** This call is made 8 days to 10 days after the respective vaccinations. If Day 08 (+2 days) falls on a weekend or holiday, the telephone call may be made on the following business day. During this 
telephone call, the staff will find out whether the subject experienced any SAE (including any AESI) not yet reported, and will remind the subject’s parent / legally acceptable representative to 
continue using the diary card, bring the diary card to the study center at the next visit, and confirm the date and time of the next visit. 
††† This call is made 5 months after Visit 3 and at least 14 days before Visit 4. During this telephone call, the staff will find out whether the subject experienced any SAE (including any AESI) not yet 
reported, will remind the subject’s parent / legally acceptable representative that routine vaccinations will be provided in the context of this study and that they should bring back the diary card to the 
study center at the next visit, and will confirm the date and time of the next visit. 
‡‡‡ Solicited injection site and systemic reactions will be recorded from Day 0 through Day 7 after each vaccination visit. 
§§§ Solicited injection site and systemic reactions will be recorded during the review and collection of DC1, DC2 and DC4 at Visits 2, 3 and 5. 
****AESIs will be collected throughout the study as SAEs to ensure that the events are communicated to the Sponsor in an expedited manner and followed up until the end of the follow-up period or 
resolution, as per the assigned causality. 
 

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Table of Study Procedures - Group 4  
Phase III study, 6 visits, 4 vaccination visits, 5 telephone calls, 11 vaccine injections, 4 blood collections per subject,  
11- to 17-month duration per subject 
Visit/Contact 
Visit 1 
Telephone 
Call (TC) 1 
Visit 2 
TC2 
Visit 3 
TC3 
Visit 4 
TC4 
Visit 5 
TC5 
Visit 6 
Age of Subject 
2 months 
(42 to 
89 days) 
 
 
 
 
 
 
 
12-18 
 months* 
 
 
Study timelines (days) 
Day 0 
Day 08 
Visit 1 + 
60 days 
Visit 2 + 
8 days 
Visit 2 + 
60 days 
Visit 3 + 
8 days 
Visit 3 + 
30 days 
Visit 4 + 
5 months 
AND  
Visit 5 –at 
least 
14 days† 
Visit 3 + at least 
180 days 
Visit 5 +  
8 days 
Visit 5 + 
30 days 
Time windows (days) 
 
+2 days 
+14 days 
+2 days 
+14 days 
+2 days 
+21 days 
 
 
+2 days 
+21 days 
Informed consent form signed and 
dated 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
Collection of demographic data 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Physical examination (including 
temperature)‡§ 
X 
 
 
 
 
 
 
 
X 
 
 
Temperature measurement§ 
 
 
X 
 
X 
 
 
 
 
 
 
Contact IRT system for vaccine 
group randomization 
X 
 
X 
 
X 
 
 
 
X 
 
 
Review of temporary 
contraindications for blood 
sampling** 
X 
 
 
 
 
 
X 
 
X 
 
X 

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Visit/Contact 
Visit 1 
Telephone 
Call (TC) 1 
Visit 2 
TC2 
Visit 3 
TC3 
Visit 4 
TC4 
Visit 5 
TC5 
Visit 6 
Age of Subject 
2 months 
(42 to 
89 days) 
 
 
 
 
 
 
 
12-18 
 months* 
 
 
Study timelines (days) 
Day 0 
Day 08 
Visit 1 + 
60 days 
Visit 2 + 
8 days 
Visit 2 + 
60 days 
Visit 3 + 
8 days 
Visit 3 + 
30 days 
Visit 4 + 
5 months 
AND  
Visit 5 –at 
least 
14 days† 
Visit 3 + at least 
180 days 
Visit 5 +  
8 days 
Visit 5 + 
30 days 
Time windows (days) 
 
+2 days 
+14 days 
+2 days 
+14 days 
+2 days 
+21 days 
 
 
+2 days 
+21 days 
Blood Sampling (BL)†† 
BL0001 (2 
or 3 mL)‡‡ 
 
 
 
 
 
BL0002 
(3 or 
4 mL) ‡‡ 
 
BL0003 (5 or 6 
mL)‡‡ 
 
BL0004 
(5 or 6 mL) 
Review warnings and precautions to 
vaccinations 
X 
 
X 
 
X 
 
 
 
X 
 
 
Review of contraindications to 
subsequent vaccinations 
 
 
X 
 
X 
 
 
 
X 
 
 
Vaccination with MenACYW 
conjugate vaccine  
X 
 
X 
 
X 
 
 
 
X 
 
 
Vaccination with routine 
pediatric vaccines§§ 
X 
 
X 
 
 
 
 
 
X 
 
 
Immediate surveillance (30 
minutes) 
X 
 
X 
 
X 
 
 
 
X 
 
 
DC provided 
DC1 
 
DC2 
 
DC3 
 
DC4 
 
DC5 
 
 
Telephone call  
 
X*** 
 
X*** 
 
X*** 
 
X††† 
 
X*** 
 
Diary card reviewed and collected 
 
 
DC1 
 
DC2 
 
DC3 
 
DC4 
 
DC5 

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Visit/Contact 
Visit 1 
Telephone 
Call (TC) 1 
Visit 2 
TC2 
Visit 3 
TC3 
Visit 4 
TC4 
Visit 5 
TC5 
Visit 6 
Age of Subject 
2 months 
(42 to 
89 days) 
 
 
 
 
 
 
 
12-18 
 months* 
 
 
Study timelines (days) 
Day 0 
Day 08 
Visit 1 + 
60 days 
Visit 2 + 
8 days 
Visit 2 + 
60 days 
Visit 3 + 
8 days 
Visit 3 + 
30 days 
Visit 4 + 
5 months 
AND  
Visit 5 –at 
least 
14 days† 
Visit 3 + at least 
180 days 
Visit 5 +  
8 days 
Visit 5 + 
30 days 
Time windows (days) 
 
+2 days 
+14 days 
+2 days 
+14 days 
+2 days 
+21 days 
 
 
+2 days 
+21 days 
Recording of solicited injection site 
and systemic reactions‡‡‡ 
X 
 
X§§§ 
 
X§§§ 
 
X§§§ 
 
X 
 
X§§§ 
Recording of unsolicited AEs 
From Day 0 to Day 30 after each vaccination visit 
Reporting of SAEs, including 
AESIs**** 
To be reported throughout the study period 
Collection of reportable 
concomitant medications 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Study termination record 
(Completion at End of study) 
 
 
 
 
 
 
 
 
 
 
X 
* Visit 5 may occur anytime from the day the subject turns 12 months to the day before the subject turns 19 months of age as long as there is an interval of at least 180 days since Visit 3. 
†Staff will contact subjects’ parent / legally acceptable representative by telephone 5 months after the last visit in infancy and at least 14 days before Visit 5. 
‡Physical examination should be performed as per standard of care.  If a routine examination had been performed within the last week by the Investigator, a sub-investigator, or a licensed nurse 
practitioner, it does not need to be repeated unless there were some changes in health status, in which case it may be limited to the affected area. 
§Temperature needs to be measured before each vaccination and recorded in the source documents. The route for this study is rectal, oral, or axillary according to local practices, with the rectal route 
preferred for infants and the axillary route preferred for toddlers. 
** Should a subject receive oral or injectable antibiotic therapy within 3 days prior to any 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. 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 appropriately documented that the sample was taken less than 3 days after stopping antibiotic treatment. 

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†† At Visits 1 and 4, the blood sample volume indicated will be taken from all subjects including those subjects in a subset to assess the antibody response to meningococcal serogroups (A, C, W, and Y) 
measured by rSBA assay in addition to hSBA assay. At Visits 5 and 6, blood sample volume of 5 mL will be taken from all subjects, except subjects included in the rSBA subset. Blood 
sample volume of 6 mL will be taken from subjects included in the rSBA subset. 
‡‡ Blood sample at Visit 1 and Visit 5 will be drawn before administration of the vaccines. 2 or 3 mL of blood are collected at Visit 1, and 3 or 4 mL of blood are collected at Visit 4 depending on the 
weight at the study visit.  
§§ Routine pediatric vaccines: Hexavalent vaccine and PCV13 at Visits 1, 2, and 5. The MMR vaccine may be administered preferably at Visit 5. 
*** This call is made 8 days to 10 days after the respective vaccinations. If Day 08 falls on a weekend or holiday, the telephone call may be made on the following business day. During this telephone 
call, the staff will find out whether the subject experienced any SAE (including any AESI) not yet reported, and will remind the subject’s parent / legally acceptable representative to continue 
using the diary card, to bring the diary card to the study center at the next visit, and confirm the date and time of the next visit. 
††† This call is made 5 months after Visit 4 and at least 14 days before Visit 5. During this telephone call, the staff will find out whether the subject experienced any SAE (including any AESI) not yet 
reported, will remind the subject’s parent / legally acceptable representative that routine vaccinations will be provided in the context of this study and that they should bring back the diary card 
to the study center at the next visit, and will confirm the date and time of the next visit. 
‡‡‡ Solicited injection site and systemic reactions will be recorded from Day 0 through Day 7 after each vaccination visit. 
§§§ Solicited injection site and systemic reactions will be recorded during the review and collection of DC1, DC2, DC3 and DC5 at Visits 2, 3, 4 and 6.  
****AESIs will be collected throughout the study as SAEs to ensure that the events are communicated to the Sponsor in an expedited manner and followed up until the end of the follow-up period or 
resolution, as per the assigned causality 
 

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List of Abbreviations  
µg 
Microgram 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immune deficiency syndrome 
AR 
adverse reaction 
BL 
blood sampling 
CCID 
cell culture infection dose 
CDM 
Clinical Data Management 
CI 
confidence interval 
CQA 
Clinical Quality Assessment 
CRA 
Clinical Research Associate 
CRB 
(electronic) case report book [all the case report forms for a subject] 
CRF 
(electronic) case report form 
CRM 
cross-reacting material 
CTA 
clinical trial agreement 
CTL 
Clinical Team Leader 
D 
Day 
DC 
diary card 
DNA 
deoxyribonucleic acid 
DOD 
delta optical density  
DTaP 
diphtheria, tetanus, and acellular pertussis 
EDC 
electronic data capture 
EIA 
enzyme immunoassay 
ELISA 
enzyme-linked immunosorbent assay  
EMA 
European Medicines Agency  
EU 
European Union 
FAS 
full analysis set 
FHA 
filamentous hemagglutinin 
FIM 
fimbriae types 2 & 3 
FVFS 
first visit, first subject 
FVLS 
first visit, last subject 
GCI 
Global Clinical Immunology 
GCP 
Good Clinical Practice 
GDPR 
Global Data Protection Regulation 
GMC 
geometric mean concentration 

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GMT 
geometric mean titer 
GPV 
Global Pharmacovigilance 
HB 
hepatitis B 
HBsAg 
hepatitis B surface antigen 
Hib 
Haemophilus influenzae type b 
HIV 
human immunodeficiency virus 
HPV 
human papilloma virus 
HRP 
horseradish peroxidase  
hSBA 
serum bactericidal assay using human complement 
IATA 
International Air Transport Association 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin 
IM 
intramuscular(ly) 
IMD 
invasive meningococcal disease 
IME 
important medical event 
IOM 
Institute of Medicine 
IPV 
inactivated polio vaccine 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
ITP 
idiopathic thrombocytopenic purpura 
IU 
International unit 
LCLS 
last contact, last subject 
LLOQ 
lower limit of quantitation 
LLT 
lowest level term 
MedDRA 
Medical Dictionary for Regulatory Activities 
mIU 
milli International unit 
mL 
Milliliter 
MMR 
measles, mumps, rubella 
NSAID 
non-steroidal anti-inflammatory drug 
OD 
optical density  
PCV10 
pneumococcal conjugate vaccine (10-valent, adsorbed)  
PCV13 
pneumococcal conjugate vaccine (13-valent, adsorbed) 
PHE 
Public Health England 
PPAS 
per-protocol analysis set 
PRP 
polyribosylribitol phosphate 
PRN 
pertactin 

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PS 
Polysaccharides 
PT 
pertussis toxoid / toxin 
PV 
Pharmacovigilance 
rDNA 
recombinant deoxyribonucleic acid 
RMO 
Responsible Medical Officer 
rSBA 
serum bactericidal assay using baby rabbit complement 
SAE 
serious adverse event 
SafAS 
safety analysis set 
SAP 
statistical analysis plan 
SD 
standard deviation 
SmPC 
Summary of Product Characteristics 
SMT 
Safety Management Team 
SOC 
system organ class 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
T 
Tetanus 
TC 
telephone call 
TCC 
tissue culture control  
TMF 
trial master file 
TT 
tetanus toxoid 
ULOQ 
upper limit of quantitation 
US 
United States 
VCR 
vaccination coverage rate 
WHO 
World Health Organization 
 

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1 
Introduction  
1.1 
Background  
This is a study using MenACYW conjugate vaccine (MenQuadfi®) against invasive 
meningococcal disease (IMD). 
This study (MET58) will compare the immunogenicity and describe the safety of MenACYW 
conjugate vaccine and Nimenrix® when administered as a 3-dose series concomitantly with 
routine pediatric vaccines to infants and toddlers in Europe. 
IMD is a serious illness caused by the bacterium Neisseria meningitidis (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 different meningococcal serogroups have been classified based on 
the immunochemistry of the capsular polysaccharides (PS). 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 
remains the main cause of epidemics in the world and is especially dominant in Africa and Asia. 
Serogroup W has been observed in Africa, as well as the United Kingdom, in residents who 
participated in the Hajj pilgrimage to the Kingdom of Saudi Arabia (4) (6) (7) and more recently 
in Chile (8), Turkey (9) (10), China (11) (12), Argentina (13), Brazil (14) (15), and 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 (2) (16). Serogroup Y has not been associated with 
outbreaks, but the frequency with which it causes sporadic cases has gradually increased in the 
US and more recently in Canada and Europe (17) (18) (19). The Y serogroup is commonly 
associated with meningococcal pneumonia, particularly in older adults ≥ 65 years of age (20). 
Outbreaks of serogroup B meningococcal disease have also been reported on college campuses in 
the United States (US) during the last five-year period: 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 (21) (22). 
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 (23) (24). 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 aged 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 (25). A gradual increase 
in serogroup Y IMD has also been recently reported in England and Wales between 2007-2009 

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(26) and in Sweden during 2005 – 2012 (27) (28). Nearly 50% of all IMD in Sweden was caused 
by serogroup Y in 2012 (27). Similarly, an increase in the proportion of IMD caused by serogroup 
Y has been observed in other Nordic countries, accounting for 31% in Norway in 2009 – 2010 (29) 
and 38% in Finland in 2010 (30). 
The goal for MenACYW conjugate vaccine is to provide broad protection against IMD caused by 
serogroups A, C, W, and Y in all age groups including children as young as 6 weeks of age, 
adolescents, and adults, including those 56 years of age and older. 
1.2 
Background of the Investigational Product  
1.2.1 
Clinical  
The 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 < 40 years of age; and 
MET32, a Phase I/II study in toddlers. 
The formulation has been evaluated in around 7115 subjects (infants, toddlers, adolescents, and 
adults > 56 years of age) in 10 completed studies: 4 Phase II studies, MET39, MET44, MET50, 
conducted in the USA, and MET54 conducted in Finland, and 6 Phase III studies, MET35, 
MET43, MET49 and MET56, conducted in the USA, MET51 conducted in EU region (Spain, 
Germany, Hungary and Finland), and MET57 conducted in Thailand, South Korea, Russia, and 
Mexico. The vaccine is currently approved under the brand name MenQuadfi® for use as single 
dose in ages 12 months and older in the European Union (31 countries under centralized 
procedurea), Australia, Canada, the United Kingdom, Brazil, Argentina, and Chile. The vaccine is 
also approved for use as single dose in ages 2 years and older in the USA. 
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. Available 
study results are presented in the Investigator’s Brochure. The relevant Phase II studies are 
discussed below. 
1.2.1.1 
Study MET39 (Phase II)  
MET39 was a Phase II, randomized, open-label, multi-center study conducted in the US for which 
580 healthy subjects from 2 to 15 months of age were enrolled. This study evaluated the optimal 
vaccination schedule in the infant/toddler population. Subjects in Group 1 through 
Group 4 received 1, 2, or 3 primary doses plus an additional dose of the MenACYW conjugate 
vaccine in the second year of life, concomitantly with routine pediatric vaccines at several 
different vaccination schedules. Subjects in Group 5 received 1 dose of the MenACYW conjugate 
                                                 
a Countries under centralized procedure include Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, 
Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, 
Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, and Sweden, United Kingdom 
(Northern Ireland) (remaining part after Brexit) and other European Economic Area countries – Iceland, 
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vaccine concomitantly with routine pediatric vaccines. The routine pediatric vaccines 
administered concomitantly with MenACYW conjugate vaccine at various schedules included 
Prevnar® (pneumococcal 7-valent conjugate vaccine) or Prevnar 13® (pneumococcal 13-valent 
conjugate vaccine [PCV13]), Pentacel® (diphtheria, tetanus, pertussis [acellular, component]-
poliovirus [inactivated]//Haemophilus influenzae type b [DTaP-IPV//Hib] ), ROTARIX® 
(monovalent rotavirus  vaccine [RV1]) or RotaTeq® (pentavalent rotavirus vaccine [RV5]), 
hepatitis B [HB] vaccine, M-M-R® II vaccine (measles, mumps, and rubella vaccine [MMR]), and 
VARIVAX® (varicella vaccine). 
Immunogenicity 
After the primary series consisting of 1, 2, or 3 doses of MenACYW conjugate vaccine, protective 
serum bactericidal assay using human complement (hSBA) threshold titers of ≥ 1:8 were attained 
by > 88% of subjects for serogroup C and by 62% to 74% for serogroup A. For serogroups Y and 
W, ≥ 90% achieved the threshold titer after 3 doses, 75% to 84% after 2 doses, but only 25% after 
a single dose administered at 6 months of age. 
After an additional dose of MenACYW conjugate vaccine in the second year of life 
(12 or 15 months), between 91% and 100% of the subjects achieved the protective threshold 
regardless of the number of doses they received in the first year of life. 
No interaction was demonstrated between the routine vaccines and MenACYW conjugate 
vaccine, compared to when the routine vaccines were given without MenACYW conjugate 
vaccine in the control groups. 
Safety 
MenACYW conjugate vaccine was well tolerated in infants and toddlers regardless of the 
immunization schedule and the number of doses administered. Safety results were comparable to 
those seen in control group subjects regardless of the immunization schedule and the number of 
doses administered. The safety profile of the licensed vaccines given concomitantly with 
MenACYW conjugate vaccine was similar to that of the licensed vaccines given concomitantly 
without MenACYW conjugate vaccine.  
No deaths occurred within 30 days. There were 2 subjects in Group 4 who died during the study, 
1 as a result of hypoxic ischemic encephalopathy which started 96 days after the 6-month 
vaccination and 1 as a result of non-accidental head trauma 36 days after the 12-month 
vaccination. These events were considered by the Investigator as unrelated to study vaccine. 
There were 2 other subjects who discontinued the study due to a serious adverse event (SAE) and 
the receipt of intravenous immunoglobulin treatment: 1 subject in Group 2 with Kawasaki 
disease, 106 days after the 6-month vaccination; and 1 subject in Group 3 with middle lobe 
pneumonia and Kawasaki disease, 50 and 52 days, respectively, after the 4-month vaccinations. 
One other subject in Group 4 was discontinued due to a non-serious adverse event (AE) (viral 
rash 1 day after the 6-month vaccinations). None of these AEs leading to discontinuation were 
considered by the Investigator as related to the vaccine. There were no vaccine- related SAEs 
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1.2.1.2 
Study MET54 (Phase II)  
MET54 was a Phase II, randomized, open-label, active-controlled, multi-center study conducted 
in Europe (Finland). This study evaluated the immunogenicity and safety profile of a single dose 
of MenACYW conjugate vaccine when given alone in healthy, meningococcal-vaccine naïve 
toddlers compared to that of the licensed vaccine Nimenrix®. A total of 188 meningococcal 
vaccine naïve subjects aged 12 to 23 months on the day of enrollment were randomized to 
1 of 2 groups. Group 1 received a single dose of MenACYW conjugate vaccine and Group 2 
received a single dose of Nimenrix®. 
Immunogenicity 
Antibody responses to the antigens (serogroups A, C, W, and Y) were evaluated by serum 
bactericidal assay using baby rabbit complement (rSBA) and hSBA. MenACYW conjugate 
vaccine immune responses evaluated by rSBA and hSBA were generally comparable to 
Nimenrix® immune responses with some variation by serogroup. 
hSBA 
Most subjects in both groups had hSBA titers ≥ 1:8 at D30: the percentages after MenACYW 
conjugate vaccine for serogroups A, Y, and W (ranging from 97.8% [89/91] to 98.9% [90/91]) 
were comparable to those after Nimenrix® (ranging from 91.9% [79/86] to 100.0% [86/86]). The 
percentage of subjects with hSBA titers ≥ 1:8 for serogroup C was higher after MenACYW 
conjugate vaccine (100.0% [91/91]) than after Nimenrix® (89.5% [77/86]). At D30, most subjects 
in both groups demonstrated an hSBA vaccine seroresponse. The percentage of subjects with an 
hSBA vaccine seroresponse for serogroups A, Y, and W was comparable in both groups (ranging 
from 96.7% [87/90] to 98.9% [90/91] after MenACYW conjugate vaccine and from  
91.9% [79/86] to 98.8% [85/86] after Nimenrix®). The percentage of subjects with an hSBA 
vaccine seroresponse for serogroup C was higher after MenACYW conjugate vaccine  
(100.0% [91/91]) than after Nimenrix® (86.0% [74/86]). 
rSBA 
Most subjects had rSBA titers ≥ 1:128 at D30. The percentages after MenACYW conjugate 
vaccine were similar (100.0% [91/91] for serogroups A, Y, and W) or numerically higher 
(100.0% [91/91] for serogroup C) compared to Nimenrix® (100.0% [86/86] for serogroups A, Y, 
and W and 94.2% [81/86] for serogroup C). At D30, most subjects in both groups demonstrated 
an rSBA vaccine seroresponse as defined in the SAP and as defined in the protocol. The 
percentage of subjects with any rSBA vaccine seroresponse by either definition for serogroup A 
was numerically lower after MenACYW conjugate vaccine (91.2% [83/91]) than Nimenrix® 
(98.8% [85/86]) and the percentages of subjects with any rSBA vaccine seroresponse by either 
definition were similar or comparable between the 2 groups for serogroups C, Y, and W (all 
> 96%). 
Safety 
Overall, vaccination with MenACYW conjugate vaccine among toddlers aged 12 to 23 months 
was found to be safe with no safety concerns identified. The MenACYW conjugate vaccine was 
well tolerated with no immediate AEs or adverse reactions (ARs), no discontinuations due to an 
SAE or other AE, and no related SAEs. 

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The safety profile of MenACYW conjugate vaccine was comparable to that of the licensed 
vaccine Nimenrix®. 
No new clinically important safety findings were identified with administration of the 
MenACYW conjugate vaccine. The MenACYW conjugate vaccine was well tolerated and 
immunogenic. Single dose of the MenACYW conjugate vaccine demonstrated excellent potential 
to be an alternative vaccine option for toddlers, receiving meningococcal vaccination for the first 
time. 
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 the MenACYW conjugate vaccine. 
However, based on the data generated from previous studies, the immunogenicity profile of the 
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 the MenACYW conjugate vaccine in humans. 
Subjects who receive Nimenrix® will likely be protected against meningococcal disease caused by 
N. meningitidis serogroups A, C, W, and Y. 
As with any vaccine, MenACYW conjugate vaccine and Nimenrix® may not protect 100% of 
individuals against the diseases they are designed to prevent. 
In countries where vaccination advisory boards or national pediatric associations have 
recommended the Meningococcal B vaccine although it is not publicly funded (ie Czech 
Republic, Spain, and Poland), subjects will be offered  2 doses of the Meningococcal B vaccine 
(Bexsero®) when parents are willing to vaccinate their child within the second year of life. This 
vaccine is a non-study vaccine to be administered as per local standard practices at additional 
optional visits after the end of the trial (ie, after the subject will have completed the last study 
procedure at the last study visit). This vaccine will be outside the scope of the study evaluations. 
No immunogenicity and safety data will be collected after its administration. The Meningococcal 
B vaccine (Bexsero®) will be reimbursed by the Sponsor. 
1.3.2 
Potential Risks to Subjects  
Like other vaccines, MenACYW conjugate vaccine or Nimenrix® may cause injection site 
reactions such as pain, swelling, and erythema, or certain systemic events such as fever, 
irritability, drowsiness, loss of appetite, abnormal crying, and vomiting when administered to 
infants / toddlers. There may be a rare possibility of an allergic reaction, which could be severe. 
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 or Nimenrix® that are not yet known. 
In a previous study with MenACYW conjugate vaccine (MET32), 1 SAE of reactive arthritis 
reported in a toddler was considered by the Investigator to be related to the investigational 

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vaccine. The subject developed right knee inflammation the day after receiving MenACYW 
conjugate vaccine, given by IM injection in the right deltoid. The subject recovered after 
treatment with ibuprofen and antibiotics. Results of the reactive arthritis investigations performed 
as part of the workup were not indicative of any specific diagnosis. A point of further 
consideration was the monoarticular nature of the inflammation in this subject; reactive arthritis 
would typically be present clinically in a polyarticular fashion. Importantly, no similar cases have 
been reported following the administration of MenACYW conjugate vaccine in any other 
completed trials. 
Guillain-Barré syndrome has been reported mostly in persons aged 11 to 19 years who had 
symptom onset within 6 weeks of administration of a US licensed meningococcal conjugate 
vaccine (31). A retrospective cohort study carried out in the US using healthcare claims data 
found no evidence of increased Guillain-Barré syndrome risk associated with the use of that 
vaccine. The study was able to exclude all but relatively small incremental risks (32). 
A review by the Institute of Medicine (IOM) found inadequate evidence to accept or reject a 
causal relationship between tetanus toxoid containing vaccines and Guillain-Barré syndrome (33). 
The IOM found evidence for a causal relation between tetanus toxoid-containing vaccines and 
brachial neuritis (34). Arthus reactions are rarely reported after vaccination and can occur after 
tetanus toxoid-containing vaccines (34). 
No occurrences of Guillain-Barré syndrome, brachial neuritis, or Arthus reaction have been 
reported with the use of MenACYW conjugate vaccine in the completed clinical trials. 
The potential risk listed here are not exhaustive. Refer to the Investigator’s Brochure of the 
investigational vaccine and to the package inserts for Nimenrix® (35) and concomitant vaccines 
for additional information regarding potential risks. 
1.4 
Rationale for the Study  
The 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, W, and Y. Compared to a previous Sanofi Pasteur meningococcal 
conjugate vaccine, Menactra® the 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. The program targets licensure of the MenACYW conjugate vaccine in many 
countries in North America, Europe, Latin America, Africa, the Middle East, and Asia Pacific. 
The MenACYW conjugate vaccine is designed to cover broader age groups than those covered by 
Menomune® -A/C/Y/W-135 and Menactra®. Menactra® has been very successful since its 
licensure in 2005; however, it is not licensed in Europe and is not indicated in persons 8 months 
of age or younger or 56 years of age and older. While Menomune® -A/C/Y/W-135 and Menactra® 
are currently licensed in different parts of the world, the MenACYW conjugate vaccine is being 
developed by Sanofi Pasteur to ultimately replace Menomune® -A/C/Y/W-135 and Menactra® in 
the global market as a quadrivalent meningococcal conjugate vaccine indicated in 

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infants/toddlers, children, adolescents, adults, and older adults > 56 years of age. 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 
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 (MET39 and 
MET44) showed the potential of the candidate vaccine as a very good immunogen in all age 
groups, including young infants and older adults. The 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 MET58 is to compare the immunogenicity and describe the safety of MenACYW 
conjugate vaccine and the licensed MenACYW conjugate vaccine (Nimenrix®) when 
administered as a 3-dose series concomitantly with routine pediatric vaccine to healthy infants and 
toddlers in Europe. 
2 
Study Objectives  
2.1 
Primary Objective  
To demonstrate the non-inferiority of the antibody response against meningococcal serogroups A, 
C, W, and Y following the administration of a 3-dose series of MenACYW conjugate vaccine 
compared to a 3-dose series of Nimenrix® when each vaccine is administered concomitantly with 
routine pediatric vaccines (PCV10 and hexavalent vaccine) to infants and toddlers from 6 weeks 
to 18 months old (Group 1 versus Group 2) 
The endpoint for the primary objective is presented in Section 9.1.2.1. 
2.2 
Secondary Objectives  
1) To demonstrate the non-inferiority of the antibody response against meningococcal 
serogroups A, C, W, and Y following the administration of 2 doses in infancy of MenACYW 
conjugate vaccine compared to 2 doses in infancy of Nimenrix® when each vaccine is 
administered concomitantly with routine pediatric vaccines (PCV10 and hexavalent vaccine) 
(Group 1 versus Group 2) 
2) To describe the antibody responses against meningococcal serogroups A, C, W, and Y when 
MenACYW conjugate vaccine is administered in a 3-dose series concomitantly with the 
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3) To describe the antibody responses against the antigens of the routine pediatric vaccines 
administered in a 3-dose series concomitantly with MenACYW conjugate vaccine or 
Nimenrix® (Groups 1, 2, and 3) 
4) To describe the antibody responses against meningococcal serogroups A, C, W, and Y 
measured by hSBA when MenACYW conjugate vaccine or Nimenrix® is administered in a  
3-dose series concomitantly with PCV10 and other routine pediatric vaccines (Groups 1 and 
2) 
5) To describe the antibody responses against meningococcal serogroups A, C, W, and Y 
measured by hSBA when MenACYW conjugate vaccine is administered in a 4-dose series 
concomitantly with PCV13 and other routine pediatric vaccines (Group 4) 
6) To describe the antibody responses against the antigens of the routine pediatric vaccines 
administered with MenACYW conjugate vaccine administered in a 4-dose series 
concomitantly (Group 4) 
The endpoints for the secondary objectives are presented in Section 9.2.2.1. 
2.3 
Observational Objectives  
Immunogenicity 
To describe the antibody responses against meningococcal serogroups A, C, W, and Y measured 
by rSBA in a subset of subjects when MenACYW conjugate vaccine or Nimenrix® is 
administered concomitantly with routine pediatric vaccines (all groups) 
Safety 
To describe the safety profile of MenACYW conjugate vaccine and Nimenrix® when 
administered concomitantly with routine pediatric vaccines in healthy infants and toddlers 
The endpoints for the observational objectives are presented in Section 9.3.2.2. 
3 
Investigators and Study Organization  
This study will be conducted in approximately 50 centers in Europe. The Principal Investigators 
and any sub-investigators at the individual sites will be coordinated by 1 Coordinating 
Investigator in each country. Details of the study centers, the Investigators at each center, and the 
Coordinating Investigators are provided in the “List of Investigators and Centers Involved in the 
Trial” document. 
The Sponsor’s Responsible Medical Officer (the RMO, the person authorized to sign this protocol 
and any amendments on behalf of the Sponsor) is 
. 

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4 
Independent Ethics Committee / Institutional Review Board  
Before the investigational product can be shipped to the investigational site and before the 
inclusion of the first subject, this protocol, the informed consent form (ICF), subject recruitment 
procedures, and any other written information to be provided to subjects must be approved by, 
and / or receive favorable opinion from, the appropriate Independent Ethics Committees (IECs) or 
Institutional Review Boards (IRBs). 
In accordance with Good Clinical Practice (GCP) and local regulations, each Investigator and / or 
the Sponsor are responsible for obtaining this approval and / or favorable opinion before the start 
of the study. If the protocol is subsequently amended, approval must be re-obtained for each 
substantial amendment. Copies of these approvals, along with information on the type, version 
number, and date of document, and the date of approval, must be both maintained by the 
Investigator and the Sponsor together with the composition of the IEC / IRB (the names and 
qualifications of the members attending and voting at the meetings). 
The Investigator or Sponsor will submit written summaries of the status of the study to the IEC / 
IRB annually, or more frequently (according to national provision) if requested. All SAEs 
occurring during the study that could be related to the product administered will be reported by 
the Investigator to the IEC / IRB, according to the IEC / IRB policy.  
5 
Investigational Plan  
5.1 
Description of the Overall Study Design and Plan  
5.1.1 
Study Design  
This is a Phase III, partially modified double-blind (open-label for some of the vaccines / study 
groups, as detailed in the note below), randomized, parallel-group, active-controlled, multi-center 
study to compare the immunogenicity and describe the safety of MenACYW conjugate vaccine 
and Nimenrix® (Meningococcal group A, C, W-135, and Y conjugate vaccine) when administered 
as a 3-dose series (ie, 2 doses administered in infancy and 1 dose in the second year of life) 
concomitantly with routine pediatric vaccines to healthy infants and toddlers in Europe. 
Subjects in Groups 1, 2, and 3 will receive either 3 doses of MenACYW conjugate vaccine or 
3 doses of Nimenrix® administered concomitantly with routine vaccines at 2 months of agea 
(Visit 1), 4 months of age (Visit 2), and 12 to 18 months of age (Visit 4). The hexavalent vaccines 
and the pneumococcal vaccines (PCV10 or PCV13) will be administered in a 2+1 regimen (ie, 2 
doses in infancy and 1 final dose in the 2nd year of life) mimicking the regimen of MenACYW 
conjugate vaccine or Nimenrix®.  
                                                 
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Subjects in Group 4 will receive 4 doses of MenACYW conjugate vaccine with routine vaccines 
at 2 months of agea (Visit 1), 4 months of age (Visit 2), 6 months of age (Visit 3; MenACYW 
conjugate vaccine only), and 12 to 18 months of age (Visit 5; MenACYW conjugate vaccine and 
routine vaccines). The hexavalent vaccine and PCV13 will be administered in a 2+1 regimen, 
concomitantly to the 1st and 2nd doses in infancy and the 4th dose of MenACYW conjugate 
vaccine. The 3rd dose of MenACYW conjugate vaccine will be administered alone, without any 
other routine pediatric vaccines. 
In all 4 vaccine groups, the MMR vaccine may be preferably administered concomitantly with the 
other study vaccines at 12 to 18 months of age. If not, the subject will receive a licensed Measles, 
Mumps and Rubella vaccine with a gap of at least 4 weeks before any study vaccines or after the 
end of the study (ie, after the subject will have completed the last study procedure at the last study 
visit). When administered outside the study visit, the licensed Measles, Mumps and Rubella 
vaccine will be sourced by the health care system, according to the national immunization 
program. 
Subjects in Finland, Sweden or Poland may receive the licensed rotavirus vaccine concomitantly 
with study vaccines at study vaccination visits Visit 1 and Visit 2. If not, the rotavirus vaccine can 
be administered with a time interval of at least 2 weeks before or 2 weeks after Visit 1 and/or 
Visit 2. The rotavirus vaccines will be sourced by the study sites and administered as per local 
standard practices.  Safety data will be collected after the administration of the rotavirus vaccine 
concomitantly with the study vaccine. No serological testing will be done for rotavirus 
immunogenicity. 
Subjects in Spain, Czech Republic, and Poland will be offered 2 doses of the Meningococcal B 
vaccine (Bexsero®) when parents are willing to vaccinate their child within the second year of 
life. This vaccine is a non-study vaccine to be administered as per local standard practices at 
additional optional visits after the end of the trial (ie, after the subject will have completed the last 
study procedure at the last study visit). This vaccine will be outside the scope of the study 
evaluations. No immunogenicity and safety data will be collected after its administration. The 
Meningococcal B vaccine (Bexsero®) will be reimbursed by the Sponsor. 
5.1.2 
Justification of the Study Design  
The MET58 study is designed to evaluate the immunogenicity and describe the safety of a 3-dose 
series (2+1 schedule) of MenACYW conjugate vaccine compared to a 3-dose series of Nimenrix® 
when administered concomitantly with routine pediatric vaccines to infants and toddlers 6 weeks 
to 18 months old in Europe. The design of the study has been based on the feedback received 
from the European Medicines Agency (EMA) as a part of multiple scientific advice documents.  
The 2+1 schedule comprises a first infant dose of MenACYW conjugate vaccine or Nimenrix® 
administered between 6 and 12 weeks of age and the second dose at least 2 months later (between 
4 and 5 months of age). The third dose is administered at 12 to 18 months, with a minimum gap of 
6 months between the second and third doses. The study will be conducted in European Union 
(EU) countries where the Sanofi Pasteur tetanus toxoid (TT) - conjugated hexavalent vaccine 
licensed in Europe (DTaP-IPV-HB-Hib vaccine having different trade names in Europe: Hexyon® 
in Western Europe, and Hexacima® in Eastern Europe) and PCV10 (Synflorix®) are licensed and 
could be administered in a 2+1 regimen (ie, 2 doses in infancy and 1 booster dose preferably 

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between 12 and 15 months of age) mimicking the meningococcal vaccine regimen. Overall, the 
meningococcal vaccines schedule may fit to the routine immunization schedules in EU countries, 
knowing its diversity. 
Additional vaccine groups (Group 3 and Group 4) will generate data on immunogenicity and 
safety of MenACYW conjugate vaccine when administered concomitantly with the hexavalent 
vaccine and PCV13 (Prevenar13®). Data will be also generated with MenACYW conjugate 
vaccine administered in a 3+1 schedule (Group 4): 3 doses during infancy and a final dose in the 
second year of life. Although the first and second doses of MenACYW conjugate vaccine in 
infancy will be administered concomitantly with PCV13 and hexavalent vaccine, the 3rd dose of 
MenACYW conjugate vaccine in infancy will be administered at least 2 months after the 2nd dose 
and alone, as there is no routine vaccination at this age in the National Immunization Programs of 
EU countries participating in MET58. Data generated in Europe with the 3+1 schedule of 
MenACYW conjugate vaccine will be descriptive only.  
In all 4 vaccine groups, the subject will receive a licensed Measles, Mumps and Rubella vaccine 
either administered concomitantly with the study vaccines at 12 to 18 months of age, or separately 
with at least a gap of 4 weeks before any study vaccines or after the end of the study (ie, after the 
subject will have completed the last study procedure at the last study visit). Those clinical data 
generated would cover any possible integration of the MenACYW conjugate vaccine use in the 
National Immunization Programs of EU countries and outside the EU. 
Despite the fact that this study is being conducted in the EU and is targeting to generate data 
relevant for the EU population and aligned with EU meningococcal conjugate vaccine schedules, 
it is also part of the global development program for the MenACYW conjugate vaccine and will 
allow for the EU and global data to be placed in context of each other through the data generated 
for subjects in all Groups (including those receiving the 3+1 schedule in Group 4). The 
descriptive set of clinical data using the 3+1 schedule of MenACYW conjugate vaccine will be 
put in perspective with data generated in the non-EU studies where the 3+1 schedule and the 
2+1 schedule of MenACYW conjugate vaccine will be assessed with different concomitant 
pediatric vaccines. Those clinical data generated would cover any possible use in EU and 
internationally (if needed due to evolution of epidemiology in the future or to adapt to the 
increasing complexity of immunization schedules in infants and toddlers worldwide).  
In the Phase II MET39 study conducted in the US, MenACYW conjugate vaccine was co-
administered in a population of infants with recommended pediatric vaccines at several schedules 
(1+1, 2+1 and 3+1) and demonstrated good safety profile regardless of the immunization schedule 
and the number of doses administered. All analyses will evaluate the immune responses to 
serogroups A, C, W, and Y. The immune response to all routine vaccines administered 
concomitantly with MenACYW conjugate vaccine or Nimenrix® will also be assessed. To avoid 
any potential immune interference the Meningococcal Group B vaccine cannot be administered 
before inclusion in the study and during the study period.  
The rotavirus program varies across MET58 countries (36). Among countries in which subjects 
will contribute to the primary objective assessment, Finland is the only country with a largely 
implemented and publicly-funded rotavirus vaccine (37). The vaccination coverage rate is quite 
high (VCR >90%) (37).  Subjects in Finland, Sweden or Poland may receive their rotavirus 
vaccine concomitantly with study vaccines at study vaccination visits Visit 1 and Visit 2. If not, 

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the rotavirus vaccine can be administered with a time interval of at least 2 weeks before or 2 
weeks after Visit 1 and/or Visit 2. The rotavirus vaccines will be sourced by the study sites and 
administered as per local standard practices. According to the respective product information, no 
immune interference has been reported between licensed rotavirus vaccines and standard of care 
vaccines administered in this study. In the ongoing phase III MET42 study conducted in infants in 
the US, the immunogenicity of  the rotavirus vaccine will be evaluated when administered 
concomitantly with MenACYW conjugate vaccine and other pediatric routine vaccines (38). 
The country selection for MET58 took into consideration the current status of the 
Meningococcal B vaccination program in the EU countries and select countries/regions where the 
implementation is not yet done or where the vaccination coverage is still low (ie, below the 
national vaccination coverage). The status of the Meningococcal B vaccination program in the 
MET58 countries/regions will be monitored on ongoing basis throughout the study conduct. 
Depending on the evolution of the local requirement for the Meningococcal B vaccination, the 
participation of the country/sites would be reassessed accordingly to ensure that the benefit for 
subjects to participate to MET58 outweigh any lack of chance for not receiving standard-of-care 
vaccines.  
After the end of their study participation, the subjects will continue with the vaccination schedule 
recommended in their respective countries according to their age. Amongst the countries which 
are part of the MET58 study, Italy is the only country where the MenB vaccination has been 
implemented in the national immunization schedule and is free of charge. In this country, the 
investigators will advise parents to contact the local health care centers after the end of the study 
for their child to receive the Meningococcal B vaccination as per Bexsero® Product Information 
(39). 
In other countries where vaccination advisory boards or national pediatric associations have 
recommended the Meningococcal B vaccine but it is not public funded (ie Czech Republic, Spain, 
and Poland) (40) (41), subjects will be offered 2 doses of the Meningococcal B vaccine 
(Bexsero®) when parents are willing to vaccinate their child within the second year of life. This 
vaccine is a non-study vaccine to be administered as per local standard practices at additional 
optional visits after the end of the trial (ie, after the subject will have completed the last study 
procedure at the last study visit). This vaccine will be outside the scope of the study evaluations. 
No immunogenicity and safety data will be collected after its administration. The Meningococcal 
B vaccine (Bexsero®) will be reimbursed by the Sponsor. 
To perform an appropriate safety description, the study will be partially modified double-blind. 
The MenACYW conjugate vaccine and Nimenrix® will be administered in a modified double-
blind manner in the vaccine groups directly compared, ie, when administered in the 2+1 schedule 
concomitantly with PCV10 (Synflorix®) and the Sanofi Pasteur hexavalent vaccine. The 
MenACYW conjugate vaccine in other vaccine groups and all other concomitant vaccines in all 
vaccine groups will be administered in an open-label manner. 
5.1.3 
Study Plan  
Approximately 1652 healthy infants aged 6 to 12 weeks at enrollment will be randomized. 
Approximately 20% of subjects 6 to 8 weeks of age (≥ 42 to ≤ 59 days) should be enrolled Groups 

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1 and 2 to provide safety and immunogenicity data for this population, as described below (refer 
to Section 6.5 for more details): 
• 
Group 1 and Group 2: approximately 144 subjects in each group; 
• 
Group 3 and Group 4: approximately 22 subjects in each group. 
The vaccination and blood sampling schedules are detailed in Table 5.1 and Table 5.2. 
 

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Table 5.1: Vaccination and blood sampling schedule in Groups 1, 2, and 3  
Visit # 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5* 
Group 
BL0001† 
3 vaccinations 
3 vaccinations 
BL0002 
BL0003† 
4 vaccinations 
BL0004 
1 
X 
MenACYW conjugate 
vaccine 
Hexavalent vaccine‡  
PCV10‡ 
 
MenACYW conjugate 
vaccine 
Hexavalent vaccine 
PCV10 
 
X 
X 
MenACYW conjugate 
vaccine 
Hexavalent vaccine‡ 
PCV10‡ 
MMR vaccine 
X 
2 
X 
Nimenrix® 
Hexavalent vaccine‡  
PCV10‡ 
 
Nimenrix® 
Hexavalent vaccine‡ 
PCV10‡ 
 
X 
X 
Nimenrix® 
Hexavalent vaccine‡ 
PCV10‡ 
MMR vaccine 
X 
3 
X 
MenACYW conjugate 
vaccine 
Hexavalent vaccine‡ 
PCV13‡ 
MenACYW conjugate 
vaccine 
Hexavalent vaccine‡ 
PCV13‡ 
X 
X 
MenACYW conjugate 
vaccine 
Hexavalent vaccine‡ 
PCV13‡ 
MMR vaccine 
X 
PCV10: Synflorix® 
PCV13: Prevenar 13® 
MMR vaccine (M-M-RVAXPRO®) may be received concomitantly with other vaccines at Visit 4.   
*Last study visit for Groups 1, 2, and 3. Other routine vaccines can be administered as per standard of care after study procedures are completed 
†Blood will be drawn prior to vaccinations 
‡The hexavalent vaccine and PCV10 (or PCV13 in Group 3) be administered in a 2+1 regimen, concomitantly with the 1st and 2nd doses in infancy and the toddler dose of 
MenACYW conjugate vaccine. Subjects in Finland, Sweden or Poland may receive the licensed rotavirus vaccine concomitantly with study vaccines at Visit 1 and Visit 2. No 
serological testing will be done for rotavirus immunogenicity 

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Table 5.2: Vaccination and blood sampling schedule in Group 4  
Visit # 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6* 
Group 
BL0001† 
3 vaccinations 
3 vaccinations 
1 vaccination 
BL0002 
BL0003† 
4 vaccinations 
BL0004 
4 
x 
MenACYW 
conjugate vaccine 
Hexavalent 
vaccine‡  
PCV13‡  
MenACYW 
conjugate vaccine 
Hexavalent 
vaccine 
PCV13 
MenACYW 
conjugate 
vaccine§ 
x 
X 
MenACYW conjugate 
vaccine 
Hexavalent vaccine 
PCV13 
MMR vaccine 
x 
PCV13: Prevenar 13® 
MMR vaccine (M-M-RVAXPRO®) may be received concomitantly with other vaccines at Visit 5.    
*Last study visit for group 4. Other routine vaccines can be administered as per standard of care after study procedures are completed 
†Blood will be drawn prior to vaccinations 
‡The hexavalent vaccine and Prevenar 13 will be administered in a 2+1 regimen, concomitantly with the 1st and 2nd doses in infancy and the toddler dose of MenACYW conjugate 
vaccine  
§The 3rd dose of MenACYW conjugate vaccine is administered alone, without any other routine pediatric vaccines 
 

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Vaccinations 
Healthy infants will be randomized as follows depending on the pneumococcal vaccines that will 
be administered in the respective countries. 
Countries where the pneumococcal vaccination administered will be PCV10 (Czech 
Republic, Romania, Sweden, Finland, and Poland): 1432 subjects will be randomized in a 1:1 
ratio to one of the following 2 groups: 
• Group 1: MenACYW conjugate vaccine (3 doses) (2+1 regimen) + PCV10 + Hexavalent 
vaccine + MMR vaccine (n=716) 
• Group 2: Nimenrix® (3 doses) (2+1 regimen) + PCV10 + Hexavalent vaccine + MMR 
vaccine (n=716) 
Countries where the pneumococcal vaccination administered will be PCV13 (Italy and 
Spain): 220 subjects will be randomized in a 1:1 ratio to one of the following 2 groups: 
• Group 3: MenACYW conjugate vaccine (3 doses) (2+1 regimen) + PCV13 + Hexavalent 
vaccine + MMR vaccine (n=110)  
• Group 4: MenACYW conjugate vaccine (4 doses) (3+1 regimen) + PCV13 + Hexavalent 
vaccine + MMR vaccine (n=110) 
For all 4 vaccine groups, the MMR vaccine may be preferably administered concomitantly with 
the other vaccines at 12 to 18 months of age. If not, the subject will receive a licensed Measles, 
Mumps and Rubella vaccine with a gap of at least 4 weeks before any study vaccines or after the 
end of the study (ie, after the subject will have completed the last study procedure at the last study 
visit). When administered outside the study visits, the licensed Measles, Mumps and Rubella 
vaccine will be sourced by the health care system, according to the national immunization 
program. 
Subjects in Finland, Sweden or Poland may receive the licensed rotavirus vaccine concomitantly 
with study vaccines at study vaccination visits Visit 1 and Visit 2. If not, the rotavirus vaccine can 
be administered with a time interval of at least 2 weeks before or 2 weeks after Visit 1 and/or 
Visit 2. The rotavirus vaccines will be administered, as per local standard practices.  
Subjects in Spain, Czech Republic, and Poland will be offered 2 doses of the Meningococcal B 
vaccine (Bexsero®) when parents are willing to vaccinate their child within the second year of 
life. This vaccine is a non-study vaccine to be administered as per local standard practices at 
additional optional visits after the end of the trial (ie, after the subject has completed the last study 
procedure at the last study visit). This vaccine will be outside the scope of the study evaluations. 
No immunogenicity and safety data will be collected after its administration. The Meningococcal 
B vaccine (Bexsero®) will be reimbursed by the Sponsor. 
Note: To perform an appropriate description of the safety of MenACYW conjugate vaccine and 
Nimenrix® in Groups 1 and 2 (ie, when each of these vaccines are administered as a 3-dose series 
concomitantly with PCV10 and hexavalent vaccine), MenACYW conjugate vaccine and 
Nimenrix® will be administered in a modified double-blind manner in these 2 groups. The 
MenACYW conjugate vaccine in Groups 3 and 4 and all other concomitant vaccines in all 
vaccine groups will be administered in an open-label manner.  

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Refer to Section 6.4 for more details. 
Blood sampling 
All subjects will provide 4 blood samples. 
Subjects in Groups 1, 2, and 3 will provide blood samples for immunogenicity assessment as 
follows: 
• at baseline (pre-primary vaccination 1, Day 0) 
• 30 days (+21 days) after the 2nd dose of MenACYW conjugate vaccine / Nimenrix® 
• prior to the 3rd dose (toddler dose) of MenACYW conjugate vaccine / Nimenrix® 
• 30 days (+21 days) after the 3rd dose (toddler dose) of MenACYW conjugate vaccine / 
Nimenrix® 
Subjects in Group 4 will provide blood samples for immunogenicity assessment as follows:  
• at baseline (pre-primary vaccination 1, Day 0) 
• 30 days (+21 days) after the 3rd dose of MenACYW conjugate vaccine 
• prior to the 4th dose (toddler dose) of MenACYW conjugate vaccine 
• 30 days (+21 days) after the 4th dose (toddler dose) of MenACYW conjugate vaccine 
Collection of safety data 
• All subjects will be followed for safety from Day 0 to the last study visit 
• All subjects will be observed for 30 minutes after each vaccination and any unsolicited 
systemic AEs occurring during that time will be recorded as immediate unsolicited systemic 
AEs in the electronic case report book (CRB). 
• The subject’s parent / legally acceptable representative will record information in a diary card 
about solicited reactions from Day 0 to Day 7 after each vaccination and unsolicited AEs will 
be recorded from Day 0 to Day 30 after each vaccination. 
• SAEs, including adverse events of special interest (AESIs) will be recorded in a diary card 
throughout the study. The 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 subjects’ parent / legally acceptable representative by telephone 
on 8 days (+2 days) after each vaccination visit to identify the occurrence of any SAEs not yet 
reported and to remind them to complete the diary card after each vaccination visit and bring 
it back to the subsequent visit so that it can be reviewed at the study site. 
• Staff will also contact subjects’ parent / legally acceptable representative by telephone  
5 months after the last visit in infancy and at least 14 days before Visit 4 (Groups 1, 2, and 3) 
or Visit 5 (Group 4). This contact is to identify the occurrence of any SAEs not yet reported, 
but also to remind them that routine vaccinations will be provided in the context of this study 
and that they should bring back the diary card to the subsequent visit so that it can be 
reviewed at the study site. If the subject does not continue in the study, the information 

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recorded on the diary card will be reviewed during this call, and the diary card will be 
retrieved by the site. 
5.1.4 
Visit Procedures  
Visit 1 (D0; 2 months [6 to 12 weeks] of age): Inclusion, Randomization, Blood Sample, and 
Vaccination 
1) 
Give the subject’s parent / legally acceptable representative information about the study, 
obtain written informed consent, and give him / her a signed copy. 
2) 
Check inclusion and exclusion criteria for eligibility. Review vaccination history from the 
child’s immunization record. 
3) 
Collect demographic data (including birth weight and gestational age). 
4) 
Obtain verbal medical history about the subject, including ongoing medication. 
5) 
Conduct a physical examination as per standard of care. Perform a physical examination, 
including, but not limited to, examination of the head (ear, nose, and throat), neck, heart, 
lungs, abdomen, and extremities. If a routine examination had been performed within the last 
week by the Investigator, a sub-investigator, or a licensed nurse practitioner, it does not need 
to be repeated unless there were some changes in health status, in which case it may be 
limited to the affected area. 
6) 
Take the subject’s temperature (Refer to Section 9.3.2.3.2 for accurate temperature 
assessment). If the temperature is ≥ 38°C, postpone vaccination until the condition is 
resolved.  
7) 
Take the subject’s weight to determine if 2 or 3 ml are to be collected for BL0001 (refer to 
the Operating Guidelines for further instructions). 
8) 
Contact the interactive response technology (IRT) system for vaccine group randomization 
(at least allocation of subject number, dose number of all vaccines). 
9) 
Review temporary contraindications for blood sampling. Ensure the subject has not had any 
antibiotics within the previous 72 hours (3 days). 
10) Collect 2 or 3 mL of blood (BL0001) depending on the weight of the subject at inclusion 
from all subjects including those subjects in the rSBA subset (see Section 7.1 for detailed 
instructions regarding the handling of blood samples and Section 6.5 for more details on the 
rSBA subset). If attempts to obtain the first blood draw are unsuccessful (after reasonable 
attempts as per local regulations) either the Visit 1 can be rescheduled to a later date at which 
point inclusion/exclusion criteria must be re-validated or the subject will be withdrawn from 
the study without being vaccinated. If during the rescheduled visit the first blood draw 
cannot be obtained, the subject will be withdrawn from the study without being vaccinated. 

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11) Review warnings and precautions to vaccinations. 
12) Administer the investigation product, the control product and other products in the assigned 
location (see Operating Guidelines) and documented appropriately: 
Table 5.3: Vaccinations and route of administration  
Vaccine  
 
Group 1 or 
Group 2 
Group 3 or 
Group 4 
Route of administration 
MenACYW 
Conjugate or 
Nimenrix® 
Modified 
double-blind 
X 
 
Inject IM into the anterolateral area of the thigh, preferably 
the right thigh 
MenACYW 
Conjugate 
Open-label 
 
X 
Inject IM into the anterolateral area of the thigh, preferably 
the right thigh 
Hexavalent 
vaccine 
Open-label 
X 
X 
Inject IM into the anterolateral area of the thigh, preferably 
the left thigh (ie, the opposite leg from that used for 
meningococcal vaccine administration) 
PCV10 
Open-label 
X 
 
Inject IM into the anterolateral area of the thigh, preferably 
the left thigh (ie, the opposite leg from that used for 
meningococcal vaccine administration) 
PCV13 
Open-label 
 
X 
Inject IM into the anterolateral area of the thigh, preferably 
the left thigh (ie, the opposite leg from that used for 
meningococcal vaccine administration) 
If multiple vaccines are administered at a single visit, each vaccine should be administered at a 
different anatomic site. If vaccines are administered in the same limb, the injection sites should be 
separated by 2.5 cm or more, so that any local reactions can be differentiated. 
Do not administer the hexavalent vaccine or pneumococcal vaccine (PCV10 or PCV 13) in the 
same thigh as the meningococcal vaccine. For details see Operating Guidelines.  
Efforts should be made to administer the vaccines at the recommended sites. Any failure to 
administer vaccines in the designated limb should be recorded as a comment in the electronic case 
report form (CRF). If the initial vaccines are administered in the wrong limbs, this should be 
corrected for subsequent injections. 
1) Keep the subject under observation for 30 minutes, and record any AEs in the source 
document. In the event of a local reaction, indicate the associated vaccine. 
2) Give the parent / legally acceptable representative a diary card (DC1), a thermometer, and 
a ruler, and go over the instructions for their use. At each subsequent visit, confirm that the 
parent / legally acceptable representative has retained the thermometer and ruler, replace 
only as necessary. 
3) Remind the parent / legally acceptable representative to expect a telephone call 8 days 
after Visit 1 and to bring back the diary card when they return for Visit 2 at a specified 
date and time. 
4) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 

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5) Complete the relevant CRFs for this visit. 
Telephone Call 1 (8 [+2] days after Visit 1)  
Note: If Day 8 falls on a weekend or a holiday, the telephone call may be made on the following 
business day. 
1) Record relevant information concerning the subject’s health status on the telephone contact 
form. If an SAE (including AESI) occurred, follow the instructions in Section 10 for reporting 
it. 
2) Remind the parent / legally acceptable representative to do the following: 
• Complete the D0 to D07 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. 
Routine pediatric vaccines and the meningococcal vaccine will be administered at Visit 2, as 
described in Table 5.1 and Table 5.2.  
Visit 2 (60 [+14] days after Visit 1): Collection of Safety Information, Vaccination, and 
Blood Sample 
1) 
Collect and review the diary card (DC1) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) 
Review vaccination history from the child’s immunization record if routine pediatric 
vaccinations have already been performed since the last study visit. 
3) 
Review contraindications to subsequent vaccinations and conditions for withdrawal.  
4) 
Review warnings and precautions to vaccinations. 
5) 
Take the subject’s temperature (Refer to Section 9.3.2.3.2 for accurate temperature 
assessment). If the temperature is ≥ 38°C, postpone vaccination until the condition is 
resolved. 
6) 
Contact the IRT system for dose number of all vaccines 
7) 
Administer the investigation product, the control product and other products to subjects. 
Each vaccine should be administered in the assigned location (see Operating Guidelines) and 
documented appropriately. Refer to Table 5.3 for details on vaccinations and route of 
administration. 
If multiple vaccines are administered at a single visit, each vaccine should be administered 
at a different anatomic site. If vaccines are administered in the same limb, the injection 
sites should be separated by 2.5 cm or more, so that any local reactions can be 
differentiated. 
Do not administer the hexavalent vaccine or pneumococcal vaccine (PCV10 or PCV 13) in 
the same thigh as the meningococcal vaccine. For details see Operating Guidelines.  

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Efforts should be made to administer the vaccines at the recommended sites. Any failure to 
administer vaccines in the designated limb should be recorded as a comment in the CRF. If 
the initial vaccines are administered in the wrong limbs, this should be corrected for 
subsequent injections. 
8) 
Observe the subject for 30 minutes and record any AEs in the source document. In the event 
of a local reaction, indicate the associated vaccine. 
9) 
Give the parent / legally acceptable representative a diary card (DC2). 
10) Remind the parent / legally acceptable representative to expect a telephone call 8 days after 
Visit 2 and to bring back the diary card when they return for Visit 3 at a specified date and 
time. 
11) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
12) Complete the relevant CRFs for this visit. 
Telephone Call 2 (8 [+2] days after Visit 2) 
Refer to steps in Telephone Call 1. 
Remind the parent / legally acceptable representative that routine pediatric vaccines will not be 
administered at Visit 3, as described in Table 5.1 and Table 5.2. 
Visit 3 for all Groups:  
Visit Procedures applicable to subjects in Groups 1, 2, and 3: Collection of Safety Information 
and Blood Sample 
Visit 3 will be conducted 30 [+21] days after Visit 2 in Groups 1, 2, and 3 
1) Collect and review the diary card (DC2) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) Take the subject’s weight to determine if 3 or 4 ml should be collected for BL0002 (refer to 
Operating Guidelines for further instructions). 
3) Review temporary contraindications for blood sampling. Ensure the subject has not had any 
antibiotics within the previous 72 hours (3 days). 
4) Collect 3 or 4 mL of blood depending on the weight of the subject at Visit 3 (BL0002) from 
all subjects including those subjects in the rSBA subset (see Section 7.1 for detailed 
instructions regarding the handling of blood samples and Section 6.5 for more details on the 
rSBA subset).  
5) Give the parent / legally acceptable representative a diary card (DC3). 
6) Remind the parent / legally acceptable representative to expect a telephone call 5 months 
after Visit 3 and to bring back the diary card when they return for Visit 4 at a specified date 
and time. 

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7) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
8) Complete the relevant CRFs for this visit. 
Telephone Call 3 (5 months after Visit 3 and at least 14 days before Visit 4) for Groups 1, 2, and 
3: 
• Staff will contact subjects’ parent / legally acceptable representative by telephone 5 months 
after the last visit in infancy and at least 14 days before Visit 4. This contact is to identify the 
occurrence of any SAEs (including any AESI) not yet reported. 
• Remind the parent / legally acceptable representative that they should bring back the diary 
card to the subsequent visit so that it can be reviewed at the study site, and to confirm the date 
and time of the next visit. If the subject does not continue in the study, the information 
recorded on the diary card will be reviewed during this call, and the diary card will be 
retrieved by the site. 
• Remind the parent / legally acceptable representative that routine pediatric vaccines will be 
administered at Visit 4. 
Visit Procedures applicable to subjects in Group 4: Collection of Safety Information and 
Vaccination 
Visit 3 will be conducted 60 [+14] days after Visit 2 in Group 4 
1) Collect and review the diary card (DC2) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) Take the subject’s temperature (Refer to Section 9.3.2.3.2 for accurate temperature 
assessment). If the temperature is ≥ 38°C, postpone vaccination until the condition is 
resolved. 
3) Review vaccination history from the child’s immunization record if routine pediatric 
vaccinations have already been performed since the last study visit. 
4) Review warnings and precautions to vaccinations. 
5) Review contraindications to subsequent vaccinations and conditions for withdrawal. 
6) Contact the IRT system for dose number of all vaccines. 
7) Administer MenACYW conjugate vaccine: inject IM into the anterolateral area of the thigh, 
preferably the right thigh. 
8) Observe the subject for 30 minutes and record any AEs in the source document.  
9) Give the parent / legally acceptable representative a diary card (DC3). 
10) Remind the parent / legally acceptable representative to expect a telephone call 8 days after 
Visit 3 and to bring back the diary card when they return for Visit 4 at a specified date and 
time. 

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11) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
12) Complete the relevant CRFs for this visit. 
Telephone Call 3 (8 [+2] days) after Visit 3 for Group 4 
• Refer to steps in Telephone Call 1. 
• None of the routine pediatric vaccines will be administered at Visit 4. 
Visit 4 for all Groups: 
Visit Procedures applicable to subjects in Groups 1, 2, and 3: Collection of Safety Information, 
Vaccination, and Blood Sample 
Visit 4 will be conducted at 12 to 18 months of age and at least 180 days after Visit 2 in Groups 
1, 2, and 3  
1) Collect and review the diary card (DC3) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) Conduct a physical examination as per standard of care. Perform a physical examination, 
including, but not limited to, examination of the head (ear, nose, and throat), neck, heart, 
lungs, abdomen, and extremities. If a routine examination had been performed within the last 
week by the Investigator, a sub-investigator, or a licensed nurse practitioner, it does not need 
to be repeated unless there were some changes in health status, in which case it may be 
limited to the affected area. 
3) Take the subject’s temperature (Refer to Section 9.3.2.3.2 for accurate temperature 
assessment). If the temperature is ≥ 38°C, postpone vaccination until the condition is 
resolved. 
4) Review vaccination history from the child’s immunization record if routine pediatric 
vaccinations have already been performed since the last study visit. 
5) Review warnings and precautions to vaccinations. 
6) Review temporary contraindications for blood sampling. Ensure the subject has not had any 
antibiotics within the previous 72 hours (3 days). 
7) Collect 5 mL of blood (BL0003) from all subjects except for subjects included in the rSBA 
subset. Collect 6 mL of blood (BL0003) from subjects included in the rSBA subset (see 
Section 7.1 for detailed instructions regarding the handling of blood samples and Section 6.5 
for more details on the rSBA subset).  
8) Review contraindications to subsequent vaccinations and conditions for withdrawal. 
9) Contact the IRT system for dose number of all vaccines. 
10) Administer the investigation product, the control product and other products to subjects. 
Each vaccine should be administered in the assigned location (see Operating Guidelines) and 

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documented appropriately. Refer to Table 5.3 for details on vaccinations and route of 
administration. 
If multiple vaccines are administered at a single visit, each vaccine should be administered at 
a different anatomic site. If vaccines are administered in the same limb, the injection sites 
should be separated by 2.5 cm or more, so that any local reactions can be differentiated. 
Do not administer the hexavalent vaccine or pneumococcal vaccine (PCV10 or PCV 13) in 
the same thigh as the meningococcal vaccine. In addition, when administered at the same 
visit, inject M-M-RVAXPRO® either IM or subcutaneously (SC) in the deltoid area of upper 
arm according to the local standard of care. For details see Operating Guidelines.  
Efforts should be made to administer the vaccines at the recommended sites. Any failure to 
administer vaccines in the designated limb should be recorded as a comment in the CRF. If 
the initial vaccines are administered in the wrong limbs, this should be corrected for 
subsequent injections. 
11) Observe the subject for 30 minutes and record any AEs in the source document. In the event 
of a local reaction, indicate the associated vaccine. 
12) Give the parent / legally acceptable representative a diary card (DC4). 
13) Remind the parent / legally acceptable representative to expect a telephone call 8 days after 
Visit 4 and to bring back the diary card when they return for Visit 5 at a specified date and 
time. 
14) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
15) Complete the relevant CRFs for this visit. 
Telephone Call 4 (8 [+2] days) after Visit 4 for Group 4 
Refer to steps in Telephone Call 1. 
Visit Procedures applicable to subjects in Group 4: Collection of Safety Information and Blood 
Sample 
Visit 4 will be conducted 30 [+21] days after Visit 3 in Group 4 
1) Collect and review the diary card (DC3) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) Take the subject’s weight to determine if 3 or 4 ml should be collected for BL0002 (refer to 
Operating Guidelines for further instructions). 
3) Review temporary contraindications for blood sampling. Ensure the subject has not had any 
antibiotics within the previous 72 hours (3 days). 
4) Collect 3 or 4 mL of blood depending on the weight of the subject at Visit 3 (BL0002) from 
all subjects including those subjects in the rSBA subset (see Section 7.1 for detailed 

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instructions regarding the handling of blood samples and Section 6.5 for more details on the 
rSBA subset).  
5) Give the parent / legally acceptable representative a diary card (DC4). 
6) Remind the parent / legally acceptable representative to expect a telephone call 5 months 
after Visit 4 and to bring back the diary card when they return for Visit 5 at a specified date 
and time. 
7) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
8) Complete the relevant CRFs for this visit. 
Telephone Call 4 (5 months after Visit 4 and at least 14 days before Visit 5) in Group 4  
• Staff will contact the subject’s parent / legally acceptable representative by telephone 
5 months after the last visit in infancy and at least 14 days before Visit 5. This contact is to 
identify the occurrence of any SAEs (including AESI) not yet reported. 
• Remind the subject’s parent / legally acceptable representative that they should bring back the 
diary card to the subsequent visit so that it can be reviewed at the study site, and to confirm 
the date and time of the next visit. If the subject does not continue in the study, the 
information recorded on the diary card will be reviewed during this call, and the diary card 
will be retrieved by the site. 
• Remind the parent / legally acceptable representative that routine pediatric vaccines will be 
administered at Visit 5. 
Visit 5 for all Groups:  
Visit Procedures applicable to subjects in Groups 1, 2, and 3: Collection of Safety Information 
and Blood Sample 
Visit 5 will be conducted 30 [+21] days after Visit 4 in Groups 1, 2, and 3  
1) Collect and review the diary card (DC4) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) Review temporary contraindications for blood sampling. Ensure the subject has not had any 
antibiotics within the previous 72 hours (3 days). 
3) Collect 5 mL of blood (BL0004) from all subjects except for subjects included in the rSBA 
subset. Collect 6 mL of blood (BL0004) from subjects included in the rSBA subset (see 
Section 7.1 for detailed instructions regarding the handling of blood samples and Section 6.5 
for more details on the rSBA subset). 
4) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
5) Complete the relevant CRFs for this visit. 
6) Complete the trial termination record. 

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Visit Procedures applicable to subjects in Group 4: Collection of Safety Information, Blood 
Sample, and Vaccination 
Visit 5 will be conducted at 12 to 18 months of age and at least 180 days after Visit 3 in Group 4 
1) Collect and review the diary card (DC4) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) Conduct a physical examination as per standard of care. Perform a physical examination, 
including, but not limited to, examination of the head (ear, nose, and throat), neck, heart, 
lungs, abdomen, and extremities. If a routine examination had been performed within the last 
week by the Investigator, a sub-investigator, or a licensed nurse practitioner, it does not need 
to be repeated unless there were some changes in health status, in which case it may be 
limited to the affected area 
3) Take the subject’s temperature (rectal, oral, or axillary according to local practices, with the 
rectal route preferred for infants and the axillary route preferred for toddlers). If the 
temperature is ≥ 38°C, postpone vaccination until the condition is resolved. 
4) Review vaccination history from the child’s immunization record if routine pediatric 
vaccinations have already been performed since the last study visit. 
5) Review warnings and precautions to vaccinations. 
6) Review temporary contraindications for blood sampling. Ensure the subject has not had any 
antibiotics within the previous 72 hours (3 days). 
7) Collect 5 mL of blood (BL0003) from all subjects except for subjects included in the rSBA 
subset. Collect 6 mL of blood (BL0003) from subjects included in the rSBA subset (see 
Section 7.1 for detailed instructions regarding the handling of blood samples and Section 6.5 
for more details on the rSBA subset).  
8) Review contraindications to subsequent vaccinations and conditions for withdrawal. 
9) Contact the IRT system for dose number of all vaccines. 
10) Administer the investigation product, the control product and other products to subjects. 
Each vaccine should be administered in the assigned location (see Operating Guidelines) and 
documented appropriately. Refer to Table 5.3 for details on vaccinations and route of 
administration. 
If multiple vaccines are administered at a single visit, each vaccine should be administered at 
a different anatomic site. If vaccines are administered in the same limb, the injection sites 
should be separated by 2.5 cm or more, so that any local reactions can be differentiated. 
Do not administer the hexavalent vaccine or pneumococcal vaccine (PCV10 or PCV 13) in 
the same thigh as the meningococcal vaccine. In addition, when administered at the same 
visit, inject M-M-RVAXPRO® either IM or subcutaneously (SC) in the deltoid area of upper 
arm according to the local standard of care. For details see Operating Guidelines.  
Efforts should be made to administer the vaccines at the recommended sites. Any failure to 
administer vaccines in the designated limb should be recorded as a comment in the CRF. If 
the initial vaccines are administered in the wrong limbs, this should be corrected for 
subsequent injections. 

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7) Observe the subject for 30 minutes and record any AEs in the source document. In the event 
of a local reaction, indicate the associated vaccine. 
8) Give the parent / legally acceptable representative a diary card (DC5). 
9) Remind the parent / legally acceptable representative to expect a telephone call 8 days after 
Visit 5 and to bring back the diary card when they return for Visit 6 at a specified date and 
time. 
10) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
11) Complete the relevant CRFs for this visit. 
Telephone Call 5 (8 [+2] days) after Visit 5 in Group 4 
Refer to steps in Telephone Call 1. 
Visit 6 (30 [+21] days after Visit 5) for Group 4: Collection of Safety Information and Blood 
Sample 
1) Collect and review the diary card (DC5) with the parent / legally acceptable representative, 
including any AEs, medications, or therapy that occurred since vaccination. If an SAE, 
including an AESI, has occurred, follow the instructions in Section 10 for reporting it. 
2) Review temporary contraindications for blood sampling. Ensure the subject has not had any 
antibiotics within the previous 72 hours (3 days). 
3) Collect 5 mL of blood (BL0004) from all subjects except for subjects included in the rSBA 
subset. Collect 6 mL of blood (BL0004) from subjects included in the rSBA subset (see 
Section 7.1 for detailed instructions regarding the handling of blood samples and Section 6.5 
for more details on the rSBA subset). 
4) Remind the parent / legally acceptable representative to notify the site in case of an SAE. 
5) Complete the relevant CRFs for this visit. 
6) Complete the trial termination record. 
Follow-up of subjects with Related AEs or with AEs That Led to Study/Vaccination 
Discontinuation: 
Unless a 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 or from vaccination. 

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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 subject period - FVFS (first visit, first subject) to LVLS (last visit, last subject): Q4 2018 
to Q4 2023 
Planned inclusion period - FVFS to FVLS (first visit, last subject): Q4 2018 to Q2 2022 
Planned end of study - LVLS (last visit, last subject): Q4 2023 
Planned date of final clinical study report: Q4 2024 
5.2 
Enrollment and Retention of Study Population  
5.2.1 
Recruitment Procedures  
Each site will be responsible for devising a recruitment plan for enrolling eligible subjects. 
Advertisements and other recruitment aids will be approved by the Sponsor and the site’s 
IRB/IEC prior to use by the clinical site. 
5.2.2 
Informed Consent Procedures  
Informed consent is the process by which a subject’s parent / legally acceptable representative 
voluntarily confirms his or her willingness to let his/her child participate in a particular study. 
Informed consent must be obtained before any study procedures are performed. The process is 
documented by means of a written, signed, and dated ICF. 
In accordance with GCP, prior to signing and dating the consent form, the subject’s parent / legally 
acceptable representative must be informed by appropriate study personnel about all aspects of the 
study that are relevant to making the decision to participate, and must have sufficient time and 
opportunity to ask any questions. 
The actual ICF used at each center may differ, depending on local regulations and IEC / IRB 
requirements. However, all versions must contain the standard information found in the sample 
ICF provided by the Sponsor. Any change to the content of the ICF must be approved by the 
Sponsor and the IEC / IRB prior to the form being used. 
If new information becomes available that may be relevant to the subject’s parent / legally 
acceptable representative’s willingness to continue participation in the study, this will be 
communicated to him / her in a timely manner. Such information will be provided via a revised 
ICF or an addendum to the original ICF. 
ICFs will be provided in duplicate, or a photocopy of the signed consent will be made. The 
original will be kept by the Investigator, and the copy will be kept by the subject’s parent / legally 
acceptable representative. 
Documentation of the consent process should be recorded in the source documents. 

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Rationale for Including Subjects Unable to Give Consent: 
MET58 is a study to be conducted in children approximately 6 weeks to 18 months of age to 
obtain safety and immunogenicity data (see Section 1.4). 
Since these subjects are unable to give their consent, written informed consent must be obtained 
from the parent or legally acceptable representative in accordance with local practices before 
participation in the study and before any study related procedure is done (eg, collection of blood 
sample). The signature on the ICF must be dated by the parent / legally acceptable representative 
in accordance with local practices. The parent / legally acceptable representative should be able to 
consent for their child. The child of minor parents must not be included in 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: 
1) Aged ≥ 42 to ≤ 89 days on the day of the first study visit 
2) Healthy infants as determined by medical history, physical examination and judgment of the 
Investigator 
3) Informed consent form has been signed and dated by the parent(s) or other legally acceptable 
representative  
4) Subject and parent/legally acceptable representative are able to attend all scheduled visits and 
to comply with all study procedures 
5) Covered by health insurance according to local regulations 
5.2.5 
Exclusion Criteria  
An individual fulfilling any of the following criteria is to be excluded from study enrollment: 
1) Participation at the time of study enrollment (or in the 4 weeks preceding the first study 
vaccination) or planned participation during the present study period in another clinical study 
investigating a vaccine, drug, medical device, or medical procedure.  
2) Receipt of any vaccine in the 4 weeks preceding the first study vaccination or planned receipt 
of any vaccine in the 4 weeks before and/or following any study vaccination except for 
influenza vaccination and rotavirus vaccination, which may be received at a gap of at least 
2 weeks before or 2 weeks after any study vaccines. This exception includes monovalent 
pandemic influenza vaccines and multivalent influenza vaccines. This exclusion criterion does 
not apply to subjects in Finland, Sweden or Poland who plan to receive the licensed rotavirus 
vaccine concomitantly with study vaccines at study vaccination visits V1 and V2.  
3) Receipt or planned receipt during the study period vaccination against meningococcal disease 
with either the study vaccine or another vaccine (ie., mono- or polyvalent, polysaccharide, or 

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conjugate meningococcal vaccine containing serogroups A, C, W, or Y; or meningococcal B 
serogroup-containing vaccine 
4) Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type b 
(Hib), poliovirus, Streptococcus pneumoniae, measles, mumps, or rubella. Previous 
vaccination against hepatitis B specific to risk groups, as per local recommendation 
5) Receipt of immune globulins, blood or blood-derived products since birth 
6) Known or suspected congenital or acquired immunodeficiency; or receipt of 
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) since birth 
7) Family history of congenital or hereditary immunodeficiency, unless the immune competence 
of the potential vaccine recipient is demonstrated 
8) Individuals with blood dyscrasias, leukemia, lymphoma of any type, or other malignant 
neoplasms affecting the bone marrow or lymphatic systems 
9) Individuals with active tuberculosis 
10) History of Neisseria meningitidis infection, confirmed either clinically, serologically, or 
microbiologically 
11) History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, measles, mumps, rubella, 
and of Haemophilus influenzae type b, and / or Streptococcus pneumoniae infection or disease  
12) 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) 
13) Individuals with underlying conditions predisposing them to invasive pneumococcal disease 
(specifically, but not limited to, subjects with sickle cell disease or human immunodeficiency 
virus [HIV] infection) 
14) History of any neurologic disorders, including seizures and progressive neurologic disorders 
15) History of Guillain-Barré syndrome 
16) Known systemic hypersensitivity to any of the vaccine components, or history of a severe 
allergic reaction (eg., anaphylaxis) to the vaccine(s) used in the study or to a vaccine 
containing any of the same substances including neomycin, streptomycin, polymyxin B, 
glutaraldehyde, formaldehyde, and gelatina 
17) Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in the 
investigator’s opinion 
18) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating intramuscular vaccination in the investigator’s opinion 
                                                 
a The components of all study vaccines are listed in Section 6 of the Investigator’s Brochure 

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19) Chronic illness (including, but not limited to, cardiac disorders, congenital heart disease, 
chronic lung disease, renal disorders, auto-immune disorders, diabetes, psychomotor diseases, 
and known congenital or genetic diseases) that, in the opinion of the investigator, is at a stage 
where it might interfere with study conduct or completion 
20) Any condition which, in the opinion of the investigator, might interfere with the evaluation of 
the study objectives 
21) Moderate or severe acute illness/infection (according to investigator judgment) on the day of 
vaccination or febrile illness (temperature ≥ 38.0°C). A prospective subject should not be 
included in the study until the condition has resolved or the febrile event has subsided. 
22) Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw 
23) Identified as a natural or adopted child of the Investigator or employee with direct 
involvement in the proposed study 
24) Infants born preterm (by less than 37 weeks of gestation) requiring specific immunization 
schedule for routine childhood vaccines and/or specific care at the time of vaccination, as per 
national recommendations 
If the subject has a primary physician who is not the Investigator, the site must contact this 
physician with the parent’s / legally acceptable representative’s consent 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 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. 
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. 

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5.2.7 
Contraindications for Subsequent Vaccinations  
5.2.7.1 
Temporary Contraindications  
Should a subject experience one of the conditions listed below, the Investigator will postpone 
further vaccination until the condition is resolved. Postponement must still be within the 
timeframe for vaccination indicated in the Table of Study Procedures. 
1) Febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) or moderate or severe acute illness / 
infection on the day of vaccination, according to Investigator judgment  
2) Receipt of any vaccine (other than the study vaccine[s]) in the 4 weeks preceding any 
vaccination or planned receipt of any vaccine in the 4 weeks following any study vaccination 
except for influenza vaccination and rotavirus vaccination, which may be received at least 2 
weeks before or 2 weeks after any study vaccines. This exception includes monovalent 
pandemic influenza vaccines and multivalent influenza vaccines. This temporary 
contraindication does not apply to subjects in Finland, Sweden or Poland who plan to receive 
the licensed rotavirus vaccine concomitantly with study vaccines at study vaccination visits 
V1 and V2. If, for any reason a subject receives any routine pediatric vaccine considered as 
study vaccine (eg, PCV10, PCV13, Hexyon®/Hexacima®) or non-study vaccine similar to the 
routine pediatric study vaccines (eg Infanrix hexa®, Priorix®) out of the study, the interval of 
at least 4 weeks following the study vaccination(s) should be respected. The investigator 
should make efforts to ensure that the subject receives these study vaccines within the 
timelines concomitantly with the investigation or control meningococcal vaccines, as per 
protocol corresponding visits. 
3) Immune globulins, blood, or blood-derived products: used in the 3 months preceding any 
study vaccination 
4) 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) used in the 6 months preceding any study vaccination.   
5.2.7.2 
Definitive Contraindications  
Should a subject experience at least 1 of the conditions listed below, the Investigator will 
discontinue vaccination:  
1) Having received Meningococcal Group B vaccination since the last visit 
2) An anaphylactic or other significant allergic reaction to the previous dose of vaccine 
3) Any related SAE after a previous study vaccination 
Subjects with a definitive contraindication will continue to be followed up for the study-defined 
safety and immunogenicity assessments, as applicable. 
In the event of a local or national immunization program with a pandemic influenza or coronavirus 
vaccine or any other vaccine as needed, subjects who receive one or more doses of a pandemic 
influenza or coronavirus vaccine at any time during the study will not be withdrawn from the study. 

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The following AEs constitute absolute contraindications to subsequent vaccinations, according to 
their respective Summary of Product Characteristics (SmPC). If a subject should experience any 
of these events during the study, irrespective of causality, that subject is not to receive any 
additional study vaccines but should continue in the study and be followed up for safety only, as 
per protocol. Only the vaccine which has a related SAE or a definite contraindication will be 
stopped wherever it is possible to identify the vaccine that caused the event. 
Meningococcal vaccines: (MenACYW conjugate vaccine or Nimenrix®): 
1) History of Guillain-Barré syndrome within 6 weeks after vaccination with a tetanus toxoid-
containing vaccine 
2) History of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine 
3) Severe allergic reaction (eg, anaphylaxis) after a previous dose of meningococcal capsular 
polysaccharide-, tetanus toxoid carrier protein – containing vaccines or to any component of 
meningococcal vaccines 
4) Persons with familial complement deficiencies (for example, C5 or C3 deficiencies) and 
persons receiving treatments that inhibit terminal complement activation (for example, 
eculizumab) are at increased risk for invasive disease caused by Neisseria meningitidis groups 
A, C, W-135 and Y, even if they develop antibodies following vaccination with Nimenrix®. 
Hexyon® or Hexacima®: 
1) History of anaphylactic reaction after a previous administration of Hexyon® or Hexacima® 
2) Hypersensitivity to the active substances, to any of the excipients, to trace residuals 
(glutaraldehyde, formaldehyde, neomycin, streptomycin, and polymyxin B), to any pertussis 
vaccine, or after previous administration of Hexyon® or Hexacima® or a vaccine containing 
the same components or constituents 
3) Encephalopathy of unknown etiology occurring within 7 days of vaccination with a previous 
pertussis-containing vaccine (whole cell or acellular pertussis vaccines) 
4) Uncontrolled neurologic disorder or uncontrolled epilepsy until a treatment regimen has been 
established and the condition has stabilized and the benefit clearly outweighs the risk 
Prevenar 13®: (pneumococcal 13-valent conjugate vaccine; PCV13) : 
1) Hypersensitivity to the active substances, to any of the excipients, to diphtheria toxoid, or to a 
previous dose of Prevenar 13® 
Synflorix®: (pneumococcal polysaccharide conjugate vaccine; PCV10): 
1) Hypersensitivity to the active substances, to any of the excipients, to any of the carrier 
proteins, or to a previous dose of Synflorix® 
M-M-RVAXPRO® (measles, mumps, and rubella vaccine): 
1) Hypersensitivity to any measles, mumps, or rubella vaccine, or to any of the excipients, 
including neomycin  
2) Active untreated tuberculosis 

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3) Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting 
the bone marrow or lymphatic systems. 
4) Severe humoral or cellular (primary or acquired) immunodeficiency (eg, severe combined 
immunodeficiency, agammaglobulinemia and acquired immune deficiency syndrome [AIDS] 
or symptomatic HIV infection) 
5) Family history of congenital or hereditary immunodeficiency, unless the immune competence 
of the potential vaccine recipient is demonstrated. 
5.2.7.3 
Warnings and Precautions to Vaccination  
Prior to vaccination, check the warnings and precautions for individual vaccines administered. For 
the licensed vaccines, refer to the individual package inserts. For MenACYW conjugate vaccine, 
refer to the Investigator’s Brochure. 
5.2.8 
Contraindications for Subsequent Blood Draw  
Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the blood 
draws, 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 or 30 to 51 days after vaccination, depending on the 
visit). If postponement would result in the sample collection falling outside of this 30 to 44 day or 
30 to 51 day timeframe, the blood sample should be collected without postponement and it should 
be documented that the sample was taken less than 3 days after stopping antibiotic treatment. 
5.2.9 
Conditions for Withdrawal  
Parents / legally acceptable representatives will be informed that they have the right to withdraw 
their child 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 
permission (withdrawal) 
• At the request of the parent / legally acceptable representative (dropout) 
The reason for a withdrawal or dropout should be clearly documented in the source documents 
and on 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. 

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5.2.10 Lost to Follow-up Procedures  
In the case of subjects who fail to return for a follow-up examination, documented reasonable 
effort (ie., 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 CRB and in the source documents. 
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 9.3.2.1. 
This category also applies if the subject experiences a definitive contraindication that is 
an SAE or AE. 
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’s 
parent/ legally acceptable representative did not give any other news and did not bring the 
child to any following visit. 
Protocol Deviation 
To be used: 
In case of significant noncompliance with the protocol (eg, 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). 
If the subject experiences a definitive contraindication that is a protocol deviation. 
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 Parent 
/ Legally Acceptable 
Representative 
To be used: 
When the subject’s parent/ legally acceptable representative indicated unwillingness to 
allow his / her child continue in the study 
When the subject or parent/ legally acceptable representative made the decision to 
discontinue his / her child’s participation in the study for any personal reason other than 
an SAE/AE (eg, 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, a protocol deviation, or loss of eligibility, 
including definitive contraindications.  
For subjects where the reason for early termination was lost to follow-up or if the subject 
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. 

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5.3 
Safety Emergency Call  
If, as per the Investigator’s judgment, a subject experiences a medical emergency, the Investigator 
may contact the Sponsor's RMO for advice on study related medical question or problem. If the 
RMO 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 Sanofi Pasteur contact, as needed. The toll-free contact information for the Call Center is 
provided in the Operating Guidelines. 
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 Global Pharmacovigilance (GPV) 
Department (Please refer to 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 
Modification of the Study and Protocol  
Any amendments to this study plan and protocol must be discussed with and approved by the 
Sponsor. If agreement is reached concerning the need for an amendment, it will be produced in 
writing by the Sponsor, and the amended version of the protocol will replace the earlier version. 
All substantial amendments (eg, those that affect the conduct of the study or the safety of 
subjects) require IEC / IRB approval, and must also be forwarded to regulatory authorities. 
An administrative amendment to a protocol is one that modifies some administrative, logistical, or 
other aspect of the study but does not affect its scientific quality or have an impact on the 
subjects’ safety. The IECs / IRBs may be notified of administrative changes and will provide 
approval according to local regulations. 
The Investigator is responsible for ensuring that changes to an approved study, during the period 
for which IEC / IRB approval has already been given, are not initiated without IEC / IRB review 
and approval, except to eliminate apparent immediate hazards to subjects. 
5.5 
Interruption of the Study  
The study may be discontinued if new data about the investigational product resulting from this or 
any other studies become available; or for administrative reasons; or on advice of the Sponsor, the 
Investigators, the IECs/IRBs, or the governing regulatory authorities in the countries where the 
study is taking place.  
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the study subjects’ parents / 
legally acceptable representative and should assure appropriate subject therapy and/or follow-up. 
There will be an internal team at the level of the Sponsor (SMT), which will review the data being 
generated from all the ongoing studies with MenACYW conjugate vaccine at regular intervals for 

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any new safety signals or safety concerns. The SMT is empowered to recommend a pause in both 
recruitment and / or further vaccination while it investigates any potential signal or concern. 
6 
Vaccines Administered  
6.1 
Identity of the Investigational Product  
6.1.1 
Identity of Study Product  
MenACYW conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, W, and Y) 
Tetanus Toxoid Conjugate Vaccine (Sanofi Pasteur Inc., Swiftwater, PA, USA) 
Form:  
 
Liquid solution 
Dose:  
 
0.5 milliliter (mL) 
Route: 
 
IM 
Batch number: 
To be determined (TBD) 
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 components: 
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 µga 
6.1.1.2 
Preparation and Administration  
MenACYW conjugate vaccine is supplied in single-dose vials (0.5 mL). 
Prior to administration, all study products must be inspected visually for cracks, broken seals, 
correct label content (see Section 6.3.1), and extraneous particulate matter and / or discoloration, 
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 (for 
vaccination and route of administration, see Table 5.3).  
                                                 
a  Tetanus toxoid protein quantity is approximate and dependent on the PS-to-protein ratio for the conjugates used in 
each formulation. 

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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 each 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  
• Subjects in Groups 1 and 3 will receive 3 doses of MenACYW conjugate vaccine 
administered concomitantly with routine vaccines at 2 months of age (Visit 1), 4 months of 
age (Visit 2), and 12 to 18 months of age (Visit 4) 
• Subjects in Group 4 will receive 4 doses of MenACYW conjugate vaccine with routine 
vaccines at 2 months of age (Visit 1), 4 months of age (Visit 2), 6 months of age (Visit 3; 
MenACYW conjugate vaccine only), and 12 to 18 months of age (Visit 5; MenACYW 
conjugate vaccine and routine vaccines) 
6.1.2 
Identity of Control Product  
Nimenrix®: Meningococcal group A, C, W-135, and Y conjugate vaccine (Pfizer Limited, 
Sandwich, United Kingdom) 
Form:  
 
Powder and solvent for solution for injection in a pre-filled syringe 
Dose:  
 
0.5 mL 
Route: 
 
IM 
Batch number: 
TBD  
6.1.2.1 
Composition  
After reconstitution, each 0.5 mL dose contains: 
Neisseria meningitidis group A polysaccharide*  ........................... 5 µg 
Neisseria meningitidis group C polysaccharide* ............................ 5 µg 
Neisseria meningitidis group W-135 polysaccharide* .................... 5 µg 
Neisseria meningitidis group Y polysaccharide* ............................ 5 µg 
*conjugated to tetanus toxoid protein carrier .................................. 44 µg 
The vaccine also contains the excipients: sucrose, trometamol, sodium chloride, water for 
injections 
6.1.2.2 
Preparation and Administration  
Nimenrix® is supplied as a white powder or cake in a single dose glass vial and a clear and 
colorless solvent in a pre-filled syringe. 

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A single dose of Nimenrix® should be administered by IM injection, usually in the upper arm or 
thigh. See the Nimenrix® EU SmPC (42) (for vaccination and route of administration, see 
Table 5.3). 
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  
• Subjects in Group 2 will receive 3 doses of Nimenrix® administered concomitantly with 
routine vaccines at 2 months of age (Visit 1), 4 months of age (Visit 2), and 12 to 18 months 
of age (Visit 4). 
6.2 
Identity of Other Products  
6.2.1 
Identity of Other Product 1  
DTaP-IPV-HB-Hib: Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), 
poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) 
(Sanofi Pasteur SA, Marcy L’Etoile, France) (licensed products: Hexyon®, Hexacima®), referred 
to as hexavalent vaccine in the protocol 
Form:  
 
Suspension for injection 
Dose:  
 
0.5 mL 
Route: 
 
IM 
Batch number: 
TBD 
6.2.1.1 
Composition  
Each 0.5 mL dosea is formulated to contain the following components: 
Diphtheria Toxoid ........................................................................... not less than 20 IUb 
Tetanus Toxoid ................................................................................ not less than 40 IUb 
Bordetella pertussis antigens 
Pertussis Toxoid ........................................................................ 25 µg 
Filamentous Haemagglutinin ..................................................... 25 µg 
Poliovirus (Inactivated)c 
                                                 
a  Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
b  As lower confidence limit (p=0.95) 
c  Produced on Vero cells 

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Type 1 (Mahoney) ..................................................................... 40 D antigen unitsa 
Type 2 (MEF-1) ......................................................................... 8 D antigen unitsd 
Type 3 (Saukett) ........................................................................ 32 D antigen unitsd 
Hepatitis B surface antigenb ............................................................ 10 µg 
Haemophilus influenzae type b polysaccharide .............................. 12 µg 
(Polyribosylribitol Phosphate) conjugated to Tetanus Protein ........ 22-36 µg 
The vaccine also contains the excipients: disodium hydrogen phosphate, potassium dihydrogen 
phosphate, trometamol, saccharose, essential amino acids including L-phenylalanine, water for 
injections. 
The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin, and 
polymyxin B, which are used during the manufacturing process. 
6.2.1.2 
Preparation and Administration  
Hexavalent vaccines are supplied as a suspension in a pre-filled syringe. 
Hexavalent vaccines should be administered as an IM injection, preferably in the antero-lateral 
area of the thigh. See the Hexyon ® (43) EU SmPC and Hexacima ® (44) EU SmPC. 
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 (for vaccination and route of administration, see 
Table 5.3). 
6.2.1.3 
Dose Selection and Timing  
• All subjects will receive 3 doses of a hexavalent vaccine administered concomitantly with 
either MenACYW conjugate vaccine or Nimenrix® at 2 months of age (Visit 1), 4 months of 
age (Visit 2), and 12 to 18 months of age (Visit 4/Visit 5). 
6.2.2 
Identity of Other Product 2  
Synflorix®: Pneumococcal polysaccharide conjugate vaccine (adsorbed) (GlaxoSmithKline 
Biologicals SA, Rixensart, Belgium), referred to as PCV10 
Form:  
 
Suspension for injection 
Dose:  
 
0.5 mL 
Route: 
 
IM 
Batch number: 
TBD 
                                                 
a  Or equivalent antigenic quantity determined by a suitable immunochemical method 
b  Produced in yeast Hansenula polymorpha cells by recombinant DNA technology 

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6.2.2.1 
Composition  
Each 0.5 mL dose is formulated to contain the following: 
Pneumococcal polysaccharide serotype 1ab ..................................... 1 µg 
Pneumococcal polysaccharide serotype 4ab ..................................... 3 µg 
Pneumococcal polysaccharide serotype 5ab ..................................... 1 µg 
Pneumococcal polysaccharide serotype 6Bab .................................. 1 µg 
Pneumococcal polysaccharide serotype 7Fab................................... 1 µg 
Pneumococcal polysaccharide serotype 9Vab .................................. 1 µg 
Pneumococcal polysaccharide serotype 14ab ................................... 1 µg 
Pneumococcal polysaccharide serotype 18Cac ................................ 3 µg 
Pneumococcal polysaccharide serotype 19Fad ................................ 3 µg 
Pneumococcal polysaccharide serotype 23Fab................................. 1 µg 
The vaccine also contains the excipients: sodium chloride, water for injections. 
6.2.2.2 
Preparation and Administration  
Synflorix® is supplied as a suspension in a pre-filled syringe. 
Synflorix® should be administered as an IM injection, preferably in the anterolateral area of the 
thigh. See the Synflorix® EU SmPC (45). 
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 (for vaccination and route of administration, see 
Table 5.3). 
6.2.2.3 
Dose Selection and Timing  
• Subjects in Group 1 and Group 2 will receive 3 doses of PCV10 vaccine administered 
concomitantly with either MenACYW conjugate vaccine or Nimenrix® at 2 months of age 
(Visit 1), 4 months of age (Visit 2), and 12 to 18 months of age (Visit 4). 
6.2.3 
Identity of Other Product 3  
Prevenar 13®: Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) (Pfizer 
Limited, Sandwich, United Kingdom), referred to as PCV13 
Form:  
 
Suspension for injection 
Dose:  
 
0.5 mL 
                                                 
a  adsorbed on aluminum phosphate  
0.5 mg Al3+ 
b  conjugated to protein D (derived from non-typable Haemophilus influenzae) 
  carrier protein 
9-16 µg 
c  conjugated to tetanus toxoid carrier protein 
5-10 µg 
d  conjugated to diphtheria toxoid carrier protein 
3-6 µg 

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Route: 
 
IM 
Batch number: 
TBD 
6.2.3.1 
Composition  
Each 0.5 mL dose is formulated to contain the following: 
Pneumococcal polysaccharide serotype 1 ....................................... 2.2 µg 
Pneumococcal polysaccharide serotype 3 ....................................... 2.2 µg 
Pneumococcal polysaccharide serotype 4 ....................................... 2.2 µg 
Pneumococcal polysaccharide serotype 5 ....................................... 2.2 µg 
Pneumococcal polysaccharide serotype 6A .................................... 2.2 µg 
Pneumococcal polysaccharide serotype 6B ..................................... 4.4 µg 
Pneumococcal polysaccharide serotype 7F ..................................... 2.2 µg 
Pneumococcal polysaccharide serotype 9V .................................... 2.2 µg 
Pneumococcal polysaccharide serotype 14 ..................................... 2.2 µg 
Pneumococcal polysaccharide serotype 18C ................................... 2.2 µg 
Pneumococcal polysaccharide serotype 19A .................................. 2.2 µg 
Pneumococcal polysaccharide serotype 19F ................................... 2.2 µg 
Pneumococcal polysaccharide serotype 23F ................................... 2.2 µg 
The pneumococcal polysaccharides are conjugated to CRM197 carrier protein and adsorbed on 
aluminum phosphate (0.125 mg aluminum). 
The vaccine also contains the excipients: sodium chloride, succinic acid, Polysorbate 80, water for 
injections. 
6.2.3.2 
Preparation and Administration  
Prevenar 13® is supplied as a suspension in a pre-filled syringe. 
Prevenar 13® should be administered as an IM injection, preferably in the anterolateral area of the 
thigh. See the Prevenar 13® EU SmPC (46). 
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 (for vaccination and route of administration, see 
Table 5.3). 
6.2.3.3 
Dose Selection and Timing  
• Subjects in Group 3 and Group 4 will receive 3 doses of PCV13 vaccine administered 
concomitantly with MenACYW conjugate vaccine at 2 months of age (Visit 1), 4 months of 
age (Visit 2), and 12 to 18 months of age (Visit 4/Visit 5). 
6.2.4 
Identity of Other Product 4  
M-M-RVAXPRO®: Measles, mumps, and rubella vaccine (live) (Merck Sharp & Dohme B.V., 
Haarlem, The Netherlands), referred to as MMR vaccine  
Form:  
 
Powder and solvent for suspension for injection 

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Dose:  
 
0.5 mL 
Route: 
 
IM  
Batch number: 
TBD 
6.2.4.1 
Composition  
Each 0.5 mL dose is formulated to contain the following: 
Measles virusa Enders’ Edmonston strain (live, attenuated) 
 ......................................................................................................... not less than 1x103 cell culture 
infection dose 50% (CCID50)b 
Mumps virusa Jeryl Lynn™ [Level B] strain (live, attenuated) 
 ......................................................................................................... not less than 12.5x103 CCID50b 
Rubella virusc Wistar RA 27/3 strain (live attenuated) 
 ......................................................................................................... not less than 1x103 CCID50b 
The vaccine contains the following excipients: sorbitol, sodium phosphate, potassium phosphate, 
sucrose, hydrolyzed gelatin, Medium 199 with Hanks’ salts, Minimum Essential Medium Eagle, 
monosodium L-glutamate, neomycin, phenol red, sodium bicarbonate, hydrochloric acid (to 
adjust pH), sodium hydroxide (to adjust pH), water for injections. The vaccine may also contain 
traces of recombinant human albumin. 
6.2.4.2 
Preparation and Administration  
M-M-RVAXPRO® is supplied as a powder and solvent for suspension for injection. 
M-M-RVAXPRO® should be administered as an IM injection or subcutaneously, preferably in the 
deltoid muscle of upper arm. See the M-M-RVAXPRO® EU SmPC (47). 
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. 
6.2.4.3 
Dose Selection and Timing  
All subjects may receive 1 dose of MMR vaccine administered concomitantly with MenACYW 
conjugate vaccine or Nimenrix® at 12 to 18 months of age (Visit 4/Visit 5). If not, the subject will 
receive a licensed Measles, Mumps and Rubella vaccine with a gap of at least 4 weeks before any 
study vaccines or after the end of the study (ie, after the subject will have completed the last study 
procedure at the last study visit). When administered outside the study visits, the licensed 
Measles, Mumps and Rubella vaccine will be sourced by the health care system, according to the 
national immunization program. 
                                                 
a  produced in chick embryo cells 
b  50% cell culture infectious dose 
c  produced in WI-38 human diploid lung fibroblasts 

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6.3 
Product Logistics  
6.3.1 
Labeling and Packaging  
The investigational product, MenACYW conjugate vaccine (single-dose vials), control product, and 
other products will be supplied with investigational labeling and packaging according to national 
regulations. Each single dose of investigational, control product or other products will be identified 
by a unique number on the detachable label and on the outer carton label. The detachable label is for 
the sites to attach to the source documents. See the Operating Guidelines for additional label detail. 
The investigational and control products are blinded for Group 1 and Group 2. The investigational 
product will be open label for Group 3 and Group 4. 
The concomitant products (licensed routine vaccines) are not blinded. 
The rotavirus vaccines will be sourced by the study sites in Finland, Sweden, and Poland. 
6.3.2 
Product Shipment, Storage, and Accountability  
6.3.2.1 
Product Shipment  
The Clinical Logistics Coordinator 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 Operating Guidelines, including checking that the 
cold chain was maintained during shipment (ie, 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 Sanofi Pasteur representative, and request authorization from Sanofi Pasteur to 
use the product. 
6.3.2.2 
Product Storage  
The Investigator will be personally responsible for product management or will designate a staff 
member 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 and should be protected from light. 
The vaccines must not be frozen. The temperature must be monitored and documented (see the 
Operating Guidelines) 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 Sanofi Pasteur 
representative for further instructions. 

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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(s) 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. If applicable, information may also be entered into the subject’s vaccination card. 
The Sponsor’s monitoring staff will verify the study site’s product accountability records against 
the record of administered doses in the CRBs and the communication from the IRT system (if 
applicable). 
In case of any expected or potential shortage of product during the study, the Investigator or an 
authorized designee should alert the Sanofi Pasteur 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 (eg, because the vial broke or particulate matter was observed in 
the syringe), the site personnel must either contact the IRT system to receive the new dose 
allocation, or follow the instructions given in the Operating Guidelines. 
6.3.4 
Disposal of Unused Products  
Unused or wasted products will be returned to the Sponsor in accordance with the instructions in 
the Operating Guidelines. 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 Investigator(s) will be 
informed of what needs to be done. 
6.4 
Blinding and Code-breaking Procedures  
To perform an appropriate description of the safety of MenACYW conjugate vaccine and 
Nimenrix® in Groups 1 and 2 (ie, when each of these vaccines is administered as a 3-dose series 
concomitantly with PCV10 and hexavalent vaccine), MenACYW conjugate vaccine and 
Nimenrix® will be administered in a modified double-blind manner in these 2 groups. The 
MenACYW conjugate vaccine in Groups 3 and 4 and all other concomitant vaccines in all 
vaccine groups will be administered in an open-label manner. 
A modified double-blind trial means that the subject’s parent / legally acceptable representative, 
the Investigator, and other study personnel remain unaware of the treatment assignments 
throughout the trial. An unblinded vaccine administrator will administer the appropriate vaccine 
but will not be involved in safety data collection.  
The Sponsor and laboratory personnel performing the serology testing for all groups will also 
remain blinded to treatment assignments throughout the trial until database lock.  

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Given that the meningococcal vaccines in Groups 3 and 4 have different vaccination schedules in 
the number of vaccines administered and timing of their administration, these vaccines will be 
administered in an open-label manner. 
Other concomitant vaccines in all groups will be administered in an open-label manner to ensure 
the subjects received appropriate vaccines as per local standard of care. 
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 Operating Guidelines. Once the emergency has 
been addressed by the site, the Investigator or a delegate must notify the Sanofi Pasteur RMO 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 GPV Department through an internal system for reporting to Health authorities in the 
case of an SAE as described in International Council for Harmonisation (ICH) E2A.a In this 
case, the code will be broken only for the subject(s) in question. The information resulting 
from code-breaking (ie, 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 GPV 
representative.  
The IEC / IRB 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 Sanofi Pasteur 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 whose parent / 
legally acceptable representative sign the ICF will be randomly assigned to Groups 1 through 4. 
Countries where PCV10 will be administered for pneumococcal vaccination, 1432 subjects will 
be randomized in a 1:1 ratio to 2 groups such that Groups 1 and 2 will have approximately 
716 subjects each; and countries where PCV13 will be administered for pneumococcal 
vaccination, 220 subjects will be randomized in a 1:1 ratio to 2 groups such Groups 3 and 4 will 
have approximately 110 subjects each. 
Randomization will be performed with permuted block method with stratification by center and 
age categories as follows: approximately 6 to 8 weeks (≥ 42 to ≤ 59 days), and 9 to 12 weeks 
(≥ 60 to ≤ 89 days). 
                                                 
a All unexpected and related SAEs submitted to EU competent authorities must be unblinded. 

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The IRT system will also be used to allocate subjects in the rSBA subset in the countries included 
in the subsets as follows: 
• 100 subjects randomized to Group 1; 100 subjects randomized to Group 2  
• 50 subjects randomized to Group 3; 50 subjects randomized to Group 4 
The rSBA subset will include subjects from all countries except Poland. 
The vaccination / site staff will connect to the IRT system, enter the identification and security 
information, and confirm a minimal amount of data in response to IRT system prompts. The IRT 
system will then provide at least the vaccine dose number (except for the rotavirus vaccine) and 
subject number. The full detailed procedures for group allocation are described in the Operating 
Guidelines. If the subject is not eligible to participate in the study, then the information will only 
be recorded on the subject recruitment log. 
Subject numbers that are assigned by the IRT system 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 724000100005 is the fifth subject enrolled in Center Number 1 in Spain (724 being the 
Spain country code).  
Subject numbers should not be reassigned for any reason. The randomization codes will be kept 
securely in the IRT system. 
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 for pediatric population. 
• 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 Medications and Other Therapies  
At the time of enrollment, ongoing medications including but not limited to other therapies (eg, 
blood products), should be recorded in the source documents. All new medications prescribed for 
new medical conditions / AEs during study participation should also be recorded in the source 
documents.  
Documentation in the CRB of concomitant medication(s) will be limited to specific categories of 
medications (Categories 1, 2, and 3 as detailed below). Those will include Category 1, 2, and 3 
medications ongoing at the time of inclusion in the study, or started at any time during the 
subject’s participation in the trial. For category 3 medication, the period of reporting in CRB will 
be restricted to only 3 days (72 hours) prior to each blood sampling time point.  
Collection period in source documents 

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Reportable medications (Category 1, 2, and 3) will be collected in the source documents from the 
day of first vaccination to the end of the trial.a  
Categories of Reportable medications and reporting period 
Reportable medications include medications that impact or may impact the consistency of the 
safety information collected after any vaccination and/or the immune response to vaccination.  
• Category 1: medications with potential impact on the evaluation of the safety of the study 
vaccines. For example, antipyretics, analgesics, non-steroidal anti-inflammatory drugs 
(NSAIDs), systemic corticosteroids (therapy duration less than 2 weeks), and other immune 
modulators. Category 1 medications do not define the Per-Protocol Analysis Set (PPAS). 
Note: Topical steroids (Inhaled, otic, ophthalmic, nasal etc.) should not be captured or reported. 
Category 1 medications will be reported in the CRB from the day of first vaccination to the end of 
the solicited and unsolicited follow-up period after each vaccination. These medications will also 
be collected in the CRB for the 30- day period prior to the subsequent doses of the vaccine, 
wherever applicable (second, third, fourth, etc., in case of a multi-dose schedule with more than a 
30-day interval between doses). 
• Category 2: Reportable medications with potential impact on immune response of the study 
vaccines and used to define the Per-Protocol Analysis Set (PPAS). For example: 
• Flu vaccines administered within 14 days pre or post each study vaccine, including the day 
of the study vaccination visit 
• Rotavirus vaccines administered within 14 days pre or post each study vaccination visitb. 
Any vaccine other than study vaccines (vaccines non-described in the Protocolc) within the 
28 days (4 weeks) preceding or after the trial vaccination, including the day of the study 
vaccination visit 
• 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 immune-suppressors, immune-modulators with 
immunosuppressive properties, long-term systemic corticosteroids therapy (prednisone or 
equivalent for more than 2 consecutive weeks) within past 3 months, anti-cancer 
chemotherapy, anti-proliferative drugs such as DNA synthesis inhibitors, or radiation 
therapy: used in the 6 months preceding the first trial vaccination, and up to the last blood 
draw. 
                                                 
a  Subject’s parents will be required to document all medications received in the Diary Cards. The sites will focus on 
only recording the medications belonging to the 3 categories in the other source documents. 
b Subjects from Finland, Sweden and Poland can receive rotavirus vaccine concomitantly with study vaccinations at 
V1 and V2 
c if for any reason a study vaccine (PCV10, or PCV13 and/or Hexyon®/Hexacima®) is not administered 
concomitantly with investigation/control meningococcal vaccine, an interval of 4 weeks between this vaccination 
prior or following the investigational/control vaccine must be respected, otherwise, this vaccine administration out 
of the study will be considered as Category 2) 

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o Category 2 medications will be reported in the CRB during the study period up to 
the last blood draw. 
In addition, the following vaccines should be recorded in the concomitant medication CRB as 
Category 2: 
• Licensed Measles, Mumps and Rubella vaccines administered during the study 
participation (if MMR vaccination [including M-M-RVAXPRO®] occurred within the  28 
days (4 weeks) preceding or after the trial vaccination visit, it will be used to define the 
PPAS definition) 
• Licensed rotavirus vaccines received during the first year of life (if rotavirus vaccination 
occurred within the 14 days (2 weeks) preceding or after the trial vaccination visit, it will 
be used to define the PPAS definition) 
• Hepatitis B Vaccine received before the inclusion in the study (if Hepatitis B vaccination 
occurred within the 28 days (4 weeks) preceding or after the trial vaccination visit, it will 
be used to define the PPAS definition) 
• Category 3: Systemic (Oral or injectable) antibiotics, as they may interfere with bioassays 
used for antibody testing when taken before a blood draw. Antibiotics that the subject received 
within 72 hours preceding each visit for blood draw related to IMP assessment 
(meningococcal vaccines) and used to define the PPAS. Category 3 medications will be 
reported in the CRB for the period of 3 days (72 hours) before each blood draw. 
Note: Topical antibiotics (Inhaled, otic, ophthalmic, nasal, etc.) should not be captured or 
reported. 
The information reported in the CRB for each reported medication will be limited to: 
• Trade name  
• Rationale for the origin of prescription: Whether it was a prophylactica medication?   
Prophylactic medications will be recorded in the Action Taken section of the AE collection 
tables. 
• Medication category (1, 2, or 3) 
• Start and stop dates 
Dosage and administration route, homeopathic medication, will not be recorded. 
If the subject has received medications other than those listed in Categories 1, 2, and 3, the 
detailed information will be collected in the source documents only.   
Medications given to treat an AE will be captured in the “Action Taken” section of the AE CRB 
only. No details will be recorded in the concomitant medication CRB unless the medication(s) 
received belongs to one of the prelisted categories. 
                                                 
a  Medication(s) prescribed for preventing AE occurrence (e.g. paracetamol to reduce the risk of fever) 

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7 
Management of Samples  
Blood samples for the assessment of antibody responses will be collected and subjects in 
Groups 1, 2, and 3 will provide blood samples for immunogenicity assessment as follows: 
• at baseline (pre-primary vaccination 1, Day 0) 
• 30 days (+21 days) after the 2nd dose of MenACYW conjugate vaccine / Nimenrix® 
• prior to the 3rd dose (toddler dose) of MenACYW conjugate vaccine / Nimenrix® 
• 30 days (+21 days) after the 3rd dose (toddler dose) of MenACYW conjugate vaccine / 
Nimenrix® 
Subjects in Group 4 will provide blood samples for immunogenicity assessment as follows:  
• at baseline (pre-primary vaccination 1, Day 0) 
• 30 days (+21 days) after the 3rd dose of MenACYW conjugate vaccine 
• prior to the 4th dose (toddler dose) of MenACYW conjugate vaccine 
• 30 days (+21 days) after the 4th dose (toddler dose) of MenACYW conjugate vaccine 
See the Table of Study Procedures and Section 5.1.3 for details of the sampling schedule. 
7.1 
Sample Collection  
A total of 4 blood samples will be collected from all subjects during their study participation by 
staff experienced in blood collection in a pediatric population.  
The Investigators should comply with European Regulation on the maximum amount of blood 
drawn that could be collected at any one time from children. According to European Regulation, 
the amount of blood drawn at any one time from the children in the study must not exceed 1% of 
their total blood volume (refer to Operating Guidelines for more detailed instructions) (48).  
At Visit 1, 2 or 3 mL of blood will be collected depending on the subject’s weight at the time of 
study visit; at Visit 3, 3 or 4 mL of blood will be collected depending on the subject’s weight at 
the time of study visit; and at Visits 4 and 5, 5 mL (or 6 mL) of blood will be collected from 
subjects in Groups 1, 2, and 3. For subjects in Group 4, 2 or 3 mL of blood will be collected at 
Visit 1 depending on the subject’s weight at the time of study visit, 3 or 4 mL of blood will be 
collected at Visit 4 depending on the subject’s weight at the time of study visit, and 5 mL (or 6 
mL) of blood will be collected at Visits 5 and 6 in tubes provided by or recommended by the 
Sponsor.  
For Groups 1, 2, and 3, the blood sample volume indicated will be taken from all subjects and 
those subjects included in a subset to assess the antibody response to meningococcal serogroups 
(A, C, W, and Y) measured by rSBA assay in addition to hSBA assay at Visits 1 and 3. At Visits 
4 and 5, blood sample volume of 5 mL will be taken from all subjects except subjects included in 
the rSBA subset. Blood sample volume of 6 mL will be taken from subjects included in the rSBA 
subset. 
For Group 4, the blood sample volume indicated will be taken from all subjects and those subjects 
included in a subset to assess the antibody response to meningococcal serogroups (A, C, W, and 

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Y) measured by rSBA assay in addition to hSBA assay at Visits 1 and 4. At Visits 5 and 6, blood 
sample volume of 5 mL will be taken from all subjects except subjects included in the rSBA 
subset. Blood sample volume of 6 mL will be taken from subjects included in the rSBA subset. 
Immediately prior to the blood draw, the staff member performing the procedure will verify the 
subject’s identity; will write the assigned subject's number on the pre-printed label that contains 
that subject’s number and the sampling stage; 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. 
7.2 
Sample Preparation  
Detailed instructions on how to prepare blood samples for assessment of immune response are 
contained in the Operating Guidelines 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 subject’s consent for future use of his / her 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 Clinical Logistics 
Coordinator must be notified. See the Operating Guidelines for further details. 
Shipments to the laboratory will be made only after appropriate monitoring, and following 
notification of the Clinical Logistics Coordinator. Sera will be shipped frozen, using dry ice to 
maintain them in a frozen state, in the packaging container provided by the carrier. Again, 
temperatures will be monitored. Shipments must be compliant with the United Nations (UN) 
Class 6.2 specifications and the International Air Transport Association (IATA) 602 packaging 
instructions. 
Samples will be shipped to R&D Global Operations at Sanofi Pasteur. The address is provided in 
the Operating Guidelines.  

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7.4 
Future Use of Stored Serum Samples for Research  
Subjects will be asked to indicate in the ICF whether they will permit the future use of any 
leftover stored serum samples for additional research not related to this study. If they consent, 
leftover serum samples will be securely stored at R&D Global Operations for up to 25 years after 
the end of the study. 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.  
8 
Clinical Supplies  
Sanofi Pasteur 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 Electronic Data Capture (EDC) will be defined by Sanofi Pasteur. If a 
computer is provided by Sanofi Pasteur, 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 staff must contact Sanofi Pasteur, 
indicating the quantity required. Contact information is provided in the Operating Guidelines.  
They must allow approximately 1 week for an order to be filled and to have the supplies sent to 
their site. 
9 
Endpoints and Assessment Methods  
9.1 
Primary Endpoints and Assessment Methods  
9.1.1 
Safety  
There are no primary objectives for safety. 

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9.1.2 
Immunogenicity  
9.1.2.1 
Immunogenicity Endpoint  
The primary endpoint for the evaluation of immunogenicity is:  
Antibody titers (geometric mean titers [GMTs]) against meningococcal serogroups A, C, W, and 
Y measured by hSBA in Groups 1 and 2, 30 days after the booster dose (third dose/toddler dose) 
of MenACYW conjugate vaccine or Nimenrix® when administered concomitantly with routine 
pediatric vaccines (PCV10 and hexavalent vaccine) to infants and toddlers from 6 weeks to 
18 months of age (Group 1 versus Group 2) 
9.1.2.2 
Immunogenicity Assessment Methods  
All assays will be performed at GCI, Swiftwater, PA or at qualified contract laboratories for GCI.  
For all samples, hSBA analysis will be done for all 4 serogroups.  
Antibodies to meningococcal antigens (hSBA Method) 
Functional meningococcal antibody activity against serogroups A, C, W, and Y will be measured 
in hSBA. 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% carbon dioxide (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 (refer to 
Table 9.1 and Table 9.2) for all study groups. In the event of insufficient serum sample volume, 
the conduct of the hSBA assay is of higher priority than the rSBA assay and the assays for 
antigens of concomitant vaccines. 
9.1.3 
Efficacy  
No clinical efficacy data will be obtained in the study. 
9.2 
Secondary Endpoints and Assessment Methods  
9.2.1 
Safety  
There are no secondary objectives for safety. 
9.2.2 
Immunogenicity  
9.2.2.1 
Immunogenicity Endpoints  
Secondary immunogenicity endpoints will include at least the following: 

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1) Antibody titers ≥ 1:8 against meningococcal serogroups A, C, W, and Y assessed at 30 days 
after Dose 2 of MenACYW conjugate vaccine or Nimenrix® measured by hSBA, when 
administered concomitantly with routine pediatric vaccines (Group 1 versus Group 2) 
2) Antibody titers (GMTs) against meningococcal serogroups A, C, W, and Y measured by 
hSBA in Group 3 at the following time points: 
• Day 0 (before Dose 1 of MenACYW conjugate vaccine) 
In addition, the following endpoints will be assessed: 
- 
Antibody titers ≥ 1:4 and titers ≥ 1:8 
• 30 days after Dose 2 of MenACYW conjugate vaccine in infancy, and before and 30 days 
after the booster dose (Dose 3) 
In addition, the following endpoints will be assessed: 
- 
Antibody titers ≥ 1:4 and titers ≥ 1:8 
- 
Post-vaccination titers ≥ 4 times the latest pre vaccination titers 
- 
hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
▪ For a subject with a pre vaccination titer < 1:8, the post-vaccination titer must be 
≥ 1:16; 
▪ For a subject with a pre vaccination titer ≥ 1:8, the post-vaccination titer must be at 
least 4-fold greater than the pre vaccination titer. 
3) Antibody titers or concentrations against the antigens of hexavalent vaccine (DTaP-IPV-HB-
Hib) in Groups 1, 2, and 3 at the following time points: 
• Day 0 (before Dose 1) 
- 
Anti-pertussis antibody concentrations (pertussis toxin [PT], filamentous 
hemagglutinin [FHA]) 
• 30 days after Dose 2 in infancy 
- 
Antibody concentrations/titers for all antigens 
- 
Anti-tetanus antibody concentrations ≥ 0.01 international units (IU)/ milliliter (mL) 
and ≥ 0.1 IU/mL 
- 
Anti-diphtheria antibody concentrations ≥ 0.01 IU/mL and ≥ 0.1 IU/mL 
- 
Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8  
- 
Anti-polyribosyl-ribitol phosphate (PRP) antibody concentrations ≥ 0.15 µg/mL 
- 
Pertussis vaccine seroresponse for anti-PT and anti-FHA, defined as: 
▪ If the pre-primary vaccination concentration is < 4 × LLOQ, post-primary 
vaccination concentration ≥ 4 × LLOQ 
▪ If the pre-primary vaccination concentration is ≥ 4 × LLOQ, post-primary 
vaccination concentration ≥ pre-primary vaccination concentration 

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- 
Anti-hepatitis B surface antigen (HBsAg) antibody concentrations ≥ 10 mIU/mL and 
≥ 100 mIU/mL 
• Before and 30 days after the booster dose (Dose 3): 
- 
Antibody concentrations/titers for all antigens 
- 
Anti-tetanus antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- 
Anti-diphtheria antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- 
Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8  
- 
Anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL 
- 
Pertussis vaccine seroresponse for anti-PT and anti-FHA, defined as: 
▪ If the pre-booster vaccination concentration is < 4 × LLOQ, post-booster 
vaccination concentration ≥ 4 × pre-booster concentration  
▪ If the pre-booster vaccination concentration is ≥ 4 × LLOQ, post-booster 
vaccination concentration ≥ 2 × pre-booster concentration 
- 
Anti-HBsAg antibody concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL 
Antibody concentrations against the antigens of PCV10 in Groups 1 and 2, 30 days after 
Dose 2 in infancy and 30 days after the booster dose (Dose 3): 
- 
Anti-pneumococcal antibody concentrations for serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 
19F, and 23F 
- 
Anti-pneumococcal antibody concentrations ≥ 0.35 μg/mL for serotypes 1, 4, 5, 6B, 
7F, 9V, 14, 18C, 19F, and 23F 
Antibody concentrations against the antigens of PCV13 in Group 3, 30 days after Dose 2 in 
infancy and 30 days after the booster dose (Dose 3): 
- 
Anti-pneumococcal antibody concentrations for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 
14, 18C, 19A, 19F, and 23F 
- 
Anti-pneumococcal antibody concentrations ≥ 0.35 μg/mL for serotypes 1, 3, 4, 5, 6A, 
6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F 
Antibody concentrations against the antigens of MMR vaccine 30 days after the MMR 
vaccine injectiona 
- 
Antibody concentrations for all antigens 
- 
Anti-measles antibody concentrations (serostatus cutoff: 255 mIU/mL)  
- 
Anti-mumps antibody concentrations (serostatus cutoff: 10 Mumps Ab units/mL)  
- 
Anti-rubella antibody concentrations (serostatus cutoff: 10 IU/mL) 
                                                 
a when the MMR vaccine has been administered concomitantly with the study vaccines 

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4) Antibody titers against meningococcal serogroups A, C, W, and Y measured by hSBA in 
Groups 1 and 2, as detailed for the Secondary Endpoints 2 (similar time points and endpoints) 
5) Antibody titers (GMTs) against meningococcal serogroups A, C, W, and Y measured by 
hSBA in Group 4 on Day 0 (before Dose 1 of MenACYW conjugate vaccine), 30 days after 
Dose 3 in infancy, and before and 30 days after the booster dose (Dose 4) at the following 
timepoints: 
• Day 0 (before Dose 1 of MenACYW conjugate vaccine  
In addition, the following endpoints will be assessed: 
- Antibody titers ≥ 1:4 and titers ≥ 1:8 
• 30 days after Dose 3 of MenACYW conjugate vaccine in infancy, and before 
and 30 days after the booster dose (Dose 4) 
In addition, the following endpoints will be assessed: 
- Antibody titers ≥ 1:4 and titers ≥ 1:8 
- Post-vaccination titers ≥ 4 times the latest pre vaccination titers 
- hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
▪ 
For a subject with a pre vaccination titer < 1:8, the post-vaccination titer must be 
≥ 1:16; 
▪ 
For a subject with a pre vaccination titer ≥ 1:8, the post-vaccination titer must be at 
least 4-fold greater than the pre vaccination titer. 
6) For Group 4, antibody titers or concentrations against the antigens of DTaP-IPV-HB-Hib 
vaccine before and 30 days after the booster dose (Dose 4), antibody concentrations against 
the antigens of PCV13 vaccine 30 days after the booster dose (Dose 4), and antibody 
concentrations against the antigens of MMR vaccine 30 days after vaccinationa.  
The timepoints are: 
Antibody titers or concentrations against the antigens of hexavalent vaccine  (DTaP-
IPV-HB-Hib): 
• Pre-booster dose 
- 
Anti-pertussis antibody concentrations anti-PT, anti-FHA 
• 30 days after the booster dose (Dose 4): 
- Antibody concentrations/titers for all antigens 
- Anti-tetanus antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- Anti-diphtheria antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL 
- Anti-poliovirus types 1, 2, and 3 antibody titers ≥ 1:8 
- Anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL 
                                                 
a when the MMR vaccine has been administered concomitantly with the study vaccines 

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- Pertussis vaccine seroresponse for anti-PT and anti-FHA, defined as: 
▪ 
If the pre-booster vaccination concentration is < 4 × LLOQ,  post-booster 
vaccination concentration ≥ 4 × pre-booster concentration 
▪ 
If the pre-booster vaccination concentration is ≥ 4 × LLOQ,  post-booster 
vaccination concentration ≥ 2 × pre-booster concentration 
Anti-HBsAg antibody concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL 
Antibody concentrations against the antigens of PCV13 in Group 4, 30 days after the 
booster dose (Dose 4): 
- 
Anti-pneumococcal antibody concentrations for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 
14, 18C, 19A, 19F, and 23F 
- 
Anti-pneumococcal antibody concentrations ≥ 0.35 μg/mL for serotypes 
1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F 
Antibody concentrations against the antigens of MMR vaccine 30 days after the MMR 
vaccine injectiona 
- 
Antibody concentrations for all antigens 
- 
Anti-measles antibody concentrations (serostatus cutoff: 255 mIU/mL) 
- 
Anti-mumps antibody concentrations (serostatus cutoff: 10 Mumps Ab units/mL) 
- 
Anti-rubella antibody concentrations (serostatus cutoff: 10 IU/mL) 
 
9.2.2.2 
Immunogenicity Assessment Methods  
The immunogenicity assessment methods for the meningococcal serogroups A, C, W, and Y 
antibody titers for the secondary endpoints are the same as that presented in Section 9.1.2.2. 
Antibody responses against the antigens of routine vaccines will also be measured in blood 
samples (see Table 9.1, Table 9.2, Table 9.3). 
Considering the number of antigens to test, and to mitigate any risk to fail testing in MET58, 
different profile testing will be performed according to odd- or even-numbered subject ID (ie, 
different ranking for testing antigens), in case of lower blood volume collected. In the event of 
insufficient serum sample volume, the immunogenicity assessment method (hSBA assay) for 
meningococcal serogroups A, C, W, and Y antibody titers will be the prioritized assay. (Refer to 
Section 9.1.2.2) 
                                                 
a when the MMR vaccine has been administered concomitantly with the study vaccines 

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Table 9.1: Blood sampling schedule and testing plan in Groups 1 and 2  
Age in months 
2 months 
5 months 
12-18 months 
13-19 months 
Visit and BL numbers 
Visit 1 
Visit 3 
Visit 4 
Visit 5 
 
(pre-vaccination) 
BL0001 
BL0002 
(pre-vaccination) 
BL0003 
BL0004 
Antigens 
Meningococcal 
serogroups A, C, W, Y 
Meningococcal 
serogroups A, C, W, 
Y 
Meningococcal 
serogroups A, C, W, Y 
Meningococcal serogroups 
A, C, W, Y 
 
Pertussis (PT, FHA) 
·    Hib (PRP) 
·    Hib (PRP) 
·    Measles† 
 
 
·    Hep B (HBsAg) 
·    Hep B (HBsAg) 
·    Mumps† 
 
 
·    Pertussis (PT, 
FHA) 
·    Pertussis (PT, FHA) 
·    Rubella† 
(Group 1 N= 716 
 
·    PCV10 
·    Poliovirus (types 1, 2, 
3) 
·    Hib (PRP) 
Group 2 N= 716) 
 
·    Poliovirus (types 
1, 2, 3) 
·    Diphtheria 
·    Hep B (HBsAg) 
 
 
·    Diphtheria 
·    Tetanus 
·    Pertussis (PT, FHA) 
 
 
·    Tetanus 
 
·    PCV10 
 
 
 
 
·    Poliovirus (types 1, 2, 
3) 
 
 
 
 
·    Diphtheria 
 
 
 
 
·    Tetanus 
Blood sample volume* 
2mL or 3 mL (depending 
on weight) 
3mL or 4 mL 
(depending on 
weight) 
5mL or 6 mL (for rSBA 
subset) 
5mL or 6 mL (for rSBA 
subset) 
PT: pertussis toxin; FHA: filamentous hemagluttinin; PRP: polyribosyl-ribitol phosphate; Hib: Haemophilus influenzae type b; 
Hep B: Hepatitis B; HBsAg: Hepatitis B surface antigen; PCV10: pneumococcal conjugate vaccine 10-valent. 
*Blood sample volume indicated for BL0001 and BL0002 will be taken from all subjects including those subjects in the rSBA 
subset, with 2 or 3 mL for BL0001 and 3 or 4 mL collected depending on weight at study visit. The blood sample volume for 
BL0003 and BL0004 is 5 mL, except for subjects included in the rSBA subset for which blood sample volume is 6 mL. In the 
rSBA subset, the antibody response to meningococcal serogroups (A, C, W, and Y) will be measured by rSBA assay in 
addition to  hSBA assay (refer to Section 6.5 for more details on the rSBA subset). 
†when the MMR vaccine has been administered concomitantly with the study vaccines 
For each visit, antigens are listed in descending order of assay priority (highest to lowest priority). 
For PCV10: Highest to lowest priority anti-pneumococcal serotypes: 1, 5, 7F, 4, 6B, 9V, 14, 18C,19F, and 23F 

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Table 9.2: Blood sampling schedule and testing plan in Group 3  
Age in 
months 
2 months 
5 months 
12-18 months 
13-19 months 
Visit and BL 
numbers 
Visit 1 
Visit 3  
Visit 4 
Visit 5 
(pre-vaccination) 
BL0001 
BL0002 
(pre-vaccination) 
BL0003 
BL0004 
Antigens 
•     Meningococcal 
serogroups A, C, W, Y 
•    Meningococcal 
serogroups A, C, W, Y 
•    Meningococcal 
serogroups A, C, W, Y 
•    Meningococcal 
serogroups A, C, W, Y 
 
•     Pertussis (PT, 
FHA) 
•    Hib (PRP) 
•    Hib (PRP) 
•    Measles† 
 
 
•    Hep B (HBsAg) 
•    Hep B (HBsAg) 
•    Mumps† 
(Group 3 N= 
110) 
 
•    Pertussis (PT, 
FHA) 
•    Pertussis (PT, 
FHA) 
•    Rubella† 
 
 
•    PCV13 
•    Poliovirus (types 
1, 2, 3) 
•    Hib (PRP) 
 
 
•    Poliovirus (types 
1, 2, 3) 
•    Diphtheria 
•    Hep B (HBsAg) 
 
 
•    Diphtheria 
•    Tetanus 
•    Pertussis (PT, FHA) 
 
 
•    Tetanus 
 
•    PCV13 
 
 
 
 
•    Poliovirus (types 1, 
2, 3) 
 
 
 
 
•    Diphtheria 
 
 
 
 
•    Tetanus 
Blood sample 
volume* 
2mL or 3 mL (depending 
on weight) 
3mL or 4 mL 
(depending on weight) 
5mL or 6 mL (for rSBA 
subset) 
5mL or 6 mL (for rSBA 
subset) 
PT: pertussis toxin; FHA: filamentous hemagluttinin; PRP: polyribosyl-ribitol phosphate; Hib: Haemophilus influenzae type b; Hep 
B: Hepatitis B; HBsAg: Hepatitis B surface antigen; PCV13:pneumococcal conjugate vaccine 13-valent. 
*Blood sample volume indicated for BL0001 and BL0002 will be taken from all subjects including those subjects in the rSBA 
subset, with 2 or 3 mL for BL0001 and 3 or 4 mL collected depending on weight at study visit. The blood sample volume for 
BL0003 and BL0004 is 5 mL, except for subjects included in the rSBA subset for which blood sample volume is 6 mL. In the 
rSBA subset, the antibody response to meningococcal serogroups (A, C, W, and Y) will be measured by rSBA assay in 
addition to hSBA assay (refer to Section 6.5 for more details on the rSBA subset). 
†when the MMR vaccine has been administered concomitantly with the study vaccines 
For each visit, antigens are listed in descending order of assay priority (highest to lowest priority). 
For PCV13: Highest to lowest priority anti-pneumococcal serotypes: 1, 3, 5, 6A, 7F, 19A, 4, 6B, 9V, 14, 18C,19F, and 23F 

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Table 9.3: Blood sampling schedule and testing plan in Group 4  
Age in 
months 
2 months 
7 months 
12-18 months 
13-19 months 
Visit and BL 
numbers 
Visit 1 
Visit 4  
Visit 5 
Visit 5 
 
(pre-vaccination) 
BL0001 
BL0002 
(pre-vaccination) 
BL0003 
BL0004 
Antigens 
•     Meningococcal 
serogroups A, C, W, Y 
•    Meningococcal 
serogroups A, C, W, Y 
•    Meningococcal 
serogroups A, C, W, Y 
•    Meningococcal 
serogroups A, C, W, Y 
  
 
 
•    Hib (PRP) 
•    Measles† 
  
  
 
•    Hep B (HBsAg) 
•    Mumps† 
(Group 4 N= 
110) 
  
 
•    Pertussis (PT, 
FHA) 
•    Rubella† 
 
  
 
•    Poliovirus (types 
1, 2, 3) 
•    Hib (PRP) 
  
  
 
•    Diphtheria 
•    Hep B (HBsAg) 
  
  
 
•    Tetanus 
•    Pertussis (PT, FHA) 
  
  
 
  
•    PCV13 
  
  
  
  
•    Poliovirus (types 1, 
2, 3) 
  
  
  
  
•    Diphtheria 
  
  
  
  
•    Tetanus 
Blood sample 
volume* 
2mL or 3 mL (depending 
on weight) 
3mL or 4 mL 
(depending on weight) 
5mL or 6 mL (for rSBA 
subset) 
5mL or 6 mL (for rSBA 
subset) 
PT: pertussis toxin; FHA: filamentous hemagluttinin; PRP: polyribosyl-ribitol phosphate; Hib: Haemophilus influenzae type b; Hep 
B: Hepatitis B; HBsAg: Hepatitis B surface antigen; PCV13: pneumococcal conjugate vaccine 13-valent. 
*Blood sample volume indicated for BL0001 and BL0002 will be taken from all subjects including those subjects in the rSBA 
subset with 2 or 3 mL for BL0001 and 3 or 4 mL collected depending on weight at study visit. The blood sample volume for 
BL0003 and BL0004 is 5 mL, except for subjects included in the rSBA subset for which blood sample volume is 6 mL. In the 
rSBA subset, the antibody response to meningococcal serogroups (A, C, W, and Y) will be measured by rSBA assay in 
addition to hSBA assay (refer to Section 6.5 for more details on the rSBA subset). 
†when the MMR vaccine has been administered concomitantly with the study vaccines 
For each visit, antigens are listed in descending order of assay priority (highest to lowest priority). 
For PCV13: Highest to lowest priority anti-pneumococcal serotypes: 1, 3, 5, 6A, 7F, 19A, 4, 6B, 9V, 14, 18C,19F, and 23F 
 
Anti-Haemophilus influenzae type b (Anti-PRP) Antibodies 
Anti-PRP concentrations will be measured using a Farr-type radioimmunoassay (RIA). Serum 
levels of anti-Haemophilus influenzae type b (Hib) capsular PRP antibody are determined by RIA, 
in which serum samples are incubated with radiolabeled PRP (3H-PRP) in the presence of 36Cl 
(volume marker). Specific antibodies bind to tritiated capsular PS to form antigen-antibody 
complexes. These complexes are precipitated with ammonium sulfate and collected by 
centrifugation. The radioactivity is measured in the precipitated pellet in counts per minute and is 

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proportional to the amount of anti-Hib capsular PS antibody present in the serum sample. The 
concentration of anti-PRP antibody in the serum sample is determined from the concentration 
response curve generated by the titration results of dilutions of the reference standard analyzed in 
the assay. Results are reported in µg/mL by comparison to the Center for Biologics Evaluation 
and Research (CBER), Lot No. 1983 reference standard. The LLOQ of the anti-PRP RIA is 
0.06 µg/mL. 
Anti-Diphtheria, Tetanus, and Pertussis Antibodies 
The DTP (Diphtheria, Tetanus, and Pertussis) ECL (electrochemiluminescent) is a multiplexed 
serological assay which allows for the simultaneous quantification of human antibodies to 
6 specific antigens including diphtheria toxoid, tetanus toxoid, and 4 pertussis antigens: PT, FHA, 
FIM and PRN. In this assay, each well of a 96-well microtiter plate is pre-coated in precise 
positions with the 6 different antigens in a multi-spot fashion. Following incubation with serum 
samples, antigen-specific antibodies bind to the respective antigens. The captured antibodies are 
then detected using a SULFO-TAG conjugated anti-human IgG conjugate. Electrical stimulation 
of the conjugate in the presence of a chemiluminescent substrate results in the generation of a 
light signal from each specific spot that is captured by a camera in relative light units. The signal 
generated is directly proportional to the amount of antibodies present in the sample, which is 
quantified using software and based on an established reference standard sample curve. The 
LLOQ for Diphtheria is 0.005 IU/mL, the LLOQ for Tetanus is 0.01 IU/mL and the LLOQ for 
Pertussis antigens is 2.00 EU/ml 
Anti-Pneumococcal Antibodies 
The pneumococcal capsular PS (PnPS) IgG ECL assay is used to quantitate the amount of anti-
Streptococcus pneumoniae antibodies in human serum for 21 serotypes including all 10 serotypes 
in Synflorix® and 13 serotypes in Prevenar 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 
11A, 12F, 14,15B, 18C, 19A, 19F, 22F, 23F and 33F). In this method, purified antigen of 8 PnPS 
are coated into defined spots within the wells of a 96-well microtiter plate by MesoScale 
Discovery using 3 types of plates to cover all 21 PnPS. Diluted serum samples (test samples, 
reference standard, and quality controls), pre-treated with pneumococcal cell wall absorbents (to 
reduce the interference of non-specific antibodies in the assay), are incubated in the wells. 
Specific antibodies in the serum samples bind to the immobilized antigen. Unbound antibodies are 
washed from the wells, and SULFO-TAG-conjugated anti-human immunoglobulin is added. The 
antibody conjugate binds to the antigen-antibody complex. Excess conjugate is washed away, and 
read buffer is added. The plate is read using electrochemiluminescence on an MSD imager. The 
intensity of the generated light is proportional to the amount of specific antibody bound to the 
antigen-coated spots. An international reference standard assayed on each plate is used to 
calculate the amount of anti-pneumococcal IgG antibodies (µg/mL) in human serum. The LLOQ 
for all PnPS serotypes is 0.15 μg/mL 
Anti-Hepatitis B Antibodies 
Anti-HB antibodies will be measured by the commercially available VITROS ECi/ECiQ 
Immunodiagnostic System using chemiluminescence detection technology. The VITROS ECi 
Immunodiagnostic system uses an antibody-mediated antigen sandwich formation to detect the 
presence of anti-HBs total immunoglobulin in human serum. This involves the reaction of anti-

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HBs in the sample with plasma-derived HBsAg (ad and ay subtypes) coated onto the wells. A 
horseradish peroxidase (HRP)-labeled HBsAg conjugate (ad and ay subtypes) then complexes 
with the bound anti-HBs forming an antigen sandwich. Substrate is then added which catalyzes 
HRP, producing light. The light signals are read by the VITROS ECi/ECiQ. Immunodiagnostic 
System and the amount of HRP conjugate bound is directly proportional to the concentration of 
anti-HepBs antibodies present in the sample. Results are reported in mIU/mL by comparison to a 
calibrator provided by the manufacturer that has been calibrated according to the World Health 
Organization (WHO) First International Reference Preparation for Antibody to HBsAg (1977). 
The LLOQ is 5 mIU/mL. 
Anti-Poliovirus (types 1, 2, and 3) Antibodies 
Anti-poliovirus types 1, 2, and 3 will be measured by neutralization assay. Serial dilutions of sera 
are mixed with challenge poliovirus and incubated with cultured Vero cells that are sensitive to 
poliovirus. Specific neutralizing antibodies contained in the sera bind to and neutralize the 
challenge poliovirus. The neutralized poliovirus does not affect cellular viability and these cells 
continue to metabolize and release CO2, reducing the pH of the culture medium. Cell survival 
correlates with the change in the pH indicator (phenol red to yellow at pH ≤ 7.0) contained in the 
medium. In the absence of neutralizing antibodies, the challenge poliovirus reduces cellular 
metabolism and CO2 production. Therefore, the pH does not decrease and a color change is not 
detected. The poliovirus mouse inoculation test measures the functional serum antibody response 
to poliovirus by utilizing Vero cells (African green monkey kidney cells) and wild type poliovirus 
strains 1, 2, and 3 (Mahoney, MEF-1, and Saukett, respectively) as the challenge virus. The 
Karber method is used to determine the serum dilution that neutralized 50% of the challenge 
virus. Results are expressed as titers (1/dilution [dil]). The LLOQ of the anti-poliovirus types 1, 2, 
and 3 assays is 4 (1/dil). 
Anti-Measles Antibodies 
The purpose of the Bulk Measles IgG EIA (Enzyme Immunoassay) is to detect total IgG antibody 
to measles virus before and after vaccination with a measles-containing vaccine. Plates are coated 
in house using inactivated measles antigen that is bound to solid phase microtiter plates. The 
antigen is derived from Measles Edmonston strain-infected Vero cells. Serum or plasma is added 
to the coated plates and samples positive for measles antibodies will bind to the measles antigen- 
coated plates, forming antibody-antigen complexes. The bound antibody-antigen complexes can 
then be detected using an Alkaline Phosphatase labeled anti-human IgG. Color development 
occurs as a result of the addition of an enzyme-specific substrate Phenolphthalein 
Monophosphate. The color intensity is then measured spectrophotometrically with the highest 
intensity of color correlating to a high level of measles antibody and lowest color intensity 
correlating to low levels of measles antibody. Quantitation of the human IgG antibody to measles 
virus or titer is determined by comparison of the resulting optical density (OD) to a standard 
curve. The reference standard is a pool of human sera that has been calibrated against the WHO 
anti-measles reference standard, lot NIBSC 66/202. The concentration of anti-measles antibody in 
a sample is reported in milli-International Units per milliliter of serum (mIU/mL). The clinical 
endpoint for the measles assay is 255 mIU/mL and the LLOQ is 60 mIU/mL 
Anti-Mumps Antibodies 

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The purpose of the mumps enzyme-linked immunosorbent assay (ELISA) is to detect IgG 
antibody to mumps virus before and after vaccination with a mumps virus-containing the vaccine. 
The assay uses an earlier passage of the Jeryl Lynn® mumps virus (Jeryl Lynn® 135 [JL135],<12 
passages) which is considered to be a wild-type (WT)-like strain. The reactivity of the sera to the 
mumps antigens prepared from uninfected Vero cells (denoted as tissue culture control [TCC] 
wells) is subtracted from that of JL135-infected Vero cells. JL135 mumps virus antigen or TCC is 
bound to solid phase microtiter plates and serum containing mumps antibody is added. The 
mumps antibody bound to the WT mumps antigen-coated plates forms an antibody-antigen 
complex. The bound antibody-antigen complex is then detected using an enzyme-labeled 
antihuman IgG. Color development occurs with the addition of a substrate and color intensity is 
measured spectrophotometrically. Results are obtained as a difference of the average duplicate of 
each optical density (OD) of JL135 mumps antigen wells and the average duplicate OD of TCC 
wells for each serum sample (noted as delta optical density [DOD]). Quantitation of the human 
IgG antibody to mumps virus, or antibody concentration, is determined by comparison of the 
resulting test DOD to a standard curve. The reference standard is an individual human serum. 
Results for the assay are reported as the concentration of antibody in Mumps antibody units/mL. 
The clinical endpoint and the LLOQ for the mumps assay is 10 Mumps Ab units/mL 
Anti-Rubella Antibodies 
The purpose of the Bulk Rubella IgG EIA (Enzyme Immunoassay) is to detect total IgG antibody 
to rubella virus before and after vaccination with a rubella-containing vaccine. Plates are coated in 
house using inactivated rubella antigen that is bound to solid phase microtiter plates. The antigen 
is derived from Rubella HPV-77 infected Vero cells. Serum is added to the coated plates and 
samples positive for rubella antibodies will bind to the rubella antigen-coated plates, forming 
antibody-antigen complexes. The bound antibody-antigen complexes can then be detected using 
an Alkaline Phosphatase labeled anti-human IgG. Color development occurs as a result of the 
addition of an enzyme-specific substrate, Phenolphthalein Monophosphate. The color intensity is 
then measured spectrophotometrically with the highest intensity of color correlating to a high 
level of rubella antibody and lowest color intensity correlating to low levels of rubella antibody. 
Quantitation of the human IgG antibody to rubella virus or titer is determined by comparison of 
the resulting analysis OD to a standard curve. The reference standard is an individual human 
serum that has been calibrated against the WHO anti-rubella reference standard. The 
concentration of anti-rubella antibody in a sample is reported in International Units per milliliter 
of serum (IU/mL). The clinical endpoint for the rubella assay is 10 IU/mL and the LLOQ is 5 
IU/mL. 
9.2.3 
Efficacy  
No clinical efficacy data will be obtained in the study. 

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9.3 
Observational Endpoints and Assessment Methods  
9.3.1 
Immunogenicity  
9.3.1.1 
Immunogenicity Endpoints  
Antibody titers (GMTs) against meningococcal serogroups A, C, W, and Y measured by rSBA in 
a subset of subjects in all groupsa at Day 0 (before Dose 1) (all groups), 30 days after Dose 2 
(Groups 1, 2, and 3) or 30 days after Dose 3 (Group 4) in infancy, and before and 30 days after 
the booster dose (in all groups) 
In addition, the following endpoints will be assessed for all groups: 
- 
Antibody titers, titers ≥ 1:8, and titers ≥ 1:128 
- 
Post-vaccination titers ≥ 4 times the latest pre vaccination titers 
- 
rSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
▪ a post-vaccination rSBA titer ≥ 1:32 for subjects with pre vaccination rSBA titer 
< 1:8, or 
▪ a post-vaccination titer ≥ 4 times the pre vaccination titer for subjects with pre 
vaccination rSBA titer ≥ 1:8. 
9.3.1.2 
Immunogenicity Assessment Methods  
The testing laboratories which will perform the assays described below will be reported in the 
final Clinical Study Report.  
The rSBA testing is planned to take place at the Public Health England, Manchester, United 
Kingdom laboratory of 
. 
Blood samples from a subset of subjects will be analyzed using rSBA for all 4 serogroups: 
100 subjects each in Group 1 and Group 2 and 50 subjects each in Group 3 and Group 4. 
Antibodies to meningococcal antigens (rSBA Method) 
Functional meningococcal antibody activity against serogroups A, C, W, and Y will be measured 
in rSBA. Two-fold dilutions of test sera are prepared in sterile 96-well microtiter plates. 
Serogroup-specific meningococcal bacteria along with baby rabbit 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 
                                                 
a The rSBA subset will comprise: 
• 
Group 1 and Group 2: 100 subjects in each group  
• 
Group 3 and Group 4: 50 subjects in each group  
Whenever collection of 6 mL of blood sample in toddler population (ie from 12 to 19 months of age) does not comply with local regulations, the 
corresponding countries will not include subjects in the rSBA subset. The rSBA subset will include subjects from all countries except Poland. 
 

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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 LLOQ of the rSBA assay is a titer of 1:4. This method will be 
performed on blood samples (refer to Table 9.1 and Table 9.2) in a subset. If the event of 
insufficient serum sample volume, the conduct of the hSBA assay is of higher priority than the 
assays for antigens of concomitant vaccines and the conduct of the assays for antigens of 
concomitant vaccines is of higher priority than the rSBA assay. 
9.3.2 
Safety  
9.3.2.1 
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 
• 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 (eg, 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. 

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An SAE is any untoward medical occurrence that at any dose  
• Results in death 
• Is life-threateninga 
• Requires inpatient hospitalization or prolongation of existing hospitalizationb 
• Results in persistent or significant disability / incapacityc 
• 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. 
Adverse Reaction: 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered 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 Sanofi Pasteur: 
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 (ieg, injection site 
tenderness or irritability occurring between D0 and D07 post-vaccination).  
                                                 
a  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. 
b  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.  
c  “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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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 D07 is a solicited reaction (ie, prelisted in the protocol and CRB), then a headache starting 
on D07 is a solicited reaction, whereas headache starting on D08 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 (eg, erythema 
that is localized but that is not occurring at the injection site). 
Adverse Event of Special Interest (AESI): 
An AESI is an event for which ongoing monitoring and rapid communication by the Investigator 
to the Sponsor must be done. Such an event might warrant further investigation in order to 
characterize and understand it. Depending on the nature of the event, rapid communication by the 
study Sponsor to other parties (eg, regulators) might also be warranted. 
9.3.2.2 
Safety Endpoints  
The following endpoints will be used for all subjects for the evaluation of safety: 
• Unsolicited systemic AEs reported in the 30 minutes after each vaccination, including 
occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), 
duration, intensity, action taken, relationship to the product administered, and whether the 
event caused termination from the study. 
• Solicited (prelisted in the subject’s diary card and CRB) injection site and systemic reactions 
starting any time from Day 0 (day of vaccination) through Day 7 after each vaccination, 
including occurrence, time of onset, number of days of occurrence, intensity, action taken, and 
whether the reaction caused termination from the study. 
• Unsolicited non-serious AEs reported up to 30 days after each vaccination, including 
occurrence, nature (MedDRA preferred term), time of onset, duration, intensity, action taken, 
relationship to the product administered, and whether the event caused termination from the 
study. 
• SAEs (including AESIs) reported throughout the study, ie, from Visit 1 (first vaccination) to 
the last study visit (Visit 5 for Groups 1, 2, and 3 and Visit 6 for Group 4, occurring 30 days 
[+21 days] after the last vaccination), including occurrence, nature (MedDRA preferred term), 

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time of onset, duration, intensity, action taken, relationship to the product administered, 
whether the event caused termination from the study, outcome, elapsed time from last 
administration (if less than 24 hours), relationship to study procedures, and seriousness 
criterion. 
9.3.2.3 
Safety Assessment Methods  
At each visit, the Investigator or a delegate will ask the 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. 
9.3.2.3.1 
Immediate Post-vaccination Observation Period  
Subjects will be kept under observation for 30 minutes after each 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. 
9.3.2.3.2 
Reactogenicity (Solicited Reactions from Day 0 to Day 7 after Each Vaccination)  
After each vaccination, subject’s 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 in the diary card on the day of vaccination 
and for the next 7 days (ie, D0 to D07) 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 (eg, medication) 
The action(s) taken by the 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 

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• Discontinuation of study vaccination 
Parents / legally acceptable representatives will be contacted by telephone 8 days after each 
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 staff will continue 
calling until contact is made. Every telephone attempt and its outcome will be documented in the 
source document. 
Table 9.4 and Table 9.5 present, respectively, the injection site reactions and systemic reactions 
that are prelisted in the diary cards and CRB, together with the intensity scales. 
 
Table 9.4: Solicited injection site reactions: terminology, definitions, and intensity scales  
CRB term 
(MedDRA 
lowest level 
term [LLT]) 
Injection site tenderness 
Injection site erythema 
Injection site swelling 
MedDRA 
preferred 
term  
Injection site pain 
Injection site erythema 
Injection site swelling 
Diary card 
term 
Tenderness 
Redness 
Swelling 
Definition 
Pain when the injection site is 
touched or injected limb 
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 
Intensity 
scale* 
 
Grade 1: Minor reaction when 
injection site is touched 
Grade 2: Cries or protests when 
injection site is touched 
Grade 3: Cries when injected 
limb is mobilized, or the 
movement of the injected limb 
is reduced 
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 
* For the subjective reaction of tenderness, parents / legally acceptable representatives will record the intensity level (Grade 1, 2, 
or 3) in the diary card. For the measurable reactions of redness and swelling, 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 9.5: Solicited systemic reactions: terminology, definitions, and intensity scales  
CRB term 
(MedDRA 
LLT) 
Fever 
Vomiting 
Crying 
abnormal  
Drowsiness 
Appetite lost 
Irritability 
MedDRA 
preferred 
term  
Pyrexia 
Vomiting  
Crying 
Somnolence 
Decreased 
appetite 
Irritability 
Diary card 
term 
Temperature 
Vomiting 
Abnormal 
crying 
Drowsiness 
Loss of 
appetite 
Irritability 
Definition 
Elevation of 
temperature to 
≥°38.0°C 
(≥ 100.4°F) 
Vomiting does 
not include 
spitting up 
Inconsolable 
crying without 
a determined 
reason 
Reduced 
interest in 
surroundings, 
or increased 
sleeping 
See intensity 
scale 
An excessive 
response to 
stimuli: 
increased 
fussiness, 
whining, and 
fretfulness 
despite 
attempts to 
comfort the 
infant and 
despite 
caregiver 
responses that 
would 
normally be 
soothing 
Intensity 
scale* 
Grade 1:  
≥ 38.0°C to 
≤ 38.5°C 
or ≥ 100.4°F to 
≤ 101.3°F 
 
Grade 1: 
1 episode per 
24 hours 
Grade 1: 
< 1 hour 
Grade 1: 
Sleepier than 
usual or less 
interested in 
surroundings 
Grade 1: 
Eating less 
than normal 
Grade 1: 
Easily 
consolable 
 
Grade 2: 
> 38.5°C to 
≤ 39.5°C 
or > 101.3°F to 
≤ 103.1°F 
 
Grade 2: 2–
5 episodes per 
24 hours 
Grade 2: 1–
3 hours  
Grade 2: Not 
interested in 
surroundings 
or did not 
wake up for a 
feed / meal 
Grade 2: 
Missed 1 or 2 
feeds / meals 
completely 
Grade 2: 
Requiring 
increased 
attention 
 
Grade 3: 
> 39.5°C 
or > 103.1°F 
 
Grade 3: 
≥ 6 episodes 
per 24 hours or 
requiring 
parenteral 
hydration 
Grade 3: 
> 3 hours 
Grade 3: 
Sleeping most 
of the time or 
difficult to 
wake up 
Grade 3: 
Refuses ≥ 3 
feeds / meals 
or refuses most 
feeds / meals 
Grade 3: 
Inconsolable 
*  For all reactions but fever, 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: 
Parents / legally acceptable representatives are to measure subject’s 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 rectal, oral or axillary according to local practices, with the rectal route 
preferred for infants and the axillary route preferred for toddlers. Pre-vaccination temperature is 
also systematically collected by the investigator on the source document. Tympanic thermometers 
must not be used. 
9.3.2.3.3 
Unsolicited Adverse Events  
In addition to recording solicited reactions, parents / legally acceptable representatives will be 
instructed to record any other medical events that may occur from Day 0 to Day 30 or until the 
subject returns for the next study visit, whichever comes first. Space will be provided in the diary 
card for this purpose.  
Information on SAEs will be collected and assessed throughout the study, from Visit 1 until 
30 days after the last 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 (eg, 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 datesa  
• 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 9.4 and Table 9.5). 
                                                 
a  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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All other unsolicited AEs will be classified according to the following intensity scale: 
• 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. 
• 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 9.3.2.3.5. 
• Action taken for each AE (eg, medication) 
The action(s) taken by the 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 
• Discontinuation of study vaccination  
• 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 
9.3.2.3.4 
Adverse Events of Special Interest  
An AESI is defined as event for which ongoing monitoring and rapid communication by the 
Investigator to the Sponsor must be done. The following AEs will be captured as AESIs 
throughout the study: 
• Generalized seizures (febrile and non-febrile) (49) (50) 
• Kawasaki disease (51) (52) (53) 
• Guillain-Barré syndrome (54) 
• Idiopathic thrombocytopenic purpura (ITP) (55) (56) 
 

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These events have been listed as AESIs based on the feedback received from the EU regulators. 
No safety concerns relating to these AESIs have been identified with the use of MenACYW 
conjugate vaccine in the completed clinical trials. Because of their medical importance and to 
ensure expedited communication to the Sponsor, these AESIs are to be considered and collected 
as SAEs and reported to the Sponsor according to the procedure described in Section 10. Further 
instructions on the data collection for these events and the relevant definitions will be provided in 
the Operating Guidelines. 
9.3.2.3.5 
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 first 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. 
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. 
9.3.3 
Efficacy  
No clinical efficacy data will be obtained in the study. 
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 and the Clinical 
Research Associate (CRA) within the notification timelines stated in the following sections. The 
Investigator will give access and provide the Sponsor and the CRA with all necessary information 
to allow the Sponsor to conduct a detailed analysis of the safety of the investigational product(s). 
It is the responsibility of the Investigator to request all necessary documentation (eg, medical 
records, discharge summary, autopsy) 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. 

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10.1 Initial Reporting by the Investigator  
Serious adverse events occurring during a subject’s participation in the study or experiment must 
be reported within 24 hours to the Sponsor’s GPV Department and to the CRA. Every SAE must 
be reported, even if the Investigator considers that it is not related to the vaccine. The investigator 
(licensed physician [M.D. or D.O.]) must validate the information entered on the AE CRF by 
completing the investigator validation form. 
The Investigator must indicate on the AE CRF that the event was serious and must complete the 
relevant SAE section of this form as well as the appropriate Safety Complementary Information 
CRFs. An e-mail alert will automatically be sent by the EDC system to the GPV mailbox, the 
CRA and the CTL with relevant SAE information details. 
If the EDC system is unavailable, the site must notify the Sponsor, using the paper version of the 
CRB, as described in the operating guidelines: 
The Investigator must complete the paper copies of the AE CRF and of the appropriate Safety 
Complementary Information CRFs and send them to the Sponsor by one of the following means: 
• By fax, to the following number: (570)-957-2782 
• In PDF format to the following e-mail address, using a method of transmission that 
includes password protection: PV.outsourcing@sanofi.com 
• By express mail, to the following address:  
Sanofi Pasteur Inc.  
Reception and Triage – Case Management 
Global Pharmacovigilance 
Mail Drop: 45D38 
Discovery Drive 
Swiftwater, PA 18370 
 
When the EDC system becomes available, the Investigator must transcribe the information from 
the paper forms into the EDC system. 
If there is need for urgent consultation, the Investigator is to contact the 
 If the RMO cannot be reached, the Investigator may contact the Call Center as 
described in Section 5.3.  
10.2 Follow-up Reporting by the Investigator  
The AE CRF completed initially must be updated within 24 hours after the Investigator has 
become aware of any new relevant information concerning the SAE (eg, outcome, precise 
description of medical history, results of the investigation). All relevant information must be 
included directly in the AE CRF and the appropriate Safety Complementary Information CRFs. 
An e-mail alert will be sent automatically to the GPV Department and to the CRA. Copies of 
documents (eg, medical records, discharge summary, autopsy) may be requested by the GPV 
Department. 

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The anonymity of the subject must always be respected when forwarding this information. 
10.3 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 
investigational product(s), other products (eg, 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. 
10.4 Assessment of Causality  
The causal relationship between the SAE and the product administered will be evaluated by the 
Investigator as described in Section 9.3.2.3.5. 
Following this, the Sponsor’s Pharmacovigilance (PV) Global Safety Officer 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).  
10.5 Reporting SAEs to Health Authorities and IECs / IRBs  
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 following definition is used for the purpose of expedited reporting of suspected unexpected 
serious adverse reactions (SUSARs): 
Suspected Unexpected Serious Adverse Reactions (SUSAR): 
‘Unexpected serious adverse reaction’ means a serious adverse reaction, the nature, severity or 
outcome of which is not consistent with the reference safety information (at the time of 
occurrence of the SUSAR, “Reference Safety Information” within Section 6.2.2 of the 
Investigator Brochure). Serious adverse events considered reasonably associated with the 
investigational medical product administered and considered unexpected are subject to expedited 
safety reporting to regulatory agencies and to the Ethics Committee concerned.   
The Sponsor’s 
 will notify the Investigators in writing of the 
occurrence of any reportable SAEs.  
The Sponsor will be responsible for informing the IECs or IRBs 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’ parent / legally acceptable representative for the 
recording of daily safety information as described in Section 9.3.2.3. These diary cards will 
include prelisted terms and intensity scales (see Table 9.4 and Table 9.5) as well as areas for free 
text to capture additional safety information or other relevant details. 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 parents / legally acceptable representatives on how to 
correctly use these tools.  
At specified intervals, the Investigator or an authorized designee will interview the 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 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 leave 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. 
11.2 Data Management  
Management of SAE Data 
During the study, SAE data (reported on the AE and Safety Complementary Information CRFs) 
will be integrated into the Sponsor’s centralized GPV database upon receipt of these forms and 

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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 PV 
Global Safety Officer and the RMO. 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 Sanofi Pasteur 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 Data warehouse. 
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 Data Management 
before database lock.  
The safety of the investigational product will be continuously monitored by the Sponsor. Periodic 
blinded (when applicable) safety data review will be performed by the Sponsor’s Safety 
Management Team (SMT). 
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.  

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12.1.1 Hypotheses and Statistical Methods for Primary Objective  
12.1.1.1 Hypotheses  
Non-inferiority of MenACYW conjugate vaccine (Group 1) compared to Nimenrix® (Group 2) in 
terms of hSBA antibody titers after a 3-dose series to infants and toddlers will be tested.  
For each of the 4 serogroups (A, C, W, and Y), GMTs 30 days after a 3- dose series vaccination 
will be used to compare Group 1 and Group 2 with the following individual hypotheses: 
H0 (Null hypothesis):  
• GMTMenACYW / GMTNimenrix ≤ 1/1.5 (or GMTNimenrix / GMTMenACYW ≥ 1.5) 
H1 (Alternative hypothesis):  
• GMTMenACYW / GMTNimenrix > 1/1.5 (or GMTNimenrix / GMTMenACYW < 1.5) 
12.1.1.2 Statistical Methods  
Assuming that Log10 transformation of the data follows a normal distribution, the Log10(data) 
will be used for the statistical analysis, then antilog transformations will be applied to the results 
of calculations, in order to provide the results in terms of GMT. 
The statistical methodology will be based on the use of the 2-sided 95% confidence interval (CI) 
of the ratio of post-vaccination GMTs between Group 1 and Group 2. The CI will be calculated 
using a normal approximation of log-transformed titers. 
Non-inferiority will be demonstrated if all 4 individual null hypotheses (4 serogroups) are 
rejected. For each serogroup, the 2-sided 95% CI of the GMT ratio Group 1 (MenACYW) / 
Group 2 (Nimenrix) should lie above 1/1.5 
12.1.2 Hypotheses and Statistical Methods for Secondary Objectives  
12.1.2.1 Hypotheses for Secondary Objective 1  
If the primary objective is met, non-inferiority of MenACYW conjugate vaccine (Group 1) 
compared to Nimenrix® (Group 2) in terms of hSBA antibody titers ≥ 1:8 after a 2-dose series in 
infants will be tested (Secondary Objective 1). 
For each of the 4 serogroups (A, C, W, and Y), the percentages of subjects who achieve an hSBA 
titer ≥ 1:8 30 days after the 2 dose administered in infancy will be used to compare responses 
between Group 1 and Group 2 with the following individual hypotheses: 
• H0 (Null hypothesis): p(MenACYW) - p(Nimenrix) ≤ -10% 
• H1 (Alternative hypothesis): p(MenACYW) - p(Nimenrix) > -10% 
where p(MenACYW) and p(Nimenrix) are the percentages of subjects who achieve an hSBA titer ≥ 1:8 
in the MenACYW conjugate vaccine group and the Nimenrix® group, respectively. 

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12.1.2.2 Statistical Methods for Secondary Objective 1  
Non-inferiority will be demonstrated if all 4 individual null hypotheses (4 serogroups) are 
rejected. If the lower limit of the 2-sided 95% CI of the difference between the 2 percentages is  
> -10%, the non-inferiority will be demonstrated. The CI of the difference in percentages will be 
computed using the Wilson score method without continuity correction. 
12.1.2.3 Hypotheses for Secondary Objectives 2, 3, 4, 5, 6 and 7  
No hypotheses will be tested. 
12.1.2.4 Statistical Methods for Secondary Objectives 2, 3, 4, 5, 6 and 7  
The statistical analyses for the Secondary Objectives 2, 3, 4, 5, 6 and 7 will be descriptive. 
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 proportions. For GMTs and geometric mean concentrations (GMCs), 95% CIs of point 
estimates will be calculated using a normal approximation assuming they are log-normally 
distributed. 
Reverse cumulative distribution curve (RCDC) figures may be also provided. 
12.1.3 Statistical Methods for Observational Objectives  
Safety 
Safety results will be described for subjects in all study groups. The main parameters for the 
safety endpoints will be described by 95% CIs (based on the Clopper-Pearson method). 
It will include but is not limited to the following: 
• Number and percentages of subjects reporting any solicited injection sites reactions and 
solicited systemic reactions occurring from Day 0 to Day 7 after each vaccination will be 
summarized by intensity, time of onset period, days of occurrence, and action taken. 
• Number and percentages of subjects reporting any immediate unsolicited systemic AEs 
occurring 30 minutes after each vaccination and unsolicited AEs occurring up to 30 minutes 
after each vaccination will be summarized 
• The number and percentage of subjects reporting any unsolicited non-serious AEs occurring 
up to Day 30 will be summarized by intensity, time of onset period, duration, and by 
MedDRA preferred term and system organ class (SOC), as well as by relationship to the study 
vaccine 
• The number and percentage of subjects reporting at least one SAEs occurring throughout the 
trial will be summarized by seriousness criterion, outcome and by MedDRA preferred term 
and SOC, as well by relationship to the study vaccine 

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• The number and percentage of subjects reporting at least one of any AESIs will be 
summarized throughout the trial 
12.1.4 Sensitivity analysis due to COVID-19 pandemic  
The impact of COVID-19 pandemic situation on study conduct will be summarized through 
impact on visit procedures, study completion and major/critical protocol deviations due to 
COVID-19. The subjects impacted by COVID-19 pandemic situation will be defined as the 
subjects with at least one major/critical protocol deviation due to COVID-19 or who did not 
complete the study due to COVID-19. If more than 10% of subjects are impacted as per this 
definition, the main immunogenicity and safety endpoints will also be summarized in these 
subjects to assess the impact of COVID-19 situation on study outcome. 
12.2 Analysis Sets  
Main immunogenicity analyses will be performed on the PPAS. Additional immunogenicity 
analyses will be performed on the Full Analysis Set (FAS) according to randomization group. All 
safety analyses will be performed on the Safety Analysis Set (SafAS). 
12.2.1 Full Analysis Set  
There will be 2 full analysis sets (FASs), one FAS for the primary series (FAS1) and one FAS for 
the booster vaccination (FAS2). 
• FAS1 is defined as the subset of randomized subjects who received at least 1 dose of the study 
vaccine in the primary series and had a valid post-primary series vaccination blood sample 
result.  
• FAS2 is defined as the subset of randomized subjects who received at least 1 dose of the study 
vaccine at booster vaccination and had a valid post-booster vaccination blood sample result.  
12.2.2 Safety Analysis Set  
The safety analysis set (SafAS is defined as those subjects who have received at least one dose of 
the study vaccine(s)a and have any safety data available. Specific safety analysis set will be 
defined and used after each vaccination. All subjects will have their safety analyzed after each 
dose according to the vaccine they actually received, and after any dose according to the vaccine 
received at the first dose. Safety data recorded for a vaccine received out of the protocol design 
will be excluded from the analysis (and listed separately). 
                                                 
a  for which safety data are scheduled to be collected 

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12.2.3 Overall Safety Analysis Set for Any Dose  
The overall SafAS is defined as those subjects who have received at least one dose of the study 
vaccines and have any safety data available. All subjects will have their safety analyzed after any 
dose according to the vaccine received at the first dose. 
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.4 Safety Analysis Set for Vaccination at 2 Months of Age  
The SafAS 1 for vaccination at around 2 months of age is defined as those subjects who have 
received the study vaccine at Visit 1 and have any safety data available. All subjects will have 
their safety analyzed after the Visit 1 dose according to the vaccines they actually received at 
Visit 1. 
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately).  
12.2.5 Safety Analysis Set for Vaccination at 4 Months of Age  
The SafAS 2 for vaccination as those subjects who have received the study vaccine at Visit 2 and 
have any safety data available. All subjects will have their safety analyzed after the Visit 2 dose 
according to the vaccines they actually received at Visit 2. 
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.6 Safety Analysis Set for Vaccination at 6 Months of Age (Group 4)  
The SafAS 3 for vaccination as those subjects who have received the study vaccine at Visit 3 and 
have any safety data available. All subjects will have their safety analyzed after the Visit 3 dose 
according to the vaccines they actually received at Visit 3. 
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.7 Safety Analysis Set for Vaccination at 12 to 18 Months of Age  
The SafAS 4 for vaccination as those subjects who have received the study vaccine at Visit 4 / 5 
(depending on the schedule) and have any safety data available. All subjects will have their safety 
analyzed after the Visit 4 / 5 dose according to the vaccines they actually received at Visit 4 / 5. 
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.8 Per-Protocol Analysis Set  
The per-protocol analysis set (PPAS) is a subset of the FAS. There will be 2 PPAS; PPAS for the 
primary series (PPAS1), PPAS for the booster (PPAS2). 

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12.2.8.1 Per-Protocol Analysis Set for Primary Series (PPAS1)  
The subjects presenting with at least one of the following relevant protocol deviations will be 
excluded from the PPAS1: 
• Subject did not meet all protocol-specified inclusion criteria or met at least one of the 
protocol-specified exclusion criteria  
• Subject did not complete the vaccination schedule 
• 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 
• Visit 2: Visit 1 + 60 days (+14 days) 
• Visit 3 (Group 4 only): Visit 2 + 60 days (+14 days) 
• Subject did not provide a post-dose serology sample in the proper time window or a post-dose 
serology sample was not drawn 
• Blood sampling 2 (BL0002): 
▪ Visit 3: Visit 2 + 30 days [+21 days] (Group 1, 2, 3)  
▪ Visit 4: Visit 3 + 30 days [+21 days] (Group 4) 
• Subject received a protocol-prohibited therapy / medication / vaccine (identified among 
category 2 / category 3, not including the rotavirus vaccine administered at V1 and V2) 
• Subject had other protocol violations that affected the subject’s immune response, as 
determined by the clinical team before locking the database 
In addition to the reasons listed above, subjects will also be excluded from the PPAS1 if their 
serology sample did not produce a valid test result (ie, results for all antigens are missing). 
Vaccine correctness criteria apply to all the vaccines administered in the protocol, (ie, 
MenACYW conjugate vaccine / Nimenrix® and the concomitants vaccines. 
In the event of a local or national immunization program with a pandemic influenza or coronavirus 
vaccine or any other vaccine as needed, subjects who receive the 1 or more doses of a pandemic 
influenza or coronavirus vaccine at any time during the study will not be withdrawn from the study. 
12.2.8.2 Per-Protocol Analysis Set for Booster Series (PPAS2)  
The subjects presenting with at least one of the following relevant protocol deviations will be 
excluded from the PPAS2: 
• Subject did not meet all protocol-specified inclusion criteria or met at least one of the 
protocol-specified exclusion criteria  
• Subject did not complete the vaccination schedule 
• Subject received a vaccine other than the one that he / she was randomized to receive 

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• Preparation and / or administration of vaccine was not done as per-protocol 
• Subject did not receive vaccine in the proper time window for the booster dose at 12 to 
18 months of age (all groups) or at least 180 days after Visit 3 (Group 4) 
• Subject did not provide a post-dose serology sample in the proper time window or a post-dose 
serology sample was not drawn 
• Blood sampling 4 (BL0004):  
▪ Visit 5: Visit 4 + 30 days [+21 days] (Group 1, 2, 3) 
▪ Visit 6: Visit 5 + 30 days [+21 days] (Group 4) 
• Subject received a protocol-prohibited therapy / medication / vaccine (identified among 
category 2 / category 3)  
• Subject had other protocol violations that affected the subject’s immune response, as 
determined by the clinical team before locking the database 
In addition to the reasons listed above, subjects will also be excluded from the PPAS2 if their 
serology sample did not produce a valid test result (ie, results for all antigens are missing). 
Vaccine correctness criteria apply to all the vaccines administered in the protocol, ie, MenACYW 
conjugate vaccine / Nimenrix® and the concomitants vaccines.  A licensed Measles, Mumps and 
Rubella vaccine must be received either during the study visit (Visit 4/Visit 5) or with a gap of at 
least 4 weeks before any study vaccines or after the end of the study. In the event of a local or 
national immunization program with a pandemic influenza or coronavirus vaccine or any other 
vaccine as needed, subjects who receive the 1 or more doses of a pandemic influenza or coronavirus 
vaccine at any time during the study will not be withdrawn from the study. 
12.2.9 Populations Used in Analyses  
The main immunogenicity analyses will be performed on the PPAS analysis set including PPAS2 
for the primary objective and PPAS1 for secondary objective 1, and will be confirmed on the 
FAS2 and FAS1. In the FAS1 and FAS2, subjects will be analyzed by the vaccine group to which 
they were randomized.  
The safety analysis will be performed on the SafAS, SafAS1 to SafAS 4. Subjects will be 
analyzed according to the vaccine they actually received. 
12.3 Handling of Missing Data and Outliers  
12.3.1 Safety  
No replacement will be done.  
12.3.2 Immunogenicity  
Missing data will not be imputed. No test or search for outliers will be performed. 

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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: 
• Calculate the fold-rise of values as the ratio of post-baseline computed value divided by 
baseline computed value 
If baseline or post baseline value is missing, then the vaccine seroresponse is missing. 
12.4 Interim / Preliminary Analysis  
No interim analyses are planned. 
12.5 Determination of Sample Size and Power Calculation  
Approximately a total of 1652 subjects will be enrolled. 
For the Primary Objective 
With 716 enrolled subjects in Group 1 and in Group 2, the study will have 96.2% power to 
declare the non-inferiority of Group 1 versus Group 2 based on A, C, W, Y hSBA antibody titers 
(ratio of GMTs in the 2 groups) after a 3-dose series to infants and toddlers 6 weeks to 18 months 
old, assuming: 
• An estimated 26.2% dropout rate from the PPAS (528 subjects evaluable by group), 
• a 1-sided alpha level of 2.5%,  
• a non-inferiority margin of 1.5 (GMT ratio), 
• a standard deviation (SD) of log10-transformed titers of 0.7 for serogroups A and C, 0.5 for 
serogroup Y, and 0.6 for serogroup W. 
Table 12.1: Power of the study based on the primary objective  
Antigen 
MenACYW Standard 
Deviation* 
Non-inferiority Margin 
Power 
A 
0.7 
1.5 
98.3% 
C 
0.7 
1.5 
98.3% 
Y 
0.5 
1.5 
> 99.9% 
W 
0.6 
1.5 
99.7% 
Overall 
 
 
96.2% 
Since the hypothesis needs to be met for all serogroups, no alpha adjustment for multiple comparisons is necessary in 
these calculations. 

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* SDs are based on the results of the MET39 (NCT01049035) MenACYW 2/4/12 months schedule (Group 3) after 
booster results. For the power computation, the same SD in the control group (Nimenrix®) is assumed. 
For the Secondary Objective 
With 716 enrolled subjects in Group 1 and in Group 2, the study will have a > 90% power 
(Farrington and Manning formula) to declare the non-inferiority of Group 1 versus Group 2 based 
on A, C, W, Y hSBA antibody titers ≥ 1:8 (difference in the percentage of seroprotected subjects 
in the 2 groups) after 2 doses in infancy at 2 months and 4 months of age, assuming: 
• An estimated 26.2% dropout rate from the PPAS (528 subjects evaluable per group) 
• A 1-sided alpha level of 2.5%, 
• A non-inferiority margin of 10% (percentage difference) 
Table 12.2: Power of the study for the secondary objective  
Antigen 
Estimated Percentage of hSBA 
Titer ≥ 1:8  
Nimenrix®* 
Non-inferiority margin† 
Power 
A 
76% 
10% 
96.7% 
C 
94% 
10% 
> 99.9% 
Y 
71% 
10% 
94.7% 
W 
82% 
10% 
98.7% 
Overall 
 
 
90% 
Since the hypothesis needs to be met for all serogroups, and the secondary objective is to be tested only if the primary 
objective succeeds, no alpha adjustment for multiple comparisons is necessary in these calculations. 
* Percentages of subjects with an hSBA titer ≥ 1:8 are based on the MET39 (NCT01049035) MenACYW 2/4/12 
months schedule (Group 3) post dose 2 results using estimates 2% lower than in the MenACYW group. The power 
is calculated with the assumption that the estimates from the investigational group equal that of the control group 
corresponding to the estimated percentages in the Nimenrix® group described above. 
† A non-inferiority margin of 10% has been widely used in previous studies evaluating the same antigens and in a 
competitor’s study of the same type. Also taking into account the level of the reference rate taken in the Nimenrix® 
group, it is reasonable to use 10%. 
The sample size has been arbitrarily set to 110 subjects in Group 3 and Group 4 as these data are 
not intended to be used for any hypothesis testing. No formal sample size calculations were 
performed. In each group, there is more than 95% probability to observe an event with an 
incidence of 2.7%. 
In case of unexpected situation or any study hold resulting in an unexpected number of 
unevaluable subjects, total sample size may be increased to replace withdrawn, or unevaluable 
subjects. 

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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 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 study coordinator will obtain verbal clarification 
from the subject, enter the response into the “investigator’s comment” page of the diary card, and 
transfer the information to the CRB. 
The subject pre-screening log should list all individuals contacted by the Investigators to 
participate in the study, regardless of the outcome. 
The Investigator must printa 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 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 Sanofi Pasteur. 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. 
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 Global Data Protection Regulation (GDPR). Data 
                                                 
a  Unless the electronic medical records are managed by validated computerized systems that are compliant with US 
21 CFR Part 11, in which case they are acceptable on their own. 

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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. 
Subjects’ race and ethnicity will be collected in this study because these data are required by 
regulatory agencies (eg, the FDA in the US).  
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 must be informed that his/her 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. 
The subject must be informed that his/her 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 (ie, 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 
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 CRAs on 
these topics may be performed as necessary, and should be documented. 
The following instruction manuals will be provided: the CRF Completion Instructions for entering 
data into the CRB, and the Operating Guidelines for detailed study procedures such as the product 
management and sample-handling procedures. 
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) 

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• Source-verify completed CRBs and any corresponding answered queries. In exceptional 
situations (eg, lock down due to COVID-19) where the monitor cannot access site, and only 
after validation with Sponsor, the subject source data verification may be done remotely, 
under conditions defined in the Monitoring Plan. 
• Determine the number of complete or ongoing issues identified at monitoring visits (ieg, 
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  
A quality assurance audit may be performed at any time by the Sponsor’s Clinical Quality 
Assessment department (CQA) or by independent auditors to verify that the study has been 
conducted according to the protocol, GCP and ICH requirements, and other applicable 
regulations. An inspection may be conducted by regulatory authorities. The Investigator must 
allow direct access to study documents during these inspections and audits. 
13.4.3 Archiving  
The Investigator must keep all study documents after the completion or discontinuation of the 
study, whatever the nature of the investigational center (private practice, hospital, or institution), 
for as long as required by applicable laws and regulations. In the absence of any applicable laws 
or regulations, study documents will be kept at a minimum for the duration indicated on the 
Clinical Trial Agreement (CTA). In no event, should study personnel destroy or permit the 
destruction of any study documents upon less than 90 days advance written notification to the 
Sponsor. In addition, study documents should continue to be stored, at Sponsor's sole expense, in 
the event that the Sponsor requests in writing that such storage continues for a period of time that 
exceeds that required by any applicable law or regulation or the CTA. The Investigator will 
inform Sanofi Pasteur of any address change or if they will no longer be able to house the study 
documents. 
Archived data may be held on electronic records, provided that a back-up exists and that a hard 
copy can be obtained if required. The protocol, documentation, approvals, and all other 
documents related to the study will be kept by the Sponsor in the Trial Master File (TMF). Data 
on AEs are included in the TMF. All data and documents will be made available if requested by 
relevant authorities. 

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13.5 Financial Contract and Insurance Coverage  
A CTA will be signed by all the parties involved in the study’s performance, if relevant. The 
Sponsor has an insurance policy to cover any liabilities that may arise from use of the product and 
/ or the study protocol. 
13.6 Stipends for Participation  
Subjects may be provided with a stipend according to local practice to compensate for the travel 
costs incurred for study visits and procedures. 
13.7 Publication Policy  
Data derived from this study are the exclusive property of Sanofi Pasteur. Any publication or 
presentation related to the study must be submitted to 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, Sanofi Pasteur shall be offered an association with all 
such publications, it being understood that Sanofi Pasteur is entitled to refuse the association. 
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 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. 
Sanofi Pasteur’s review can be expedited to meet publication guidelines. 

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14 Reference List  
1) Harrison LH, Granoff DM, Pollard AJ. Meningococcal capsular group A, C, W, and Y 
conjugate vaccines. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM, editors. Vaccines. 
7th ed. Philadelphia (PA): Elsevier;2018:619-43. 
2) Borrow R, Alarcón P, Carlos J, et al. The Global Meningococcal Initiative: global 
epidemiology, the impact of vaccines on meningococcal disease and the importance of herd 
protection. Expert Rev Vaccines. 2017;16(4):313-28. 
3) Harrison OB, Claus H, Jiang Y, et al. Description and nomenclature of Neisseria meningitidis 
capsule locus. Emerg Infect Dis. 2013;19(4):566-73. 
4) Pollard AJ. Global epidemiology of meningococcal disease and vaccine efficacy. Pediatr 
Infect Dis J. 2004;23(12 Supp):S274-9. 
5) Kvalsvig AJ, Unsworth DJ. The immunopathogenesis of meningococcal disease. J Clin 
Pathol. 2003;56(6):417-22. 
6) Sidikou F, Djibo S, Taha MK, et al. Polymerase chain reaction assay and bacterial meningitis 
surveillance in remote areas, Niger. Emerg Infect Dis. 2003;9(11):1486-8. 
7) World Health Organization. Meningococcal disease, serogroup W135 (update). WER. 
2001;76(28):213-4. 
8) Sáfadi MA, O'Ryan M, Valenzuela Bravo MT, et al. The current situation of meningococcal 
disease in Latin America and updated Global Meningococcal Initiative (GMI) 
recommendations. Vaccine. 2015;33(48):6529-36. 
9) Ceyhan M, Yildirim I, Balmer P, et al. A prospective study of etiology of childhood acute 
bacterial meningitis, Turkey. Emerg Infect Dis. 2008;14(7):1089-96. 
10) Kilic A, Urwin R, Li H, Saracli MA, Stratton CW, Tang YW. Clonal spread of serogroup 
W135 meningococcal disease in Turkey. J Clin Microbiol. 2006;44(1)222-4. 
11) Shao Z, Zhou H, Gao Y, et al. Neisseria meningitidis serogroup W135, China. Emerg Infect 
Dis. 2010;16(2):348-9. 
12) Zhou H, Liu W, Xu L, et al. Spread of Neisseria meningitidis serogroup W clone, China. 
Emerg Infect Dis. 2013;19(9):1496-9. 
13) Efron AM, Sorhouet C, Salcedo C, Abad R, Regueira M, Vasquez JA. W135 invasive 
meningococcal strains spreading in South America: significant increase in incidence rate in 
Argentina. J Clin Microbiol. 2009;47(6):1979-80. 
14) Weidlich L, Baethgen LF, Mayer LW, et al. High prevalence of Neisseria meningitidis 
hypervirulent lineages and emergence of W135:P1.5,2:ST-11 clone in southern Brazil. J 
Infect. 2008;57(4):324-31. 
15) Barroso DE, Rebelo MC. Recognition of the epidemiological significance of Neisseria 
meningitidis capsular serogroup W135 in the Rio de Janeiro region, Brazil. Mem Inst 
Oswaldo Crus. 2007;102(6):773-5. 

Sanofi Pasteur 
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16) Boisier P, Nicholas P, Djibo S, et al. Meningococcal meningitis: unprecedented incidence of 
serogroup X-related cases in 2006 in Niger. Clin Infect Dis. 2007;44(5):657-63. 
17) Rosenstein NE, Perkins BA, Stephens DS, et al. The changing epidemiology of 
meningococcal disease in the United States, 1992-1996. J Infect Dis. 1999;180(6):1894-901. 
18) Canadian Immunization Committee and Public Health Agency of Canada. Advice for 
consideration of quadrivalent (A, C, Y, W135) meningococcal conjugate vaccine, for use by 
provinces and territories. CCDR. 2010;36(S2):1-35. 
19) Bröker M, Jacobsson S, Kuusi M, et al. Meningococcal serogroup Y emergence in Europe: 
update 2011. Hum Vaccin Immunother. 2012;8(12):1907-11. 
20) Cohn AC, MacNeil JR, Harrison LH, et al. Changes in Neisseria meningitidis disease 
epidemiology in the United States, 1998-2007: implications for prevention of meningococcal 
disease. Clin Infect Dis. 2010;50(2):184-91. 
21) National Foundation for Infectious Diseases. Addressing the challenges of serogroup B 
meningococcal disease outbreaks on campuses: A report by the National Foundation for 
Infectious Diseases. May 2014. Available online: http://www.nfid.org/meningococcal-b. 
Accessed 05 July 2017. 
22) Centers for Disease Control and Prevention. Interim guidance for control of serogroup B 
meningococcal disease outbreaks in organizational settings. Available online: 
http://www.cdc.gov/meningococcal/downloads/interim-guidance.pdf. Accessed 05 July 2017. 
23) European Centre for Disease Prevention and Control. Surveillance of invasive bacterial 
diseases in Europe 2008/2009. Stockholm: ECDC; 2011. Available at: 
https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/1107_SUR_IBD_
2008-09.pdf. Accessed on 12 July 2017. 
24) Drozd-Dabrowska M, Topczewska K, Korzen M, Salacka A, Ganczak M. Parental 
Knowledge about Meningococcal Disease and Vaccination Uptake among 0(1)5 years Old 
Polish Children.Int J Environ Res Public Health. 2019;16(2) 
25) Public Health England. Increase in endemic meningococcal group W (MenW) ST-11 
complex associated with severe invasive disease in England and Wales. Health Protection 
Weekly Report. Vol 8 No 41 Published on: 24 October 2014. Available online: 
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/367588/hpr41
14.pdf. Accessed 05 July 2017. 
26) Ladhani S, Lucidarme J, Newbold LS, et al. Investigations into an increase in reported 
meningococcal serogroup Y disease in England and Wales in 2007-9. Presented at: The 
European Meningococcal Disease Society (EMGM). 11th EMGM Meeting, 18-20 May 2011. 
Ljubljana Slovenia. Poster 035:107. 
27) Törös B, Thulin Hedberg S, Jacobsson S, Fredlund H, Olcén P, Mölling P. Surveillance of 
invasive Neisseria meningitidis with a serogroup Y update, Sweden 2010 to 2012. Euro 
Surveill. 2014;19(42):pii=20940. 

Sanofi Pasteur 
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395 – MenACYW Conjugate Vaccine 
Protocol Version 7.0 
 
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Page 127 of 130 
28) Thulin Hedberg S, Törös B, Fredlund H, Olcén P, Mölling P. Genetic characterisation of the 
emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 2010. Euro 
Surveill. 2011;16(23):pii=19885. 
29) Caugant DA, Løvoll Ø, Blystad H. Meningococcal disease in Norway, 2009-2010: 
emergence of serogroup Y. Presented at: The European Meningococcal Disease Society 
(EMGM). 11th EMGM Meeting, 18-20 May 2011. Ljubljana Slovenia. Poster 040:117. 
30) Vainio A, Toropainen M, Kuusi M, Virolainen A. Characteristics of invasive meningococcal 
serogroup Y isolates in Finland, 1995-2010. Presented at: The European Meningococcal 
Disease Society (EMGM). 11th EMGM Meeting, 18-20 May 2011. Ljubljana Slovenia. 
Poster 037:110. 
31) Centers for Disease Control and Prevention. Update: Guillain-Barré syndrome among 
recipients of Menactra meningococcal conjugate vaccine--United States, June 2005-
September 2006. MMWR. 2006; 55(41):1120-4. 
32) Velentgas P, Amato AA, Bohn RL, et al. Risk of Guillain-Barré syndrome after 
meningococcal conjugate vaccination. Pharmacoepidemiol Drug Saf. 2012;21(12):1350-8. 
33) Institute of Medicine. Diphtheria toxoid, tetanus toxoid, and acellular pertussis-containing 
vaccines. In: Adverse effects of vaccines: evidence and causality. Washington, DC: The 
National Academies Press;2012:557-8. https://doi.org/10.17226/13164. 
34) Institute of Medicine. Diphtheria and tetanus toxoids. In: Adverse events associated with 
childhood vaccines: evidence bearing on causality. Washington, DC. The National 
Academies Press; 1994:67-117. https://doi.org/10.17226/2138. 
35) Centers for Disease Control and Prevention. General recommendations on immunization: 
recommendations of the Advisory Committee on Immunization Practices (ACIP):MMWR. 
2011;60(2):1-60. 
36) https://ecdc.europa.eu/sites/portal/files/documents/rotavirus-vaccination-expert%20opinion-
september-2017.pdf 
37) https://thl.fi/en/web/vaccination/national-vaccination-programme/vaccination-programme-
for-children-and-adolescents 
38) https://clinicaltrials.gov/ct2/show/NCT03537508 
39) Bexsero® Package insert 
(https://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm431
447.pdf. Accessed on 25 July 2018), Novartis Vaccines and Diagnostics S.r.l., Bellaria-Rosia 
53018, Sovicille (SI), Italy. 
40) Recommendations of the Czech Vaccinology Society of the J. E. Purkyn? Czech Medical 
Association for vaccination against invasive meningococcal disease. 15 January 2018. 
http://www.szu.cz/uploads/IMO/2018_Recommendation_for_vaccination_againts_IMD.pdf 
41) Immunisation schedule of the Spanish Association of Paediatrics: 2019 recommendations. 
Anales de Pediatria. Vol. 90. Issue 1. pages 1-58. http://www.analesdepediatria.org/es-
linkresolver-calendario-vacunaciones-asociacion-espanola-pediatria-S169540331730334X 

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42) NIMENRIX EU Summary of Product Characteristics. 
https://www.ema.europa.eu/en/medicines/human/EPAR/nimenrix#product-information-
section 
43) Hexyon EU Summary of Product Characteristics. 
https://www.ema.europa.eu/en/medicines/human/EPAR/hexyon#product-information-section 
44) Hexacima EU Summary of Product Characteristics. 
https://www.ema.europa.eu/en/medicines/human/EPAR/hexacima#product-information-
section 
45) Synflorix EU Summary of Product Characteristics. 
https://www.ema.europa.eu/en/medicines/human/EPAR/synflorix#product-information-
section 
46) Prevenar EU Summary of Product Characteristics. 
https://www.ema.europa.eu/en/medicines/human/EPAR/prevenar-13#product-information-
section 
47) M-M-RVAXPRO EU Summary of Product Characteristics. 
https://www.ema.europa.eu/en/medicines/human/EPAR/m-m-rvaxpro#product-information-
section 
48) Ethical considerations for clinical trials on medicinal products conducted with minors, 2017 
chapter 13.2. 
49) Bonhoeffer J, Menkes J, Gold M, et al. Generalized convulsive seizure as an adverse event 
following immunization: case definition and guidelines for data collection, analysis, and 
presentation. Vaccine. 2004;22:557-62. 
50) Marcy SM, Kohl KS, Dagan R, et al. Fever as an adverse event following immunization: case 
definition and guidelines of data collection, analysis and presentation. Vaccine. 2004; 22:551-
556. 
51) Phuong LK, Bonetto C, Buttery J, et al and The Brighton Collaboration Kawasaki Disease 
Working Group. Kawasaki disease and immunisation: standardised case definition & 
guidelines for data collection, analysis. Vaccine. 2016;34(51):6582-96. 
52) Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term 
management of Kawasaki disease: a statement for health professionals from the Committee 
on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular 
Disease in the Young, American Heart Association. Pediatrics. 2004;114(6):1708-33. 
53) Centers for Disease Control and Prevention. Kawasaki Syndrome Case Report 2003. 
Available online: http://www.cdc.gov/kawasaki/pdf/ks_case_report-fillable.pdf. Accessed 17 
November 2017. 
54) Sejvar JJ, Kohl KS, Gidudu J, et al. Guillain-Barré syndrome and Fisher syndrome: case 
definitions and guidelines for collection, analysis, and presentation of immunization safety 
data. Vaccine. 2011;29(3):599-612. 

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55) Wise RP, Bonhoeffer J, Beeler J, et al. Thrombocytopenia: case definition and guidelines for 
collection, analysis, and presentation of immunization safety data. 
Vaccine.2007;25(31):5717-24 
56) Chu YW, Korb J, Sakamoto M. Idiopathic thrombocytopenic purpura. Pediatr Rev. 
2000;21(3):95-104 
 

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15 Signature Page  

Signature Page for VV-CLIN-0541887 v7.0
Protocol Body_CLI_00002486_MET58
Approve & eSign
Clinical
VV-CLIN-0541887 7.0