Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix® or NeisVac-C® in Healthy Toddlers 12 to 23 Months of Age
Phase: PHASE3
Conditions: Meningococcal Immunisation (Healthy Volunteers)
Sponsor: Sanofi Pasteur, a Sanofi Company

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 1 of 90 
Immunogenicity and Safety of an Investigational Quadrivalent 
Meningococcal Conjugate Vaccine Versus Nimenrix® or 
NeisVac-C® in Healthy Toddlers 12 to 23 Months of Age 
Phase III, modified double-blind, randomized, active-controlled, multi-center trial to compare 
the immunogenicity and describe the safety of a single dose of MenACYW conjugate vaccine to 
a single dose of licensed NeisVac-C® or Nimenrix® in toddlers in Europe. 
Clinical Study Protocol, Amendment 1 
Health Authority File Number(s): 
EudraCT #: 2018-003790-10 
WHO Universal Trial Number (UTN): U1111-1217-2456 
Study Code: 
MEQ00065 
Development Phase: 
Phase III 
Sponsor: 
Sanofi Pasteur 
14 Espace Henry Vallée, 69007 Lyon, France 
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 as a single dose in toddlers 12 to 23 
months old 
Manufacturer: 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, USA 
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: 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 1 of 91
NCT03890367

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 2 of 90 
Local Medical Officer: 
Project Manager and Study Leader: 
Global Safety Officer: 
Regional Trial Manager: 
Version and Date of the Protocol: 
Version 4.0, dated 15 May 2020  
 
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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 2 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 3 of 90 
History of Protocol Versions 
Version 
Date 
Comments 
1.0 
20 December 2018 
Internal version not submitted to the Health 
Authorities and the IEC/IRB 
2.0 
08 January 2019 
Initial version submitted to the Health Authorities 
3.0 
15 March 2019 
First approved version used in the study 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 3 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 4 of 90 
Table of Contents 
History of Protocol Versions................................................................................................. 3 
List of Tables .......................................................................................................................... 9 
List of Figures ...................................................................................................................... 10 
Synopsis ................................................................................................................................ 11 
Table of Study Procedures .................................................................................................. 22 
List of Abbreviations ........................................................................................................... 23 
1 
Introduction ........................................................................................................... 25 
1.1 
Background ........................................................................................................... 25 
1.2 
Background of the Investigational Product ........................................................... 27 
1.2.1 
Clinical ............................................................................................................... 27 
1.2.1.1 
Study MET54 (Phase II) .................................................................................. 27 
1.2.1.2 
Study MET51 (Phase III) ................................................................................. 28 
1.2.1.3 
Study MET57 (Phase III) ................................................................................. 30 
1.3 
Potential Benefits and Risks ................................................................................. 31 
1.3.1 
Potential Benefits to Subjects ............................................................................. 31 
1.3.2 
Potential Risks to Subjects ................................................................................. 31 
1.3.3 
COVID-19 Risk Assessment .............................................................................. 32 
1.4 
Rationale for the Study ......................................................................................... 32 
2 
Study Objectives .................................................................................................... 34 
2.1 
Primary Objectives ................................................................................................ 34 
2.2 
Secondary Objectives ............................................................................................ 34 
2.3 
Observational Objectives ...................................................................................... 35 
3 
Investigators and Study Organization ................................................................. 35 
4 
Independent Ethics Committee / Institutional Review Board .......................... 36 
5 
Investigational Plan ............................................................................................... 37 
5.1 
Description of the Overall Study Design and Plan ............................................... 37 
5.1.1 
Study Design ...................................................................................................... 37 
5.1.2 
Justification of the Study Design ........................................................................ 37 
5.1.3 
Study Plan ........................................................................................................... 38 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 4 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 5 of 90 
5.1.4 
Visit Procedures .................................................................................................. 38 
5.1.4.1 
V01 (D0): Inclusion, Randomization, Blood Sample, and Vaccination .......... 39 
5.1.4.2 
TC (8 days [+2 days] after Visit 1) .................................................................. 40 
5.1.4.3 
V02 (D30 [+14 days] after V01): Collection of Safety Information and Blood 
Sample .............................................................................................................. 40 
5.1.5 
Planned Study Calendar ..................................................................................... 41 
5.2 
Enrollment and Retention of Study Population .................................................... 41 
5.2.1 
Recruitment Procedures ...................................................................................... 41 
5.2.2 
Informed Consent Procedures ............................................................................ 42 
5.2.3 
Screening Criteria ............................................................................................... 43 
5.2.4 
Inclusion Criteria ................................................................................................ 43 
5.2.5 
Exclusion Criteria ............................................................................................... 43 
5.2.6 
Medical History .................................................................................................. 44 
5.2.7 
Contraindications for Subsequent Vaccinations ................................................. 45 
5.2.8 
Temporary Contraindications for Visit 2 Blood Sample .................................... 45 
5.2.9 
Conditions for Withdrawal ................................................................................. 45 
5.2.10 
Lost to Follow-up Procedures............................................................................. 45 
5.2.11 
Classification of Subjects Who Discontinue the Study ...................................... 46 
5.2.12 
Follow-up of Discontinuations ........................................................................... 46 
5.3 
Modification of the Study and Protocol ................................................................ 47 
5.3.1 
Amendment Justification .................................................................................... 47 
6 
Products Administered ......................................................................................... 48 
6.1 
Identity of the Investigational Products ................................................................ 48 
6.1.1 
Identity of Study Product .................................................................................... 48 
6.1.1.1 
Preparation and Administration ....................................................................... 48 
6.1.1.2 
Dose Selection and Timing .............................................................................. 49 
6.1.2 
Identity of the Control Products ......................................................................... 49 
6.1.2.1 
Nimenrix® ........................................................................................................ 49 
6.1.2.1.1 
Composition ................................................................................................... 49 
6.1.2.1.2 
Preparation and Administration ..................................................................... 49 
6.1.2.1.3 
Dose Selection and Timing ............................................................................ 50 
6.1.2.2 
NeisVac-C® ...................................................................................................... 50 
6.1.2.2.1 
Composition ................................................................................................... 50 
6.1.2.2.2 
Preparation and Administration ..................................................................... 50 
6.1.2.2.3 
Dose Selection and Timing ............................................................................ 50 
6.2 
Identity of Other Product(s) .................................................................................. 50 
6.3 
Product Logistics .................................................................................................. 51 
6.3.1 
Labeling and Packaging ..................................................................................... 51 
6.3.2 
Product Shipment, Storage, and Accountability ................................................. 51 
6.3.2.1 
Product Shipment ............................................................................................. 51 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 5 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 6 of 90 
6.3.2.2 
Product Storage ................................................................................................ 51 
6.3.2.3 
Product Accountability ..................................................................................... 51 
6.3.3 
Replacement Doses............................................................................................. 52 
6.3.4 
Disposal of Unused Products .............................................................................. 52 
6.3.5 
Recall of Products ............................................................................................... 52 
6.4 
Blinding and Code-breaking Procedures .............................................................. 52 
6.5 
Randomization and Allocation Procedures ........................................................... 53 
6.6 
Treatment Compliance .......................................................................................... 53 
6.7 
Concomitant Medications and Other Therapies ................................................... 54 
7 
Management of Samples ....................................................................................... 55 
7.1 
Sample Collection ................................................................................................. 55 
7.2 
Sample Preparation ............................................................................................... 56 
7.3 
Sample Storage and Shipment .............................................................................. 56 
7.4 
Future Use of Stored Serum Samples for Research .............................................. 56 
8 
Clinical Supplies .................................................................................................... 57 
9 
Endpoints and Assessment Methods ................................................................... 57 
9.1 
Primary Endpoints and Assessment Methods ....................................................... 57 
9.1.1 
Immunogenicity .................................................................................................. 57 
9.1.1.1 
Immunogenicity Endpoints .............................................................................. 57 
9.1.1.2 
Immunogenicity Assessment Methods ............................................................ 58 
9.1.2 
Safety .................................................................................................................. 58 
9.1.3 
Efficacy ............................................................................................................... 58 
9.2 
Secondary Endpoints and Assessment Methods ................................................... 59 
9.2.1 
Immunogenicity .................................................................................................. 59 
9.2.1.1 
Immunogenicity Endpoints .............................................................................. 59 
9.2.1.2 
Immunogenicity Assessment Methods ............................................................ 59 
9.2.2 
Safety .................................................................................................................. 59 
9.2.3 
Efficacy ............................................................................................................... 59 
9.3 
Observational Endpoints and Assessment Methods ............................................. 59 
9.3.1 
Immunogenicity .................................................................................................. 59 
9.3.1.1 
Immunogenicity Endpoints .............................................................................. 59 
9.3.1.2 
Immunogenicity Assessment Methods ............................................................ 60 
9.3.2 
Safety .................................................................................................................. 60 
9.3.2.1 
Safety Definitions ............................................................................................. 60 
9.3.2.2 
Safety Endpoints .............................................................................................. 63 
9.3.2.3 
Safety Assessment Methods ............................................................................. 63 
9.3.2.3.1 
Immediate Post-vaccination Observation Period ........................................... 63 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 6 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 7 of 90 
9.3.2.3.2 
Reactogenicity (Solicited Reactions From Day 0 to Day 7 After 
Vaccination) ................................................................................................... 64 
9.3.2.3.3 
Unsolicited Adverse Events ........................................................................... 67 
9.3.2.3.4 
Adverse Events of Special Interest ................................................................ 68 
9.3.2.3.5 
Assessment of Causality ................................................................................ 69 
9.3.3 
Efficacy ............................................................................................................... 69 
10 
Reporting of Serious Adverse Events .................................................................. 69 
10.1 
Initial Reporting by the Investigator ..................................................................... 69 
10.2 
Follow-up Reporting by the Investigator .............................................................. 70 
10.3 
Reporting of SAEs Occurring After a Subject Has Completed the Study ............ 70 
10.4 
Assessment of Causality ....................................................................................... 71 
10.5 
Reporting SAEs to Health Authorities and IECs / IRBs....................................... 71 
11 
Data Collection and Management ....................................................................... 71 
11.1 
Data Collection and CRB Completion .................................................................. 71 
11.2 
Data Management ................................................................................................. 72 
11.3 
Data Review .......................................................................................................... 73 
12 
Statistical Methods and Determination of Sample Size ..................................... 73 
12.1 
Statistical Methods ................................................................................................ 73 
12.1.1 
Hypotheses and Statistical Methods for Primary Objectives ............................. 73 
12.1.1.1 
Hypotheses ....................................................................................................... 73 
12.1.1.2 
Statistical Methods ........................................................................................... 73 
12.1.2 
Hypotheses and Statistical Methods for Secondary Objectives ......................... 77 
12.1.2.1 
Hypotheses ....................................................................................................... 77 
12.1.2.2 
Statistical Methods ........................................................................................... 77 
12.1.3 
Statistical Methods for Observational Objectives .............................................. 78 
12.2 
Analysis Sets ......................................................................................................... 79 
12.2.1 
Full Analysis Set ................................................................................................. 80 
12.2.2 
Per-Protocol Analysis Sets ................................................................................. 80 
12.2.3 
Safety Analysis Set ............................................................................................. 80 
12.2.4 
Populations Used in Analyses ............................................................................ 81 
12.3 
Handling of Missing Data and Outliers ................................................................ 81 
12.3.1 
Safety .................................................................................................................. 81 
12.3.2 
Immunogenicity .................................................................................................. 81 
12.3.3 
Efficacy ............................................................................................................... 81 
12.4 
Interim / Preliminary Analysis .............................................................................. 81 
12.5 
Determination of Sample Size and Power Calculation ......................................... 82 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 7 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 8 of 90 
13 
Ethical and Legal Issues and Investigator / Sponsor Responsibilities.............. 83 
13.1 
Ethical Conduct of the Study / Good Clinical Practice ......................................... 83 
13.2 
Source Data and Source Documents ..................................................................... 83 
13.3 
Confidentiality of Data and Access to Subject Records ....................................... 84 
13.4 
Monitoring, Auditing, and Archiving ................................................................... 84 
13.4.1 
Monitoring .......................................................................................................... 84 
13.4.2 
Audits and Inspections ....................................................................................... 85 
13.4.3 
Archiving ............................................................................................................ 85 
13.5 
Financial Contract and Insurance Coverage ......................................................... 86 
13.6 
Stipends for Participation ...................................................................................... 86 
13.7 
Publication Policy ................................................................................................. 86 
14 
Reference List ........................................................................................................ 87 
15 
Signature Page ....................................................................................................... 90 
 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 8 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 9 of 90 
List of Tables 
Table 9.1: Solicited injection site reactions: terminology, definitions, and intensity scales ...........65 
Table 9.2: Solicited systemic reactions: terminology, definitions, and intensity scales .................66 
Table 12.1: Statistical hypotheses and powers for the primary objective .......................................82 
Table 12.2: Statistical hypotheses for the secondary objective .......................................................83 
 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 9 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 10 of 90 
List of Figures 
Figure 1: Sequential statistical testing approach for primary objectives .........................................76 
Figure 2: Sequential statistical testing approach for secondary objectives .....................................78 
 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 10 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 11 of 90 
Synopsis 
Company: 
Sanofi Pasteur 
Investigational 
Product: 
MenACYW conjugate vaccine 
Active 
Substance(s): 
Capsular polysaccharide from meningococcal serogroups A, C, Y, and W conjugated to tetanus 
toxoid 
 
 
Title of the 
Study: 
Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate 
Vaccine Versus Nimenrix® and NeisVac-C® in Healthy Toddlers 12 to 23 Months of Age  
Development 
Phase: 
Phase III 
Coordinating 
Investigator: 
This is a multi-center trial with multiple investigators. 
Study Sites: 
This will be a multi-center, multi-country trial with approximately 31 trial centers in European 
countries.  
Investigators and sites will be listed in the “List of Investigators and Centers Involved in the 
Trial” document. 
Planned Study 
Period: 
3Q 2019 –4Q 2020 
Study Design, 
Schedule of 
Study 
Procedures, 
and 
Methodology: 
This will be a Phase III, modified double-blind, randomized, parallel-groups,  active-controlled, 
multi-center trial to compare the immunogenicity of a single dose of MenACYW conjugate 
vaccine to a single dose of a licensed quadrivalent meningococcal polysaccharide groups A, C, 
W-135, Y conjugate vaccine (MenACWY-TT, Nimenrix® ) or of a licensed monovalent 
meningococcal group C conjugate vaccine (MenC-TT, NeisVac-C® )  in toddlers, 12 to 
23 months of age in Europe who are meningococcal vaccine naïve. 
Vaccination  
Approximately 705 healthy toddlers aged 12 to 23 months who have not received any 
meningococcal vaccine during infancy will be randomized in a 1:1:1 ratio to receive one dose of 
vaccine on Day (D) 0 (D0) at Visit 1 (V01) in one of the following 3 arms : 
• 
Group 1: MenACYW conjugate vaccine (n=235)  
• 
Group 2: Nimenrix® vaccine (MenACWY-TT conjugate vaccine) (n=235) 
• 
Group 3: NeisVac-C® vaccine (MenC-TT conjugate vaccine) (n=235) 
The randomization will be stratified by Center. 
Blood sampling 
All subjects will provide a pre-vaccination blood sample at V01 on D0 and a post-vaccination 
blood sample at Visit 2 (V02) (30 to 44 days after the vaccination at V01), for immunogenicity 
assessment.  
Collection of safety data 
- 
All subjects will be followed for safety from V01 on D0 to V02 after vaccination. 
- 
All subjects will be observed for 30 minutes after vaccination and any unsolicited systemic 
adverse events (AEs) occurring during that time will be recorded as immediate unsolicited 
AEs in the electronic case report book (eCRB).  
- 
The subject’s parent or another legally acceptable representative will record information in 
a diary card about solicited reactions from D0 to D7 after vaccination and unsolicited AEs 
will be recorded from D0 to D30. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 11 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 12 of 90 
- 
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 V01 to identify the occurrence of any SAEs (including AESIs) 
not yet reported and to remind them to complete the diary card and bring it back to V02. 
- 
The completed diary card will be collected and reviewed with the subject’s parent / legally 
acceptable representative at V02. 
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 IECs (Independent Ethics Committees)/IRBs (Institutional 
Review Boards), 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 recruitment 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 
Objectives: 
1) 
To demonstrate the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or Nimenrix® as measured by serum bactericidal assay using human 
complement (hSBA). If the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) 
is demonstrated, then 
1.1) To demonstrate the non-inferiority of the antibody response (geometric mean titers 
[GMT]) to meningococcal serogroup C following the administration of a single dose 
of MenACYW conjugate vaccine or Nimenrix® as measured by hSBA. If the non-
inferiority of the antibody response (GMT) is demonstrated, then 
1.2) To demonstrate the superiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or Nimenrix® as measured by hSBA. If the superiority of the antibody 
response (GMT) is demonstrated, then 
1.3) To demonstrate the superiority of the seroprotection rate to meningococcal serogroup 
C following the administration of a single dose of MenACYW conjugate vaccine or 
Nimenrix® as measured by hSBA.  
2) 
To demonstrate the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or NeisVac-C® as measured by serum bactericidal assay using baby 
rabbit complement (rSBA). If the non-inferiority of the seroprotection rate is demonstrated, 
then  
2.1) To demonstrate the non-inferiority of the antibody response (GMT) to 
meningococcal serogroup C following the administration of a single dose of 
MenACYW conjugate vaccine or NeisVac-C® as measured by rSBA. If the non-
inferiority of the antibody response (GMT) is demonstrated, then  
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 12 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 13 of 90 
2.2) To demonstrate the superiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or NeisVac-C® as measured by rSBA.  
Overall, the primary objective for the study will be met if, objective 1) - non-inferiority of the 
seroprotection rate versus Nimenrix® as measured by hSBA, or objective 2) - non-inferiority of 
the seroprotection rate versus NeisVac-C® as measured by rSBA, is met. 
Primary 
Endpoints: 
1) 
Antibody titers against meningococcal serogroup C measured by hSBA, 30 days (+ 14 
days) after vaccination: 
• 
≥ 1:8, with MenACYW conjugate vaccine or Nimenrix® 
• 
With MenACYW conjugate vaccine or Nimenrix®  
2) 
Antibody titers against meningococcal serogroup C measured by rSBA, 30 days (+ 14 
days) after vaccination: 
• 
≥ 1:8, with MenACYW conjugate vaccine or NeisVac-C®  
• 
With MenACYW conjugate vaccine or NeisVac-C® 
Secondary 
Objectives: 
1) 
To demonstrate the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or Nimenrix® as measured by rSBA. If the non-inferiority of the 
seroprotection rate is demonstrated, then 
1.1) 
To demonstrate the non-inferiority of the antibody response (GMT) to 
meningococcal serogroup C following the administration of a single dose of 
MenACYW conjugate vaccine or Nimenrix® as measured by rSBA. If the non-
inferiority of the antibody response (GMT) is demonstrated, then  
1.2) 
To demonstrate the superiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or Nimenrix® as measured by rSBA  
2) 
To demonstrate the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or NeisVac-C® as measured by hSBA. If the non-inferiority of the 
seroprotection rate is demonstrated, then 
2.1) 
To demonstrate the non-inferiority of the antibody response (GMT) to 
meningococcal serogroup C following the administration of a single dose of 
MenACYW conjugate vaccine or NeisVac-C® as measured by hSBA. If the non-
inferiority of the antibody response (GMT) is demonstrated, then 
2.2) 
To demonstrate the superiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or NeisVac-C® as measured by hSBA  
Overall, the secondary objective for the study will be met if objective 1) - non-inferiority of the 
seroprotection rate versus Nimenrix® as measured by rSBA, or objective 2) - non-inferiority of 
the seroprotection rate versus NeisVac-C® as measured by hSBA, is met. 
Secondary 
Endpoints: 
1) 
Antibody titers against meningococcal serogroup C measured by rSBA,30 days (+ 14 
days) after vaccination: 
• 
≥ 1:8, with MenACYW conjugate vaccine or Nimenrix® 
• 
With MenACYW conjugate vaccine or Nimenrix®  
2) 
Antibody titers against meningococcal serogroup C measured by hSBA, 30 days (+ 14 
days) after vaccination: 
• 
≥ 1:8 with MenACYW conjugate vaccine or NeisVac-C®  
• 
With MenACYW conjugate vaccine or NeisVac-C® 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 13 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 14 of 90 
Observational 
Objectives: 
Immunogenicity 
1) To describe the antibody response to meningococcal serogroup C before and 30 days 
(+ 14 days) after vaccination in each group using hSBA in toddlers 
2) To describe the antibody response to meningococcal serogroup C before and 30 days 
(+ 14 days) after vaccination in each group using rSBA in toddlers  
Safety 
To describe the safety profile of MenACYW conjugate vaccine, Nimenrix® and NeisVac-C®. 
Observational 
Endpoints: 
Immunogenicity 
Observational Objective 1: 
• Antibody titer against meningococcal serogroup C measured by hSBA in each group:  
• 
Assessed before and at 30 days (+ 14 days) after vaccination  
• 
≥ 1:4 and ≥ 1:8, assessed at 30 days (+ 14 days) after vaccination  
• 
≥ 4-fold rise from pre-vaccination to post-vaccination  
• 
Post-vaccination / pre-vaccination titer ratio 
• 
Vaccine seroresponse measured by hSBA* in each group  
 with seroresponse defined as: 
- For a subject with a pre-vaccination titer < 1:8, a post-vaccination titer ≥ 1:16 
- For a subject with a pre-vaccination titer ≥ 1:8, a post-vaccination titer at least 
4-fold greater that the pre-vaccination titer. 
Observational Objective 2: 
• Antibody titers against meningococcal serogroup C measured by rSBA in each group: 
• 
Assessed before and at 30 days (+ 14 days) after vaccination 
• 
≥ 1:8 and ≥ 1:128, assessed before and at 30 days (+ 14 days) after vaccination 
• 
Post-vaccination / pre-vaccination titers ratio 
• 
≥ 4-fold rise from pre-vaccination to post-vaccination  
• 
Vaccine seroresponse measured by rSBA, with seroresponse defined as: 
- For a subject with pre-vaccination titer < 1:8, a post-vaccination titer ≥ 1:32  
- For subjects with pre-vaccination titer ≥ 1:8, a post-vaccination titer at least 4-
fold greater that the pre-vaccination titer 
 
Safety 
The safety profile of the 3 vaccines will be evaluated within 30 days (+ 14 days) after the 
vaccination. The following endpoints will be used for all subjects for the evaluation of safety: 
• 
Unsolicited systemic AEs reported in the 30 minutes following the vaccination 
• 
Solicited (pre-listed in the subject diary and the electronic Case Report Form [CRF]) 
injection site reactions and systemic reactions starting anytime from D0 (Day of 
vaccination) through D7 after the vaccination 
• 
Unsolicited (spontaneously reported) non-serious AEs up to from D0 and D30 
• 
SAEs (including AESIs) throughout the study, ie, from D0 to Visit 2 
Depending on the items, the endpoints recorded or derived could include: 
Nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), time of onset, 
duration / number of days of occurrence, intensity, relationship to vaccine, whether the AE led 
to early termination from the study, seriousness criterion, outcome. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 14 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 15 of 90 
Planned 
Sample Size: 
A total of 675 subjects were initially planned to be enrolled (with an estimated drop-out rate of 
10%). 
• 
Group 1: MenACYW conjugate vaccine  ..........  n=225 to be enrolled (202 evaluable) 
• 
Group 2: Nimenrix® vaccine  .............................  n=225 to be enrolled (202 evaluable) 
• 
Group 3: NeisVac-C® vaccine  ..........................  n=225 to be enrolled (202 evaluable) 
As a consequence of the COVID-19 pandemic, enrollment was paused on17 March 2020. 
Approximately 30 subjects were identified to be excluded from the per-protocol analysis set 
(PPAS) due to COVID-19 as they were unable to complete their follow-up visit as planned per 
the protocol. The sample size of the study will then be modified to replace these subjects. 
Approximately 705 subjects will now be enrolled (235 in each group). 
In the event of any new unexpected situations impacting study visits, the sample size might be 
increased to replace subjects excluded from the PPAS. 
Duration of 
Participation 
in the Study: 
The duration of each subject’s participation in the trial will be approximately 30 to 44 days. 
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  
  
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 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.  
 Route: 
Intramuscular (IM) 
 Batch #  
To be determined 
Control 
Product: 
Nimenrix®: Meningococcal polysaccharide groups A, C, W-135 and Y conjugate vaccine 
(Pfizer Limited, Sandwich, United Kingdom) 
 Form: 
Lyophilized powder in a vial and diluent for reconstitution in a pre-filled syringe 
 Composition: 
Each 0.5 mL dose of Nimenrix® vaccine is formulated to contain: 
Neisseria meningitidis polysaccharides: 
Serogroup A ............................................................................................ 5 µg 
Serogroup C ............................................................................................ 5 µg 
Serogroup W-135 .................................................................................... 5 µg 
Serogroup Y ............................................................................................ 5 µg 
Tetanus toxoid protein carrier ....................................... approximately 44 µg 
Excipients: 
In the powder: Sucrose, Trometamol 
In the solvent: Sodium chloride, Water for injections 
 Route: 
IM 
 Batch #  
Commercial lot to be supplied by Sponsor 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 15 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 16 of 90 
Control 
Product: 
NeisVac-C®: Meningococcal Group C Polysaccharide Conjugate Vaccine Adsorbed (Pfizer 
Limited, Sandwich, United Kingdom) 
 Form: 
Suspension for injection in pre-filled syringe 
 Composition: 
Each 0.5 mL dose of NeisVac-C® vaccine is formulated to contain: 
Neisseria meningitidis serogroup C (strain C11) polysaccharide (de-O-acetylated) ........ 10 µg 
conjugated to tetanus toxoid ........................................................................................ 10-20 µg 
adsorbed on aluminium hydroxide, hydrated ........................................................ 0.5 mg Al3+ 
Excipients: Sodium chloride, Water for injections 
 Route: 
IM 
 Batch #  
Commercial lot to be supplied by Sponsor 
Inclusion 
Criteria: 
An individual must fulfill all of the following criteria in order to be eligible for study 
enrollment: 
1) Aged 12 to 23 months on the day of the first study visit 
2) Informed consent form (ICF) has been signed and dated by the parent(s) / legally 
acceptable representative(s)  
3) Subject and parent / legally acceptable representative are able to attend all scheduled visits 
and to comply with all study procedures 
4) Covered by health insurance if required by local regulations 
Exclusion 
Criteria: 
An individual fulfilling any of the following criteria is to be excluded from study enrollment: 
1) 
Participation in the 4 weeks (28 days) preceding the study vaccination or planned 
participation during the present study period in another clinical study investigating a 
vaccine, drug, medical device, or medical procedure  
2) 
Receipt of any vaccine in the 4 weeks (28 days) preceding the study vaccination or 
planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, which 
may be received at least 2 weeks before or after study investigational vaccines. This 
exception includes monovalent pandemic influenza vaccines and multivalent influenza 
vaccines 
 
3) 
Receipt of immune globulins, blood or blood-derived products in the past 3 months 
4) 
Previous 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 vaccine)  
5) 
Known or suspected congenital or acquired immunodeficiency; or receipt of 
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, 
within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone 
or equivalent for more than 2 consecutive weeks within the past 3 months) 
 
6) 
History of meningococcal infection, confirmed either clinically, serologically, or 
microbiologically 
7) 
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 travelling to countries with high endemic or epidemic disease) 
8) 
Known systemic hypersensitivity to any of the vaccine components, or history of a life-
threatening reaction to the vaccines used in the study or to a vaccine containing any of the 
same substances 
9) 
Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-
containing vaccine 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 16 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 17 of 90 
 
10) Personal history of Guillain-Barré syndrome (GBS) 
11) Thrombocytopenia, as reported by the parent/ legally acceptable representative or 
suspected thrombocytopenia contraindicating intramuscular vaccination in the 
Investigator’s opinion 
12) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating intramuscular vaccination in the Investigator’s opinion 
13) Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere 
with study conduct or completion 
14) 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. 
15) Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw 
16) Identified as a natural or adopted child of the Investigator or employee with direct 
involvement in the proposed study 
Statistical 
Methods: 
Primary Objective 
The immunogenicity of MenACYW conjugate vaccine serogroup C will be compared to that of 
Nimenrix® vaccine and to that of NeisVac-C® vaccine using sequential testing approaches. 
Non-Inferiority 
A non-inferiority testing approach will be used to compare post-vaccination (ie, 30 days after 
the vaccination) seroprotection rates and GMTs of MenACYW conjugate vaccine to that of 
Nimenrix® and NeisVac-C®, using a two-sided 95% Confidence Interval (CI) with the 
following hypotheses: 
For seroprotection rates: 
𝐻𝐻0 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝑝𝑝𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎≤−0.1  
𝐻𝐻1 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> −0.1  
Or 
For GMTs 
𝐻𝐻0 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶≤1/𝛿𝛿  
𝐻𝐻1 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/ 𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> 1/𝛿𝛿 
with: 
• 
Comparator: Nimenrix® or NeisVac-C® 
• 
π: seroprotection rates 
• 
δ: non-inferiority margin set at 1.5 
Superiority 
If the non-inferiority testing succeeds then a superiority approach will be used to compare post-
vaccination (ie, 30 days after the vaccination) seroprotection rates and/or GMTs of  MenACYW 
conjugate vaccine to that of Nimenrix® and NeisVac-C®, using a two-sided 95% CI with the 
following hypotheses: 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 17 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 18 of 90 
 
For seroprotection rates 
𝐻𝐻0 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶≤0  
𝐻𝐻1 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> 0  
Or 
For GMTs 
𝐻𝐻0 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/ 𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶≤1  
𝐻𝐻1 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/ 𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> 1 
with: 
• 
Comparator: Nimenrix® or NeisVac-C® 
• 
π: seroprotection rates 
For the seroprotection rates, the 95% CI of the difference in proportions will be computed using 
the Wilson Score method without continuity correction (Newcombe method).  
For the GMTs, the two-sided 95% CI of the ratio of post-vaccination GMTs will be calculated 
using normal approximation of log-transformed titers. 
The non-inferiority will be demonstrated against seroprotection rates if the null hypothesis is 
rejected, ie, if the lower limit of the two-sided 95% CI for the difference between the 
seroprotection rates is > -10%. 
The non-inferiority will be demonstrated against GMTs if the null hypothesis is rejected, ie, 
lower limit of the two-sided 95% CI for the ratio of GMTs > 1/1.5. 
The superiority will be demonstrated against seroprotection rates if the null hypothesis is 
rejected, ie, if the lower limit of the two-sided 95% CI for the difference between the 
seroprotection rates is > 0%. 
The superiority will be demonstrated against GMTs if the null hypothesis is rejected, ie, lower 
limit of the two-sided 95% CI for the ratio of GMTs > 1. 
 
The testing approach will be done in parallel and using a step by step approach for the 2 
comparators: 
Nimenrix®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate vaccine against 
Nimenrix® measured by hSBA is demonstrated then the non-inferiority using hSBA GMTs will 
be tested. If the non-inferiority using hSBA GMTs of MenACYW conjugate vaccine against 
Nimenrix® is demonstrated then the superiority using hSBA GMTs will be tested. If the 
superiority using hSBA GMTs is demonstrated then the superiority using hSBA seroprotection 
rates will be tested. 
NeisVac-C®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate vaccine against 
NeisVac-C® measured by rSBA is demonstrated then the non-inferiority using rSBA GMTs 
will be tested. If the non-inferiority using rSBA GMTs is demonstrated then the superiority 
using rSBA GMTs will be tested. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 18 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 19 of 90 
 
Figure 1: Sequential statistical testing approach for primary objectives 
 
 
 
 
To conclude, non-inferiority using seroprotection rates of MenACYW conjugate vaccine 
against Nimenrix® measured by hSBA or non-inferiority using seroprotection rates of 
MenACYW conjugate vaccine against NeisVac-C® measured by rSBA have to be 
demonstrated. 
 
Secondary Objectives 
A similar statistical approach as for the primary objective will be used considering the rSBA 
antibody titers for Nimenrix® and hSBA antibody titers for NeisVac-C®.   
The testing approach will be done in parallel and using a step by step approach for the 2 
comparators: 
Nimenrix®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate vaccine against 
Nimenrix® measured by rSBA is demonstrated then the non-inferiority using rSBA GMTs will 
be tested. If the non-inferiority using rSBA GMTs of MenACYW conjugate vaccine against 
Nimenrix® is demonstrated then the superiority using rSBA GMTs will be tested. 
NeisVac-C®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate vaccine against 
NeisVac-C® measured by hSBA is demonstrated then the non-inferiority using hSBA GMTs 
will be tested. And if the non-inferiority using hSBA GMTs is demonstrated then the 
superiority using hSBA GMTs will be tested. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 19 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 20 of 90 
 
Figure 2: Sequential statistical testing approach for secondary objectives 
 
To conclude, non-inferiority using seroprotection rates of MenACYW conjugate vaccine 
against Nimenrix® measured by rSBA or non-inferiority using seroprotection rates of 
MenACYW conjugate vaccine against NeisVac-C® measured by hSBA have to be 
demonstrated. 
 
Observational Objectives 
For immunogenicity and safety observational objectives, the descriptive analyses will be done 
according to each vaccine group. The main parameters will be described with 95% CI using the 
exact binomial distribution (Clopper-Pearson method) for proportions and using the normal 
approximation of the Log10 concentrations/titers, followed by a back transformation for GMTs. 
 
Calculation of Sample Size: 
To complete the primary objective a total of 675 subjects were initially planned to be enrolled 
according to a ratio 1:1:1 (MenACYW: Nimenrix®: NeisVac-C®). This sample size will provide 
acceptable global powers considering an overall one-sided alpha of 2.5% (ie, 1.25% adjusted 
alpha for each of the 2 main non-inferiority tested, then same level of alpha is used for the 
subsequent tests as a ranking testing strategy is used), an initial drop-out rate of 10% (ie, 202 
evaluable subjects per group; not taking into account the impact of COVID-19)  and based on 
the following additional hypotheses: 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 20 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 21 of 90 
 
Statistical hypotheses and powers for the primary objective 
Objective 
number 
Step 
Comparator 
Statistical 
test 
Endpoint 
Ref. 
MenACYW 
vs 
Comparator 
Clinical 
margin 
Standard 
deviation 
(SD) 
Indivi-
dual 
power 
Sequential 
power 
1 
1 
Nimenrix 
hSBA 
NI 
Seroprote
ction rates 
98% vs 88% 
10% 
 
>99.9% 
>99.9% 
2 
Nimenrix 
hSBA 
NI 
GMTs 
GMTR=1.5 
1.5 
0.5 
>99.9% 
>99.9% 
3 
Nimenrix 
hSBA 
Sup 
GMTs 
GMTR=1.5 
- 
0.5 
90.1% 
89.9% 
4 
Nimenrix 
hSBA 
Sup 
Seroprote
ction rates 
98% vs 88% 
10% 
 
95.8% 
86.1% 
2 
1 
Neisvac-C 
rSBA 
NI 
Seroprote
ction rates 
98% vs 98% 
10% 
 
>99.9% 
>99.9% 
2 
Neisvac-C 
rSBA 
NI 
GMTs 
GMTR=1 
1.5 
0.5 
90.1% 
90.1% 
3 
Neisvac-C 
rSBA 
Sup 
GMTs 
GMTR=1.5 
- 
0.5 
90.1% 
81.2% 
NI: non-inferiority; Sup: superiority 
GMTR: Geometric Mean of Titers ratios of MenACYW vs Comparator 
One-sided Alpha of 1.25% used for all calculations 
Sequential power correspond to the overall power of each step of the statistical tests to be performed 
Reference seroresponse rates and SDs made from Phase II and III toddler studies MET51, MET32 and MET54. 
In addition, considering such sample size will also provide acceptable global powers to achieve 
the secondary objective, considering an overall one-sided alpha of 2.5% (ie, 1.25% adjusted 
alpha for each of the 2 main non-inferiority tested, then same level of alpha is used for the 
subsequent tests as a ranking testing strategy is used), an initial drop-out rate of 10% (not taking 
into account the impact of COVID-19), and based on the following additional hypotheses: 
Statistical hypotheses for the secondary objective 
Objective 
number 
Step Comparator Statistical 
test 
Endpoint 
Ref. 
MenACYW 
vs 
Comparator 
Clinical 
margin 
Standard 
deviation 
(SD) 
Indivi-
dual 
power 
Sequential 
power 
1 
1 
Nimenrix 
rSBA 
NI 
Seroprotec
tion rates 
98% vs 98% 
10% 
  
>99.9% >99.9% 
2 
Nimenrix 
rSBA 
NI 
GMTs 
GMTR=1.5 
1.5 
0.5 
>99.9% >99.9% 
3 
Nimenrix 
rSBA 
Sup 
GMTs 
GMTR=1.5 
- 
0.5 
90.1% 
90.1% 
2 
1 
Neisvac-C 
hSBA 
NI 
Seroprotec
tion rates 
98% vs 98%  
10% 
  
>99.9% >99.9% 
2 
Neisvac-C 
hSBA 
NI 
GMTs 
GMTR=1 
1.5 
0.5 
90.1% 
90.1% 
3 
Neisvac-C 
hSBA 
Sup 
GMTs 
GMTR=1.5 
- 
0.5 
90.1% 
81.2% 
NI: non-inferiority; Sup: superiority 
GMTR: Geometric Mean of Titers ratios of MenACYW vs Comparator 
One-sided Alpha of 1.25% used for all calculations 
Sequential power correspond to the sequential power of each step of the statistical tests to be performed 
Reference seroresponse rates and SDs made from Phase II and III toddler studies MET51, MET32 and MET54. 
As a consequence of the COVID-19 hold, approximately 30 subjects were identified to be 
excluded from the PPAS as they were unable to complete their follow-up visit as planned in the 
protocol. To maintain the planned study power and the randomization ratio, approximately 30 
additional subjects are planned to be enrolled, with a planned final distribution of 235:235:235.  
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 21 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 22 of 90 
Table of Study Procedures 
Phase III Trial, 2 Visits, 1 Phone Call, 1 Vaccination, 2 Blood Samples, 30 to 44 Days’ 
Duration per Subject 
Visit/Contact 
Visit 1 
Telephone 
Call 1 
Visit 2 
Trial timelines (days) 
D0 
D8 
D30 
Time windows (days) 
- 
+2 days 
+14 days 
Informed consent  
X 
 
 
Inclusion/exclusion criteria 
X 
 
 
Collection of demographic data 
X 
 
 
Medical history 
X 
 
 
Physical examination and Temperature 
X 
 
 
Contact Interactive Response Technology (IRT) for 
randomization 
X 
 
 
Review of temporary contraindications for blood 
sampling* 
 
 
X 
Blood sample (BL), 4 mL† 
BL0001 
 
BL0002 
Vaccination‡ 
X 
 
 
Immediate surveillance (30 minutes) 
X 
 
 
Diary card provided 
X 
 
 
Telephone call 
 
X§ 
 
Recording of solicited injection site & systemic reactions 
D0 to D7 
 
Recording of unsolicited AEs 
D0 to D30 
Reporting of SAEs (including AESIs) 
To be reported throughout the study period 
Diary card reviewed and collected 
 
 
X 
Collection of reportable concomitant medications 
To be reported throughout the study period 
Termination record 
 
 
X 
* Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the second blood draw, the 
Investigator will postpone that blood draw until it has been 3 days since the subject last received oral or injectable 
antibiotic therapy. Postponement must still be within the timeframe for blood draw (30 to 44 days after vaccination 
at D0), when possible. 
† Blood sample at Visit 1 will be drawn before administration of the vaccine. 
‡ Subjects will receive 1 dose of MenACYW conjugate vaccine or Nimenrix® or NeisVac-C®. 
§ This call is made 8 to 10 days after the vaccination at Visit 1. If D8 (+ 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 AESIs) not yet reported, and will remind the subject’s parent 
/ legally acceptable representative to continue using the diary card up to Visit 2, to bring the diary card to the study 
center at Visit 2, and confirm the date and time of Visit 2. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 22 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 23 of 90 
List of Abbreviations 
AE 
adverse event 
AESI 
adverse event of special interest 
AR 
BL 
adverse reaction 
blood sample 
CDM 
CI 
Clinical Data Management 
Confidence Interval 
COVID-19 
Coronavirus Disease 2019 
CQA 
Clinical Quality Assessment 
CRA 
Clinical Research Associate 
CRB 
(electronic) case report book [all the case report forms for a subject] 
CRF 
CSU 
(electronic) case report form 
Sanofi Clinical Study Units 
CTA 
clinical trial agreement 
CTL 
DC 
Clinical Team Leader 
diary card 
EDC 
electronic data capture 
EU 
European Union 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FVFS 
first visit, first subject 
FVLS 
GBS 
first visit, last subject 
Guillain-Barré syndrome 
GCI 
Global Clinical Immunology 
GCP 
Good Clinical Practice 
GMT 
geometric mean titers 
GPV 
hSBA 
Global Pharmacovigilance 
serum bactericidal assay using human complement 
IATA 
IB 
International Air Transport Association 
Investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonization 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 23 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 24 of 90 
IDMC 
Independent Data Monitoring Committee 
IEC 
IMD 
Independent Ethics Committee 
invasive meningococcal disease 
IME 
important medical event 
IND 
IOM 
investigational new drug (application) 
Institute of Medicine 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
LCLS 
last contact, last subject 
LLOQ 
lower limit of quantification 
LLT 
lowest level term 
MAAE 
medically attended adverse event 
MedDRA 
MenC 
Medical Dictionary for Regulatory Activities 
Meningococcal C 
mL 
Milliliter 
MTL 
Medical Team Leader 
NSAID 
non-steroidal anti-inflammatory drug 
PPAS 
PMSL 
RME 
per-protocol analysis set 
Project Manager and Study Leader 
Regional Medical Expert 
RMO 
rSBA 
Responsible Medical Officer 
serum bactericidal assay using baby rabbit complement 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SafAS 
safety analysis set 
SD 
SMT 
SP 
standard deviation 
Safety Management Team 
Sanofi Pasteur 
TC 
telephone call 
TMF 
TT 
trial master file 
tetanus toxoid 
ULOQ 
US 
upper limit of quantification 
United States 
WHO 
World Health Organization 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 24 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 25 of 90 
1 
Introduction 
1.1 
Background 
This is a study using the quadrivalent meningococcal polysaccharide (serogroups A, C, Y and W) 
tetanus toxoid conjugate vaccine (hereafter referred to as MenACYW conjugate vaccine) against 
invasive meningococcal disease (IMD) in healthy toddlers 12 to 23 months of age who are 
meningococcal vaccine naïve. 
The purpose of this study (MEQ00065) is to compare the immunogenicity of Serogroup C of a 
single dose of MenACYW conjugate vaccine to a single dose of licensed vaccines, NeisVac-C® 
(Meningococcal C–TT conjugate vaccine) or Nimenrix® (quadrivalent Meningococcal ACWY-TT 
conjugate vaccine) and to describe the safety in healthy toddlers 12 to 23 months of age who are 
meningococcal vaccine naïve in Europe. The purpose of this study is to demonstrate that the 
immunogenicity of MenACYW conjugate vaccine is at least non-inferior to that of Nimenrix® 
(MenACWY-TT conjugate vaccine), and NeisVac-C® (meningococcal C [MenC]-TT conjugate 
vaccine), for serogroup C.  
IMD is a serious illness caused by the bacterium Neisseria meningitidis (N. meningitidis), a 
Gram-negative diplococcus found exclusively in humans. It is associated with high morbidity and 
mortality. Symptoms may include intense headache, fever, nausea, vomiting, photophobia, stiff 
neck, lethargy, myalgia, and a characteristic petechial or purpuric rash (1). Invasive infection 
usually results in septicemia (~35%–40% of cases), meningitis (~50% of cases), or both. 
Bacteremic pneumonia is less common (~9% of cases) (2). 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, 3, 4). Worldwide, most cases 
of meningococcal disease are caused by serogroups A, B, C, X, Y, and W (3-5). Serogroup B is 
responsible for endemic disease and some outbreaks, while serogroup C is responsible for large 
outbreaks (6). Serogroup A remains the main cause of epidemics in the world and is especially 
dominant in Africa and Asia but is only minor in Europe. Serogroup W has been observed in 
Africa, as well as in the United Kingdom (UK), in residents who participated in the Hajj 
pilgrimage to the Kingdom of Saudi Arabia (5, 7, 8) and in other parts of the world. An increasing 
trend of the notification rate of W serogroup is seen in Europe (9). Serogroup X causes substantial 
meningococcal disease in parts of Africa, but rarely causes disease in other parts of the world 
(3, 10). Serogroup Y has not been associated with outbreaks, but the frequency with which it 
causes sporadic cases has gradually increased in the United States (US) and more recently in 
Canada and Europe (11-13). The Y serogroup is commonly associated with meningococcal 
pneumonia, particularly in older adults ≥ 65 years of age (14).  
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 European Center for Disease Prevention and Control (ECDC) publish annually an 
epidemiological report on Invasive Meningococcal Disease, based on data retrieved from the 
European Surveillance System (TESSy) which is used to collect, analyze and disseminate data on 
communicable diseases. Thirty EU/EEA Member states contribute to the system by uploading 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 25 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 26 of 90 
regularly their infectious disease surveillance data. The last report has been published in August 
2018, based on 2016 data (9). In 2016, the overall incidence rate of IMD in European Union 
(EU)/European Economic Area (EEA) countries was 0.6 per 100 000 similar to the notification 
rate for previous years. Four countries (France, Germany, Spain and the United Kingdom) 
accounted for 60% of all confirmed cases. The incidence per 100 000 was of 0.3 in Finland, 0.7 in 
Denmark and 0.4 in Germany. In 2016, IMD notification rate was 2.7 confirmed cases per 
100 000 population in 1-4-year-olds (1). IMD was predominantly notified in infants and young 
children with a notification rate of 8.5 confirmed cases per 100 000 population in children under 
one year of age and 2.7 confirmed cases per 100 000 population in 1-4-years-old. Infants were the 
most affected age group in the majority of Member States.  
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 
(9). By 2016, meningococcal C conjugate (MCC) vaccine was integrated into the national routine 
childhood immunization programs of 14 EU/EEA countries. In countries without national routine 
MCC vaccination, serogroup C accounted for 21% of cases. In countries with national routine 
MCC vaccination, 15% of cases were attributed to serogroup C. 
The trend in serogroup C was stable at the EU level. Although the trend in serogroup Y was stable 
at the EU level during the time period presented in this report, several EU/EEA countries have 
reported increasing trends in serogroup Y in recent years. Serogroup W has increased at the 
European level since 2011, predominantly due to the rapid epidemic expansion of a single clone 
in the UK that started in 2009, but other EU Member States also experienced an increase in 
serogroup W.  
The incidence of IMD due to serogroup C is declining in Germany, the incidence of IMD due to 
serogroup W and Y are increasing. The numbers of IMD cases due to these three serogroups are 
now very similar. For instance, in 2017, the number of cases reported for serogroup C, W and Y 
were 39, 21 and 35, respectively, although in 2014, they were 41, 10 and 19, respectively. In 
2017, most MenB cases were reported in infants aged below 1 year with an increase again at 15 
years. MenC was more common in adolescents and young adults aged between 15 and 20 years. 
MenW and MenY were more common in the 15–24 years group and over 50 years group. There 
was only one case of MenA, observed in a 3-year-old. The upward trend since 2014 in MenW and 
MenY cases has been especially clear in the adolescent and young adult population (15–24 years) 
with a spike in MenY incidences in 2016. 
Over the last ten years Denmark had shown a similar picture as described above for Germany 
(15).  
In this context of increasing trends for serogroups W and Y, Austria, the Czech Republic, Greece, 
Italy and the UK have introduced the quadrivalent conjugate vaccine MenACYW into their 
routine vaccination schedules, predominantly as booster doses for adolescents. As carriage rates 
of Neisseria meningitidis are highest in adolescents and young adults, high coverage rate and 
levels of immunity in this age group are critical to ensure the protection of other vulnerable age 
groups. That is the reason why in 2018, the Netherlands have introduced also MenACWY 
vaccination targeting both toddlers (14 months of age) and adolescents (14 years of age). Some 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 26 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 27 of 90 
Italian regions have also the same strategy with a switch from MenC to MenACWY vaccination 
in toddlers aged 14 months and MenACWY vaccination in adolescents.   
MenACYW conjugate vaccine will 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 final formulation has been evaluated in over 7000 subjects (infants, toddlers, adolescents, and 
adults > 56 years of age) in completed phase II and phase III studies MET35, MET39, MET43, 
MET44, MET49, MET50, MET51, MET54 and MET56. MenACYW conjugate vaccine is also 
being evaluated in ongoing Phase III studies: MET57 (in toddlers 12 to 23 months of age), 
MET58 (in infants and toddlers 6 weeks to 18 months of age), MET41 (in infants and toddlers 6 
weeks to 15 months of age), MET42 (in infants and toddlers 6 weeks to 15 months of age), 
MET52 (in infants and toddlers 3 to 13 months of age), MET33 (in infants and toddlers from 6 
weeks to 15 months of age) MET61 (in infants and toddlers 6 months to 23 months of age), and 
MET62 (in children 4 to 5 years of age).  
Approximately 1500 toddlers (12 to 23 months of age) have received one dose of MenACYW 
conjugate vaccine in studies MET54, MET51, and MET57. 
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. The 
relevant Phase II and Phase III studies are discussed below. 
1.2.1.1 
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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 27 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 28 of 90 
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 statistical analysis plan (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. 
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. 
1.2.1.2 
Study MET51 (Phase III) 
This study focused on evaluating the immunogenicity and safety profiles of a single dose of 
MenACYW conjugate vaccine compared to that of the licensed quadrivalent meningococcal 
serogroups A, C, W, and Y tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix®) in 
toddlers in the European Union who were either meningococcal vaccine naïve or received MenC 
vaccination during infancy. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 28 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 29 of 90 
A total of 918 subjects were randomized to the following groups: 
Meningococcal Vaccine-Naïve Subjects were randomized to the following 2 groups: 
Group 1: MenACYW conjugate vaccine 
Group 2: Nimenrix® 
MenC-Primed Subjects: were randomized to the following 2 groups: 
Group 3: MenACYW conjugate vaccine 
Group 4: Nimenrix® 
Immunogenicity 
Non-Inferiority of MenACYW Conjugate Vaccine to Nimenrix® who were either meningococcal 
vaccine naïve or had received monovalent MenC vaccination during infancy  
Thirty days after vaccination, the lower limit of the 2-sided 95% CI of the overall stratified 
difference in hSBA response rates (antibody titers ≥ 1:8) between MenACYW Conjugate vaccine 
and Nimenrix® recipients were > -10% for all 4 serogroups. Non inferiority of immune response, 
based on percentage of subjects achieving a post vaccination titer ≥ 1:8 at D30 regardless of their 
meningococcal vaccine background, was demonstrated for MenACYW conjugate vaccine versus 
Nimenrix® for all serogroups.  
Non-Inferiority of MenACYW Conjugate Vaccine to Nimenrix® who were meningococcal vaccine 
naïve  
Thirty days after vaccination, the lower limit of the 2-sided 95% CI of the difference in hSBA 
response rates (antibody titers ≥ 1:8) MenACYW Conjugate Vaccine (Group 1) and Nimenrix® 
recipients (Group 2) were > -10% for all 4 serogroups. Non inferiority of immune response, based 
on percentage of subjects achieving a post vaccination titer ≥ 1:8 at D30 in meningococcal 
vaccine-naïve toddlers, was demonstrated for MenACYW conjugate vaccine versus Nimenrix® 
for all serogroups.   
hSBA Vaccine Seroresponse at D30 
At D30, the percentages of subjects with an hSBA vaccine seroresponse were higher in 
MenACYW-recipients than in Nimenrix®-recipients for serogroup C. For the other serogroups, 
percentages were similar between MenACYW-recipients and Nimenrix®-recipients. 
Antibody Responses (hSBA GMTs) at D30 
Toddlers who either were meningococcal vaccine naïve or had received monovalent MenC 
vaccination during infancy 
The GMTRs (stratified on priming vaccination background) were 7.59, 1.28, and 1.32 for 
serogroups C, Y and W, respectively, with the lower bound of the 95% CI greater than 1.0; and 
the GMTR (stratified on priming vaccination background) was 0.819 for serogroup A, with the 
upper bound of the 95% CI lower than 1.0.  
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 29 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 30 of 90 
Meningococcal vaccine-naïve toddlers  
The GMTRs were 1.03 and 1.18 (with the lower bound of the 95% CI below 1.0) for serogroups 
A and Y, respectively, and 16.5 and 1.34 (with the lower bound of the 95% CI greater than 1.0) 
for serogroups C and W, respectively. 
Toddlers who received monovalent MenC vaccination during infancy 
The GMTRs were 0.496 (with the upper bound of the 95% CI lower than 1.0) for serogroup A, 
1.34 and 1.29 (with the lower bound of the 95% CI below 1.0) for serogroups C and W, 
respectively, and 1.53 (with the lower bound of the 95% CI greater than 1.0) for serogroup Y. 
Antibody Responses (rSBA GMTs and seroresponse Titers ≥1:8 seroresponse) at D30 
Toddlers who either were meningococcal vaccine naïve or had received monovalent MenC 
vaccination during infancy 
At D30, meningococcal rSBA GMTs were lower in MenACYW-recipients than in Nimenrix®-
recipients for serogroup A (1382 and 4882, respectively), and higher in MenACYW-recipients 
than in Nimenrix®-recipients for serogroup C (2150 and 686, respectively).  
Thirty days after vaccination, the percentages of subjects with rSBA antibody titers ≥ 1:8 were 
high and comparable between MenACYW- and Nimenrix®-recipients ranging from 97.3% to 
100.0%. 
Safety 
Overall, vaccination with MenACYW conjugate vaccine among toddlers aged 12 to 23 months 
was found to be well tolerated, with no safety concerns identified, no immediate hypersensitivity 
reactions, no discontinuations due to an SAE or other AE, and no related SAEs. 
There was only 1 solicited injection site reaction reported larger than 100 mm. The subject, 
randomized in Group 1 (MenACYW–naïve), reported injection site erythema at 30 mm on D0 
that lasted for 4 days. No action was taken. The majority of the solicited injection sites were of 
Grade 1 or 2 intensity, most started between D0 and D03, and most lasted 1 to 3 days. Overall, 
most solicited systemic reactions were of Grade 1 or Grade 2 intensity, started between D0 and 
D30, and lasted 1 to 3 days. 
Seven subjects experienced a total of 11 SAEs during the study. None of these SAEs were 
considered as related to the investigational vaccine by the Investigator, and none led to 
discontinuation from the study. The percentages of subjects who reported at least 1 SAE during 
the study were less than 1% and comparable between MenACYW- and Nimenrix®-recipients. No 
deaths were reported during the study.  
Vaccination with MenACYW conjugate vaccine among toddlers aged 12 to 23 months was found 
to be well tolerated, with no safety concerns identified. 
1.2.1.3 
Study MET57 (Phase III) 
MET57, a Phase III study in 1200 toddlers aged 12 to 23 months, is currently ongoing in South 
Korea, Russia, Mexico, and Thailand. The study is designed to evaluate the safety and 
immunogenicity profile of the MenACYW conjugate vaccine when administered alone or 
concomitantly with routine pediatric vaccines for the age group being evaluated in the study 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 30 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 31 of 90 
(Measles, Mumps, Rubella (MMR) and varicella in South Korea and Thailand; pneumococcal 13-
valent conjugate (PCV13) vaccine in Russia; and DTaP, HB, IPV, and Hib conjugate combination 
vaccine in Mexico). 
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 NeisVac-C® will likely be protected against meningococcal disease caused 
by N. meningitidis serogroup C. 
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, NeisVac-C® and Nimenrix® may not protect 
100% of individuals against the diseases they are designed to prevent. 
1.3.2 
Potential Risks to Subjects 
Like other vaccines, MenACYW conjugate vaccine, NeisVac-C® 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, NeisVac-C® 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 
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 (GBS) has been reported in persons aged 11 to 19 years who had 
symptom onset within 6 weeks of administration of a US licensed meningococcal conjugate 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 31 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 32 of 90 
vaccine (16). A retrospective cohort study carried out in the US using healthcare claims data 
found no evidence of increased GBS risk associated with the use of that vaccine. The study was 
able to exclude all but relatively small incremental risks (17). 
A review by the Institute of Medicine (IOM) found inadequate evidence to accept or reject a 
causal relationship between tetanus toxoid-containing vaccines and GBS (18). The IOM found 
evidence for a causal relation between tetanus toxoid-containing vaccines and brachial neuritis 
(19). Arthus reactions are rarely reported after vaccination and can occur after tetanus toxoid-
containing vaccines (20). 
No occurrences of GBS, brachial neuritis, or Arthus reaction have been reported with the use of 
MenACYW conjugate vaccine in the completed clinical trials. 
The potential risk listed here are not exhaustive. Refer to the Investigator’s Brochure (IB) of the 
investigational vaccine and to the Summary of Product Characteristics for NeisVac-C® (21) and 
Nimenrix® (22) for additional information regarding potential risks. 
1.3.3 
COVID-19 Risk Assessment 
MenACYW conjugate vaccine, NeisVac-C®, and Nimenrix® would not cause immune 
suppression. Therefore, the risk that a participant in this study will contract COVID-19 solely due 
to the administration of the study vaccine will be similar to the risk that a person not participating 
in this study will contract COVID-19. However, the risk of exposure to infected people cannot be 
completely excluded as subjects may need to be exposed to public areas (eg, commute to the site 
and at the site).  
Risk mitigation:  
• Do not restart the study until local confinement measures or other safety restrictions linked to 
the COVID-19 pandemic are lifted by local Authorities.  
• Continued risk assessment by the Investigator and Sponsor before deciding to restart the trial.  
• Reduce public exposure while ambulatory when possible. 
1.4 
Rationale for the Study 
Vaccination is currently the best option to prevent IMD. A number of vaccines are, either 
targeting single serogroup (such as serogroup C vaccines ) or a combination or multiserogroups 
(quadrivalent vaccines) which provide broad coverage and have the potential to protect 
individuals in countries with several predominant circulating serogroups (as currently observed in 
Europe with C serogroups and increasing W and Y serogroups). 
Two meningococcal C (MenC) conjugate vaccines are currently licensed in European countries 
from 2 months of age. The MenC conjugate vaccines are made from capsular polysaccharide that 
has been extracted from cultures of capsular group C Neisseria meningitidis. The polysaccharide 
is linked (conjugated) to a carrier protein, either CRM197 (a non-toxic variant of diphtheria toxin) 
(Menjugate®) or tetanus toxoid (NeisVac-C®). The conjugation increases the immunogenicity, 
especially in young children in whom the plain polysaccharide vaccines are less immunogenic. 
The vaccination schedule and the number of vaccinations vary across the EU countries. In 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 32 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 33 of 90 
vaccinating countries, an infant may have 1 to 2 doses of meningococcal C conjugate vaccine 
during the first two years of life ) (23). 
Quadrivalent meningococcal A, C, W and Y vaccines conjugated to CRM197 (Menveo®) or 
tetanus toxoid (Nimenrix®) are also licensed in Europe, with Nimenrix® approved for use from 6 
weeks of age, while Menveo® is only licensed from 2 years of age. 
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 > 65 years of age) against 
IMD. The purpose of the vaccine is to provide broad coverage against circulating meningococcal 
strains from serogroups A, C, Y, and W. Compared to a previous Sanofi Pasteur meningococcal 
vaccine which is not licensed in Europe, Menactra®, the MenACYW conjugate vaccine is 
prepared by using tetanus toxoid as the carrier protein. Conjugation of PS 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. 
Recommendations / National Immunization programs are heterogeneous in Europe, with some 
countries recommending only monovalent MenC vaccines in infancy/early childhood, while other 
countries have recently revised their recommendations to quadrivalent Men A, C, W, Y vaccines 
(some regions in Italy, NL*(24) 
NeisVac-C® is considered the standard of care in several countries for meningococcal MenC 
vaccination in toddlers. So far none of the currently licensed meningococcal ACWY conjugate 
vaccines have been able to demonstrate non-inferiority of MenC immune response versus 
NeisVac-C®.  
MenC has been one of the most important disease-causing serogroup in Europe and many 
countries in the world (eg, Australia, Brazil, and Canada), and is still circulating. Therefore, 
health authorities are reluctant to use a ACWY vaccine of which the MenC component has not 
been shown to be non-inferior to monovalent MenC-TT vaccine. However, epidemiology is 
changing with increasing notification rates of serogroups W & Y and a vaccine able to offer at 
least the same protection against MenC as monovalent MenC vaccine, while offering also a 
protection against other serogroups (W, Y) will provide an interesting option.  
The purpose of MEQ00065 is to evaluate the investigational quadrivalent meningococcal 
MenACYW conjugate vaccine when used as a single dose toddler vaccine in individuals who are 
meningococcal vaccine naïve.  
The study will aim to compare the immunogenicity of MenACYW conjugate vaccine versus 
quadrivalent MenACWY-TT conjugate vaccine, Nimenrix®, or versus monovalent MenC-TT 
conjugate vaccine, NeisVac-C®, and to describe the safety of 1 dose of MenACYW conjugate 
vaccine compared to 1 dose of Nimenrix® or to 1 dose NeisVac-C® in toddlers 12 to 23 months of 
age. 
High titers for serogroup C were observed with MenACYW conjugate vaccine vs Nimenrix® in 
MET54 Phase II study and MET51 Phase III study. While the non-inferiority of seroresponse as 
measured by hSBA versus Nimenrix® was demonstrated, the statistical superiority of the MenC 
response of MenACYW conjugate vaccine was not tested as a primary objective in MET51 study. 
The proposed study will address statistical superiority of serogroup C titers vs Nimenrix® as part 
of the primary objective; other serogroups (A, W, Y) will not be evaluated. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 33 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 34 of 90 
2 
Study Objectives 
2.1 
Primary Objectives 
1) To demonstrate the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or Nimenrix® as measured by hSBA. If the non-inferiority of the 
seroprotection rate (antibody titers ≥ 1:8) is demonstrated, then 
1.1) 
to demonstrate the non-inferiority of the antibody response (geometric mean titers 
[GMT]) to meningococcal serogroup C following the administration of a single dose 
of MenACYW conjugate vaccine or Nimenrix® as measured by hSBA. If the non-
inferiority of the antibody response (GMT) is demonstrated, then 
1.2) 
to demonstrate the superiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or Nimenrix® as measured by hSBA. If the superiority of the antibody 
response (GMT) is demonstrated, then 
1.3) 
to demonstrate the superiority of the seroprotection rate to meningococcal serogroup C 
following the administration of a single dose of MenACYW conjugate vaccine or 
Nimenrix® as measured by hSBA.  
2) To demonstrate the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or NeisVac-C® as measured by rSBA. If the non-inferiority of the 
seroprotection rate is demonstrated, then  
2.1) 
to demonstrate the non-inferiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or NeisVac-C® as measured by rSBA. If the non-inferiority of the antibody 
response (GMT) is demonstrated, then  
2.2) 
to demonstrate the superiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or NeisVac-C® as measured by rSBA. 
The endpoints for the primary objectives are presented in Section 9.1. 
Overall, the primary objective for the study will be met if, objective 1) - non-inferiority of the 
seroprotection rate versus Nimenrix® as measured by hSBA, or objective 2) - non-inferiority of 
the seroprotection rate versus NeisVac-C® as measured by rSBA, is met. 
2.2 
Secondary Objectives 
1) To demonstrate the non-inferiority of the seroprotection ate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or Nimenrix® as measured by rSBA. If the non-inferiority of the 
seroprotection rate is demonstrated, then 
1.1) 
to demonstrate the non-inferiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 34 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 35 of 90 
vaccine or Nimenrix® as measured by rSBA. If the non-inferiority of the antibody 
response (GMT) is demonstrated, then  
1.1.1) 
to demonstrate the superiority of the antibody response (GMT) to 
meningococcal serogroup C following the administration of a single dose of 
MenACYW conjugate vaccine or Nimenrix® as measured by rSBA  
2) To demonstrate the non-inferiority of the seroprotection rate (antibody titers ≥ 1:8) to 
meningococcal serogroup C following the administration of a single dose of MenACYW 
conjugate vaccine or NeisVac-C® as measured by hSBA. If the non-inferiority of the 
seroprotection rate is demonstrated, then 
2.1) 
to demonstrate the non-inferiority of the antibody response (GMT) to meningococcal 
serogroup C following the administration of a single dose of MenACYW conjugate 
vaccine or NeisVac-C® as measured by hSBA. If the non-inferiority of the antibody 
response (GMT) is demonstrated, then 
2.1.1) 
to demonstrate the superiority of the antibody response (GMT) to 
meningococcal serogroup C following the administration of a single dose of 
MenACYW conjugate vaccine or NeisVac-C® as measured by hSBA. 
The endpoints for the secondary objectives are presented in Section 9.2. 
Overall, the secondary objective for the study will be met if objective 1) - non-inferiority of the 
seroprotection rate versus Nimenrix® as measured by rSBA, or objective 2) - non-inferiority of the 
seroprotection rate versus NeisVac-C® as measured by hSBA, is met. 
2.3 
Observational Objectives 
Immunogenicity 
1) To describe the antibody response to meningococcal serogroup C before and 30 days 
(+14 days) after vaccination in each group using hSBA in toddlers 
2) To describe the antibody response to meningococcal serogroup C before and 30 days 
(+14 days) after vaccination in each group using rSBA in toddlers  
Safety 
To describe the safety profile of MenACYW conjugate vaccine, Nimenrix® and NeisVac-C®. 
The endpoints for the observational objectives are presented in Section 9.3. 
3 
Investigators and Study Organization 
This study will be conducted in approximately 31 centers in European countries. 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 35 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 36 of 90 
An internal safety management team (SMT) will review the data being generated from all the 
ongoing studies with MenACYW conjugate vaccine at regular intervals for any new safety signals 
or safety concerns. 
Monitoring activities on sites will be conducted by the Sanofi Clinical Study Units (CSU) or a 
Contract Research Organization under the responsibility of Sanofi Pasteur. During the trial, 
clinical data reported in the electronic Case Report Books (CRBs) will be integrated into the 
clinical database under the responsibility of the Sanofi Pasteur Clinical Data Management (CDM) 
platform. Statistical activities will be performed under the responsibility of the Sponsor’s 
Biostatistics Platform. Medical writing activities will be performed under the responsibility of the 
Sponsor’s Medical Writing and Translation Platform. 
The Sponsor’s Responsible Medical Officer (the RMO, the person authorized to sign this protocol 
and any amendments on behalf of the Sponsor) is 
 
  
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 forwarded by the Investigator to 
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 if requested. All SAEs occurring during the study that are 
related to the product administered will be reported by the Investigator to the IEC / IRB, 
according to the IEC / IRB policy. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 36 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 37 of 90 
5 
Investigational Plan 
5.1 
Description of the Overall Study Design and Plan 
5.1.1 
Study Design 
This is a Phase III, modified double-blind, randomized, active-controlled, multi-center trial to 
compare the immunogenicity for serogroup C of a single dose of MenACYW conjugate vaccine 
to a single dose of Nimenrix® vaccine or NeisVac-C® vaccine in toddlers, 12 to 23 months of age. 
A total of approximately 705 healthy toddlers aged 12 to 23 months who have not received any 
meningococcal vaccine during infancy, are planned to be enrolled and randomized to receive one 
dose of vaccine at Day (D) 0-Visit (V) 01, in one of the following 3 arms (1:1:1 ratio): 
• Group 1: MenACYW conjugate vaccine 
• Group 2: Nimenrix® vaccine (MenACWY-TT conjugate vaccine) 
• Group 3: NeisVac-C® vaccine (MenC-TT conjugate vaccine) 
All subjects will provide blood samples for immunogenicity assessment at V01 on D0 (pre-
vaccination) and at V02 (30 to 44 days post-vaccination), which corresponds to the planned end 
of this study.  
Solicited AE information will be collected for 7 days after vaccination, unsolicited AE 
information will be collected from D0 to D30, and SAE information, including adverse events of 
special interest (AESIs), will be collected throughout the trial. 
5.1.2 
Justification of the Study Design 
This study is designed to evaluate the MenC immune responses and safety profiles following the 
administration of a single dose of the MenACYW conjugate vaccine in toddlers 12 to 23 months 
of age, compared to NeisVac-C® and Nimenrix® licensed vaccines. 
In the MET51 pivotal Phase III study as well as in other studies to be included in the MenACYW 
conjugate vaccine Common Technical Dossier (CTD) for initial licensure, titers were measured 
by hSBA for the primary endpoint; the same assay will therefore be used in this study for the 
comparison to Nimenrix®. Titers measured by rSBA will also be compared as a secondary 
endpoint. 
NeisVac-C® has been developed using rSBA testing method at Public Health England (PHE) 
laboratory and no references are available for titers measured by hSBA. In order to evaluate 
whether non-inferiority can be demonstrated, titers measured by rSBA generated in the same 
laboratory, PHE, should be used. Therefore, this study will use rSBA as the primary endpoint for 
the comparison to NeisVac-C®. Titers measured by hSBA will also be compared as a secondary 
endpoint. 
In the countries where this study will be carried-out, the routine vaccination schedule does not 
include at the time of the study any vaccination against Meningococcal disease during the first 
year of life, which allows enrolment of naïve subjects. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 37 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 38 of 90 
Since the primary objectives of this study have serological endpoints and the vaccines for the 
study groups have different appearances, the study has a modified double-blind design. This 
means it contains an unblinded vaccine administrator while the rest of the study team, including 
laboratory technicians in charge of executing the serological testing, remain blinded to the 
subjects’ group allocations throughout the entire study up to the database lock to avoid any bias. 
5.1.3 
Study Plan 
Eligible subjects will be identified and recruited. 
A schedule of assessments and study vaccinations is provided in the Table of Study Procedures. 
Vaccination 
All subjects will receive a single dose of either MenACYW conjugate vaccine, NeisVac-C® or 
Nimenrix® on D0 (V01). 
Blood Sampling 
All subjects will provide a pre-vaccination blood sample at V01 (D0) and a post-vaccination 
sample at V02 (30 to 44 days after vaccination at V01). 
Collection of Safety Data 
All subjects will be followed for safety from V01 on D0 to V02 after vaccination. 
All subjects will be observed for 30 minutes after vaccination and any unsolicited systemic 
adverse events (AEs) occurring during that time will be recorded as immediate unsolicited AEs in 
the electronic case report book (eCRB) (see Section 9.3.2.3.1).  
The subject’s parent or other legally acceptable representative will record information in a diary 
card (DC) about solicited reactions from D0 to D7 after vaccination and unsolicited AEs will be 
recorded from D0 to D30.  
Serious adverse events (SAEs, including adverse events of special interest [AESIs]) will be 
recorded in the DC 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 V01 to identify the occurrence of any SAEs (including AESIs) not yet 
reported and to remind them to complete the DC and bring it back to V02. 
The completed DC will be collected and reviewed with the subject’s parent / legally acceptable 
representative at V02. 
5.1.4 
Visit Procedures 
Medical procedures (examinations, injections, etc.) must be conducted by appropriately licensed 
or credentialed study site staff working within the scope of their license/credentials. All 
information collected during the study visits must be recorded in the source documents. Some of 
the following information will also be recorded in the eCRF. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 38 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 39 of 90 
5.1.4.1 
V01 (D0): Inclusion, Randomization, Blood Sample, and Vaccination 
The Investigator or delegate will: 
1) 
Give the subject’s parent/legally acceptable representative information about the trial, answer 
any questions, obtain signed informed consent, and give him/her a signed copy. 
2) 
Check inclusion and exclusion criteria (see Section 5.2.4 and Section 5.2.5) for eligibility. 
Review vaccination history from the child’s immunization record: 
a. Collect demographic data. 
b. Obtain verbal significant medical history about the subject, including ongoing 
medication. 
c. Take the subject’s temperature (axillary, rectal, or oral, but axillary preferred) and record 
in the source document. If the temperature is ≥ 38°C, postpone vaccination until the 
condition is resolved. 
d. Perform a physical examination, including but not limited to examination of the head 
(including ear, nose, and throat), neck, thorax (including heart and 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) 
If subject satisfies all eligibility criteria, call the interactive response technology (IRT) for 
randomization (at least allocation of subject number and dose number of vaccine). 
4) 
Obtain 4-milliliter (mL) of blood sample (BL0001) (see Section 7.1 for detailed instructions 
regarding the handling of blood samples). 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. 
The unblinded qualified study staff member will: 
5) 
Administer the appropriate study vaccine IM in the anterolateral area of the thigh or the 
deltoid muscle of the upper arm according to country specific recommendations and 
according to the study group listed below: 
Group 1 = MenACYW conjugate vaccine 
Group 2 = Nimenrix® 
Group 3 = NeisVac-C® 
and record the date, the site, side, the route of injection, and the dose number. Affix the 
vaccine label(s) into the subject’s source documents. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 39 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 40 of 90 
The Investigator or delegate will: 
6) 
Keep the subject under observation for 30 minutes and record any AE in the source 
document. 
7) 
Give the subject’s parent/legally acceptable representative: 
- 
a DC, to record any injection site reactions and systemic adverse events, together 
with instructions for its completion, including explanations on the definition and use 
of intensity scales for collection of AEs 
- 
a thermometer, for temperature measurement 
- 
and a ruler, to measure the size of any injection site reaction 
and go over the instructions for their use. 
8) 
Remind the subject’s parent/legally acceptable representative to expect a telephone call (TC) 
8 days (+2 days) after V01 (D0) and to bring back the DC when they return for V02 (D30 + 
14 days). 
9) 
Remind the subject’s parent/legally acceptable representative to notify the site in case of an 
SAE. 
10) Complete the source documents and relevant eCRF pages for this visit. 
5.1.4.2 
TC (8 days [+2 days] after Visit 1) 
Note: If D8 falls on a weekend or a holiday, the TC may be made on the following business day. 
The Investigator or an authorized designee will: 
1) 
Record relevant information concerning the subject’s health status on the telephone contact 
form or subject’s source document. If an SAE occurred, follow the instructions in Section 10 
for reporting it. 
2) 
Remind the subject’s parent/legally acceptable representative to do the following: 
• 
Complete the D0 to D7 pages of the DC 
• 
Complete the remaining pages of the DC, and bring them on V02 (D30 + 14 days) 
• 
Notify the site in case of an SAE 
3) 
Confirm the date of the next visit. 
5.1.4.3 
V02 (D30 [+14 days] after V01): Collection of Safety Information and Blood 
Sample 
The Investigator or delegate will: 
1) Review and collect the pages of the DC (for clarity, content, and completeness) with the 
subject’s 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 40 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 41 of 90 
2) Review temporary contraindications for V02 blood sampling (see Section 5.2.8). 
3) Obtain the second 4 mL blood sample (BL0002) (see Section 7.1 for detailed instructions 
regarding the handling of blood samples). 
Note: If the attempt to collect blood is unsuccessful, the subject should be given the 
opportunity for another attempt within the protocol time windows. If ultimately a blood 
sample cannot be obtained, the reason will be recorded in the electronic CRB. 
4) Complete the source documents, relevant CRF pages including the end of study record. 
5) If the subject’s parent/legally acceptable representative does not return for V02 and the DC is 
not received at the site, site personnel will contact the subject’s parent/legally acceptable 
representative by telephone. During the TC, the subject’s legally acceptable representative 
will be reminded to return the DC to the study site. TCs will be documented on the 
Telephone/Interview Record. If the study personnel are unable to contact the subject’s 
parent/legally acceptable representative with 3 attempts, the study personnel will follow 
instructions given in Section 5.2.10. 
Follow-up of Subjects with Related AEs or with AEs That Led to Study/Discontinuation: 
Unless a subject or subject’s parent/legally acceptable representative refuses further contact, each 
subject who experiences an AE (whether serious or non-serious) during the study must be 
followed until the condition resolves, becomes stable, or becomes chronic (even after the end of 
the subject’s participation in the study) if either of the following is true: 
• The AE is considered by the Investigator to be related to the product administered 
• The AE caused the discontinuation of the subject from the study. 
5.1.5 
Planned Study Calendar 
The following dates are approximate. The actual dates may differ as, for example, the study will 
not start until all the appropriate regulatory and ethical approvals have been obtained. 
Planned study period - FVFS (first visit, first subject) to LCLS (last contact, last subject): 
Q3 2019 to Q4 2020 
Planned inclusion period - FVFS to FVLS (first visit, last subject): Q3 2019 to Q4 2020 
Planned vaccination period: Q3 2019 to Q4 2020 
Planned end of study: Q4 2020 
Planned date of final clinical study report: Q2 2021 
5.2 
Enrollment and Retention of Study Population 
5.2.1 
Recruitment Procedures 
Before the start of the trial, the Investigator or sub-investigator may contact the parents/legally 
acceptable representatives of an appropriate pool of potential subjects and invite them to 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 41 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 42 of 90 
participate in the trial. The site will ensure that any advertisements used to recruit subjects (e.g. 
letters, pamphlets, posters) are submitted to Sanofi Pasteur before submission to the IEC/IRB for 
approval. 
In addition, a parent who brings a child to the trial site for a routine visit may be invited to enroll 
the subject in the trial, if eligible. Subjects may also be recruited from the general population. 
Recruitment procedures and materials will be submitted to the IEC/IRB for approval before 
implementation. Recruitment will be conducted in a competitive manner. 
5.2.2 
Informed Consent Procedures 
Informed consent is the process by which a subject or an appropriate and legally acceptable 
representative voluntarily confirms his or her willingness to 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 or 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. 
Rationale for Including Subjects Unable to Give Consent: 
MEQ00065 is a study to be conducted in toddlers 12 to 23 months of age to obtain safety and 
immunogenicity data in this age group (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. 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 42 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 43 of 90 
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 12 to 23 months on the day of the first study visita. 
2) ICF has been signed and dated by the parent(s) / legally acceptable representative(s). 
3) Subject and parent / legally acceptable representative are able to attend all scheduled visits 
and to comply with all trial procedures. 
4) Covered by health insurance if required by local regulations. 
5.2.5 
Exclusion Criteria 
An individual fulfilling any of the following criteria is to be excluded from study enrollment: 
1) Participation in the 4 weeks (28 days) preceding the study vaccination or planned participation 
during the present study period in another clinical study investigating a vaccine, drug, medical 
device, or medical procedure. 
2) Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned 
receipt of any vaccine prior to Visit 2 except for influenza vaccination, which may be received 
at least 2 weeks before or after study vaccines. This exception includes monovalent pandemic 
influenza vaccines and multivalent influenza vaccines. 
3) Receipt of immune globulins, blood or blood-derived products in the past 3 months. 
4) Previous vaccination against meningococcal disease with either the trial vaccine or another 
vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine 
containing serogroups A, C, W, or Y; or meningococcal B vaccine). 
5) Known or suspected congenital or acquired immunodeficiency; or receipt of 
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within 
the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or 
equivalent for more than 2 consecutive weeks within the past 3 months). 
6) History of meningococcal infection, confirmed either clinically, serologically, or 
microbiologically. 
7) At high risk for meningococcal infection during the trial (specifically, but not limited to, 
subjects with persistent complement deficiency, with anatomic or functional asplenia, or 
subjects travelling to countries with high endemic or epidemic disease). 
                                                 
a  “12 to 23 months” means from the 12th month after birth to the day before the 24th month after birth. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 43 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 44 of 90 
8) Known systemic hypersensitivity to any of the vaccine components, or history of a life-
threatening reaction to the vaccines used in the study or to a vaccine containing any of the 
same substancesa. 
9) Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing 
vaccine. 
10) Personal history of Guillain-Barré syndrome (GBS). 
11) Thrombocytopenia, as reported by the parent/ legally acceptable representative or suspected 
thrombocytopenia contraindicating intramuscular vaccination in the Investigator’s opinion. 
12) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating intramuscular vaccination in the Investigator’s opinion. 
13) Chronic illnessb that, in the opinion of the Investigator, is at a stage where it might interfere 
with trial conduct or completion. 
14) 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. 
15) Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw. 
16) Identified as a natural or adopted child of the Investigator or employee with direct 
involvement in the proposed study. 
According to local regulations, if the subject has a primary physician who is not the Investigator, 
the site may contact this physician to inform him/her of the subject’s participation in the study. 
5.2.6 
Medical History 
Prior to enrollment, subjects will be assessed for pre-existing conditions and illnesses, both past 
and ongoing. Any such conditions will be documented in the source document. Significant 
(clinically relevant) medical history (reported as diagnosis) including conditions/illnesses for 
which the subject is or has been followed by a physician or conditions/illnesses that could resume 
during the course of the study or lead to an SAE or to a repetitive outpatient care will be collected 
in the case report book (CRB). The significant medical history section of the CRB contains a core 
list of body systems and disorders that could be used to prompt comprehensive reporting, as well 
as space for the reporting of specific conditions and illnesses. 
For each condition, the data collected will be limited to: 
• Diagnosis (this is preferable to reporting signs and symptoms) 
• Presence or absence of the condition at enrollment 
The reporting of signs and symptoms in lieu of a diagnosis is strongly discouraged. 
                                                 
a  The components of the vaccines used in the study are listed in Section 6.1 and in the Investigator’s Brochure. 
b  Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, autoimmune disorders, 
diabetes, psychomotor diseases, and known congenital or genetic diseases. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 44 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 45 of 90 
Dates, medications, and body systems are not to be recorded, and the information collected will not 
be coded. Its purpose is to assist in the later interpretation of safety data collected during the 
study. 
5.2.7 
Contraindications for Subsequent Vaccinations 
Not applicable since only 1 dose of vaccine will be administered in this study. 
5.2.8 
Temporary Contraindications for Visit 2 Blood Sample 
Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the second 
blood draw, the Investigator will postpone that blood draw until it has been 3 days since the 
subject last received oral or injectable antibiotic therapy. Postponement must still be within the 
timeframe for blood draw (30 to 44 days after vaccination at D0). If postponement would result in 
the sample collection falling outside of the appropriate timeframe, the blood sample should be 
collected without postponement, and it should be documented appropriately that the sample was 
taken less than 3 days after stopping antibiotic treatment. 
5.2.9 
Conditions for Withdrawal  
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/ 
the subject’s parent/legally acceptable representative permission (withdrawal) 
• At the request of the subject’s parent/legally acceptable representative (drop-out) 
The reason for a withdrawal or drop-out should be clearly documented in the source documents 
and in the CRB.  
The Investigator must determine whether voluntary withdrawal is due to safety concerns (in 
which case, the reason for discontinuation will be noted as “Adverse Event”) or for another 
reason. 
Withdrawn subjects will not be replaced, with the following exception: As a consequence of the 
COVID-19 hold, approximately 30 subjects were identified to be excluded from the PPAS as they 
were unable to complete their follow-up visit as planned in the protocol. To maintain the planned 
study power and the randomization ratio, approximately 30 additional subjects are planned to be 
enrolled. 
In the event of any new unexpected situations impacting study visits, the sample size might be 
increased to replace subjects excluded from the PPAS. 
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 TCs and certified mail) should be undertaken to locate or recall them, or at 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 45 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 46 of 90 
least to determine their health status while fully respecting their rights. These efforts should be 
documented 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. 
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 parent/legally acceptable representative cannot be found or 
contacted in spite of efforts to locate him/her before the date of their child planned 
last visit, as outlined in Section 5.2.10. The certified letter was sent by the 
Investigator and returned unsigned, and the parent/legally acceptable 
representative did not give any other news and did not come to any following visit. 
Protocol Deviation 
To be used: 
• 
In case of significant non-compliance with the protocol (e.g., deviation of the 
Inclusion / Exclusion criteria, non-compliance with time windows, blood 
sampling or vaccination refusal, missed injection/treatment, or error in the 
vaccine/treatment administration) 
• 
If the subject experiences a definitive contraindication that is not an SAE or 
AE 
• 
If the parent/legally acceptable representative signed the certified letter sent by 
the Investigator but did not give any other news and did not come to any 
following visit 
Withdrawal by 
Subject or Parent / 
Legally Acceptable 
Representative 
To be used: 
• 
When the parent/legally acceptable representative indicated unwillingness to 
continue in the study 
• 
When the parent/legally acceptable representative made the decision to 
discontinue his/her child participation in the study for any personal reason 
other than an SAE/AE (e.g., parent/legally acceptable representative is 
relocating, inform consent withdrawal, etc.) 
5.2.12 Follow-up of Discontinuations 
The site should complete all scheduled safety follow-ups and contact the parent/legally acceptable 
representative of subject who has prematurely terminated the study because of an AE or a 
protocol deviation.  
For subjects where the reason for early termination was lost to follow-up or if the subject’s 
parent/legally acceptable representative withdrew their 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 46 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 47 of 90 
5.3 
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 (e.g., 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 / non-substantial 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. In case of non-substantial amendment, IECs / IRBs have to 
be notified. 
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. 
5.3.1 
Amendment Justification 
Amendment 1 
Due to the COVID-19 pandemic, subject enrollment was put on hold on 17 March 2020. 
As this is a one-dose schedule, no ongoing participants were expected to receive further 
vaccination. The decision for each individual participant to remain in the study was to be made on 
a case by case basis based on the investigator’s best medical judgement and the evolving situation 
at each site. Participants who could not be followed up as per protocol or could be followed up but 
out of the protocol defined window period, were to be kept in the study till the end of the study 
period and not automatically withdrawn from the study. Safety follow up could be accomplished 
via phone contact if an office or home visit was not possible. 
These measures were taken by the Sponsor to ensure the well-being of subjects (ie, to limit 
exposure to COVID-19) and were implemented without IRB/EC approval, as per national and 
international guidance. However, IRB/EC and health authorities were informed promptly about 
the measures reported in the current amendment. 
After ensuring subject safety, and with national health authority approval, enrollment will resume.  
In the current amendment, the Sponsor will increase the sample size of the study to replace 
subjects excluded from the PPAS (see Section 12.5) to ensure the adequate power to fulfill the 
endpoints (see Section 9). 
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 applicable regulatory 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 47 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 48 of 90 
requirements. The Investigator shall promptly inform the study subject’s parents/legally 
acceptable representatives and should assure appropriate subject therapy and/or follow-up. 
6 
Products Administered 
6.1 
Identity of the Investigational Products  
6.1.1 
Identity of Study Product 
MenACYW conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) 
Tetanus Toxoid Conjugate Vaccine (Sanofi Pasteur Inc., Swiftwater, PA, USA) 
Form:  
 
Liquid solution 
Dose:  
 
0.5 mL 
Route: 
 
IM 
Batch number:  
To be determined 
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 
6.1.1.1 
Preparation and Administration 
MenACYW conjugate vaccine is supplied in single-dose (0.5 mL) vials. 
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.  
The rubber stopper should not be removed from any of the vaccine vials. 
The site of IM injection should be prepared with a suitable antiseptic prior to administration of 
1 dose (0.5 mL) of MenACYW conjugate vaccine. After vaccine administration, the used syringe 
and needle will be disposed of in accordance with currently established guidelines. 
                                                 
a  Tetanus toxoid protein quantity is approximate and dependent on the polysaccharide-to-protein ratio for the 
conjugates used in each formulation. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 48 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 49 of 90 
Subjects must be kept under observation for 30 minutes after vaccination to ensure their safety, 
and any reactions during this period will be documented in the CRB. Appropriate medical 
equipment and emergency medications, including epinephrine (1:1000), must be available on site 
in the event of an anaphylactic, vasovagal, or other immediate allergic reaction. 
6.1.1.2 
Dose Selection and Timing 
All subjects in Group 1 will receive 1 dose of MenACYW conjugate vaccine at V01 (D0). 
6.1.2 
Identity of the Control Products 
6.1.2.1 
Nimenrix® 
Nimenrix®: Meningococcal polysaccharide groups A, C, W-135 and Y conjugate vaccine (Pfizer 
Limited, Sandwich, UK) 
Form:  
 
Powder in a vial and solvent, for reconstitution, in a pre-filled syringe 
Dose:   
 
0.5 mL 
Route:  
 
IM 
Batch number:  
Commercial lot to be supplied by Sponsor 
6.1.2.1.1 
Composition 
Each 0.5 mL dose of Nimenrix® is formulated to contain: 
N meningitidis polysaccharides: 
Serogroup A ............................................................................................... 5 µg 
Serogroup C ............................................................................................... 5 µg 
Serogroup W-135 ....................................................................................... 5 µg 
Serogroup Y ............................................................................................... 5 µg 
Tetanus toxoid protein carrier ............................................................................. 44 µg 
Excipients: 
 
 
In the powder: Sucrose, Trometamol 
 
In the solvent: Sodium chloride, Water for injections 
6.1.2.1.2 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. The supplied solvent is used to reconstitute the powder in 
the vial. 
After reconstitution, a single dose of Nimenrix® should be administered by IM injection. See the 
Nimenrix® EU SmPC for additional information on preparation of the reconstituted dose (22). 
The procedures for preparing and administering this control product are the same as those 
described for the study product in Section 6.1.1.1. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 49 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 50 of 90 
6.1.2.1.3 Dose Selection and Timing 
All subjects in Group 2 will receive 1 dose of Nimenrix® vaccine on V01 (D0). 
6.1.2.2 
NeisVac-C® 
NeisVac-C®: Meningococcal Group C Polysaccharide Conjugate Vaccine Adsorbed (Pfizer 
Limited, Sandwich, UK) 
Form:  
 
Suspension for injection in a pre-filled syringe 
Dose:   
 
0.5 mL 
Route:  
 
IM 
Batch number:  
Commercial lot to be supplied by Sponsor 
6.1.2.2.1 Composition 
Each 0.5 mL dose of NeisVac-C® vaccine is formulated to contain: 
Neisseria meningitidis serogroup C (strain C11) polysaccharide (de-O-acetylated). .... 10 µg 
conjugated to tetanus toxoid ........................................................................................... 10-20 µg 
adsorbed on aluminium hydroxide, hydrated ................................................................. 0.5 mg Al3+ 
Excipients: Sodium chloride, Water for injections 
6.1.2.2.2 Preparation and Administration 
NeisVac-C® is supplied as a suspension for injection in a pre-filled syringe. 
A single dose of NeisVac-C® should be administered by IM injection. See the NeisVac-C® EU 
SmPC for additional information (21). 
The procedures for preparing and administering this control product are the same as those 
described for the study product in Section 6.1.1.1. 
6.1.2.2.3 Dose Selection and Timing 
All subjects in Group 3 will receive 1 dose of NeisVac-C® vaccine on V01 (D0). 
6.2 
Identity of Other Product(s) 
Not applicable. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 50 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 51 of 90 
6.3 
Product Logistics 
6.3.1 
Labeling and Packaging 
MenACYW conjugate vaccine will be supplied in single-dose vials, labeled and packaged with 
the required information according to national regulations. 
Commercial lots of Nimenrix® and NeisVac-C® vaccines will be supplied by Sanofi Pasteur Inc. and 
labeled with the required information according to national regulations. 
6.3.2 
Product Shipment, Storage, and Accountability 
6.3.2.1 
Product Shipment 
The Clinical Logistics Coordinator or designee 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. 
6.3.2.3 
Product Accountability 
The person in charge of product management at the site will maintain records of product delivery 
to the study site, product inventory at the site, the dose given to each subject, and the disposal of 
or return to the Sponsor of unused doses. 
The necessary information on the product labels is to be entered in the source document and the 
CRB. If applicable, information may also be entered in 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 51 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 52 of 90 
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 syringe/vial broke or particulate matter was 
observed in the syringe/vial), the site personnel must follow the instructions given in the 
Operating Guidelines. 
6.3.4 
Disposal of Unused Products  
Unused or wasted products will be either disposed of or 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 
The MEQ00065 study is modified double-blind, which means that both the subject and the 
Investigator remain unaware of the treatment assignments throughout the study. 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 will also 
remain blinded to treatment assignments throughout the study until database lock. 
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 ICH E2Aa. 
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.  
                                                 
a All unexpected and related SAEs submitted to European Union competent authorities must be unblinded. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 52 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 53 of 90 
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 signs the ICF will be randomly assigned to Groups 1 through 3 
in a 1:1:1 ratio, such that Groups 1 to 3 will have approximately 235 subjects each.  
Unblinded vaccine administrator will connect to the IRT, enter the identification and security 
information, and confirm a minimal amount of data in response to IRT prompts. The IRT will 
then provide at least the subject number and vaccine dose number. The full detailed procedures 
for group and dose 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 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 246000100005 is the fifth subject enrolled in Center Number 1 in Finland (246 being the 
Finland country code). 
Subject 208001400006 is the sixth subject enrolled in Center Number 14 in Denmark (208 being 
the Denmark country code). 
Subject 276002300005 is the fifth subject enrolled in Center Number 23 in Germany (276 being 
the Germany country code). 
Subject numbers should not be reassigned for any reason. The randomization lists of subjects will 
be stratified by Center. The randomization codes will be kept securely in the IRT. 
6.6 
Treatment Compliance 
The following measures will ensure that the vaccine doses administered comply with those planned, 
and that any non-compliance is documented so that it can be accounted for in the data analyses: 
• All vaccinations will be administered by qualified study personnel 
• The person in charge of product management at the site will maintain accountability records 
of product delivery to the study site, product inventory at the site, dose(s) given to each 
subject, and the disposal of unused or wasted doses 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 53 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 54 of 90 
6.7 
Concomitant Medications and Other Therapies 
At the time of enrollment, ongoing medications and other therapies (eg, blood products) should be 
recorded in the source document. All new medications prescribed for new medical conditions / 
AEs during study participation should also be recorded in the source document.  
Documentation in the CRB of ongoing concomitant medication(s) will be limited to specific 
categories of medication(s) (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.  
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.  
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: Reportable 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 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.  
• Category 2: Reportable medications with potential impact on immune response of the 
study vaccines and used to define the PPAS. For example: 
a. Influenza and other non-study vaccines: Influenza vaccine in the 2 weeks (14 days) 
preceding the trial vaccination up to the last blood draw and any other vaccines (other 
than the study vaccine) in the 4 weeks preceding the trial vaccination up to the last 
blood draw 
b. Immune globulins, blood or blood-derived products: used in the 3 months preceding 
the first blood draw and up to the last blood draw 
c. 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. 
Category 2 medications will be reported in the CRB according to the collection period detailed 
above up to the last blood draw. 
• Category 3: Systemic (Oral or injectable) antibiotics, as they may interfere with bioassays 
used for antibody testing when taken before a blood draw.  
Category 3 medications will be reported in the CRB for the period of 3 days (72 hours) before 
each blood draw. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 54 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 55 of 90 
Medications should be collected as concomitant if there is a reasonable possibility that they may 
still impact on safety and/or immune assessment, even when the treatment was stopped before 
collection (eg medications characterized by long half-life, dose accumulation, or which might 
cause delayed adverse reactions). 
Additionally, given the COVID-19 pandemic and the possible use of medications with or without 
medical prescription, medications that interfere with the immune response should be actively 
evaluated.  
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 prophylactic* 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 (medication(s) prescribed for preventing AE occurrence (e.g. 
paracetamol to reduce the risk of fever)) 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.  
7 
Management of Samples 
Blood samples for the assessment of antibody responses will be collected at Visits V01 and V02. 
See the Table of Study Procedures and Section 5.1.3 for details of the sampling schedule. 
7.1 
Sample Collection 
At Visits V01 and V02, 4 mL of blood will be collected by staff experienced in blood collection 
in a pediatric population in tubes provided by or recommended by the Sponsor. Immediately prior 
to the blood draw, the staff member performing the procedure will verify the subject’s identity as 
well as the assigned subject’s number and sampling stage on the pre-printed label and will attach 
the label to the tube. When vaccination and blood sample collection occur at the same visit and 
vaccine is given only in one of the arms, blood is to be taken from the limb opposite to the one 
that will be used for vaccination, if possible. 
If attempts to obtain the first blood draw are unsuccessful (after reasonable attempts as per local 
regulations) then V01 can be rescheduled to a later date at which point inclusion/exclusion criteria 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 55 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 56 of 90 
must be re-validated. If during the rescheduled visit the first blood draw cannot be obtained, the 
subject will be withdrawn from the study without being vaccinated. 
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. 
After the blood draw, gently invert the tube several times. Then allow the tube to clot by standing 
it vertically at room temperature for 60 to 120 minutes (no more and no less) prior to centrifuging. 
The maximum amount of time the blood can stand at room temperature in the upright position is 
2 hours.  If the time between blood sampling and centrifugation is longer than 2 hours, the 
vacutainer should be refrigerated at 2°C to 8°C after the period of clotting at room temperature. 
The sample must be centrifuged within 24 hours from the initial blood draw time. 
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 laboratories 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 Class 6.2 
specifications and the International Air Transport Association (IATA) 602 packaging instructions. 
Samples will be shipped to GCI at Sanofi Pasteur. The address is provided in the Operating 
Guidelines. 
7.4 
Future Use of Stored Serum Samples for Research 
Any unused part of the serum samples will be securely stored at the Sanofi Pasteur serology 
laboratory (GCI) for at least 5 years after the last license approval in the relevant market areas has 
been obtained for the vaccine being tested. 
Subjects’ parents/legally acceptable representatives will be asked to indicate in the ICF whether 
they will permit the future use of any unused stored serum samples for other tests. If they refuse 
permission, the samples will not be used for any testing other than that directly related to this 
study. If they agree to this use, they will not be paid for giving permission. Anonymity of samples 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 56 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 57 of 90 
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.  
9 
Endpoints and Assessment Methods 
9.1 
Primary Endpoints and Assessment Methods 
9.1.1 
Immunogenicity 
9.1.1.1 
Immunogenicity Endpoints 
The primary endpoints for the evaluation of immunogenicity are: 
1) Antibody titers against meningococcal serogroup C measured by hSBA,30 days (+ 14 days) 
after vaccination: 
• ≥ 1:8, with MenACYW conjugate vaccine or Nimenrix® 
• With MenACYW conjugate vaccine or Nimenrix®  
2) Antibody titers against meningococcal serogroup C measured by rSBA, 30 days (+ 14 days) 
after vaccination: 
• 
≥ 1:8, with MenACYW conjugate vaccine or NeisVac-C®  
• 
With MenACYW conjugate vaccine or NeisVac-C® 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 57 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 58 of 90 
9.1.1.2 
Immunogenicity Assessment Methods  
All assays will be performed at GCI, Swiftwater, Pennsylvania (PA) or at a qualified contract 
laboratory for GCI unless otherwise stated. 
The assay method to be used is summarized below. Laboratory technicians conducting the 
immunogenicity assays will be blinded to the group to which each subject was assigned. 
Antibodies to meningococcal antigens (hSBA Method) 
Functional meningococcal antibody activity against serogroups A, C, Y, and W will be measured 
in 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 
Antibodies to Meningococcal Antigens (rSBA method) 
Functional meningococcal antibody activity against serogroups A, C, Y, and W will be measured 
in an SBA utilizing baby rabbit complement. 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, 10 microliters of the serum / complement / bacteria mixture is removed and added to a 
blood agar plate using the tilt method, and then incubated overnight at 37°C with 5% CO2. 
Bacterial colonies present on the blood agar plate are then counted. The bactericidal titer of each 
sample is expressed as the final reciprocal dilution yielding ≥ 50% killing as compared to the T60 
(average number of bacteria in each control well after incubation) colony-forming unit (CFU). To 
report a titer greater than 1:4, clear bactericidal activity must be noted and the next dilution must 
have a CFU count less than the calculated 20% T60. The LLOQ of the rSBA assay is a titer of 
1:4. 
9.1.2 
Safety 
There are no primary objectives for safety. 
9.1.3 
Efficacy 
No clinical efficacy data will be obtained in the study. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 58 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 59 of 90 
9.2 
Secondary Endpoints and Assessment Methods 
9.2.1 
Immunogenicity 
9.2.1.1 
Immunogenicity Endpoints 
The secondary endpoints for the evaluation of immunogenicity are: 
1) Antibody titers against meningococcal serogroup C measured by rSBA, 30 days (+ 14 days) 
after vaccination: 
• 
≥ 1:8, with MenACYW conjugate vaccine or Nimenrix® 
• 
With MenACYW conjugate vaccine or Nimenrix®  
2) Antibody titers against meningococcal serogroup C measured by hSBA, 30 days (+ 14 days) 
after vaccination: 
• 
≥ 1:8 with MenACYW conjugate vaccine or NeisVac-C®  
• 
With MenACYW conjugate vaccine or NeisVac-C® 
9.2.1.2 
Immunogenicity Assessment Methods 
The immunogenicity assessment methods for the secondary endpoints are the same as those 
presented in Section 9.1.1.2. 
9.2.2 
Safety 
There are no secondary objectives for safety. 
9.2.3 
Efficacy 
No clinical efficacy data will be obtained in the study. 
9.3 
Observational Endpoints and Assessment Methods 
9.3.1 
Immunogenicity 
9.3.1.1 
Immunogenicity Endpoints 
The observational endpoints for the evaluation of immunogenicity are: 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 59 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 60 of 90 
Observational Objective 1: 
Antibody titer against meningococcal serogroup C measured by hSBA in each group:  
• 
Assessed before and at 30 days (+ 14 days) after vaccination  
• 
≥ 1:4 and ≥ 1:8, assessed at 30 days (+ 14 days) after vaccination  
• 
Post-vaccination/pre-vaccination titers ratio  
• 
≥ 4-fold rise from pre-vaccination to post-vaccination 
• 
Vaccine seroresponse measured by hSBA, with seroresponse defined as: 
• For a subject with a pre-vaccination titer < 1:8, a post-vaccination titer ≥ 1:16 
• For a subject with a pre-vaccination titer ≥ 1:8, a post-vaccination titer at least 4-fold 
greater that the pre-vaccination titer. 
Observational Objective 2: 
Antibody titers against meningococcal serogroup C measured by rSBA in each group: 
• 
Assessed before and at 30 days (+ 14 days) after vaccination 
• 
≥ 1:8 and ≥ 1:128, assessed before and at 30 days (+ 14 days) after vaccination 
• 
Post-vaccination/pre-vaccination titers ratio 
• 
≥ 4-fold rise from pre-vaccination to post-vaccination  
• 
Vaccine seroresponse measured by rSBA, with seroresponse defined as: 
• For a subject with pre-vaccination titer < 1:8, a post-vaccination titer ≥ 1:32  
• For subjects with pre-vaccination titer ≥ 1:8, a post-vaccination titer at least 4-fold 
greater that the pre-vaccination titer. 
9.3.1.2 
Immunogenicity Assessment Methods 
The immunogenicity assessment methods for the observational endpoints are the same as those 
presented in Section 9.1.1.2. 
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: 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 60 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 61 of 90 
• 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. 
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 
                                                 
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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 61 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 62 of 90 
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 (AR): 
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) pre-listed in the protocol and CRB (eg, injection site 
tenderness occurring between D0 and D7 post-vaccination).  
By definition, solicited reactions are to be considered as being related to the product administered. 
For injectable vaccines, solicited reactions can either be solicited injection site reactions or 
solicited systemic reactions. 
The assessment of these reactions by the Investigator is mandatory. 
Unsolicited AE/AR: 
An unsolicited AE is an observed AE that does not fulfill the conditions pre-listed in the CRB in 
terms of diagnosis and/or onset window post-vaccination. For example, if headache between D0 
and D7 is a solicited reaction (ie, pre-listed in the protocol and CRB), then a headache starting on 
D7 is a solicited reaction, whereas headache starting on D8 post-vaccination is an unsolicited AE. 
Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. 
Injection Site Reaction: 
An injection site reaction is an AR at and around the injection site. Injection site reactions are 
commonly inflammatory reactions. They are considered to be related to the product administered. 
Systemic AE: 
Systemic AEs are all AEs that are not injection or administration site reactions. They therefore 
include systemic manifestations such as headache, fever, as well as localized or topical 
manifestations that are not associated with the vaccination or administration site (eg, erythema 
that is localized but that is not occurring at the injection site). 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 62 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 63 of 90 
Adverse Event of Special Interest (AESI): 
An AESI is one of scientific and medical concern specific to the Sponsor’s product or program, 
for which ongoing monitoring and rapid communication by the Investigator to the Sponsor can be 
appropriate. 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 safety profile of the 3 vaccines will be evaluated within 30 days (+ 14 days) after the 
vaccination. The following observational endpoints for the evaluation of safety are: 
• Unsolicited systemic AEs reported in the 30 minutes following the vaccination 
• Solicited (pre-listed in the subject diary and the electronic CRF) injection site reactions and 
systemic reactions starting anytime from D0 (Day of vaccination) through D7 after the 
vaccination 
• Unsolicited (spontaneously reported) non-serious AEs between D0 and D30  
• SAEs (including AESIs) throughout the study, ie, from D0 to Visit 2 
Depending on the items, the endpoints recorded or derived could include: 
Nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), time of onset, 
duration/number of days of occurrence, intensity, relationship to vaccine, whether the AE led to 
early termination from the study, seriousness criterion, outcome. 
9.3.2.3 
Safety Assessment Methods 
At V02, the Investigator or a delegate will perform a clinical or medically-driven physical 
examination, and will ask the subject’s parent(s)/legally acceptable representative(s) 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 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 63 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 64 of 90 
9.3.2.3.2 Reactogenicity (Solicited Reactions From Day 0 to Day 7 After Vaccination) 
After vaccination of subjects, subject’s parent(s)/legally acceptable representative(s) 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, Day 0 through Day 7) 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 subject’s parent(s)/legally acceptable representative(s) 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 
The subject’s parent(s)/legally acceptable representative(s) will be contacted by telephone 8 days 
(+ 2 days) after vaccination to remind them to record all safety information in the diary card. 
If the timing of the TC 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 9.1 and Table 9.2  present, respectively, the injection site reactions and systemic reactions 
that are pre-listed in the diary cards and CRB, together with the intensity scales. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 64 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 65 of 90 
Table 9.1: 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 
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, subject’s parent(s)/legally acceptable representative(s) 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 65 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 66 of 90 
Table 9.2: Solicited systemic reactions: terminology, definitions, and intensity scales 
CRB term 
(MedDRA 
lowest level 
term [LLT]) 
Fever 
Vomiting 
Crying 
abnormal  
Drowsiness Appetite lost 
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, subject’s parent(s)/legally acceptable representative(s) 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 66 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 67 of 90 
Important notes for the accurate assessment of temperature: 
Parent(s)/legally acceptable representative(s) are to measure body temperature once per day, 
preferably always at the same time. The optimal time for measurement is the evening, when body 
temperature is the highest. Temperature is also to be measured at the time of any apparent fever. 
The observed daily temperature and the route of measurement are to be recorded in the diary card, 
and the highest temperature will be recorded by the site in the CRB. The preferred route for this 
study is axillary. Pre-vaccination temperature is also systematically collected by the Investigator 
on the source document. Tympanic thermometers must not be used. 
9.3.2.3.3 Unsolicited Adverse Events 
In addition to recording solicited reactions, parent(s)/legally acceptable representative(s) will be 
instructed to record any other medical events that may occur during the 30 days (+ 14 days) 
period after vaccination. Space will be provided in the diary card for this purpose.  
Information on SAEs will be collected and assessed throughout the study, from D0 to Visit 2 (ie, 
between D0 and D30 (+ 14 days)). 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 9.1 and Table 9.2). 
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. 
                                                 
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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 67 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 68 of 90 
• 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 subject’s parent(s)/legally acceptable representative(s) to treat 
and/or manage any unsolicited AEs will be classified in the CRB using the following list (all 
applicable items should be checked): 
• None 
• Medication 
• Health care provider contact 
• Hospitalized 
• Whether the AE was serious 
For each SAE, the Investigator will complete all seriousness criteria that apply (outcome, 
elapsed time, and relationship to study procedures) 
• Whether the AE caused study discontinuation 
9.3.2.3.4 Adverse Events of Special Interest 
The following AEs will be captured as AESIs throughout the study: 
• Generalized seizures (febrile and non-febrile) (25, 26) 
• Kawasaki disease (27-29)  
• GBS (30) 
• Idiopathic thrombocytopenic purpura (ITP) (31, 32) 
 
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 studies. Due to their medical importance and to ensure 
expedited communication to the Sponsor, these AESIs are to be considered 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 68 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 69 of 90 
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 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. 
AEs 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) in order to provide comprehensive safety information. All relevant 
information must then be transcribed onto the AE CRF and the appropriate Safety 
Complementary Information CRFs. 
10.1 Initial Reporting by the Investigator 
SAEs 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 69 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 70 of 90 
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 PMSL and the RMO 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: +1 (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 RMO. If the RMO cannot 
be reached, the Investigator may contact the Local Medical Officer as described in the Operating 
Guidelines. 
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. 
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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 70 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 71 of 90 
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 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 
Directive 2001/EC article 17. The sponsor will ensure that all relevant information about 
suspected serious unexpected adverse reactions (SUSARs) that are fatal or life-threatening is 
recorded and reported as soon as possible to the competent authorities in all the Member States 
concerned, and to the Ethics Committee(s), and in any case no later than seven days after 
knowledge by the sponsor of such a case, and that relevant follow-up information is subsequently 
communicated within an additional eight days. All other SUSARs will be reported to the 
competent authorities concerned and to the Ethics Committee(s) concerned as soon as possible but 
within a maximum of fifteen days of first knowledge by the sponsor. 
The Sponsor’s RMO will also notify the Investigators in writing of the occurrence of any 
reportable SAEs.  
Once a year throughout the clinical trial, the sponsor will provide the Member States in whose 
territory the clinical trial is being conducted and the Ethics Committee(s) with a listing of all 
suspected serious adverse reactions which have occurred over this period and a report of the 
subjects’ safety. 
11 Data Collection and Management 
11.1 Data Collection and CRB Completion 
Individual diary cards, specifically designed for this study by the Sponsor and provided to the 
study sites, will be given to study participants for the recording of daily safety information as 
described in Section 9.3.2.3. These diary cards will include pre-listed terms and intensity scales 
(see Table 9.1 and Table 9.2) 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.  
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 71 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 72 of 90 
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.  
Participant race and ethnicity will be collected in this study because these characteristics may 
influence the immune response to the vaccine.  
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, Death, and Safety Complementary Information 
CRFs) will be integrated into the Sponsor’s centralized GPV database upon receipt of these forms 
and after a duplicate check. Each case will be assigned a case identification number. Each case 
will be assessed by the case management platform or its delegate before being reported to the 
relevant authorities as necessary. The assessment of related cases will be done in collaboration 
with the Global Safety Officer 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 72 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 73 of 90 
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 Datawarehouse. 
After integration of all corrections in the complete set of data, and after the SAE information 
available from CDM and the GPV Department has been reconciled, the database will be released for 
statistical analysis. 
11.3 Data Review 
A 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 on a blinded manner. Periodic safety data review will be performed by the Sponsor’s 
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. 
An SAP will be written and peer reviewed before any analyses. In accordance with the protocol, 
the SAP will describe all analyses to be performed under the responsibility of the Sponsor and all 
the conventions to be taken. 
12.1.1 Hypotheses and Statistical Methods for Primary Objectives 
12.1.1.1 Hypotheses 
12.1.1.2 Statistical Methods 
The immunogenicity of MenACYW conjugate vaccine serogroup C will be compared to that of 
Nimenrix® vaccine and to that of NeisVac-C® vaccine using sequential testing approaches. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 73 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 74 of 90 
Non-Inferiority 
A non-inferiority testing approach will be used to compare post-vaccination (ie, 30 days after the 
vaccination) seroprotection rates and GMTs of MenACYW conjugate vaccine to that of 
Nimenrix® and NeisVac-C®, using a two-sided 97.5% Confidence Interval (CI) with the following 
hypotheses: 
For seroprotection rates: 
𝐻𝐻0 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶≤−0.1  
𝐻𝐻1 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> −0.1  
Or 
For GMTs 
𝐻𝐻0 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶≤1/𝛿𝛿  
𝐻𝐻1 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/ 𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> 1/𝛿𝛿 
with: 
• Comparator: Nimenrix® or NeisVac-C® 
• π: seroprotection rates 
• δ: non-inferiority margin set at 1.5 
Superiority 
If the non-inferiority testing succeeds then a superiority approach will be used to compare post-
vaccination (ie, 30 days after the vaccination) seroprotection rates and/or GMTs of  MenACYW 
conjugate vaccine to that of Nimenrix® and NeisVac-C®, using a two-sided 97.5% CI with the 
following hypotheses: 
For seroprotection rates 
𝐻𝐻0 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶≤0  
𝐻𝐻1 : 𝜋𝜋MenACYW −𝜋𝜋𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> 0  
Or 
For GMTs 
𝐻𝐻0 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/ 𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶≤1  
𝐻𝐻1 : 𝐺𝐺𝐺𝐺𝐺𝐺MenACYW/ 𝐺𝐺𝐺𝐺𝐺𝐺𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶> 1 
with: 
• Comparator: Nimenrix® or NeisVac-C® 
• π: seroprotection rates 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 74 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 75 of 90 
For the seroprotection rates, the 97.5% CI of the difference in proportions will be computed using 
the Wilson Score method without continuity correction (Newcombe method).  
For the GMTs, the two-sided 97.5% CI of the ratio of post-vaccination GMTs will be calculated 
using normal approximation of log-transformed titers. 
The non-inferiority will be demonstrated against seroprotection rates if the null hypothesis is 
rejected, ie, if the lower limit of the two-sided 97.5% CI for the difference between the 
seroprotection rates is > -10%. 
The non-inferiority will be demonstrated against GMTs if the null hypothesis is rejected, ie, lower 
limit of the two-sided 97.5% CI for the ratio of GMTs > 1/1.5. 
The superiority will be demonstrated against seroprotection rates if the null hypothesis is rejected, 
ie, if the lower limit of the two-sided 97.5% CI for the difference between the seroprotection rates 
is > 0%. 
The superiority will be demonstrated against GMTs if the null hypothesis is rejected, ie, lower 
limit of the two-sided 97.5% CI for the ratio of GMTs > 1. 
The testing approach will be done in parallel and using a step by step approach for the 2 
comparators (3 steps): 
Nimenrix®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate against Nimenrix® 
measured by hSBA is demonstrated then the non-inferiority using hSBA GMTs will be tested. If 
the non-inferiority using hSBA GMTs of MenACYW conjugate against Nimenrix® is 
demonstrated then the superiority using hSBA GMTs will be tested. If the superiority using hSBA 
GMTs is demonstrated then the superiority using hSBA seroprotection rates will be tested. 
NeisVac-C®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate against NeisVac-C® 
measured by rSBA is demonstrated then the non-inferiority using rSBA GMTs will be tested. And 
if the non-inferiority using rSBA GMTs is demonstrated then the superiority using rSBA GMTs 
will be tested. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 75 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 76 of 90 
Figure 1: Sequential statistical testing approach for primary objectives 
 
To conclude, non-inferiority using seroprotection rates of MenACYW conjugate against 
Nimenrix® measured by hSBA or non-inferiority using seroprotection rates of MenACYW 
conjugate against NeisVac-C® measured by rSBA have to be demonstrated. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 76 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 77 of 90 
12.1.2 Hypotheses and Statistical Methods for Secondary Objectives 
12.1.2.1 Hypotheses 
12.1.2.2 Statistical Methods 
A similar statistical approach as for the primary objective will be used considering the rSBA 
antibody titers for Nimenrix® and hSBA antibody titers for NeisVac-C®. 
The testing approach will be done in parallel and using a step by step approach for the 2 
comparators (3 steps): 
Nimenrix®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate against Nimenrix® 
measured by rSBA is demonstrated then the non-inferiority using rSBA GMTs will be tested. If 
the non-inferiority using rSBA GMTs of MenACYW conjugate against Nimenrix® is 
demonstrated then the superiority using rSBA GMTs will be tested. 
NeisVac-C®: 
If the non-inferiority using seroprotection rates of MenACYW conjugate against NeisVac-C® 
measured by hSBA is demonstrated then the non-inferiority using hSBA GMTs will be tested. 
And if the non-inferiority using hSBA GMTs is demonstrated then the superiority using hSBA 
GMTs will be tested. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 77 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 78 of 90 
Figure 2: Sequential statistical testing approach for secondary objectives 
 
To conclude, non-inferiority using seroprotection rates of MenACYW conjugate vaccine against 
Nimenrix® measured by rSBA or non-inferiority using seroprotection rates of MenACYW 
conjugate vaccine against NeisVac-C® measured by hSBA have to be demonstrated. 
12.1.3 Statistical Methods for Observational Objectives 
For immunogenicity and safety observational objectives, the descriptive analyses will be done 
according to each vaccine group. The main parameters will be described with 95% CI using the 
exact binomial distribution (Clopper-Pearson method) for proportions and using the normal 
approximation of the Log10 concentrations/titers, followed by a back transformation for GMTs. 
The main parameters for observational objectives are: 
Immunogenicity Observational Objective 1: Antibody titer against meningococcal serogroup C by 
hSBA in each group:  
• GMTs before and at 30 days (+ 14 days) after vaccination  
• Percentage of subjects with antibody titers ≥ 1:4 and ≥ 1:8, assessed at baseline and 30 days 
(+14 days) after vaccination  
• Post-vaccination/pre-vaccination GMTR of titers  
• Percentage of subjects with a ≥ 4-fold rise from pre-vaccination to post-vaccination  
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 78 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 79 of 90 
• Vaccine seroresponse rate, with a seroresponse defined as: 
• For a subject with a pre-vaccination titer < 1:8, a post-vaccination titer ≥ 1:16 
• For a subject with a pre-vaccination titer ≥ 1:8, a post-vaccination titer at least 4-fold 
greater that the pre-vaccination titer 
Immunogenicity Observational Objective 2: Antibody titers against meningococcal serogroup C 
measured by rSBA  
• GMTs before and at 30 days (+ 14 days) after vaccination  
• Percentage of subjects with antibody titers ≥ 1:8 and ≥ 1:128, assessed before and at 30 days (+ 
14 days) after vaccination in each group 
• Post-vaccination/pre-vaccination GMTR of titers  
• Percentage of subjects with a ≥ 4-fold rise from pre-vaccination to post-vaccination  
• Vaccine seroresponse rate, with a seroresponse defined as: 
• For a subject with pre-vaccination titer < 1:8, a post-vaccination titer ≥ 1:32  
• For subjects with pre-vaccination titer ≥ 1:8, a post-vaccination titer at least 4-fold 
greater that the pre-vaccination titer 
Reverse cumulative distribution curves (RCDCs) figures will also be provided. 
Safety Observational Objective:  
The following parameters will be used in each group for the evaluation of safety: counts, percents 
and 95%Cis as well as number of AEs when considered of interest for each of the followings: 
• Unsolicited systemic AEs reported in the 30 minutes following the vaccination 
• Solicited injection site reactions and systemic reactions starting anytime from D0 through D7 
after the vaccination 
• Unsolicited non-serious AEs up to D30 after the vaccination 
• SAEs (including AESIs) up to D30 after the vaccination and throughout the study, ie, from D0 
to Visit 2 
Depending on the items, the parameters could be detailed according to: 
Nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), time of onset, 
duration/number of days of occurrence, intensity, relationship to vaccine, whether the AE led to 
early termination from the study, seriousness criterion, outcome. 
12.2 Analysis Sets 
Four main analysis sets will be used in the study: the full analysis set (FAS), 2 per protocol 
analysis sets (PPAS) and the safety analysis set (SafAS). 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 79 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 80 of 90 
12.2.1 Full Analysis Set 
The FAS is defined as the subset of randomized subjects who received one dose of study vaccine. 
Subjects will be analyzed according to the vaccine treatment group to which they were 
randomized. 
12.2.2 Per-Protocol Analysis Sets 
The PPAS are subsets of the FAS. The subjects presenting with at least one of the following 
relevant protocol deviations will be excluded from all PPAS: 
• Subject did not meet all protocol-specified inclusion criteria or met at least one of the 
protocol-specified exclusion criteria 
• Subject did not receive vaccine 
• Subject received a vaccine other than the one that he / she was randomized to receive 
• Preparation and/or administration of vaccine was not done as per-protocol 
• Subject did not provide post-dose serology sample at V02 in the proper time window (ie, D30 
+ 14 days) or the post-dose serology sample was not drawn 
• Subject received a protocol-prohibited therapy/medication/vaccine as defined in Section 6.7 
• Subject had other protocol violations or deviations 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 hSBA PPAS if: 
2.2) Subject post-dose serology sample at V02 did not produce a valid test result (ie, hSBA result 
is missing or not reported) 
And from the rSBA PPAS if: 
2.3) Subject post-dose serology sample at V02 did not produce a valid test result (ie, rSBA result 
is missing or not reported) 
Subjects will be analyzed according to the vaccine treatment group to which they were 
randomized. 
12.2.3 Safety Analysis Set 
The SafAS is defined as those subjects who have received one dose of study vaccine. All subjects 
will have their safety analyzed according to the vaccine they actually received.  
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 80 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 81 of 90 
12.2.4 Populations Used in Analyses 
The primary immunogenicity analyses will be performed on the hSBA PPAS for comparisons to 
Nimenrix® and on the rSBA PPAS for comparisons to NeisVac-C® and will be confirmed on the 
FAS.  
The secondary immunogenicity analyses will be performed on the rSBA PPAS for comparisons to 
Nimenrix® and on the hSBA PPAS for comparisons to NeisVac-C® and will be confirmed on the 
FAS.  
Observational objectives on immunogenicity will be performed on the PPASs and the FAS. 
Observational objectives on safety will be performed on the SafAS.  
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. 
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-dose computed value divided by baseline 
computed value 
If baseline or post-dose value is missing, then the seroconversion is missing.  
12.3.3 Efficacy 
No clinical efficacy data will be obtained in the study. 
12.4 Interim / Preliminary Analysis 
No interim or preliminary analyses are planned. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 81 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 82 of 90 
12.5 Determination of Sample Size and Power Calculation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 82 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 83 of 90 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
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 form, telephone contact logs, and worksheets. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 83 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 84 of 90 
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 or designee 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. 
If electronic medical records are to be used, 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 and Access to Subject Records 
Prior to initiation of the study, the Investigator will sign a fully executed confidentiality 
agreement with Sanofi Pasteur. 
Sanofi Pasteur personnel (or designates), the IECs / IRBs, and regulatory agencies, including the 
FDA, require direct access to all study records, and will treat these documents in a confidential 
manner. 
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. 
13.4 Monitoring, Auditing, and Archiving 
13.4.1 Monitoring  
Before the start of the study (i.e., before the inclusion of the first subject), 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 
                                                 
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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 84 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 85 of 90 
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 TCs and regular follow-up visits. The Investigator or delegate 
must be available for these visits, and must allow the Sponsor/delegate staff direct access to 
subject medical files and CRBs. During these visits, the Sponsor/delegate staff will: 
• Evaluate the quality of the study progress (adherence to protocol and any study-specific 
guidelines, quality of data collection and document completion, signature of consent forms, 
occurrence of SAEs, sample and product management, cold-chain monitoring, archiving). 
• Source-verify completed CRBs and any corresponding answered queries. 
• Determine the number of complete or ongoing issues identified at monitoring visits (e.g., 
protocol deviations, SAEs). Any identified problems will be discussed with the Investigator, 
and corrective or preventive actions will be determined, as appropriate. 
• After all protocol procedures have been completed and the data have been entered into the 
CRB, the Investigator must still be available to answer any queries forwarded by the Sponsor. 
All data-related queries must be completed prior to database lock. 
At the end of the study, a close-out Visit will be performed to ensure that: 
• The center has all the documents necessary for archiving 
• All samples have been shipped to the appropriate laboratories 
• All unused materials and products have been either destroyed or returned to the Sponsor 
13.4.2 Audits and Inspections 
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 and the study site shall retain and preserve 1 copy of the Study File containing 
the essential documents related to the study and records generated during the study (“Study File”) 
for the longer of the 2 following periods (“Retention Period”): 
• 25 years after the signature of the final study report or  
• Such longer period as required by applicable regulatory requirements 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 85 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 86 of 90 
If during the Retention Period, the study site is no longer able to retain the Study File due to 
exceptional circumstances (such as bankruptcy), the study site shall contact the Sponsor to 
organize the transfer of the Study File to the Sponsor’s designee at the Sponsor’s expense. 
Following the Retention Period, the Investigator and/or the study site are responsible to dispose of 
the Study File according to the applicable regulations. Patient medical records shall be retained in 
compliance with local regulations. 
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. 
13.5 Financial Contract and Insurance Coverage 
A Clinical Trial Agreement 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 time 
and travel costs required 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. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 86 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 87 of 90 
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. Plotkin's 
Vaccines. 7 ed. Philadelphia (PA): Elsevier; 2018. p. 619-43. 
2. 
American Academy of Pediatrics. Meningococcal Infections. In: Kimberlin D, Brady M, 
Jackson M, Long S editors. Red Book: 2018 Report of the Committee on Infectious Diseases: 
American Academy of Pediatrics; 2018. p. 550-61. 
3. 
Borrow R, Alarcón P, Carlos J, Caugant DA, Christensen H, Debbag R, et al. The Global 
Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease 
and the importance of herd protection. Expert review of vaccines. 2017;16(4):313-28. 
4. 
Harrison OB, Claus H, Jiang Y, Bennett JS, Bratcher HB, Jolley KA, et al. Description 
and nomenclature of Neisseria meningitidis capsule locus. Emerging infectious diseases. 
2013;19(4):566. 
5. 
Pollard AJ. Global epidemiology of meningococcal disease and vaccine efficacy. The 
Pediatric infectious disease journal. 2004;23(12):S274-S9. 
6. 
Kvalsvig A, Unsworth D. The immunopathogenesis of meningococcal disease. Journal of 
clinical pathology. 2003;56(6):417-22. 
7. 
Sidikou F, Djibo S, Taha MK, Alonso JM, Djibo A, Kairo KK, et al. Polymerase chain 
reaction assay and bacterial meningitis surveillance in remote areas, Niger. Emerging infectious 
diseases. 2003;9(11):1486. 
8. 
WHO. Meningococcal disease, serogroup W135 (update). Wkly Epidemiol Rec. 
2001;76(28):213-4. 
9. 
ECDC. Invasive meningococcal disease - Annual Epidemiological Report for 2016. 
Stockholm: European Centre for Disease Prevention and Control; 2018. Available from: 
https://ecdc.europa.eu/sites/portal/files/documents/AER_for_2016-invasive-meningococcal-
disease_1.pdf. 
10. 
Boisier P, Nicolas P, Djibo S, Taha M-K, Jeanne I, Maïnassara HB, et al. Meningococcal 
meningitis: unprecedented incidence of serogroup X—related cases in 2006 in Niger. Clinical 
Infectious Diseases. 2007;44(5):657-63. 
11. 
Rosenstein NE, Perkins BA, Stephens DS, Lefkowitz L, Cartter ML, Danila R, et al. The 
changing epidemiology of meningococcal disease in the United States, 1992–1996. Journal of 
Infectious Diseases. 1999;180(6):1894-901. 
12. 
Canadian Immunization Committee. Advice for consideration of quadrivalent (A, C, Y, 
W-135) meningococcal conjugate vaccine, for use by provinces and territories. Can Commun Dis 
Rep. 2010;26:1-35. 
13. 
Bröker M, Jacobsson S, Kuusi M, Pace D, Simões MJ, Skoczynska A, et al. 
Meningococcal serogroup Y emergence in Europe: update 2011. Human vaccines & 
immunotherapeutics. 2012;8(12):1907-11. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 87 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 88 of 90 
14. 
Cohn AC, MacNeil JR, Harrison LH, Hatcher C, Theodore J, Schmidt M, et al. Changes in 
Neisseria meningitidis disease epidemiology in the United States, 1998–2007: implications for 
prevention of meningococcal disease. Clinical Infectious Diseases. 2010;50(2):184-91. 
15. 
Statens Serum Institute. Meningococcal Disease 2016, EPI-NYT, week 49-2017. 
Copenhagen (Danemark): Statens Serum Institute; 2017. Available from: 
https://www.ssi.dk/Aktuelt/Nyhedsbreve/EPI-NYT/2017/Uge%2049%20-%202017.aspx. 
16. 
Centers for Disease Control Prevention. Update: Guillain-Barre syndrome among 
recipients of Menactra meningococcal conjugate vaccine--United States, June 2005-September 
2006. MMWR. 2006;55(41):1120. 
17. 
Velentgas P, Amato AA, Bohn RL, Arnold Chan K, Cochrane T, Funch DP, et al. Risk of 
Guillain–Barré syndrome after meningococcal conjugate vaccination. Pharmacoepidemiology and 
drug safety. 2012;21(12):1350-8. 
18. 
Institute of Medicine. Diphtheria toxoid, tetanus toxoid, and acellular pertussis-containing 
vaccines. In: Stratton KR, Ford A, Rusch E, Clayton EW editors. Adverse Events Associated with 
Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies 
Press; 2012. p. 525-89. 
19. 
Institute of Medicine. Diphtheria and tetanus toxoids. In: Stratton KR, Howe CJ, Johnston 
RB, Jr. editors. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on 
Causality. Washington, DC: The National Academies Press; 1994. p. 67-117. 
20. 
National Center for Immunization and Respiratory Diseases. General recommendations on 
immunization - recommendations of the Advisory Committee on Immunization Practices (ACIP). 
MMWR Recomm Rep. 2011;60(2):1-64. 
21. 
Pfizer Limited. NeisVac-C [Meningococcal Group C Polysaccharide Conjugate Vaccine 
Adsorbed] 0.5ml Suspension for injection in pre-filled syringe [Summary of Product 
Characteristics]. Sandwich, Kent (UK): Pfizer Limited; [last updated 08 May 2015]. Available 
from: https://www.medicines.org.uk/emc/product/1924/smpc. 
22. 
Pfizer Limited. Nimenrix® [Meningococcal group A, C, W-135 and Y conjugate vaccine] 
powder and solvent for solution for injection in pre-filled syringe [Summary of Product 
Characteristics]. Sandwich, Kent (UK): Pfizer Limited; [last updated 22 Oct 2018]. Available 
from: https://www.medicines.org.uk/emc/product/4118/smpc. 
23. 
ECDC. Vaccine schedule platform: European Centre for Disease Prevention and Control; 
2013 [last updated 23 Aug 2017]. Available from: https://ecdc.europa.eu/en/publications-
data/vaccine-schedule-platform. 
24. 
Knol MJ, de Melker HE, Berbers GAM, van Ravenhorst MB, Ruijs WLM, van Vliet JA, 
et al. Meningococcal disease in the Netherlands -Background information for the Health Council. 
Bilthoven (The Netherlands): National Institute for Public Health and the Environment -Ministry 
of Health, Welfare and Sport; 2017. Available from: 
https://www.rivm.nl/bibliotheek/rapporten/2017-0031.pdf. 
25. 
Bonhoeffer J, Menkes J, Gold MS, de Souza-Brito G, Fisher MC, Halsey N, et al. 
Generalized convulsive seizure as an adverse event following immunization: case definition and 
guidelines for data collection, analysis, and presentation. Vaccine. 2004;22(5-6):557-62. 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 88 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 89 of 90 
26. 
Marcy SM, Kohl KS, Dagan R, Nalin D, Blum M, Jones MC, et al. Fever as an adverse 
event following immunization: case definition and guidelines of data collection, analysis, and 
presentation. Vaccine. 2004;22(5-6):551-6. 
27. 
Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, 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. Circulation. 
2004;110(17):2747-71. 
28. 
CDC. Kawasaki Syndrome Case Report. Atlanta: Department of Health & Human 
Services - Centers for Disease Control and Prevention; 2003. Available from: 
https://www.cdc.gov/kawasaki/pdf/ks_case_report-fillable.pdf. 
29. 
Phuong LK, Bonetto C, Buttery J, Pernus YB, Chandler R, Goldenthal KL, et al. Kawasaki 
disease and immunisation: Standardised case definition & guidelines for data collection, analysis. 
Vaccine. 2016;34(51):6582-96. 
30. 
Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, et al. Guillain-Barre 
syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and 
presentation of immunization safety data. Vaccine. 2011;29(3):599-612. 
31. 
Wise RP, Bonhoeffer J, Beeler J, Donato H, Downie P, Matthews D, et al. 
Thrombocytopenia: case definition and guidelines for collection, analysis, and presentation of 
immunization safety data. Vaccine. 2007;25(31):5717-24. 
32. 
Chu YW, Korb J, Sakamoto KM. Idiopathic thrombocytopenic purpura. Pediatr Rev. 
2000;21(3):95-104. 
 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 89 of 91

Sanofi Pasteur 
MEQ00065 
395 – MenACYW Conjugate Vaccine 
 
Confidential/Proprietary Information 
Page 90 of 90 
15 Signature Page 
 
Sanofi Pasteur 
Confidential/Proprietary Information 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 90 of 91

Sanoli Pasteur
395 - MerÂCYW Conjugate Vaccine
MEQ0006s
Protocol Version 4.0
Sponsor Signature
I cont-rrm that this protocol (version 4.0 dated 15 May 2020) is in accordance with applicabie
regulations and Good Clinical Practice.
Function
Name
Date
Signature
Sponsor's Responsible
Medical OIficer
Project Manager and
Study Leâder
Sanofi Pasteur 
 
 
Confidential/Proprietary Information 
               
 
MEQ00065
Protocol Version 4.0
395 – MenACYW Conjugate Vaccine
Page 91 of 91