Safety and Immunogenicity of a Single Dose of MenACYW Conjugate Vaccine at Least 3 Years Following Initial Vaccination With Either Menomune® Vaccine or MenACYW Conjugate Vaccine in Older Adults
Phase: PHASE3
Conditions: Meningococcal Infection (Healthy Volunteers)
Sponsor: Sanofi Pasteur, a Sanofi Company

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Safety and Immunogenicity of a Single Dose of MenACYW 
Conjugate Vaccine at Least 3 Years Following Initial 
Vaccination With Either Menomune® Vaccine or MenACYW 
Conjugate Vaccine in Older Adults 
Phase III, randomized, open-label, multi-center study to evaluate the safety and 
immunogenicity of a single dose of MenACYW conjugate vaccine in subjects who received a 
dose of Menomune® vaccine or MenACYW conjugate vaccine ≥ 3 years previously, at 
≥ 56 years of age. Antibody persistence following the primary dose of either Menomune 
vaccine or MenACYW conjugate vaccine will also be evaluated. 
Clinical Study Protocol, Amendment 2 
Health Authority File Number: 
BB-IND #: 14171 
WHO Universal Trial Number (UTN): 
U1111-1217-2058 
Study Code: 
MEQ00066 
Development Phase: 
Phase III 
Sponsor: 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, USA 
Investigational Product: 
MenACYW conjugate vaccine: Meningococcal Polysaccharide  
(Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine 
Form/Route: 
Liquid Solution/Intramuscular (IM) 
Indication For This Study: 
Single dose of MenACYW conjugate vaccine for adults ≥ 56 years of age 3 years 
after the primary dose 
Manufacturer: 
Same as Sponsor 
Coordinating Investigator: 
To be determined 
Sponsor’s Responsible 
Medical Officer: 
Pharmacovigilance 
Global Safety Expert: 
Global Pharmacovigilance & Epidemiology, Sanofi Pasteur Inc. 
Clinical Trial Manager: 
Version and Date of the 
Protocol: 
Version 3.0 dated 11 September 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. 
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NCT04142242

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History of Protocol Versions 
 
Version* 
Date 
Comments 
1.0 
24 April 2019 
First version used in the study 
2.0 
09 April 2020 
Protocol Amendment 1 
* Version in bold font has been approved by the Independent Ethics Committee(s) (IEC[s]) / Institutional Review 
Board(s) (IRB[s]) and used in the study. 
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Table of Contents 
History of Protocol Versions ................................................................................................. 2 
List of Tables .......................................................................................................................... 8 
Synopsis .................................................................................................................................. 9 
Table of Study Procedures – Groups 1 and 2: Subjects Without a Day 6 Visit ............ 20 
Table of Study Procedures – Groups 1 and 2:  Subjects With a Day 6 Visit ................. 21 
Table of Study Procedures – Groups 3 and 4 ................................................................... 22 
Table of Study Procedures – Groups 5 and 6 ................................................................... 24 
List of Abbreviations ........................................................................................................... 25 
1 
Introduction ........................................................................................................... 27 
1.1 
Background ........................................................................................................... 27 
1.2 
Background of the Investigational Product ........................................................... 28 
1.3 
Potential Benefits and Risks ................................................................................. 29 
1.3.1 
Potential Benefits to Subjects ............................................................................. 29 
1.3.2 
Potential Risks to Subjects ................................................................................. 30 
1.4 
Rationale for the Study ......................................................................................... 31 
2 
Study Objectives .................................................................................................... 32 
2.1 
Primary Objective ................................................................................................. 32 
2.2 
Secondary Objectives ............................................................................................ 32 
2.3 
Observational Objectives ...................................................................................... 32 
3 
Investigators and Study Organization ................................................................. 33 
4 
Independent Ethics Committee/Institutional Review Board............................. 33 
5 
Investigational Plan ............................................................................................... 34 
5.1 
Description of the Overall Study Design and Plan ............................................... 34 
5.1.1 
Study Design ....................................................................................................... 34 
5.1.2 
Justification of the Study Design ........................................................................ 35 
5.1.3 
Study Plan ........................................................................................................... 36 
5.1.4 
Visit Procedures .................................................................................................. 37 
5.1.4.1 
Groups 1 and 2 ................................................................................................. 37 
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5.1.4.2 
Groups 3 and 4 ................................................................................................. 39 
5.1.4.3 
Groups 5 and 6 ................................................................................................. 42 
5.1.5 
Planned Study Calendar ...................................................................................... 43 
5.2 
Enrollment and Retention of Study Population .................................................... 43 
5.2.1 
Recruitment Procedures ...................................................................................... 43 
5.2.2 
Informed Consent Procedures ............................................................................ 44 
5.2.3 
Screening Criteria ............................................................................................... 44 
5.2.4 
Inclusion Criteria ................................................................................................ 44 
5.2.5 
Exclusion Criteria ............................................................................................... 44 
5.2.6 
Medical History .................................................................................................. 46 
5.2.7 
Contraindications for Subsequent Vaccinations ................................................. 47 
5.2.8 
Contraindication for Subsequent Blood Samples ............................................... 47 
5.2.9 
Conditions for Withdrawal ................................................................................. 47 
5.2.10 
Lost to Follow-up Procedures ............................................................................. 47 
5.2.11 
Classification of Subjects Who Discontinue the Study ...................................... 48 
5.2.12 
Follow-up of Discontinuations ........................................................................... 48 
5.2.13 
Follow-up and Reporting of Pregnancies ........................................................... 48 
5.3 
Safety Emergency Call ......................................................................................... 49 
5.4 
Modification of the Study and Protocol ................................................................ 49 
5.5 
Interruption of the Study ....................................................................................... 50 
6 
Vaccines Administered ......................................................................................... 50 
6.1 
Identity of the Investigational Product .................................................................. 50 
6.1.1 
Identity of Study Product .................................................................................... 50 
6.1.1.1 
Composition ..................................................................................................... 51 
6.1.1.2 
Preparation and Administration ....................................................................... 51 
6.1.1.3 
Dose Selection and Timing .............................................................................. 51 
6.1.2 
Identity of Control Product ................................................................................. 51 
6.2 
Identity of Other Products ..................................................................................... 51 
6.3 
Product Logistics .................................................................................................. 52 
6.3.1 
Labeling and Packaging ...................................................................................... 52 
6.3.2 
Product Shipment, Storage, and Accountability ................................................. 52 
6.3.2.1 
Product Shipment ............................................................................................. 52 
6.3.2.2 
Product Storage ................................................................................................ 52 
6.3.2.3 
Product Accountability ..................................................................................... 52 
6.3.3 
Replacement Doses ............................................................................................. 53 
6.3.4 
Disposal of Unused Products .............................................................................. 53 
6.3.5 
Recall of Products ............................................................................................... 53 
6.4 
Blinding and Code-breaking Procedures .............................................................. 53 
6.5 
Randomization and Allocation Procedures ........................................................... 53 
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6.6 
Treatment Compliance .......................................................................................... 54 
6.7 
Concomitant Medications and Other Therapies ................................................... 54 
7 
Management of Samples ....................................................................................... 55 
7.1 
Sample Collection ................................................................................................. 55 
7.2 
Sample Preparation ............................................................................................... 55 
7.3 
Sample Storage and Shipment .............................................................................. 56 
7.4 
Future Use of Stored Serum Samples for Research .............................................. 56 
8 
Clinical Supplies .................................................................................................... 56 
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 ............................................................. 57 
9.1.2 
Safety .................................................................................................................. 58 
9.1.3 
Efficacy ............................................................................................................... 58 
9.2 
Secondary Endpoints and Assessment Methods ................................................... 58 
9.2.1 
Immunogenicity .................................................................................................. 58 
9.2.1.1 
Immunogenicity Endpoints .............................................................................. 58 
9.2.1.2 
Immunogenicity Assessment Methods ............................................................. 58 
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 ............................................................. 59 
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 
9.3.2.3.2 
Reactogenicity (Solicited Reactions From Day 0 Through Day 7 After 
Vaccination) ................................................................................................... 64 
9.3.2.3.3 
Unsolicited Adverse Events ........................................................................... 68 
9.3.2.3.4 
Adverse Events of Special Interest ................................................................ 69 
9.3.2.3.5 
Assessment of Causality ................................................................................ 69 
9.3.3 
Efficacy ............................................................................................................... 70 
10 
Reporting of Serious Adverse Events .................................................................. 70 
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10.1 
Initial Reporting by the Investigator ..................................................................... 70 
10.2 
Follow-up Reporting by the Investigator .............................................................. 71 
10.3 
Reporting of SAEs Occurring After a Subject Has Completed the Study ............ 71 
10.4 
Assessment of Causality ....................................................................................... 71 
10.5 
Reporting SAEs to Health Authorities and IECs/IRBs ......................................... 72 
11 
Data Collection and Management ....................................................................... 72 
11.1 
Data Collection and CRF Completion .................................................................. 72 
11.2 
Data Management ................................................................................................. 73 
11.3 
Data Review .......................................................................................................... 74 
12 
Statistical Methods and Determination of Sample Size ..................................... 74 
12.1 
Statistical Methods ................................................................................................ 74 
12.1.1 
Hypothesis and Statistical Methods for the Primary Objective .......................... 74 
12.1.2 
Hypotheses and Statistical Methods for Secondary Objectives ......................... 75 
12.1.2.1 
Secondary Objective 1 ..................................................................................... 75 
12.1.2.2 
Secondary Objective 2 ..................................................................................... 75 
12.1.2.3 
Secondary Objective 3 ..................................................................................... 75 
12.1.3 
Statistical Methods for Observational Objectives .............................................. 76 
12.2 
Analysis Sets ......................................................................................................... 77 
12.2.1 
Stage I Analysis Sets .......................................................................................... 77 
12.2.1.1 
Full Analysis Sets ............................................................................................. 77 
12.2.1.2 
Per-Protocol Analysis Sets ............................................................................... 78 
12.2.1.2.1 
Day 30 Per-Protocol Analysis Set  Groups 1 and 2 ...................................... 78 
12.2.1.2.2 
Day 6 Per-Protocol Analysis Set Groups 1 and 2 ......................................... 78 
12.2.1.3 
Safety Analysis Set Groups 1 and 2................................................................. 79 
12.2.2 
Stage II Analysis Sets Groups 3 and 4 ............................................................... 79 
12.2.2.1 
Full Analysis Sets ............................................................................................. 79 
12.2.2.2 
Day 30 Per-Protocol Analysis Set .................................................................... 79 
12.2.2.3 
Safety Analysis Set........................................................................................... 80 
12.2.3 
Populations Used in Analyses ............................................................................ 80 
12.2.3.1 
Stage I ............................................................................................................... 80 
12.2.3.2 
Stage II ............................................................................................................. 80 
12.3 
Handling of Missing Data and Outliers ................................................................ 81 
12.3.1 
Immunogenicity .................................................................................................. 81 
12.3.2 
Safety .................................................................................................................. 81 
12.3.3 
Efficacy ............................................................................................................... 81 
12.4 
Interim/Preliminary Analysis ................................................................................ 81 
12.5 
Determination of Sample Size and Power Calculation ......................................... 82 
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13 
Ethical and Legal Issues and Investigator/Sponsor Responsibilities ................ 82 
13.1 
Ethical Conduct of the Study/Good Clinical Practice ........................................... 82 
13.2 
Source Data and Source Documents ..................................................................... 82 
13.3 
Confidentiality of Data, Data Protection, and Access to Subject Records ........... 83 
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 ......................................................... 85 
13.6 
Stipends for Participation ...................................................................................... 85 
13.7 
Publication Policy ................................................................................................. 85 
14 
Reference List ........................................................................................................ 87 
15 
Signature Page ....................................................................................................... 90 
 
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List of Tables 
Table 5.1: MEQ00066 Study Design ............................................................................................. 35 
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 
 
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Synopsis 
Company: 
Sanofi Pasteur 
Investigational Product: 
MenACYW conjugate vaccine: Meningococcal Polysaccharide  
(Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine 
Active Substances: 
Capsular polysaccharide from meningococcal serogroups A, C, W, and Y 
conjugated to tetanus toxoid 
Title of the Study: 
Safety and Immunogenicity of a Single Dose of MenACYW Conjugate 
Vaccine At Least 3 Years Following Initial Vaccination With Either 
Menomune Vaccine or MenACYW Conjugate Vaccine in Older Adults 
Development Phase: 
Phase III 
Coordinating Investigator: 
To be determined 
Study Sites: 
This study will be conducted in 34 centers in in the United States. 
Investigators and sites are listed in the “List of Investigators and Centers 
Involved in the Trial” document. 
Planned Study Period: 
Q3 2019 to Q1 2022 
Study Design, Schedule of Study 
Procedures, and Methodology: 
This will be a Phase III, 2-stage, randomized, open-label, multi-center study 
to evaluate the safety and immunogenicity of a single dose of MenACYW 
conjugate vaccine ≥ 3 years after a prior dose of either Menomune® vaccine 
or MenACYW conjugate vaccine in subjects ≥ 56 years of age at the time of 
primary vaccination. Antibody persistence after primary vaccination with 
Menomune vaccine or MenACYW conjugate vaccine will also be evaluated. 
The study will be conducted in 2 stages. 
Subjects who received Menomune vaccine or MenACYW conjugate vaccine 
in Study MET49 or Study MET44 are eligible for enrollment in 
Study MEQ00066.  
A planned minimum of 440 subjects who participated in Study MET49 (i.e., 
3 years prior to enrollment in the current study) will be randomly assigned to  
Group 1 or Group 3, or Group 2 or Group 4, depending on the vaccine 
originally received in Study MET49. These subjects will have antibody 
persistence assessed, followed by receipt of a single dose of MenACYW 
conjugate vaccine as per the stages described below. 
Stage I: 
Group 1: Approximately 180 subjects who received Menomune vaccine in 
Study MET49 will provide a blood sample at enrollment in 
Study MEQ00066 (to assess antibody persistence 3 years after 
primary vaccination), followed by receipt of a single dose of 
MenACYW conjugate vaccine (ratio 9:2 [Group 1:Group 3]). The 
first 60 subjects enrolled in Group 1 will comprise a subset from 
which an additional blood sample will be obtained at 6 (window, 
5–7) days post-vaccination. 
Group 2: Approximately180 subjects who received MenACYW conjugate 
vaccine in Study MET49 will provide a blood sample at 
enrollment in Study MEQ00066 (to assess antibody persistence 
3 years after primary vaccination), followed by receipt of a single 
dose of MenACYW conjugate vaccine 
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(ratio 9:2 [Group 2:Group 4]). The first 60 subjects enrolled in 
Group 2 will comprise a subset from which an additional blood 
sample will be obtained at 6 (window, 5–7) days post-vaccination. 
Group 3: Approximately 40 subjects who received Menomune vaccine in 
Study MET49 will provide a blood sample at enrollment in Study 
MEQ00066 for the assessment of antibody persistence 3 years 
after primary vaccination. 
Group 4: Approximately 40 subjects who received MenACYW conjugate 
vaccine in Study MET49 will provide a blood sample at 
enrollment in Study MEQ00066 for the assessment of antibody 
persistence 3 years after primary vaccination.  
A planned total of 120 subjects who participated in Study MET44  
(i.e., 6–7 years prior to enrollment in the current study) will provide a blood 
sample at enrollment in Study MEQ00066 for the assessment of antibody 
persistence 6–7 years after primary vaccination with either Menomune 
vaccine or MenACYW conjugate vaccine. These subjects will not receive a 
vaccination with MenACYW conjugate vaccine at enrollment. The subjects 
will be grouped as follows:  
Group 5: 60 subjects who received Menomune vaccine in Study MET44 
Group 6: 60 subjects who received MenACYW conjugate vaccine in 
Study MET44  
Stage II (2 years after enrollment) 
Group 3: The approximately 40 subjects who were randomly assigned to this 
group at the time of initial enrollment in Study MEQ00066 will 
provide an additional blood sample (to assess antibody persistence 
at 5 years), followed by receipt of a single dose MenACYW 
conjugate vaccine. 
Group 4: The approximately 40 subjects who were randomly assigned to this 
group at the time of initial enrollment in Study MEQ00066 will 
provide an additional blood sample (to assess antibody persistence 
at 5 years), followed by receipt of a single dose of MenACYW 
conjugate vaccine. 
Immunogenicity 
Stage I 
All subjects (Groups 1–6) will provide a blood sample at enrollment 
(Visit 1) to be tested for antibody persistence 3 years (Groups 1–4) or 6–
7 years (Groups 5 and 6) after having received primary vaccination in Study 
MET49 or Study MET44, respectively. 
Subjects in Group 1 and Group 2 will receive a single dose of MenACYW 
conjugate vaccine and will provide a blood sample 30 (window, + 14) days 
later. A subset of subjects, approximately 60 in Group 1 and 60 in Group 2, 
will also provide a blood sample 6 (window, 5–7) days following 
vaccination.  
Subjects in Groups 3 and 4 will not receive vaccination during Stage I. 
These subjects will continue into Stage II of the study (see below).  
Subjects in Groups 5 and 6 will provide a blood sample at the time of 
enrollment in Study MEQ000666 to assess for antibody persistence 6–
7 years after primary vaccination with Menomune vaccine or MenACYW 
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conjugate vaccine. Subjects in Groups 5 and 6 will not receive vaccination, 
and no further follow-up is planned for these groups. It is possible that some 
subjects in Groups 5 and 6 may have serum bactericidal assay using human 
complement (hSBA) titers < 1:8 (the putative level of protection against 
invasive meningococcal disease) to 1 or more vaccine serogroups (A, C, W, 
or Y). Investigators will be informed of and notify all subjects in Groups 5 
and 6 whose hSBA titers are < 1:8. 
Regardless of group assignment, it is possible that some subjects may have 
antitetanus antibody titers < 0.1 IU/mL (the putative level of protection 
against tetanus disease). Investigators will be informed of and notify all 
subjects whose antitetanus antibody titers are < 0.1 IU/mL. 
Stage II 
Two years after enrollment in Study MEQ00066 (i.e., approximately 5 years 
after primary vaccination in Study MET49), subjects in Groups 3 and 4 will 
provide a blood sample for assessment of antibody persistence, followed by 
receipt of a single dose of MenACYW conjugate vaccine, and a post-
vaccination blood sample 30 days later. 
Safety 
Stages I and II 
Subjects who are revaccinated with MenACYW conjugate vaccine (i.e., 
subjects in Groups 1 and 2 during Stage I, and subjects in Groups 3 and 4 
during Stage II) will record information about solicited reactions from Day 0 
through Day 7 after vaccination. Information on unsolicited adverse events 
(AEs), including medically attended adverse events (MAAEs), adverse 
events of special interest (AESIs), and serious adverse events (SAEs), will 
be collected from Day 0 through ~Day 30 after vaccination. For Groups 3 
and 4 after Visit 1 and 5 and 6, only SAEs considered by the Investigator to 
be related to study procedures (e.g., blood sampling) will be collected.  
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 that warrant 
study discontinuation; or for administrative reasons; or on advice of the 
Sponsor, the Investigators, the Institutional Review Boards (IRBs), or the 
governing regulatory authorities in the country where the study is taking 
place.  
If the study is prematurely terminated or suspended, the Sponsor shall 
promptly inform the Investigators, the IRBs, the regulatory authorities, and 
any contract research organization(s) used in the study of the reason for 
termination or suspension, as specified by the applicable regulatory 
requirements. The Investigator shall promptly inform the study subjects and 
should assure appropriate subject therapy and/or follow-up. 
Primary Objective: 
To demonstrate sufficiency of the vaccine seroresponse to meningococcal 
serogroups A, C, W, and Y following administration of a single dose of 
MenACYW conjugate vaccine to Group 1 subjects (who received primary 
vaccination with Menomune vaccine ≥ 3 years earlier at ≥ 56 years of age in 
Study MET49). 
Primary Endpoint: 
Vaccine seroresponse to meningococcal serogroups A, C, W, and Y as 
measured by hSBA at baseline (D0, pre-vaccination) and 30 (window, +14) 
days after vaccination in Group 1 (Menomune-primed) subjects. 
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Secondary Objectives: 
Secondary Objective 1 
• 
To demonstrate sufficiency of the vaccine seroresponse to 
meningococcal serogroups A, C, W, and Y following administration of 
a single dose of MenACYW conjugate vaccine to Group 2 subjects 
(who received primary vaccination with MenACYW conjugate vaccine 
≥ 3 years earlier at ≥ 56 years of age in Study MET49). 
Secondary Objective 2 
• 
To describe vaccine seroresponse rates with respect to serogroups A, C, 
W, and Y in serum specimens collected 6 (window, 5–7) days post-
vaccination in approximately 60 subjects from Group 1 (Menomune-
primed) and approximately 60 subjects from Group 2 (MenACYW 
conjugate vaccine-primed). 
Secondary Objective 3 
• 
To describe antibody persistence ≥ 3 years after primary vaccination 
with Menomune vaccine or MenACYW conjugate vaccine for subjects 
from all groups.  
Secondary Endpoints: 
• 
Vaccine seroresponse to meningococcal serogroups A, C, W, and Y as 
measured by hSBA at baseline (D0, pre-vaccination) and 30 (window, 
+14) days after vaccination in Group 2 (MenACYW conjugate vaccine-
primed) subjects. 
• 
Vaccine seroresponse 6 (window, 5–7) days after vaccination as 
measured by hSBA in approximately 60 subjects from Group 1 and 
approximately 60 subjects from Group 2. 
• 
During Stage I, antibody persistence after primary vaccination with 
Menomune vaccine or MenACYW conjugate vaccine as measured by 
hSBA and serum bactericidal assay using baby rabbit complement 
(rSBA) will be evaluated at Day 0 in Groups 1-4 (3 years after primary 
vaccination in Study MET49) and in Groups 5 and 6 (6-7 years after 
primary vaccination in Study MET44). Two years later, during Stage II, 
antibody persistence will be evaluated again in Groups 3 and 4 (5 years 
after primary vaccination in Study MET49). 
Observational Objectives: 
Immunogenicity 
• 
To describe the immunogenicity of a single dose of MenACYW 
conjugate vaccine, as assessed by hSBA and rSBA antibody titers, 
among persons who previously received Menomune vaccine or 
MenACYW conjugate vaccine ≥ 3 years earlier. 
• 
To describe antibody levels against tetanus toxoid at enrollment (all 
groups), 2 years after enrollment (Groups 3 and 4), and 30 (window, 
+ 14) days after a single dose of MenACYW conjugate vaccine (Groups 
1–4) in Study MEQ00066.  
Safety 
To describe the safety profile of a single dose of MenACYW conjugate 
vaccine administered to adults who received Menomune vaccine or 
MenACYW conjugate vaccine ≥ 3 years earlier (Groups 1 and 2 during 
Stage I; Groups 3 and 4 during Stage II).  
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Observational Endpoints: 
Immunogenicity 
Antibody titers (hSBA and rSBA) will be measured for each meningococcal 
serogroup for the following groups of subjects: 
• 
For all subjects on Day 0 
• 
For a subset of subjects in Groups 1 and 2, on Day 6 (window,  
Days 5–7) following vaccination 
• 
For subjects in Group 3 and 4, on Day 0 + 2 years 
• 
For all subjects who receive a single dose of MenACYW conjugate 
vaccine, 30 (window, + 14) days following vaccination  
Tetanus toxoid is contained in the investigational vaccine as a carrier 
protein. Therefore, blood samples will also be tested to assess: 
• 
Antibody concentrations against tetanus toxoid at Day 0 (all groups), 
2 years after enrollment (Groups 3 and 4), and 30 (window, + 14) days 
after the administration of a single dose of MenACYW conjugate 
vaccine in Study MEQ00066 (Groups 1–4) 
Safety 
• 
Occurrence, nature (Medical Dictionary for Regulatory Activities 
[MedDRA] preferred term), duration, intensity, and relationship to 
vaccination of any unsolicited systemic AEs reported in the 30 minutes 
after vaccination. 
• 
Occurrence, time to onset, number of days of occurrence, intensity, 
action taken, and whether the reaction led to early termination from the 
study, of solicited (prelisted in the subject’s diary card and case report 
book [CRB]) injection site reactions occurring from Day 0 through 
Day 7 after vaccination. 
• 
Occurrence, time to onset, number of days of occurrence, intensity, 
action taken, and whether the reaction led to early termination from the 
study, of solicited (prelisted in the subject’s diary card and CRB) 
systemic reactions occurring from Day 0 through Day 7 after 
vaccination. 
• 
Occurrence, nature (MedDRA preferred term), time to onset, duration, 
intensity, action taken, relationship to vaccination (for systemic AEs 
only), and whether the event led to early termination from the study, of 
unsolicited AEs occurring from Day 0 through ~Day 30 after 
vaccination. MAAEs will be collected as unsolicited non-serious AEs 
from Day 0 through ~Day 30 after vaccination. 
• 
Occurrence, nature (MedDRA preferred term), time to onset, duration, 
seriousness criteria, relationship to vaccination, outcome, and whether 
the event led to early termination from the study, of SAEs, including 
AESIs, throughout the study.  
Planned Sample Size: 
A total of 560 subjects are planned to be enrolled: 
• 
Group 1 (subjects who received Menomune vaccine in Study MET49) 
will receive a single dose of MenACYW conjugate vaccine at 
enrollment in Study MEQ00066: n=180 
• 
Group 2 (subjects who received MenACYW conjugate vaccine in Study 
MET49) will receive a single dose of MenACYW conjugate vaccine at 
enrollment in Study MEQ00066: n=180 
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• 
Group 3 (subjects who received Menomune vaccine in Study MET49) 
will receive a single dose of MenACYW conjugate vaccine 2 years after 
enrollment in Study MEQ00066: n=40 
• 
Group 4 (subjects who received MenACYW conjugate vaccine in Study 
MET49) will receive a single dose of MenACYW conjugate vaccine 
2 years after enrollment in Study MEQ00066: n =40 
• 
Group 5 (subjects who previously received Menomune vaccine in 
Study MET44): n=60 
• 
Group 6 (subjects who previously received MenACYW conjugate 
vaccine in Study MET44): n=60 
Duration of Participation in the 
Study: 
The duration of active participation in the study will be 30  
(window, + 14) days for subjects in Groups 1 and 2; 2 years plus 
30 (window, + 14) days for Groups 3 and 4; and 1 day for Groups 5 and 6.  
Investigational 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 
 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 
a Tetanus toxoid protein quantity is approximate and dependent on the  
polysaccharide-to-protein ratio for the conjugates used in each formulation. 
 Route: 
IM 
 Batch Number: 
To be determined 
Inclusion Criteria: 
An individual must fulfill all of the following criteria to be eligible for study 
enrollment: 
1) 
Received primary vaccination at ≥ 56 years of age with either 
Menomune vaccine or MenACYW conjugate vaccine, as assigned by 
randomization, in Study MET49 or Study MET44. 
2) 
Informed consent form has been signed and dated. 
3) 
Able to attend all scheduled visits and to comply with all study 
procedures. 
Exclusion Criteria: 
An individual fulfilling any of the following criteria is to be excluded from 
study enrollment: 
1) 
Subject is pregnant, or lactating, or of child-bearing potential and not 
using an effective method of contraception or abstinence for at least 
4 weeks prior to vaccination and until at least 4 weeks after 
vaccination. To be considered of non-childbearing potential, a female 
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must be post-menopausal for at least 1 year, surgically sterile, or 
≥ 60 years of age. 
2) 
Participation in the 4 weeks preceding study enrollment/vaccination or 
planned participation during the active phase of the present study 
period in another clinical study investigating a vaccine, drug, medical 
device, or medical procedure. 
Note: “Active phase” refers to the period of time from revaccination 
with MenACYW conjugate vaccine to the end of the short-term (i.e., 
~30 days) follow-up after the vaccination. Accordingly, following the 
blood draw at Visit 1, subjects in Group 3 and Group 4 will have a 2-
year inactive phase prior to Visit 2. Prior to Visit 2, subjects in Group 3 
and Group 4 will have inclusion and exclusion criteria reassessed and 
will continue with or be excluded from further participation in the 
study as appropriate. 
3) 
Receipt of any vaccine in the 4 weeks (28 days) preceding the study 
vaccination or planned receipt of any vaccine during the active phase 
of the present study except for influenza vaccination, which may be 
received at least 2 weeks before or after study vaccine. This exception 
includes monovalent pandemic influenza vaccines and multivalent 
influenza vaccines. 
4) 
Receipt or planned receipt of any meningococcal vaccine since receipt 
of a single dose of MenACYW conjugate vaccine or Menomune 
vaccine in Study MET49 or Study MET44. 
5) 
Receipt of immune globulins, blood, or blood-derived products in the 
3 months prior to either enrollment or MenACYW conjugate 
vaccination in the current study. 
6) 
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 prior either to 
enrollment or MenACYW conjugate vaccination in the current study). 
7) 
History of meningococcal infection, confirmed either clinically, 
serologically, or microbiologically. 
8) 
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). 
9) 
Known systemic hypersensitivity to any of the vaccine components, or 
history of a life-threatening reaction to the vaccine used in the study or 
to a vaccine containing any of the same substances (excluding subjects 
in Group 5 and Group 6). 
10) Verbal report of thrombocytopenia, contraindicating IM vaccination, in 
the Investigator’s opinion (excluding subjects in Group 5 and Group 6)  
11) Personal history of Guillain-Barré syndrome (GBS) (excluding 
subjects in Group 5 and Group 6). 
12) Personal history of an Arthus-like reaction after vaccination with a 
tetanus toxoid-containing vaccine within at least 10 years of the 
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proposed study vaccination (excluding subjects in Group 5 and Group 
6). 
13) Bleeding disorder, or receipt of anticoagulants in the 3 weeks 
preceding inclusion (excluding subjects in Group 5 and Group 6), 
contraindicating IM vaccination in the Investigator’s opinion.  
14) Deprived of freedom by an administrative or court order, or in an 
emergency setting, or hospitalized involuntarily. 
15) Current alcohol abuse or drug addiction. 
16) Chronic illness that, in the opinion of the Investigator, is at a stage 
where it might interfere with study conduct or completion. 
17) Moderate or severe acute illness/infection (according to investigator 
judgment) on the day of vaccination or febrile illness (temperature 
≥ 100.4°F). A prospective subject should not be included in the study 
or receive study vaccination until the condition has resolved or the 
febrile event has subsided. 
18) Receipt of oral or injectable antibiotic therapy within 72 hours prior to 
the first blood draw. A prospective subject should not be included in 
the study or receive study vaccination until 72 hours have elapsed since 
receipt of oral or injectable antibiotic therapy. 
19) Identified as an Investigator or employee of the Investigator or study 
center with direct involvement in the proposed study, or identified as 
an immediate family member (i.e., parent, spouse, natural or adopted 
child) of the Investigator or employee with direct involvement in the 
proposed study. 
Statistical Methods: 
The number of subjects enrolled and their age at enrollment, sex, race, and 
ethnic origin will be summarized for each group, as well as the number and 
description of protocol deviations. 
In general, categorical variables will be summarized and presented by 
frequency counts, percentages, and 95% confidence intervals (CIs). 
Continuous variables will be summarized and presented with means, 
standard deviations, and 95% CIs. The 95% CIs of point estimates will be 
calculated using the normal approximation for quantitative data and the 
exact binomial distribution (Clopper-Pearson method) for percentages. For 
geometric mean titers (GMTs), 95% CIs of point estimates will be 
calculated using the normal approximation assuming they are log-normally 
distributed. 
Relevant analyses will be completed for subjects in Groups 1, 2, 3, 4, 5, and 
6 after completion of Stage I. After collecting all planned data for Groups 1, 
2, 3, 4, 5, and 6 after completion of Stage I, the study database will be 
cleaned and locked. All statistical analyses planned for these groups will be 
conducted, and a final study report will be written. 
After the post-revaccination safety and immunogenicity data for Group 3 
and Group 4 are collected during Stage II, the database will be updated to 
include the newly collected data, which will be cleaned, and the database 
will be relocked. Analysis of the new data will be conducted and an 
addendum to the clinical study report will be written. 
 
 
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Primary Objective 
Thirty days after the administration of MenACYW conjugate vaccine, the 
sufficiency of the vaccine seroresponse, as assessed by the percentages of 
subjects who achieve an hSBA vaccine seroresponse* for meningococcal 
serogroups A, C, W, and Y, in Group 1 will be tested. 
Vaccine seroresponse will be considered sufficient if the lower limit of the 
1-sided 97.5% CI for the percentage of subjects with an hSBA vaccine 
seroresponse against serogroups A, C, W, and Y is greater than 40%.  
This is equivalent to testing H0: p ≤ 0.40 against H1: p > 0.40, where p is 
the observed proportion of subjects with hSBA vaccine seroresponse against 
serogroups A, C, W, and Y. The 1-sided 97.5% CI for the single proportion 
will be calculated using the exact method (Clopper-Pearson method). 
*hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
• 
For a subject with a pre-vaccination titer < 1:8, the post-vaccination titer 
must be ≥ 1:16. 
• 
For a subject with a pre-vaccination titer ≥ 1:8, the post-vaccination titer 
must be at least 4-fold greater than the pre-vaccination titer. 
Secondary Objective 1 
Thirty days after the administration of MenACYW conjugate vaccine, the 
sufficiency of the vaccine seroresponse, as assessed by the percentages of 
subjects who achieve an hSBA vaccine seroresponse* for meningococcal 
serogroups A, C, W, and Y, in Group 2 will be tested. 
Vaccine seroresponse will be considered sufficient if the lower limit of the 
1-sided 97.5% CI for the percentage of subjects with an hSBA vaccine 
seroresponse against serogroups A, C, W, and Y is greater than 40%. 
This is equivalent to testing H0: p ≤ 0.40 against H1: p > 0.40, where p is 
the observed proportion of subjects with hSBA vaccine seroresponse against 
serogroups A, C, W, and Y. The 1-sided 97.5% CI for the single proportion 
will be calculated using the exact method (Clopper-Pearson method). 
*hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
• 
For a subject with a pre-vaccination titer < 1:8, the post-vaccination titer 
must be ≥ 1:16. 
• 
For a subject with a pre-vaccination titer ≥ 1:8, the post-vaccination titer 
must be at least 4-fold greater than the pre-vaccination titer. 
Secondary Objective 2 
The proportions of subjects in a planned nonrandom subset (approximately 
60 subjects from Group 1 and approximately 60 subjects from Group 2) with 
vaccine seroresponse for meningococcal serogroups A, C, W, and Y at 
6 (window, 5–7) days following vaccination will be determined; 95% CIs of 
point estimates will be calculated assuming proportions follow a binomial 
distribution using the Exact method. No hypotheses are being tested with 
respect to this secondary objective. 
Secondary Objective 3 
For GMTs, the 95% CIs of point estimates will be calculated using the 
normal approximation assuming antibody titers/concentrations are log 
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normally distributed. For proportions, 95% CIs of point estimates will be 
calculated assuming proportions follow a binomial distribution using the 
Exact method. 
Categorical variables will be summarized and presented by frequency 
counts, proportion percentages, and CIs. The 95% CIs of point estimates 
will be calculated using the normal approximation for quantitative data and 
the exact binomial distribution (Clopper-Pearson method) for percentages.  
RCDC figures and kinetic curves will be provided for the antibody titers 
against meningococcal serogroups contained in MenACYW conjugate 
vaccine. 
Descriptive analyses on A, C, W, and Y serogroups will include: 
• 
hSBA and rSBA GMTs and corresponding 95% CIs 
• 
hSBA and rSBA titer distribution and RCDCs 
• 
Percentages of subjects with hSBA titer ≥ 1:4 and ≥ 1:8 and 
corresponding 95% CIs 
• 
Percentages of subjects with rSBA titer ≥ 1:8 and ≥ 1:128 and 
corresponding 95% CIs 
Observational Objectives 
Immunogenicity 
For GMTs and geometric mean concentrations (GMCs), 95% CIs of point 
estimates will be calculated using the normal approximation assuming 
antibody titers/concentrations are log normally distributed. For proportions, 
95% CIs of point estimates will be calculated assuming proportions follow a 
binomial distribution using the Exact method. 
Descriptive analyses on A, C, W, and Y serogroups will include: 
• 
hSBA and rSBA GMTs and corresponding 95% CIs 
• 
hSBA and rSBA titer distribution and RCDCs 
• 
Percentages of subjects with hSBA titer ≥ 1:4 and ≥ 1:8 and 
corresponding 95% CIs 
• 
Percentages of subjects with rSBA titer ≥ 1:8 and ≥ 1:128 and 
corresponding 95% CIs 
• 
Proportion with at least a 4-fold increase in hSBA and rSBA antibody 
titer compared to baseline (Group 1 and Group 2 during Stage I and 
Group 3 and Group 4 during Stage II) 
• An hSBA vaccine seroresponse for serogroups A, C, W, and Y is 
defined as a post-vaccination titer ≥ 1:16 for subjects with pre-
vaccination titer < 1:8, or a post-vaccination titer  ≥ 4 times the pre-
vaccination titer for subjects with a pre-vaccination titer ≥ 1:8. 
• An rSBA vaccine seroresponse is defined as a post-vaccination titer 
≥ 1:32 for subjects with pre-vaccination rSBA titer <1:8, or a post-
vaccination titer ≥ 4 times the pre-vaccination titer for subjects with 
pre-vaccination rSBA titer ≥ 1:8. 
• 
Ratio of the GMT post-vaccination/GMT pre-vaccination and the 
associated 95% CI of the ratio (at Day 30 for Group 1 and Group 2 and 
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at Day 6 in a subset of Group 1 and Group 2 [during Stage I], and at 
Day 30 for Group 3 and Group 4 [during Stage II]). 
Descriptive analyses on anti-tetanus antibody concentrations will include: 
• 
Geometric mean concentrations at Day 0 (all groups), 2 years after 
enrollment (Groups 3 and 4), and 30 (window, + 14) days after the 
administration of a single dose of MenACYW conjugate vaccine in 
Study MEQ00066 (Groups 1–4) 
• 
Proportion of subjects achieving seroprotective antibody levels 
≥ 0.01 IU (international units) /mL, ≥ 0.1 IU/mL, and ≥ 1.0 IU/mL to 
tetanus toxoid 30 (window, + 14) days after the administration of a 
single dose of MenACYW conjugate vaccine in Study MEQ00066 
(Groups 1–4)  
• 
RCDCs and kinetic curves 
Safety 
Safety results will be described for subjects revaccinated with MenACYW 
conjugate vaccine (i.e., Groups 1–4). The main parameters for the safety 
endpoints will be described by 95% CIs (based on the Clopper-Pearson 
method). 
The frequency and percentage of subjects who had solicited injection site 
and systemic reactions and their 95% CIs will be provided. These events 
will be tabulated by type of reactions and intensity for each study group. 
These events will also be summarized by other categories specified in the 
endpoints (e.g., time of onset, number of days of occurrence, action taken). 
Unsolicited AEs will be collected, coded, and summarized by MedDRA 
system organ class and PT. For each unsolicited AE, the number of subjects 
with at least one instance of that event will be reported. Unsolicited AEs will 
also be tabulated by intensity and relatedness of study vaccine and by other 
categories specified in the endpoints. 
Immediate reactions, SAEs, and any event that leads to subject withdrawal 
from the study will be tabulated separately. 
Calculation of Sample Size 
Primary Objective and Secondary Objective 1: For Group 1 and Group 2, 
a sample size of 120 achieves at least 90.0% power to detect that the lower 
bound of the one-sided 97.5% CI is greater than 0.40 (proportion under the 
null hypothesis) using a 1-sided exact test with a significance level (alpha) 
of 0.025. 
For all other groups (i.e., Groups 3–6), descriptive statistics will be 
calculated and presented in this study; hence, no sample size or study power 
was calculated for these groups. 
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Table of Study Procedures – Groups 1 and 2: 
Subjects Without a Day 6 Visit 
2 Visits, 1 Vaccination, 2 Blood Samples, 30 Days Duration per Subject 
Visit/Contact 
Visit 1 
Telephone Call 
Visit 2 
Study timelines (days) 
D0 
D08 
(Visit 1 + 8 days) 
D30 
(Visit 1 + 30 days) 
Time windows (days) 
-- 
+ 2 days 
+ 14 days 
Informed consent form 
X 
 
 
Inclusion/exclusion criteria 
X 
 
 
Collect subject number from Study MET49 
X 
 
 
Collection of demographic data 
X 
 
 
Urine pregnancy test (if applicable) 
X 
 
 
Medical history 
X 
 
 
Physical examinationa 
X 
 
 
Review of temporary contraindications for blood 
samplingb 
 
 
X 
Randomization/allocation of subject number via 
IRT 
X 
 
 
Blood sampling (BL) 10 mLc 
BL0001 
 
BL0002 
Vaccinationd 
X 
 
 
Immediate surveillance (30 minutes) 
X 
 
 
DC provided  
X 
 
 
Telephone call 
 
Xe 
 
Recording of solicited injection site and systemic 
reactions 
D0 to D07 
 
 
Recording of unsolicited AEs, including MAAEsf 
To be reported throughout the study period 
DC reviewed and collected 
 
 
X 
Reporting of SAEs, including AESIs 
To be reported throughout the study period 
Collection of reportable concomitant medications 
X 
 
X 
Termination of study 
 
 
X 
AE: adverse event; AESI: adverse event of special interest; D: day; DC: diary card; IRT; interactive response technology; 
MA: memory aid; MAAE: medically attended adverse event; SAE: serious adverse event 
a 
Temperature needs to be measured and recorded in source documents. 
b  Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the second blood draw, the Investigator 
 will postpone that blood draw until it has been 3 days since the subject last received oral or injectable antibiotic therapy. 
 Postponement must still be within the timeframe for blood draw (30 to 44 days after vaccination at Visit 1). If 
 postponement would result in the sample collection falling outside of this timeframe, the blood sample should be collected 
 without postponement, and it should be documented appropriately that the sample was taken less than 3 days after 
 stopping antibiotic treatment. 
c  A pre-vaccination blood sample will be collected from all subjects at Day 0. A post-vaccination blood sample will be 
 collected from all Group 1 and Group 2 subjects 30 (window, + 14) days following vaccination. 
d 
Subjects in Groups 1 and 2 will receive 1 dose of MenACYW conjugate vaccine. 
e   This call is made 8 to10 days after the vaccinations on Day 0. If Day 8 (+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 not yet reported, and will remind the subject to continue using the DC up to Visit 2, to bring 
 the DC to the study center at Visit 2, and confirm the date and time of Visit 2. 
f 
MAAEs that occur between Visit 1 (Day 0) and Visit 2 will be recorded as unsolicited AEs. 
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Table of Study Procedures – Groups 1 and 2:  
Subjects With a Day 6 Visit 
3 Visits, 1 Vaccination, 3 Blood Samples, 30 Days Duration per Subject  
Visit Number  
Visit 1 
Visit 2 
Telephone Call 
Visit 3 
Study Timelines (Days) 
D0 
D06 
(Visit 1 + 6 days) 
D08 
(Visit 1 + 8 days) 
D30 
(Visit 1 + 30 days) 
Time Windows (Days) 
-- 
± 1 day 
+ 2 days 
+ 14 days 
Informed consent  
X 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
Collect subject number from Study MET49 
X 
 
 
 
Collection of demographic data 
X 
 
 
 
Urine pregnancy test (if applicable) 
X 
 
 
 
Medical history  
X 
 
 
 
Physical examinationa  
X 
 
 
 
Review of temporary contraindications for blood 
samplingb 
 
X 
 
X 
Randomization/allocation of subject number via IRT 
X 
 
 
 
Blood sampling (BL) – 10 mLc 
BL0001 
BL0002d 
 
BL0003 
Vaccinatione 
X 
 
 
 
Immediate surveillance (30 minutes) 
X 
 
 
 
DC provided 
X 
 
 
 
Telephone callf 
 
 
X 
 
Recording of solicited injection site and systemic 
reactions 
D0 to D07 
 
 
Recording of unsolicited AEs, including MAAEs g 
To be reported throughout the study period 
DC reviewed and collected 
 
 
 
X 
Reporting of SAEs, including AESIs 
To be reported throughout the study period 
Collection of reportable concomitant medications 
X 
X 
 
X 
Termination of study 
 
 
 
X 
AE: adverse event; AESI: adverse event of special interest; D: day; DC: diary card; IRT: interactive response technology; MAAE: 
medically attended adverse event; SAE: serious adverse event 
a 
Temperature needs to be measured and recorded in source documents. 
b 
Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the second or third 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 (6 [window, 5–7] days after vaccination at Visit 1 
and 30 [window, + 14] days after vaccination at Visit 1). If postponement would result in the sample collection falling outside 
of this timeframe, the blood sample should be collected without postponement, and it should be documented appropriately that 
the sample was taken less than 3 days after stopping antibiotic treatment. 
c 
A pre-vaccination blood sample will be collected from all subjects at Day 0. A post-vaccination blood sample will be collected 
from all subjects in the Group 1 and Group 2 subset approximately 6 (window, 5–7) days and 30 (window, + 14) days 
following vaccination. 
d 
A planned total of 120 subjects (the first 60 subjects in Group 1 and the first 60 subjects in Group 2). 
e 
Subjects in Groups 1 and 2 will receive 1 dose of MenACYW conjugate vaccine. 
f 
This call is made 8 to 10 days after the vaccinations on Day 0. If Day 8 (+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 not yet reported, and will remind the subject to continue using the DC up to Visit 3, to bring the DC to 
the study center at Visit 3, and confirm the date and time of Visit 3. 
g 
MAAEs that occur between Visit 1 (Day 0) and Visit 3 will be recorded as unsolicited AEs. 
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Table of Study Procedures – Groups 3 and 4  
3 Visits, 1 Vaccination, 3 Blood Samples, 2 years + 30 Days Duration Per Subject  
Visit/Contact 
Visit 1 
Telephone 
Call 
 
Visit 2 
Telephone  
Call 
Visit 3 
Study timelines (days) 
D0 
Visit 1 + 
8 days 
 
Visit 1 + 2 years 
Visit 2 + 8 days 
Visit 2 + 30 days 
Time windows (days) 
-- 
+ 2 days 
 
+ 44 days 
+ 2 days 
+ 14 days 
Informed consent form 
X 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
X 
 
 
Collect subject number from Study MET49 
X 
 
 
 
 
 
Collection of demographic data 
X 
 
 
 
 
 
Urine pregnancy test (if applicable) 
X 
 
 
X  
 
 
Medical history 
X 
 
 
X 
 
 
Physical examinationa 
X 
 
 
X 
 
 
Review of temporary contraindications for blood samplingb 
 
 
 
X 
 
X 
Randomization/allocation of subject number via IRT 
X 
 
 
 
 
 
Blood sampling (BL) 10 mLc 
BL0001 
 
 
BL0002 
 
BL0003 
Immediate surveillance after blood sampling (15 minutes) for 
the occurrence of a syncopal episode 
X 
 
 
 
 
 
MA provided to collect any SAEs related to blood sampling 
performed at Visit 1 
X 
 
 
 
 
 
Vaccinationd 
 
 
 
X 
 
 
Immediate surveillance (30  minutes) 
 
 
 
X 
 
 
DC provided  
 
 
 
X 
 
 
Telephone call 
 
Xe 
 
 
Xf 
 
Recording of solicited injection site and systemic reactions 
 
 
 
Visit 2 + 7 days 
 
Recording of unsolicited AEs, including MAAEsg 
 
 
 
Visit 2 through Visit 3 
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Visit/Contact 
Visit 1 
Telephone 
Call 
 
Visit 2 
Telephone  
Call 
Visit 3 
Study timelines (days) 
D0 
Visit 1 + 
8 days 
 
Visit 1 + 2 years 
Visit 2 + 8 days 
Visit 2 + 30 days 
Time windows (days) 
-- 
+ 2 days 
 
+ 44 days 
+ 2 days 
+ 14 days 
DC reviewed and collected 
 
 
 
 
 
X 
Periodic follow-up during inactive phase of study (i.e., at least 
1 call every 3 months) 
 
 
X 
 
 
 
Reporting of SAEs, including AESIs 
X 
 
 
To be reported throughout the study period 
Collection of reportable concomitant medications 
X 
 
 
X 
 
X 
Termination of study 
 
 
 
 
 
X 
AE: adverse event; AESI: adverse event of special interest; D: day; DC: diary card; IRT: interactive response technology; MA: memory aid; MAAE: medically attended adverse event; SAE: serious 
adverse event 
a 
Temperature needs to be measured and recorded in source documents. 
b 
Should a subject receive oral or injectable antibiotic therapy within 3 days prior to the second or third 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 [window, + 14] days after vaccination at Visit 2). If postponement would 
result in the sample collection falling outside of this timeframe, the blood sample should be collected without postponement, and it should be documented appropriately that the sample was taken less 
than 3 days after stopping antibiotic treatment. 
c 
A blood sample will be collected from all subjects at Visit 1, at Visit 2 prior to vaccination, and at Visit 3 approximately 30 (window, + 14) days after vaccination. 
d 
Subjects will receive 1 dose of MenACYW conjugate vaccine. 
e 
This call is made 8 to10 days after blood sampling at Visit 1. If Visit 1 + 8 (window, +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 SAEs in the first 3 days after blood sampling. 
f  
This call is made 8 to10 days after the vaccinations at Visit 2. If Visit 2 + 8 (window, +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 not yet reported, and will remind the subject to continue using the DC up to Visit 3, to bring the DC to the study 
center at Visit 3, and confirm the date and time of Visit 3. 
g 
MAAEs will be recorded as unsolicited AEs. 
 
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Table of Study Procedures – Groups 5 and 6 
1 Visit, 1 Blood Sample, 1 Day Duration per Subject 
Visit/Contact 
Visit 1 
Telephone Call 
Study timelines (days) 
D0 
D08 
(Visit 1 + 8 days) 
Time windows (days) 
-- 
+ 2 days 
Informed consent form 
X 
 
Inclusion/exclusion criteria 
X 
 
Collect subject number from Study MET44 
X 
 
Collection of demographic data 
X 
 
Medical history 
X 
 
Physical examinationa 
X 
 
Allocation of subject number via IRT 
X 
 
Blood sampling (BL) 10 mL 
BL0001 
 
Immediate surveillance after blood sampling (15 minutes) 
for the occurrence of a syncopal episode 
X 
 
MA provided to collect any SAEs related to blood sampling 
performed at Visit 1 
X 
 
Telephone callb 
 
X 
Reporting of SAEs related to study procedures 
X 
 
Collection of reportable concomitant medications 
X 
 
Termination of study 
X 
 
IRT: interactive response technology; SAE: serious adverse event 
a 
Temperature needs to be measured and recorded in source documents. 
b 
This call is made 8 to10 days after blood sampling at Visit 1. If Visit 1 + 8 (window, +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 SAEs in the first 3 days after blood sampling. 
 
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List of Abbreviations 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AR 
Adverse Reaction 
CDM 
Clinical Data Management 
CI 
Confidence Interval 
CRA 
Clinical Research Associate 
CRB 
(electronic) Case Report Book [all the case report forms for a subject] 
CRF 
(electronic) Case Report Form 
CSR 
Clinical Study Report 
ECL 
Electrochemiluminescence 
EDC 
Electronic Data Capture 
FAS 
Full Analysis Set 
FVFS 
First Visit, First Subject 
GBS 
Guillain-Barré Syndrome  
GCI 
Global Clinical Immunology 
GCP 
Good Clinical Practice 
GMC 
Geometric Mean Concentration 
GMT 
Geometric Mean Titer 
GPV 
Global Pharmacovigilance  
hSBA 
Serum Bactericidal Assay Using Human Complement 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
IM 
Intramuscular 
IMD 
Invasive Meningococcal Disease 
IME 
Important Medical Event 
IOM 
Institute of Medicine 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
LLOQ 
Lower Limit of Quantification 
LLT 
Lowest Level Term 
LVLS 
Last Visit, Last Subject 
MAAE 
Medically Attended Adverse Event 
MedDRA 
Medical Dictionary for Regulatory Activities 
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MTL 
Medical Team Leader 
PPAS 
Per-Protocol Analysis Set 
rSBA 
Serum Bactericidal Assay Using Baby Rabbit Complement 
RMO 
Responsible Medical Officer 
SAE 
Serious Adverse Event 
TMF 
Trial Master File 
ULOQ 
Upper Limit of Quantification 
US 
United States 
 
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1 
Introduction 
1.1 
Background 
This is a study using MenACYW conjugate vaccine against invasive meningococcal disease 
(IMD).  
Meningococcal disease is caused by the gram-negative aerobic diplococcus Neisseria 
meningitidis, an exclusively human pathogen. Meningococci colonize the nasopharynx of an 
estimated 10% to 20% of the population at any given time and are transmitted by respiratory 
secretions (1).Yet, only a small proportion of carriers develop invasive disease, and predicting an 
individual’s risk is difficult. 
The 2 most common clinical presentations are meningococcemia or sepsis, which is accompanied 
by a petechial or purpuric rash in the majority of patients, and purulent meningitis. Despite 
appropriate treatment, the overall mortality rate for meningococcal disease has been reported to be 
7%–19% (2). Approximately 10%–20% of cases result in permanent disabilities such as limb loss, 
deafness, seizures, or psychomotor retardation.  
The current classification system for identifying meningococci by serogroup is based on the 
immunochemistry of the polysaccharide capsule surrounding the bacterium (3). The capsule is a 
major virulence factor of N. meningitidis. At least 12 distinct meningococcal serogroups have 
been classified based on the biochemical structure of the capsular polysaccharides (4). Of these, 
N. meningitidis serogroups A, B, C, W, X, and Y are responsible for most cases of disease (5). 
N. meningitidis causes both endemic and epidemic disease. Over 500,000 cases of meningococcal 
disease occur worldwide per year, resulting in approximately 135,000 deaths (6). The incidence of 
meningococcal disease has been steadily decreasing in the United States since the late 1990s. 
During 2012–2015, there were 350–550 cases reported annually with an incidence of 0.1–0.2 
cases per 100,000 population (7). The peak incidence of disease occurs during the winter and 
early spring. With respect to age, the highest rates of meningococcal disease in the United States 
occur among infants and children aged < 5 years, followed by a second peak among adolescents 
and young adults aged 16 through 21 years, and a third peak in adults aged ≥ 65 years. In the 
latter age group, the highest case-fatality ratio (23.8%) is observed (8). 
The epidemiology of meningococcal disease varies by the causative serogroup. Serogroups A, 
B, C, and W-135 have caused large epidemics worldwide. Serogroup A remains the leading cause 
of meningococcal disease in developing countries, particularly in the so-called meningitis belt 
of sub-Saharan Africa where it can cause tens of thousands of cases annually. More recently, 
serogroup W-135 disease has been associated with Hajj pilgrims and epidemics in sub-
Saharan Africa. Serogroups B and C predominate in developed countries. In the United States, 
disease is most commonly due to serogroups B, C, and Y, with serogroup Y disease having 
emerged as a more common threat within the past 2 to 3 decades and accounting for about one-
third of reported cases in recent years (9) (10). Approximately 60% of cases among adults aged 
≥ 65 years are caused by serogroup Y, and 43% are characterized by bacteremic pneumonia (8). 
To help prevent IMD among those considered at increased risk for the disease, vaccination is 
recommended (11). For example, the Advisory Committee on Immunization Practices 
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recommends that travelers who visit or reside in the so-called meningitis belt during the dry 
season (December–June) receive vaccination with a quadrivalent (serogroup A, C, W, and Y) 
meningococcal vaccine before travel. In addition, Kingdom of Saudi Arabia visitors travelling to 
the Hajj and Umrah are required to submit a valid vaccination certificate indicating administration 
of either a quadrivalent polysaccharide meningococcal vaccine within the last 3 years or a 
quadrivalent conjugate vaccine within the last 5 years (12). This requirement stems from evidence 
demonstrating that protection following MenACWY vaccination may wane 3 to 5 years after 
primary vaccination (8) (13) (14) (15). 
1.2 
Background of the Investigational Product 
MenACYW conjugate vaccine is designed for active immunization of individuals 6 weeks of age 
and older, including older adults ≥ 56 years of age, against IMD. The purpose of the vaccine is to 
provide broad coverage against circulating meningococcal strains from serogroups A, C, W, and 
Y. In contrast to the previous Sanofi Pasteur meningococcal conjugate vaccine, MenACYW 
conjugate vaccine is prepared by using tetanus toxoid as the carrier protein. Conjugation of 
polysaccharide antigens to a protein carrier can induce T-cell-dependent immune responses, 
which have been shown to give rise to higher antibody titers, longer duration of the immune 
response, and enhanced immunologic memory that allows for a booster response. The program 
targets licensure of MenACYW conjugate vaccine in many countries in North America, Europe, 
Latin America, Africa, the Middle East, and Asia Pacific. 
Meningococcal polysaccharide vaccines have 2 important limitations: a) the antibody response is 
age-dependent, with the poorest response seen in infants; and b) polysaccharides alone are T-cell 
independent immunogens, and therefore no anamnestic response is seen. The immunogenicity of 
polysaccharide vaccines in infants and children has been shown to be improved by conjugating 
the polysaccharides to protein carriers. Among the key advantages expected of the tetanus carrier 
is improved immunogenicity in infants and older adults. Pre-clinical studies, using a mouse model 
and investigating different carriers, showed significant levels of polysaccharide-specific total 
immunoglobulin G (IgG) and bactericidal antibodies in response to the formulations with tetanus 
toxoid as a carrier. Early Phase I/II trials, including those evaluating the final formulation of 
MenACYW conjugate vaccine (studies MET39 and MET44), showed the potential of the 
candidate vaccine to be a potent immunogen in all age groups, including young infants and older 
adults.  
All of the core components of MenACYW conjugate vaccine have been used extensively in 
licensed vaccines and have been shown to be safe. The meningococcal polysaccharides are the 
same as those used in Menactra® and Menomune® - A/C/Y/W-135 vaccines, and the source of 
tetanus toxoid protein used as a protein carrier in MenACYW conjugate vaccine is the same as 
that used in ActHIB® (a vaccine against Haemophilus influenzae type b [Hib]), in the Hib portion 
of Pentacel® (DTaP5-IPV//Hib), and as the tetanus antigen in Hexaxim® (DTaP2-IPV-Hep B-
Hib). The safety of the combination of these components as they are used in MenACYW 
conjugate vaccine has been evaluated in 6 Phase I/II clinical trials and in 10 Phase III clinical 
trials as part of the development program in adults, toddlers, and infants. Two of these studies 
(MET44 and MET49) were conducted in subjects ≥ 56 years of age and evaluated the safety and 
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immunogenicity of MenACYW conjugate vaccine compared to quadrivalent plain polysaccharide 
meningococcal (Menomune) vaccine: 
• MET44 (Phase II, 2012) enrolled 301 subjects who were randomly assigned to receive either 
MenACYW conjugate or Menomune vaccine. Within each vaccine group, subjects were 
stratified into 2 age groups, 56 to 64 years and ≥ 65 years of age. Proportions of subjects 
demonstrating antibody titers ≥ 1:8 with serum bactericidal assay using human complement 
(hSBA) following administration of MenACYW conjugate vaccine were similar to, or for 
serogroups W and Y, higher than those for subjects who received Menomune vaccine. Within 
each group of subjects who received MenACYW conjugate or Menomune vaccine, 
proportions of subjects with hSBA titers ≥ 1:8 were comparable between the 56 to 64 year and 
≥ 65 year age subgroups.  
• MET49 (Phase III, 2016–2017) enrolled 907 subjects who were randomly assigned to receive 
either MenACYW conjugate or Menomune vaccine. Within each vaccine group, subjects were 
stratified into 2 age groups, 56 to 64 years and ≥ 65 years of age. Thirty days after 
vaccination, the seroresponse of MenACYW conjugate vaccine was demonstrated to be 
non-inferior to that of Menomune vaccine for all 4 serogroups as measured by hSBA. 
Seroresponse was defined by either a post-vaccination titer of ≥ 1:16 for subjects with a  
pre-vaccination titer < 1:8, or at least a 4-fold rise in titer for subjects with a pre-vaccination 
titer ≥ 1:8. Geometric mean titers (GMTs) were higher for the MenACYW conjugate vaccine 
group than for the Menomune vaccine group for all serogroups. For subjects 56 to 64 years of 
age and subjects ≥ 65 years of age, immunogenicity was comparable to immune responses in 
the overall study population of adults ≥ 56 years of age. 
Overall, vaccination with MenACYW conjugate vaccine was found to be well tolerated, with no 
safety concerns identified. Solicited reactions, both injection site and systemic reactions, were 
more frequently reported in subjects aged 56 to 64 years than in subjects aged ≥ 65 years for both 
the MenACYW conjugate vaccine and Menomune vaccine groups. The rates of solicited 
reactions, particularly injection site reactions, were higher in subjects who received MenACYW 
conjugate vaccine than in subjects who received Menomune vaccine; however, no increase in the 
severity of these reactions was observed. The observed differences in local reactogenicity are 
likely attributable to differences in formulation (use of tetanus toxoid as a protein carrier in 
MenACYW vaccine vs. no use of a protein carrier in Menomune vaccine) and differences in 
routes of administration (intramuscular [IM] for MenACYW conjugate vaccine vs. subcutaneous 
for Menomune vaccine).  
1.3 
Potential Benefits and Risks 
1.3.1 
Potential Benefits to Subjects 
MenACYW conjugate vaccine is an investigational vaccine that is undergoing active clinical 
investigation. There may be no direct benefit from receiving 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 
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that the vaccine is well-tolerated, with no safety concerns having been detected to date. In all, the 
data support further evaluation of the MenACYW conjugate vaccine in humans. 
Subjects who receive MenACYW conjugate vaccine will likely be protected against 
meningococcal disease caused by N. meningitidis serogroups A, C, W, and Y. As with any 
vaccine, MenACYW conjugate vaccine may not protect 100% of individuals against the diseases 
the vaccine is designed to prevent. 
1.3.2 
Potential Risks to Subjects 
Like other vaccines, MenACYW conjugate vaccine may cause local reactions such as pain, 
swelling, erythema, pruritus, warmth, and ecchymosis at the injection site, or certain systemic 
events such as fever, headache, malaise, or myalgia. There may be a rare possibility of an allergic 
reaction, which could be severe. There may be other risks for MenACYW conjugate vaccine that 
are not yet known. 
The following additional adverse events (AEs) have been reported during post-approval use of the 
United States (US)-licensed quadrivalent meningococcal conjugate vaccine manufactured by the 
Sponsor, Menactra vaccine, which contains detoxified diphtheria toxoid as a protein carrier: 
Guillain-Barré syndrome (GBS), transverse myelitis, acute disseminated encephalomyelitis, 
vasovagal syncope, facial palsy, dizziness, paraesthesia, convulsion, and hypersensitivity 
reactions such as anaphylactic/anaphylactoid reaction, wheezing, difficulty breathing, upper 
airway swelling, urticaria, erythema, pruritus, and hypotension. Because these events were 
reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their 
frequency or to establish a causal relationship to Menactra vaccine exposure. 
Guillain-Barré syndrome has been reported mostly in persons aged 11 to 19 years who had 
symptom onset within 6 weeks of administration of a US licensed quadrivalent meningococcal 
conjugate vaccine, Menactra vaccine (16). A retrospective cohort study carried out in the United 
States using healthcare claims data found no evidence of increased GBS risk associated with the 
use of that vaccine. This study was able to exclude all but relatively small incremental risks (17).  
Because the MenACYW conjugate vaccine used in this study contains tetanus toxoid as a protein 
carrier, experience with tetanus toxoid antigen is relevant. 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 (17). Arthus reactions are rarely reported after 
vaccination and can occur after tetanus toxoid-containing vaccines (18). 
No occurrences of GBS, brachial neuritis, or Arthus reaction have been reported with the use of 
MenACYW conjugate vaccine in the completed clinical trials. 
In a previous study with MenACYW conjugate vaccine, 1 serious adverse event (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 
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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 trials. 
No other SAEs reported in completed or ongoing clinical trials were considered by the 
Investigator as related to MenACYW conjugate vaccine. 
The risk of vasovagal syncope exists after any vaccination, although it has not been specifically 
reported after MenACYW conjugate vaccine in the age group under study as part of this protocol. 
The potential risks listed here are not exhaustive. Refer to the Investigational Brochure for 
MenACYW conjugate vaccine for additional information regarding the potential risks. 
The potential risks associated with blood drawing include local pain, bruising and, rarely, fainting. 
1.4 
Rationale for the Study 
The purpose of MEQ00066 is to further evaluate MenACYW conjugate vaccine in older adults, 
including those ≥ 65 years of age, which is the age group that has the third highest incidence of 
meningococcal disease in the United States (0.5 cases per 100,000 population) and the highest 
case-fatality ratio (23.8%) (8). Specifically, MEQ00066 seeks to assess the safety and 
immunogenicity of a single dose of MenACYW conjugate vaccine ≥ 3 years after a primary 
vaccination with Menomune vaccine or MenACYW conjugate vaccine in subjects who were ≥ 56 
years of age at primary vaccination. Data from this study are intended to support use of 
MenACYW conjugate vaccine in older adults who previously received a polysaccharide vaccine 
and might be in need of repeat meningococcal vaccination because of increased risk of exposure 
(e.g., travel to an area where meningococcal disease is hyperendemic or epidemic). Antibody 
persistence 3, 5, or 7 years following a primary dose of either Menomune vaccine or MenACYW 
conjugate vaccine will also be evaluated.
 
 
titers will be determined using both hSBA and serum bactericidal assay using baby 
rabbit complement (rSBA). 
No early safety data review is planned for this study as MenACYW conjugate vaccine has been 
previously administered to more than 5000 infants, toddlers, children, adolescents, and adults, 
including over 650 older adults (i.e., ≥ 56 years of age) with no confirmed safety signals occurring 
in the clinical trials completed to date. MenACYW conjugate vaccine has been well tolerated 
regardless of the immunization schedule and the number of doses administered (e.g., up to 4 doses 
in young children, with the minimal interval between each dose being approximately 2 months). 
 
 
 
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2 
Study Objectives 
2.1 
Primary Objective 
To demonstrate sufficiency of the vaccine seroresponse to meningococcal serogroups A, C, W, 
and Y following administration of a single dose of MenACYW conjugate vaccine to Group 1 
subjects (who received primary vaccination with Menomune vaccine ≥ 3 years earlier at 
≥ 56 years of age in Study MET49). 
The endpoint for the primary objective is presented in Section 9.1.1.1.  
2.2 
Secondary Objectives 
Secondary Objective 1 
• To demonstrate sufficiency of the vaccine seroresponse to meningococcal serogroups A, C, 
W, and Y following administration of a single dose of MenACYW conjugate vaccine to 
Group 2 subjects (who received primary vaccination with MenACYW conjugate vaccine 
≥ 3 years earlier at ≥ 56 years of age in Study MET49).  
Secondary Objective 2 
• To describe vaccine seroresponse rates with respect to serogroups A, C, W, and Y in serum 
specimens collected 6 (window, 5–7) days post-vaccination in approximately 60 subjects from 
Group 1 (Menomune-primed) and approximately 60 subjects from Group 2 (MenACYW 
conjugate vaccine-primed). 
Secondary Objective 3 
• To describe antibody persistence ≥ 3 years after primary vaccination with Menomune vaccine 
or MenACYW conjugate vaccine for subjects from all groups. 
The endpoints for the secondary objective are presented in Section 9.2.1.1. 
2.3 
Observational Objectives 
Immunogenicity 
• To describe the immunogenicity of a single dose of MenACYW conjugate vaccine, as 
assessed by hSBA and rSBA antibody titers, among persons who previously received 
Menomune vaccine or MenACYW conjugate vaccine ≥ 3 years earlier. 
• To describe antibody levels against tetanus toxoid at enrollment (all groups), 2 years after 
enrollment (Groups 3 and 4), and 30 (window, + 14) days after a single dose of MenACYW 
conjugate vaccine (Groups 1–4) in Study MEQ00066. 
 
 
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Safety 
To describe the safety profile of a single dose of MenACYW conjugate vaccine administered to 
adults who received Menomune vaccine or MenACYW conjugate vaccine ≥ 3 years earlier 
(Groups 1 and 2 during Stage I; Groups 3 and 4 during Stage II). 
The endpoints for the immunogenicity and safety observational objectives are presented in 
Section 9.3.1.1 and Section 9.3.2.2, respectively. 
3 
Investigators and Study Organization 
This study will be conducted in 34 centers in in the United States. The Principal Investigators and 
any sub-investigators at the individual sites will be coordinated by 1 Coordinating Investigator. 
Details of the study centers, the Investigators at each center, and the Coordinating Investigator are 
provided in the “List of Investigators and Centers Involved in the Trial” document. 
The Sponsor’s Responsible Medical Officers (RMOs) (the persons authorized to sign this protocol 
and any amendments on behalf of the Sponsor) are 
 
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 Institutional Review Board(s) (IRB[s]). 
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 IRB(s) (the names and qualifications of the 
members attending and voting at the meetings). 
The Investigator and Sponsor will submit written summaries of the status of the study to the 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 IRB, according to the IRB 
policy. 
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5 
Investigational Plan 
5.1 
Description of the Overall Study Design and Plan 
5.1.1 
Study Design 
This will be a Phase III, 2-stage, randomized, open-label, multi-center study to evaluate the safety 
and immunogenicity of a single dose of MenACYW conjugate vaccine ≥ 3 years after a prior dose 
of either Menomune vaccine or MenACYW conjugate vaccine in subjects ≥ 56 years of age at the 
time of primary vaccination. Antibody persistence after primary vaccination with Menomune 
vaccine or MenACYW conjugate vaccine will also be evaluated. The study will be conducted in 
2 stages. 
Subjects who received Menomune vaccine or MenACYW conjugate vaccine in Study MET49 or 
Study MET44 are eligible for enrollment in Study MEQ00066.  
A planned minimum of 440 subjects who participated in Study MET49 (i.e., 3 years prior to 
enrollment in the current study) will be randomly assigned to Group 1 or Group 3, or Group 2 or 
Group 4, depending on the vaccine originally received in Study MET49. These subjects will have 
antibody persistence assessed, followed by receipt of a single dose of MenACYW conjugate 
vaccine as per the stages described below. 
Stage I: 
Group 1: Approximately 180 subjects who received Menomune vaccine in Study MET49 will 
provide a blood sample at enrollment in Study MEQ00066 (to assess antibody 
persistence 3 years after primary vaccination), followed by receipt of a single dose of 
MenACYW conjugate vaccine (ratio 9:2 [Group 1:Group 3]). The first 60 subjects 
enrolled in Group 1 will comprise a subset from which an additional blood sample will 
be obtained at 6 (window, 5–7) days post-vaccination. 
Group 2: Approximately180 subjects who received MenACYW conjugate vaccine in Study 
MET49 will provide a blood sample at enrollment in Study MEQ00066 (to assess 
antibody persistence 3 years after primary vaccination), followed by receipt of a single 
dose of MenACYW conjugate vaccine (ratio 9:2 [Group 2:Group 4]). The first 
60 subjects enrolled in Group 2 will comprise a subset from which an additional blood 
sample will be obtained at 6 (window, 5–7) days post-vaccination. 
Group 3: Approximately 40 subjects who received Menomune vaccine in Study MET49 will 
provide a blood sample at enrollment in Study MEQ00066 for the assessment of 
antibody persistence 3 years after primary vaccination. 
Group 4: Approximately 40 subjects who received MenACYW conjugate vaccine in 
Study MET49 will provide a blood sample at enrollment in Study MEQ00066 for the 
assessment of antibody persistence 3 years after primary vaccination.  
A planned total of 120 subjects who participated in Study MET44 (i.e., 6–7 years prior to 
enrollment in the current study) will provide a blood sample at enrollment in Study MEQ00066 
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for the assessment of antibody persistence 6–7 years after primary vaccination with either 
Menomune vaccine or MenACYW conjugate vaccine. These subjects will not receive a 
vaccination with MenACYW conjugate vaccine at enrollment. The subjects will be grouped as 
follows:  
Group 5: 60 subjects who received Menomune vaccine in Study MET44 
Group 6: 60 subjects who received MenACYW conjugate vaccine in Study MET44 
Stage II (2 years after enrollment) 
Group 3: The approximately 40 subjects who were randomly assigned to this group at the time of 
initial enrollment in Study MEQ00066 will provide an additional blood sample (to 
assess antibody persistence at 5 years), followed by receipt of a single dose of 
MenACYW conjugate vaccine. 
Group 4: The approximately 40 subjects who were randomly assigned to this group at the time of 
initial enrollment in Study MEQ00066 will provide an additional blood sample (to 
assess antibody persistence at 5 years), followed by receipt of a single dose of 
MenACYW conjugate vaccine. 
The study design is summarized in Table 5.1.  
Table 5.1: MEQ00066 Study Design 
Stage 
Group 
 Vaccine 
Received in 
MET49 
Vaccine 
Received in 
MET44 
Antibody 
Persistence 
Will Receive 
MenACYW 
Conjugate 
Vaccine in 
MEQ00066 
Planned 
Sample Size 
I 
1 
Menomune 
 
3 years 
Yes 
180 
2 
MenACYW 
 
3 years 
Yes 
180 
3 
Menomune 
 
3 years 
At Stage II 
40 
4 
MenACYW 
 
3 years 
At Stage II 
40 
5 
 
Menomune 
7 years 
No 
60 
6 
 
MenACYW 
7 years 
No 
60 
II 
3 
Menomune 
 
5 years 
Yes 
See Stage I 
4 
MenACYW 
 
5 years 
Yes 
See Stage I 
 
5.1.2 
Justification of the Study Design 
This study is part of the ongoing clinical development program that focuses on demonstrating the 
safety and immunogenicity of MenACYW conjugate vaccine. MEQ00066 is a study that will be 
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conducted as part of the Phase III of development of the MenACYW conjugate vaccine in which 
the vaccine would be evaluated in older adults who previously received a meningococcal vaccine 
at 56 years of age or older during Study MET49 or Study MET44. Since MenACYW conjugate 
vaccine has been evaluated in infants, toddlers, and adults (including adults 56 years of age and 
older) without raising any safety concerns, safety assessments will be done up to 30 days after 
vaccination. 
The study is open label, as only 1 vaccine will be administered.  
See Section 1.4 for the justification for the selection of subjects and the choice of groups. 
5.1.3 
Study Plan 
Vaccination 
• Subjects in Groups 1 and 2 will receive a single dose of MenACYW conjugate vaccine at 
Visit 1. 
• Subjects in Groups 3 and 4 will receive a single dose of MenACYW conjugate vaccine 
2 years after the enrollment visit (i.e., approximately 5 years after having received primary 
vaccination in Study MET49). 
• Subjects in Groups 5 and 6 will not receive a vaccination. 
Blood Sampling 
• All subjects (Groups 1–6) will provide a blood sample at enrollment (Visit 1) to be tested for 
antibody persistence 3 years (Groups 1–4) or 6–7 years (Groups 5 and 6) after having received 
primary vaccination in Study MET49 or Study MET44, respectively. 
• Subjects in Groups 1 and 2 will provide a blood sample 30 (window, + 14) days after 
receiving a single dose of MenACYW conjugate vaccine at Visit 1. A subset of subjects, 
approximately 60 in Group 1 and 60 in Group 2, will also provide a blood sample 
6 (window, 5–7) days following vaccination.  
• Subjects in Groups 3 and 4 will provide 2 additional blood samples after enrollment: 1 at 2 
years (window, + 44 days) after the enrollment visit prior to vaccination with a single dose of 
MenACYW conjugate vaccine and 1 at 30 (window, + 14) days post-vaccination.  
Handling of Low Serum Bactericidal Antibody Levels (Groups 5 and 6 Only) 
• It is possible that some subjects in Groups 5 and 6 may have hSBA titers < 1:8 (the putative 
level of protection against IMD) to 1 or more of vaccine serogroups (A, C, W, or Y). 
Investigators will be informed of and notify all subjects in Groups 5 and 6 whose hSBA titers 
are < 1:8. 
Handling of Low Serum Antitetanus Antibody Levels (All Groups) 
• Regardless of group assignment, it is possible that some subjects may have serum antitetanus 
antibody titers < 0.1 IU/mL (the putative level of protection against tetanus disease). 
Investigators will be informed of and notify all subjects whose antitetanus antibody titers are 
< 0.1 IU/mL. 
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Collection of Safety Data 
Collection of safety data for subjects who are revaccinated with MenACYW conjugate vaccine 
(i.e., subjects in Groups 1 and 2 during Stage I, and subjects in Groups 3 and 4 during Stage II) 
Staff will observe subjects for 30 minutes following vaccination and will record the occurrence of 
any immediate unsolicited systemic AEs. Subjects will record information about solicited 
injection site and systemic reactions from Day 0 through Day 7 after vaccination. Information on 
unsolicited AEs, including medically attended adverse events (MAAEs), adverse events of special 
interest (AESIs), and SAEs, will be collected from Day 0 through ~Day 30 after vaccination. 
Collection of safety data for subjects in Groups 3 and 4 after Visit 1 and Groups 5 and 6 during 
Stage I 
Safety follow-up for subjects in Groups 3 and 4 after Visit 1 and Group 5 and Group 6 will be 
limited to the collection of SAEs considered by the Investigator to be related to study procedures 
(e.g., blood sampling). 
Pregnancy Testing 
A urine human chorionic gonadotropin pregnancy test supplied by Sanofi Pasteur will be used to 
test females of child-bearing potential for pregnancy prior to vaccination. Subjects will not 
participate in the study if the initial pregnancy test was positive. For the purposes of the study, 
female subjects ≥ 60 years of age are defined as not of childbearing potential. 
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 licenses/credentials. 
5.1.4.1 
Groups 1 and 2 
Visit 1 (Day 0): Inclusion, Randomization, Blood Sample, and Vaccination  
1) Explain the study objectives and design to the subject, including but not limited to its 
objectives, design, and risks and benefits, and answer any questions the subject may have. 
2) Obtain a signed informed consent from the subject. The Investigator or delegate will also sign 
and date the ICF, retain the original, and give a copy of the signed and dated form to the 
subject. 
3) Check eligibility of the subject by reviewing applicable inclusion and exclusion criteria (see 
Section 5.2.4 and Section 5.2.5, respectively). 
4) Collect subject number from Study MET49. 
5) Collect relevant demographic data. 
6) When applicable, perform a urine pregnancy test. 
7) Obtain significant medical history (see Section 5.2.6 for details) 
8) Perform a directed physical examination, if indicated, based on medical history. 
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9) Measure the temperature by the preferred route (see Section 9.3.2.3.2) and record this 
information in the source document. If the temperature is ≥ 100.4°F (38.0°C), defer 
enrollment until the subject is afebrile for at least 24 hours. 
10) If the subject meets all inclusion and no exclusion criteria, connect to the interactive response 
technology (IRT) system for randomization, group assignment, and allocation of subject 
number (see Section 6.5 for instructions). 
11) Obtain a pre-vaccination blood sample (approximately 10 mL; see Section 7.1 for details 
regarding the collection of blood samples. If attempts to obtain the first blood draw are 
unsuccessful (3 attempts), then Visit 1 can be rescheduled to a later date at which point 
inclusion/exclusion criteria must be re-validated. 
12) Prepare vaccine to be administered based on the information provided in Section 6.1.1.2. 
13) Within 30 minutes of removing the MenACYW vaccine from the refrigerator, inject 1 dose 
of vaccine into the deltoid muscle of the arm (see Section 6.1.1.2). 
14) Observe the subject for 30 minutes following the injection and record any AE in the source 
document. 
15) Provide the subject a diary card, a digital thermometer, and a flexible ruler, along with 
instructions for their use, to record solicited injection site and systemic reactions from Day 0 
through Day 7 post-vaccination, unsolicited AEs and SAEs, as well as any concomitant 
medications (see Section 6.7) from Visit 1 to 30 (window, + 14) days post-vaccination. 
16) Schedule the next visit. 
17) Remind the subject that they will be contacted by telephone on or about Day 8 post-
vaccination to remind them to complete the diary card and to bring the completed diary card 
with them to Visit 2 or Visit 3 (for subjects in the Day 6 subset). 
18) Remind the subject to notify the site immediately if an SAE occurs. 
19) Collect reportable concomitant medications (see Section 6.7). 
20) Complete the relevant case report forms (CRFs) for this visit. 
Visit 2 (Day 6): Blood Sample - Subjects in the Day 6 Subset Only 
1) Review the temporary contraindications for blood sampling (see Section 5.2.8). 
2) Obtain the second blood sample (approximately 10 mL; see Section 7.1 for details regarding 
the collection of blood samples). 
3) Collect reportable concomitant medications (see Section 6.7). 
4) Complete the relevant CRFs for this visit. 
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Telephone Contact – Visit 1 + 8 (window, 8–10) Days 
Note: If Day 8 falls on a weekend or a holiday, the telephone call may be made on the following 
business day. If the subject is not available, the study staff should document the attempts to make 
contact. 
1) Record relevant information concerning the subject’s health status on the telephone contact 
form. If an SAE occurred, follow the instructions in Section 10 for reporting it. 
2) Remind the subject to do the following: 
• Complete the remaining pages of the diary card and bring them to Visit 2 or Visit 3 
(for subjects in the Day 6 subset). 
• Notify the site immediately if an SAE occurs. 
Final Visit (Visit 2 or Visit 3 [for subjects in the Day 6 subset]) (30 [+ 14] days after Visit 1): 
Collection of Safety Information and Blood Sample 
1) Collect the diary card and review each page with the subject, including any AEs, 
medications, or therapy that occurred since vaccination. 
2) Review the temporary contraindications for blood sampling (see Section 5.2.8). 
3) Obtain the blood sample (approximately 10 mL; see Section 7.1 for details regarding the 
collection of blood samples). 
4) Collect reportable concomitant medications (see Section 6.7). 
5) Complete the relevant CRFs for this visit and the End of Study CRF.  
6) If the subject does not return for Visit 2 (Visit 3 for subjects in the Day 6 subset), and the 
diary card is not received at the site, site personnel will contact the subject by telephone. 
During the telephone call, the subject will be reminded to return the diary card to the study 
site. Telephone calls will be documented on the Telephone/Interview Record. If the study 
personnel are unable to contact the subject with 3 attempts, the study personnel will follow 
instructions given in Section 5.2.10. 
5.1.4.2 
Groups 3 and 4 
Visit 1 (Day 0): Inclusion, Randomization, and Blood Sample  
1) Explain the study objectives and design to the subject, including but not limited to its 
objectives, design, and risks and benefits, and answer any questions the subject may have. 
2) Obtain a signed informed consent from the subject. The Investigator or delegate will also sign 
and date the ICF, retain the original, and give a copy of the signed and dated form to the 
subject.  
3) Check eligibility of the subject by reviewing applicable inclusion and exclusion criteria 
eligibility (see Section 5.2.4 and Section 5.2.5, respectively).   
4) Collect subject number from Study MET49. 
5) Collect relevant demographic data. 
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6) When applicable, perform a urine pregnancy test. 
7) Obtain significant medical history (see Section 5.2.6 for details). 
8) Perform a directed physical examination, if indicated, based on medical history. 
9) Measure the temperature by the preferred route (see Section 9.3.2.3.2) and record this 
information in the source document. If the temperature is ≥ 100.4°F (38.0°C), defer 
enrollment until the subject is afebrile for at least 24 hours. 
10) If the subject meets all inclusion and no exclusion criteria, connect to the IRT system for 
randomization, group assignment, and allocation of subject number (see Section 6.5 for 
instructions). 
11) Obtain the first blood sample (approximately 10 mL; see Section 7.1 for details regarding the 
collection of blood samples). If attempts to obtain the first blood draw are unsuccessful 
(3 attempts), then Visit 1 can be rescheduled to a later date at which point inclusion/exclusion 
criteria must be re-validated. 
12) Observe the subject for 15 minutes following blood sampling for the occurrence of a 
syncopal episode. 
13) Collect any SAEs related to study procedures. 
14) Provide the subject with a memory aid to record any SAEs related to blood sampling for the 
first 3 days after Visit 1. 
15) Remind the subject that they will be contacted by telephone on or about Day 8 post-Visit 1 to 
ask them about any SAEs that might be related to blood sampling. 
16) Remind the subject to notify the site immediately if an SAE occurs. 
17) Collect reportable concomitant medications (see Section 6.7). 
18) Schedule the next visit. 
19) Complete the relevant CRFs for this visit. 
Periodic Telephone Contact During the 2-Year Inactive Phase 
1) Subjects will receive periodic follow-up calls (e.g., at least 1 call every 3 months) during the 
2-year inactive phase.  
2) Record relevant information concerning the subject’s health status on the telephone contact 
form.  
Visit 2 (2 years after Visit 1): Blood Sample, Vaccination, and Collection of Safety Information  
1) Check eligibility of the subject by reviewing applicable inclusion and exclusion criteria 
eligibility (see Section 5.2.4 and Section 5.2.5, respectively). 
2) When applicable, perform a urine pregnancy test. 
3) Obtain significant medical history (see Section 5.2.6 for details). 
4) Perform a directed physical examination, if indicated, based on medical history. 
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5) Measure the temperature by the preferred route (see Section 9.3.2.3.2) and record this 
information in the source document. If the temperature is ≥ 100.4°F (38.0°C), defer Visit 2 
until the subject is afebrile for at least 24 hours. 
6) Review the temporary contraindications for blood sampling (see Section 5.2.8). 
7) Obtain the second blood sample (approximately 10 mL; see Section 7.1 for details regarding 
the collection of blood samples). If attempts to obtain the second blood draw are unsuccessful 
(3 attempts), then Visit 2 can be rescheduled to a later date at which point inclusion/exclusion 
criteria must be re-validated. 
8) Prepare vaccine to be administered based on the information provided in Section 6.1.1.2. 
9) Within 30 minutes of removing the MenACYW vaccine from the refrigerator, inject 1 dose 
of the vaccine into the deltoid muscle of the arm (see Section 6.1.1.2). 
10) Observe the subject for 30 minutes following the injection and record any AE in the source 
document. 
11) Provide the subject with a diary card, a digital thermometer, and a flexible ruler, along with 
instructions for their use, to record solicited injection site and systemic reactions from Day 0 
through Day 7 post-vaccination, unsolicited AEs and SAEs, as well as any concomitant 
medications (see Section 6.7) from Visit 2 to 30 (window, + 14) days post-vaccination. 
12) Schedule Visit 3. 
13) Remind the subject that they will be contacted by telephone on or about Day 8 post-
vaccination to remind them to complete the diary card and to bring the diary card with them 
to Visit 3. 
14) Remind the subject to notify the site immediately if an SAE occurs. 
15) Collect reportable concomitant medications (see Section 6.7). 
16) Complete the relevant CRFs for this visit. 
Telephone Contact – Visit 2 + 8 (window, 8–10) Days 
Note: If Day 8 falls on a weekend or a holiday, the telephone call may be made on the following 
business day. If the subject is not available, the study staff should document the attempts to make 
contact. 
1) Record relevant information concerning the subject’s health status on the telephone contact 
form. If an SAE occurred, follow the instructions in Section 10 for reporting it. 
2) Remind the subject to do the following: 
• Complete the remaining pages of the diary card and bring them to Visit 3. 
• Notify the site immediately if an SAE occurs. 
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Visit 3 (30 [+ 14] days after Visit 2): Collection of Safety Information and Blood Sample 
1) Collect the diary card and review each page with the subject, including any AEs, 
medications, or therapy that occurred since vaccination. 
2) Review the temporary contraindications for blood sampling (see Section 5.2.8). 
3) Obtain the third blood sample (approximately 10 mL; see Section 7.1 for details regarding the 
collection of blood samples). 
4) Complete the relevant CRFs for this visit and the End of Study CRF. 
5) If the subject does not return for Visit 3, and the diary card is not received at the site, site 
personnel will contact the subject by telephone. During the telephone call, the subject will be 
reminded to return the diary card to the study site. Telephone calls will be documented on the 
Telephone/Interview Record. If the study personnel are unable to contact the subject with 
3 attempts, the study personnel will follow instructions given in Section 5.2.10. 
5.1.4.3 
Groups 5 and 6 
Visit 1 (Day 0): Inclusion and Blood Sample 
1) Explain the study objectives and design to the subject, including but not limited to its 
objectives, design, and risks and benefits, and answer any questions the subject may have. 
2) Obtain a signed informed consent from the subject. The investigator or delegate will also sign 
and date the ICF, retain the original, and give a copy of the signed and dated form to the 
subject. 
3) Check eligibility of the subject by reviewing applicable inclusion and exclusion criteria (see 
Section 5.2.4 and Section 5.2.5, respectively). 
4) Collect subject number from Study MET44. 
5) Collect relevant demographic data. 
6) Obtain significant medical history (see Section 5.2.6 for details). 
7) Perform a directed physical examination, if indicated, based on medical history. 
8) Measure the temperature by the preferred route (see Section 9.3.2.3.2) and record this 
information in the source document. If the temperature is ≥ 100.4°F (38.0°C), defer 
enrollment until the subject is afebrile for at least 24 hours. 
9) If the subject meets all inclusion and no exclusion criteria, connect to the IRT system for 
group assignment and allocation of subject number (see Section 6.5 for instructions). 
10) Obtain the blood sample (approximately 10 mL; see Section 7.1 for details regarding the 
collection of blood samples). If attempts to obtain the blood draw are unsuccessful 
(3 attempts), then Visit 1 can be rescheduled to a later date at which point inclusion/exclusion 
criteria must be re-validated. 
11) Observe the subject for 15 minutes following blood sampling for the occurrence of a 
syncopal episode. 
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12) Collect any SAEs related to study procedures. 
13) Provide the subject with a memory aid to record any SAEs related to blood sampling for the 
first 3 days after Visit 1. 
14) Remind the subject that they will be contacted by telephone on or about Day 8 post-Visit 1 to 
ask them about any SAEs that might be related to blood sampling. 
15) Collect reportable concomitant medications (see Section 6.7). 
16) Complete the relevant CRFs for this visit and the End of Study CRF. 
Follow-up of subjects with Related AEs or with AEs That Led to Study/Vaccination 
Discontinuation: 
Unless a subject refuses further contact, each subject who experiences an AE (whether serious or 
non-serious) during the study must be followed until the condition resolves, becomes stable, or 
becomes chronic (even after the end of the subject’s participation in the study) if either of the 
following is true: 
• The AE is considered by the Investigator to be related to the product administered. 
• The AE caused the discontinuation of the subject from the study or from vaccination. 
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 LVLS (last visit, last subject):  
Q3 2019 to Q1 2022 
Planned end of study: Q1 2022 
Planned date of final clinical study report (CSR): 10 months after completion of Stage I  
Planned date of CSR addendum: 10 months after completion of Stage II 
5.2 
Enrollment and Retention of Study Population 
5.2.1 
Recruitment Procedures 
Subjects who received MenACYW conjugate vaccine or Menomune vaccine at least 3 years ago 
in Study MET49 or Study MET44 at age ≥ 56 years will be recruited for this study. The site will 
ensure that any advertisements used to recruit subjects (informational brochures, letters, 
pamphlets, posters, and other advertisements) are submitted to Sanofi Pasteur prior to submission 
to the IRB(s) for approval. 
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5.2.2 
Informed Consent Procedures 
Informed consent is the process by which a subject 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 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 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 IRB prior to the form being used. 
If new information becomes available that may be relevant to the subject’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. 
Informed consent forms 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. 
Documentation of the consent process should be recorded in the source documents. 
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) Received primary vaccination at ≥ 56 years of age with either Menomune vaccine or 
MenACYW conjugate vaccine, as assigned by randomization, in Study MET49 or Study 
MET44.a 
2) Informed consent form has been signed and dated. 
3) Able to attend all scheduled visits and to comply with all study procedures. 
5.2.5 
Exclusion Criteria 
An individual fulfilling any of the following criteria is to be excluded from study enrollment: 
1) Subject is pregnant, or lactating, or of childbearing potential and not using an effective 
method of contraception or abstinence from at least 4 weeks prior to vaccination and until at 
least 4 weeks after vaccination. To be considered of non-childbearing potential, a female 
must be post-menopausal for at least 1 year, surgically sterile, or ≥ 60 years of age.  
                                                 
a  “≥ 56 years” means from the day of the 56th birthday onwards. 
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2) Participation in the 4 weeks preceding study enrollment/vaccination or planned participation 
during the active phase of the present study period in another clinical study investigating a 
vaccine, drug, medical device, or medical procedure. 
Note: “Active phase” refers to the period of time from revaccination with MenACYW 
conjugate vaccine to the end of the short-term (i.e., ~30 days) follow-up after the vaccination. 
Accordingly, following the blood draw at Visit 1, subjects in Group 3 and Group 4 will have 
a 2-year inactive phase prior to Visit 2. Prior to Visit 2, subjects in Group 3 and Group 4 will 
have inclusion and exclusion criteria reassessed and will continue with or be excluded from 
further participation in the study as appropriate. 
3) Receipt of any vaccine in the 4 weeks (28 days) preceding the study vaccination or planned 
receipt of any vaccine during the active phase of the present study except for influenza 
vaccination, which may be received at least 2 weeks before or after study vaccine. This 
exception includes monovalent pandemic influenza vaccines and multivalent influenza 
vaccines. 
4) Receipt or planned receipt of any meningococcal vaccine since receipt of a single dose of 
MenACYW conjugate vaccine or Menomune vaccine in Study MET49 or Study MET44. 
5) Receipt of immune globulins, blood, or blood-derived products in the 3 months prior to either 
enrollment or MenACYW conjugate vaccination in the current study. 
6) 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 prior either to 
enrollment or MenACYW conjugate vaccination in the current study). 
7) History of meningococcal infection, confirmed either clinically, serologically, or 
microbiologically. 
8) 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). 
9) Known systemic hypersensitivity to any of the vaccine components, or history of a life-
threatening reaction to the vaccine used in the study or to a vaccine containing any of the 
same substancesa (excluding subjects in Group 5 and Group 6). 
10) Verbal report of thrombocytopenia, contraindicating IM vaccination, in the Investigator’s 
opinion (excluding subjects in Group 5 and Group 6)  
11) Personal history of GBS (excluding subjects in Group 5 and Group 6). 
12) Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing 
vaccine within at least 10 years of the proposed study vaccination (excluding subjects in 
Group 5 and Group 6). 
                                                 
a  The components of MenACYW conjugate vaccine are listed in Section 6.1 and in the Investigator’s Brochure. 
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13) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion (excluding 
subjects in Group 5 and Group 6), contraindicating IM vaccination in the Investigator’s 
opinion.  
14) Deprived of freedom by an administrative or court order, or in an emergency setting, or 
hospitalized involuntarily. 
15) Current alcohol abuse or drug addiction. 
16) Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere 
with study conduct or completion.a 
17) Moderate or severe acute illness/infection (according to investigator judgment) on the day of 
vaccination or febrile illness (temperature ≥ 100.4°F). A prospective subject should not be 
included in the study or receive study vaccination until the condition has resolved or the 
febrile event has subsided. 
18) Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw. 
A prospective subject should not be included in the study or receive study vaccination until 
72 hours have elapsed since receipt of oral or injectable antibiotic therapy.  
19) Identified as an Investigator or employee of the Investigator or study center with direct 
involvement in the proposed study, or identified as an immediate family member (i.e., parent, 
spouse, natural or adopted child) of the Investigator or employee with direct involvement in 
the proposed study. 
If the subject has a primary physician who is not the Investigator, the site must contact this 
physician with the subject’s consent to inform him/her of the subject’s participation in the study. 
In addition, the site should ask this primary physician to verify exclusion criteria relating to 
previous therapies, such as receipt of blood products or previous vaccines. 
5.2.6 
Medical History 
Prior to enrollment, subjects will be assessed for pre-existing conditions and illnesses, both past 
and ongoing. Any such conditions will be documented in the source document. Significant 
(clinically relevant) medical history (reported as diagnosis) including conditions/illnesses for 
which the subject is or has been followed by a physician or conditions/illnesses that could resume 
during the course of the study or lead to an SAE or to a repetitive outpatient care will be collected 
in the 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 
                                                 
a  Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, 
diabetes, psychomotor diseases, and known congenital or genetic diseases 
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The reporting of signs and symptoms in lieu of a diagnosis is strongly discouraged. 
Dates, medications, and body systems are not to be recorded, and the information collected will not 
be coded. Its purpose is to assist in the later interpretation of safety data collected during the 
study. 
5.2.7 
Contraindications for Subsequent Vaccinations 
Not applicable. 
5.2.8 
Contraindication for Subsequent Blood Samples 
Should a subject receive oral or injectable antibiotic therapy within 3 days before the second or 
third 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 the blood draw. If postponement would result in the sample collection falling 
outside of this timeframe, the blood sample should be collected without postponement, and it 
should be documented appropriately that the sample was taken less than 3 days after stopping 
antibiotic treatment. 
5.2.9 
Conditions for Withdrawal  
Subjects will be informed that they have the right to withdraw from the study at any time.  
A subject may be withdrawn from the study: 
• At the discretion of the Investigator or Sponsor due to safety concerns (withdrawal) without 
the subject’s permission 
• At the request of the subject (dropout) 
The following will result in automatic withdrawal or exclusion of a subject from the study: 
• Significant non-compliance with the protocol, based on the Investigator’s judgment 
The reason for a withdrawal or dropout should be clearly documented in the source documents 
and in the CRB.  
The Investigator must determine whether voluntary withdrawal is due to safety concerns (in 
which case, the reason for discontinuation will be noted as “Adverse Event”) or for another 
reason. 
Withdrawn subjects will not be replaced. 
5.2.10 Lost to Follow-up Procedures 
In the case of subjects who fail to return for a follow-up examination, documented reasonable 
effort (i.e., documented telephone calls and certified mail) should be undertaken to locate or recall 
them, or at least to determine their health status while fully respecting their rights. These efforts 
should be documented in the source documents. 
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5.2.11 Classification of Subjects Who Discontinue the Study 
For any subject who discontinues the study prior to completion, the most significant reason for 
early termination will be checked in the CRB. Reasons are listed below from the most significant 
to the least significant (refer to the CRF completion instructions for additional details and 
examples): 
Adverse 
Event 
To be used when the subject is permanently terminated from the study because of an 
AE (including an SAE), as defined in Section 9.3.2.1. 
This category also applies if the subject experiences a definitive contraindication that is 
an SAE or AE. 
Lost to 
Follow-up 
To be used when the subject cannot be found or contacted in spite of efforts to locate 
him/her before the date of his/her planned last visit, as outlined in Section 5.2.10. The 
certified letter was sent by the investigator and returned unsigned, and the subject did 
not give any other news and did not come to any following visit. 
Protocol 
Deviation 
To be used: 
• 
In case of significant noncompliance with the protocol (e.g., deviation of the 
Inclusion/Exclusion criteria, non-compliance with time windows, blood sampling 
or vaccination refusal, missed injection/treatment, or error in the vaccine/treatment 
administration). 
• 
If the subject experiences a definitive contraindication that is not an SAE or AE. 
• 
The subject 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 
To be used: 
• 
When the subject indicated unwillingness to continue in the study. 
• 
When the subject made the decision to discontinue participation in the study for any 
personal reason other than an SAE/AE (e.g., subject is relocating, inform consent 
withdrawal, etc.). 
5.2.12 Follow-up of Discontinuations 
The site should complete all scheduled safety follow-ups and contact any subject who has 
prematurely terminated the study because of an AE or a protocol deviation.  
For subjects where the reason for early termination was lost to follow-up or if the subject 
withdrew informed consent and specified that they do not want to be contacted again and it is 
documented in the source document, the site will not attempt to obtain further safety information. 
If the subject’s status at the end of the study is “Withdrawal by Subject or Parent/Guardian / 
Legally Acceptable Representative”, the site will attempt to contact them except if they specified 
that they do not want to be contacted again and it is documented in the source document. 
5.2.13 Follow-up and Reporting of Pregnancies 
Pregnancy is an exclusion criterion for enrollment in this study, but a subject could potentially 
become pregnant during her participation. In case of pregnancy and if the study vaccine has been 
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administered, the subject will not be discontinued from the study. However, the subject will be 
followed for safety assessment (and may be followed for immunogenicity assessment, if 
applicable). 
All pregnancy cases should be reported if they occurred during the study. To report the pregnancy 
case, the Investigator must fill out Pregnancy Reporting forms in the electronic data capture 
(EDC) system and inform the Sponsor within 1 month of identifying a pregnancy case.  
If the EDC system is not available, the investigator must fill out a paper Pregnancy Reporting 
Form (provided by the Sponsor at the start of the study) and inform the Sponsor within 1 month of 
identifying a pregnancy case. 
Study staff must then maintain contact with the subject to obtain information about the outcome 
(i.e., details about the delivery and the newborn, or about pregnancy termination) and must update 
the Pregnancy Reporting forms even after the end of the study. This information should be 
provided to the Sponsor within 1 month of delivery. 
Pregnancy itself is not considered an AE, but any complications during pregnancy are to be 
considered as AEs, and in some cases could be considered SAEs. Spontaneous abortions, blighted 
ovum, fetal death, stillbirth, and congenital anomalies reported in the baby are always considered 
as SAEs, and the information should be provided to the Global Pharmacovigilance (GPV) 
Department regardless of when the SAE occurs (e.g., even after the end of the study). 
5.3 
Safety Emergency Call 
If, as per the Investigator’s judgment, a subject experiences a medical emergency, the Investigator 
may contact the Sponsor’s RMOs for advice on how to address any study related medical question 
or problem. The RMOs will be available 24 hours a day, 7 days a week, as needed. Contact 
information for the RMOs is provided in the Operating Guidelines. 
This process does not replace the need to report an SAE. The Investigator is still required to 
follow the protocol-defined process for reporting SAEs to the GPV Department (please refer to 
Section 10). 
5.4 
Modification of the Study and Protocol 
Any amendments to this study plan and protocol must be discussed with and approved by the 
Sponsor. If agreement is reached concerning the need for an amendment, it will be produced in 
writing by the Sponsor, and the amended version of the protocol will replace the earlier version. 
All substantial amendments (e.g., those that affect the conduct of the study or the safety of 
subjects) require IRB approval, and must also be forwarded to regulatory authorities. 
An administrative amendment to a protocol is one that modifies some administrative, logistical, or 
other aspect of the study but does not affect its scientific quality or have an impact on the 
subjects’ safety. Administrative changes do not require IRB approval; however, the IRB must be 
notified whenever one is made. 
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The Investigator is responsible for ensuring that changes to an approved study, during the period 
for which IRB approval has already been given, are not initiated without IRB review and 
approval, except to eliminate apparent immediate hazards to subjects. 
5.5 
Interruption of the Study 
The study may be discontinued if new data about the investigational product resulting from this or 
any other studies become available that warrant study discontinuation; or for administrative 
reasons; or on advice of the Sponsor, the Investigators, the IRB(s), or the governing regulatory 
authorities in the country where the study is taking place.  
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IRB(s), 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 
requirements. The Investigator shall promptly inform the study subjects and should assure 
appropriate subject therapy and/or follow-up. 
6 
Vaccines Administered 
6.1 
Identity of the Investigational Product 
MenACYW conjugate vaccine is composed of 4 distinct meningococcal capsular polysaccharides 
(serogroups A, C, W, and Y) from N. meningitidis, which are each covalently bound to tetanus 
toxoid protein prepared from cultures of Clostridium tetani. The final bulk of MenACYW 
conjugate vaccine is formulated from the 4 monovalent polysaccharide-protein conjugates and 
diluted in sodium acetate buffered saline solution to a final concentration of 10 µg 
polysaccharide/serogroup/0.5 mL. 
MenACYW conjugate vaccine is manufactured at Sanofi Pasteur Inc., Swiftwater, Pennsylvania, 
USA. The purified meningococcal capsular polysaccharides used for the manufacturing of 
MenACYW conjugate vaccine are the same as those used for the manufacturing of the licensed 
vaccine, Menactra (and had been used for Menomune A/C/Y/W-135), manufactured at the same 
site. The tetanus toxoid protein used to prepare the polysaccharide-protein monovalent conjugate 
concentrates is manufactured at Sanofi Pasteur SA, Marcy l 'Etoile, France, and is derived from 
the licensed manufacturing process used for the preparation of the licensed ActHIB vaccine. 
6.1.1 
Identity of Study Product 
MenACYW conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) 
Tetanus Toxoid Conjugate vaccine 
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6.1.1.1 
Composition 
Each 0.5 mL dose of MenACYW conjugate vaccine is formulated in sodium acetate buffered 
saline solution to contain the following components: 
Meningococcal capsular polysaccharides: 
Serogroup A........................................................................................................................... 10 µg 
Serogroup C ........................................................................................................................... 10 µg 
Serogroup Y........................................................................................................................... 10 µg 
Serogroup W .......................................................................................................................... 10 µg 
Tetanus toxoid protein carrier ..................................................................... approximately 55 µga 
a 
Tetanus toxoid protein quantity is approximate and dependent on the polysaccharide-to-protein ratio for the 
 
conjugates used in each formulation. 
6.1.1.2 
Preparation and Administration 
MenACYW conjugate vaccine is a liquid preparation; as such, no diluent is required. This product 
is provided in 0.5-mL single-dose vials. The vaccine will be administered intramuscularly into the 
deltoid muscle of the arm. The vaccine must be administered within 30 minutes of removing the 
vaccine from the refrigerator. 
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; another dose is to be used, and the event is to be reported to the Sponsor. 
Subjects must be kept under observation for 30 minutes after vaccination to ensure their safety, 
and any reactions during this period will be documented in the CRB. Appropriate medical 
equipment and emergency medications, including epinephrine (1:1000), must be available on site 
in the event of an anaphylactic, vasovagal, or other immediate allergic reaction. 
6.1.1.3 
Dose Selection and Timing 
All subjects in Groups 1 and 2 will receive 1 dose of MenACYW conjugate vaccine at Visit 1. All 
subjects in Groups 3 and 4 will receive 1 dose of MenACYW vaccine at Visit 2, 2 years after 
enrollment in the study. 
6.1.2 
Identity of Control Product 
Not applicable. 
6.2 
Identity of Other Products 
Not applicable. 
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6.3 
Product Logistics 
6.3.1 
Labeling and Packaging 
MenACYW conjugate vaccine will be supplied by the Sponsor in single-dose vials, labeled and 
packaged according to national regulations. 
6.3.2 
Product Shipment, Storage, and Accountability 
6.3.2.1 
Product Shipment 
The Clinical Logistics Coordinator will contact the Investigator or a designee to determine the 
dates and times of delivery of products. 
Each vaccine shipment will include a temperature-monitoring device to verify maintenance of the 
cold chain during transit. On delivery of the product to the site, the person in charge of product 
receipt will follow the instructions given in the Operating Guidelines, including checking that the 
cold chain was maintained during shipment (i.e., verification of the temperature recorders). If 
there is an indication that the cold chain was broken, this person should immediately quarantine 
the product, alert the 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 into the source document and the 
CRB. If applicable, information may also be entered into the subject’s vaccination card. 
The Sponsor’s monitoring staff will verify the study site’s product accountability records against 
the record of administered doses in the CRBs and the communication from the IRT (if 
applicable). 
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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 (e.g., because the syringe broke or particulate matter was 
observed in the syringe), the site personnel must either contact the IRT to receive the new dose 
allocation, or follow the instructions given in the Operating Guidelines. 
6.3.4 
Disposal of Unused Products 
Unused or wasted products will be returned to the Sponsor in accordance with the instructions in 
the Operating Guidelines. Product accountability will be verified throughout the study period. 
6.3.5 
Recall of Products 
If the Sponsor decides to launch a retrieval procedure, the Investigators will be informed of what 
needs to be done. 
6.4 
Blinding and Code-breaking Procedures 
Not applicable. This is an open-label study. 
6.5 
Randomization and Allocation Procedures 
On the day of enrollment, a planned minimum of 440 subjects who meet all inclusion criteria and 
no exclusion criteria, sign the ICF, and who participated in Study MET49 will be randomly 
assigned in a 9:2 ratio to Group 1 (180 subjects) or Group 3 (40 subjects), or Group 2 
(180 subjects) or Group 4 (40 subjects), depending on the vaccine originally received in 
Study MET49. A planned nonrandom subset (i.e., the first 60 subjects enrolled in Group 1 and the 
first 60 subjects enrolled in Group 2) will provide an additional blood sample 6 (window, 5 to 7) 
days post-vaccination. A planned total of 120 subjects who participated in Study MET44 and who 
meet all inclusion criteria and no exclusion criteria and sign the ICF will be assigned to Group 5 
(60 subjects) or Group 6 (60 subjects), depending on the vaccine originally received in Study 
MET44.  
Site staff will connect to the IRT system, enter the identification and security information, and 
confirm a minimal amount of data in response to IRT system prompts. The IRT system will then 
provide the group assignment and subject number and have the site staff confirm it. The full 
detailed procedures for using the IRT system are described in the Operating Guidelines. If the 
subject is not eligible to participate in the study, information will only be recorded on the subject 
recruitment log. 
Subject numbers that are assigned by the IRT system will consist of a 12-digit string (a 3-digit 
country code, 4-digit study center identifier and a 5-digit subject identifier). For example, 
Subject 840000100001 is the first subject enrolled in center number 1 in the United States 
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(840 being the US country code). Subject numbers should not be reassigned for any reason. The 
randomization codes will be kept securely in the IRT system. To maximize the opportunity to 
achieve a 9:2 ratio (Group 1:Group 3 and Group 2:Group 4), randomization will not be performed 
at the site level, but across all sites. 
6.6 
Treatment Compliance 
The following measures will ensure that the vaccine doses administered comply with those planned, 
and that any non-compliance is documented so that it can be accounted for in the data analyses: 
• All vaccinations will be administered by qualified study personnel 
• The person in charge of product management at the site will maintain accountability records 
of product delivery to the study site, product inventory at the site, dose(s) given to each 
subject, and the disposal of unused or wasted doses 
6.7 
Concomitant Medications and Other Therapies 
At the time of enrollment, ongoing medications and other therapies (e.g., blood products) should 
be recorded in the source document as well as new medications prescribed for new medical 
conditions/AEs during study participation.  
Documentation in the CRB of ongoing concomitant medication(s) will be limited to specific 
categories of medication(s) of interest beginning on the day of vaccination. This may include 
medications of interest that were started prior to the day of vaccination. 
Reportable medications will be collected in the CRB from the day of vaccination to the end of the 
solicited and unsolicited follow-up period (e.g., 30-day safety follow-up). For Groups 3, 4, 5, and 
6 during Stage I, only information on systemic (oral or injectable) antibiotics will be collected in 
the CRB at Visit 1 prior to the blood draw. 
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. Three 
standard categories of reportable medications are defined: 
• Category 1: medications impacting or that may have an impact on the evaluation of the safety 
(e.g., antipyretics, analgesics, and non-steroidal anti-inflammatory drugs, 
steroids/corticosteroids). 
• Category 2: medications impacting or that may have an impact on the immune response 
(e.g., other vaccines, blood products, steroids/corticosteroids, immune-suppressors, immune-
modulators with immunosuppressive properties, anti-proliferative drugs such as DNA 
synthesis inhibitors) 
• Category 3: Systemic (oral or injectable) antibiotics, as they may interfere with bioassays used 
for antibody testing when taken before a blood draw.  
The information reported in the CRB for each reported medication will be limited to: 
• Trade name 
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• Origin of prescription: prophylaxis Yes/No. Medication(s) prescribed for AE prophylaxis will 
be recorded in the Action Taken of the AE collection tables. 
• Medication category (1, 2, or 3) 
• Start and stop dates 
Dosage and administration route, homeopathic medication, topical and inhaled steroids, as well as 
topical, ophthalmic, and ear treatments will not be recorded.  
Topical analgesics should not be applied at the site of vaccination; however, if they are applied 
inadvertently to the vaccination site, they should be recorded as a Category 1 medication in this 
specific instance, not as a Category 2 medication. 
Medications given in response to an AE will be captured in the “Action Taken” section of the AE 
CRF only. No details will be recorded in the concomitant medication CRF unless the medication(s) 
received belongs to one of the prelisted categories. Medications will not be coded. 
7 
Management of Samples 
Blood samples for the assessment of antibody responses will be collected from subjects in 
Groups 1 and 2 at Visits 1 and 2 (or at Visits 1, 2, and 3 for those subjects included in the Day 6 
subset); from subjects in Groups 3 and 4 at Visits 1, 2, and 3; and from subjects in Groups 5 and 6 
at Visit 1. See the Tables of Study Procedures and Section 5.1.3 for details of the sampling 
schedule. 
7.1 
Sample Collection 
Blood sample collection by group is described in Section 5.1.3. 
For each sample, approximately 10 mL of blood will be collected 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. Blood is to be taken 
from the limb opposite to the one that will be used for vaccination, if possible. 
7.2 
Sample Preparation 
Detailed instructions on how to prepare blood samples for assessment of immune response are 
contained in the Operating Guidelines provided to the site. An overview of the procedures is 
provided here. 
Following the blood draw, the tubes are to be left undisturbed, positioned vertically and not 
shaken, for a minimum of 1 hour and a maximum of 24 hours to allow the blood to clot. Samples 
can be stored at room temperature for up to 2 hours; beyond 2 hours, they must be refrigerated at 
a temperature of +2°C to +8°C up to a maximum of 24 hours. The samples are then centrifuged, 
and the serum is transferred to the appropriate number of aliquoting tubes. These tubes should be 
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pre-labeled with adhesive labels that identify the study code, the subject’s number, and the 
sampling stage or visit number (see Section 5.1.3 and Section 7.1).  
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 (UN) 
Class 6.2 specifications and the International Air Transport Association (IATA) 602 packaging 
instructions. 
Samples will be shipped to Global Clinical Immunology (GCI) at Sanofi Pasteur. The address is 
provided in the Operating Guidelines. 
Any unused part of the serum samples will be securely stored for any testing directly related to 
this study at the Sanofi Pasteur serology laboratory (GCI) for up to 25 years after the end of the 
study.  
7.4 
Future Use of Stored Serum Samples for Research 
Subjects will be asked to indicate in the ICF whether they will permit the future use of any 
leftover stored serum samples for additional research not related to this study. If they consent, 
leftover serum samples will be securely stored at GCI for up to 25 years after the end of the study. 
If they refuse permission, the samples will not be used for any testing other than that directly 
related to this study. If they agree to this use, they will not be paid for giving permission. 
Anonymity of samples will be ensured. The aim of any possible future research is unknown today 
and may not be related to this particular study. It may be to improve the knowledge of vaccines or 
infectious diseases, or to improve existing tests or develop new tests to assess vaccines. Human 
genetic tests will never be performed on these samples without specific individual informed 
consent.  
8 
Clinical Supplies 
Sanofi Pasteur will supply the study sites with protocols, ICFs, CRBs, SAE reporting forms, diary 
cards, memory aids, and other study documents, as well as with the following study materials: all 
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study vaccines, blood collection tubes, cryotubes, cryotube storage boxes, cryotube labels, 
temperature recorders, shipping containers, rulers, and digital thermometers. 
The means for performing EDC will be defined by 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 endpoint for the evaluation of immunogenicity is:  
Vaccine seroresponse to meningococcal serogroups A, C, W, and Y as measured by hSBA at 
baseline (D0, pre-vaccination) and 30 (window, +14) days after vaccination in Group 1 
(Menomune-primed) subjects. 
The definition of seroresponse is presented in Section 12.1.1.  
9.1.1.2 
Immunogenicity Assessment Methods  
Antibodies to Meningococcal Antigens (hSBA Method) 
Functional meningococcal antibody activity against serogroups A, C, W, and Y will be measured 
in an 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% 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 quantification (LLOQ) of the hSBA assay is a 
titer of 1:4. 
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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. 
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:  
• Vaccine seroresponse to meningococcal serogroups A, C, W, and Y as measured by hSBA at 
baseline (D0, pre-vaccination) and 30 (window, +14) days after vaccination in Group 2 
(MenACYW conjugate vaccine-primed) subjects. 
• Vaccine seroresponse 6 (window, 5–7) days after vaccination as measured by hSBA in 
approximately 60 subjects from Group 1 and approximately 60 subjects from Group 2. 
The definition of seroresponse is presented in Section 12.1.2.1. 
• During Stage I, antibody persistence after primary vaccination with Menomune vaccine or 
MenACYW conjugate vaccine as measured by hSBA and rSBA will be evaluated at Day 0 in 
Groups 1-4 (3 years after primary vaccination in Study MET49) and in Groups 5 and 6 
(6-7 years after primary vaccination in Study MET44). Two years later, during Stage II, 
antibody persistence will be evaluated again in Groups 3 and 4 (5 years after primary 
vaccination in Study MET49). 
9.2.1.2 
Immunogenicity Assessment Methods 
Antibodies to Meningococcal Antigens (hSBA Method) 
The immunogenicity assessment method for the secondary endpoints for hSBA is the same as that 
presented in Section 9.1.1.2. 
Antibodies to Meningococcal Antigens (rSBA Method) 
Functional meningococcal antibody activity against serogroups A, C, W, and Y will be measured 
in an rSBA. Two-fold dilutions of test sera are prepared in sterile 96-well microtiter plates. 
Serogroup-specific meningococcal bacteria along with baby rabbit complement are added to the 
serum dilutions and allowed to incubate. After this incubation period, 10 μL 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.  
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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. The LLOQ for this assay is a titer of 1:4. 
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 
Antibody titers (hSBA and rSBA) will be measured for each meningococcal serogroup for the 
following groups of subjects: 
• For all subjects on Day 0 
• For a subset of subjects in Groups 1 and 2, on Day 6 (window, Days 5–7) following 
vaccination 
• For subjects in Group 3 and 4, on Day 0 + 2 years 
• For all subjects who receive a single dose of MenACYW conjugate vaccine, 
30 (window, + 14) days following vaccination  
Tetanus toxoid is contained in the investigational vaccine as a carrier protein. Therefore, blood 
samples will also be tested to assess: 
• Antibody concentrations against tetanus toxoid at Day 0 (all groups), 2 years after enrollment 
(Groups 3 and 4), and 30 (window, + 14) days after the administration of a single dose of 
MenACYW conjugate vaccine in Study MEQ00066 (Groups 1-4) 
9.3.1.2 
Immunogenicity Assessment Methods 
Antibodies to Meningococcal Antigens (hSBA Method) 
The immunogenicity assessment method for the observational endpoints for hSBA is the same as 
that presented in Section 9.1.1.2. 
Antibodies to Meningococcal Antigens (rSBA Method) 
The immunogenicity assessment method for the observational endpoints for rSBA is the same as 
that presented in Section 9.2.1.2. 
Antibodies to Tetanus Toxin 
Anti-tetanus antibodies will be measured by electrochemiluminescence (ECL). 
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The Diphtheria, Tetanus, and Pertussis ECL is a multiplexed serological assay which allows for 
the simultaneous quantification of human antibodies to 6 specific antigens including diphtheria 
toxoid, tetanus toxoid, and 4 pertussis antigens: pertussis toxin, filamentous haemagglutinin, 
fimbriae and pertactin. 
In this assay, each well of a 96-well microtiter plate is pre-coated in precise positions with the 
6 different antigens in a multi-spot fashion. Following incubation with serum samples, antigen 
specific antibodies bind to the respective antigens. The captured antibodies are then detected 
using a sulfotag-conjugated anti-human IgG conjugate. Electrical stimulation of the conjugate in 
the presence of a chemiluminescent substrate results in the generation of a light signal from each 
specific spot that is captured by a camera in relative light units. The signal generated is directly 
proportional to the amount of antibodies present in the sample, which is quantified using software 
and based on an established reference standard sample curve. For this study, only tetanus results 
will be calculated. 
9.3.2 
Safety 
9.3.2.1 
Safety Definitions 
The following definitions are taken from the International Council for Harmonisation (ICH) E2A 
Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited 
Reporting. 
Adverse Event (AE): 
An AE is any untoward medical occurrence in a patient or in a clinical investigation subject 
administered a medicinal product and which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom or disease temporally associated with the use 
of a medicinal product, whether or not considered related to the medicinal product.  
Therefore an AE may be: 
• A new illness 
• The worsening of a pre-existing condition 
• An effect of the vaccination, including the comparator 
• A combination of the above 
All AEs include serious and non-serious AEs. 
Surgical procedures are not AEs; they are the actions taken to treat a medical condition. It is the 
condition leading to the action taken that is the AE (if it occurs during the study period). 
Pre-existing medical conditions are not to be reported as AEs. However, if a pre-existing medical 
condition worsens following study interventions in frequency or intensity, or if according to the 
Investigator there is a change in its clinical significance, this change should be reported as an AE 
(exacerbation). This applies equally to recurring episodes of pre-existing conditions (e.g., asthma) 
if the frequency or intensity increases post-vaccination. 
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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 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse, new-onset diabetes, or autoimmune disease. 
Adverse Reaction: 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered adverse reactions (AR). 
(The phrase “responses to a medicinal product” means that a causal relationship between a 
medicinal product and an AE is at least a reasonable possibility) 
                                                 
a  The term “life-threatening” refers to an event in which the subject was at risk of death at the time of the event; it 
does not refer to an event which hypothetically might have caused death if it were more severe. 
b  All medical events leading to hospitalizations will be recorded and reported as SAEs, with the exception of: 
hospitalization planned before inclusion into the study or outpatient treatment with no hospitalization.  
c  “Persistent or significant disability or incapacity” means that there is a substantial disruption of a person’s ability 
to carry out normal life functions. 
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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” AR (sign or symptom) observed and reported under the 
conditions (nature and onset) prelisted in the protocol and CRB (e.g., injection site pain or 
headache occurring between Day 0 and Day 7 post-vaccination). By definition, solicited reactions 
are to be considered as being related to the product administered. 
For injectable vaccines, solicited reactions can either be solicited injection site reactions or 
solicited systemic reactions. 
Unsolicited AE/AR: 
An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the CRB in 
terms of diagnosis and/or onset window post-vaccination. For example, if headache between 
Day 0 and Day 7 is a solicited reaction (i.e., prelisted in the protocol and CRB), then a headache 
starting on Day 7 is a solicited reaction, whereas headache starting on Day 8 post-vaccination is 
an unsolicited AE. Unsolicited AEs include both SAEs and non-serious unsolicited AEs. 
Medically Attended AE (MAAE)  
An MAAE is a new onset or a worsening of a condition that prompts the subject to seek 
unplanned medical advice at a physician’s office or emergency department. A physician contact 
made over the phone or by email will be considered a physician office visit for the purpose of 
MAAE collection. This definition excludes pre-planned medical office visits for routine medical 
care, as well as follow-up visits of chronic conditions with an onset prior to entry in the study. An 
AE discovered during a planned routine visit (e.g., upper respiratory tract infection, otitis) will be 
collected as an MAAE. 
Injection Site Reaction: 
An injection site reaction is an AR at and around the injection site. Injection site reactions are 
commonly inflammatory reactions. They are considered to be related to the product administered. 
Systemic AE: 
Systemic AEs are all AEs that are not injection or administration site reactions. They therefore 
include systemic manifestations such as headache, fever, as well as localized or topical 
manifestations that are not associated with the vaccination or administration site (e.g., erythema 
that is localized but that does not occur at the injection site). 
Adverse Event of Special Interest (AESI): 
An AESI is an event for which ongoing monitoring and rapid communication by the Investigator 
to the Sponsor must be done. Such an event might warrant further investigation in order to 
characterize and understand it. Depending on the nature of the event, rapid communication by the 
study Sponsor to other parties (e.g., regulators) might also be warranted. 
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9.3.2.2 
Safety Endpoints 
The observational endpoints for the evaluation of safety are: 
• Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), 
duration, intensity, and relationship to vaccination of any unsolicited systemic AEs reported in 
the 30 minutes after vaccination. 
• Occurrence, time to onset, number of days of occurrence, intensity, action taken, and whether 
the reaction led to early termination from the study, of solicited (prelisted in the subject’s 
diary card and CRB) injection site reactions occurring from Day 0 through Day 7 after 
vaccination. 
• Occurrence, time to onset, number of days of occurrence, intensity, action taken, and whether 
the reaction led to early termination from the study, of solicited (prelisted in the subject’s 
diary card and CRB) systemic reactions occurring from Day 0 through Day 7 after 
vaccination. 
• Occurrence, nature (MedDRA preferred term), time to onset, duration, intensity, action taken, 
relationship to vaccination (for systemic AEs only), and whether the event led to early 
termination from the study, of unsolicited AEs occurring from Day 0 through ~Day 30 after 
vaccination. MAAEs will be collected as unsolicited non-serious AEs from Day 0 through 
~Day 30 after vaccination. 
• Occurrence, nature (MedDRA preferred term), time to onset, duration, seriousness criteria, 
relationship to vaccination, outcome, and whether the event led to early termination from the 
study, of SAEs, including AESIs, throughout the study. 
9.3.2.3 
Safety Assessment Methods 
At each visit, the Investigator or a delegate will perform a directed physical examination, if 
indicated, based on interim history and will ask the subject 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.  
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• SAEs will be recorded in the CRB and reported to the Sponsor in the same way as any other 
SAEs, according to the procedures described in Section 10. 
9.3.2.3.2 
Reactogenicity (Solicited Reactions From Day 0 Through Day 7 After 
Vaccination) 
After vaccination, subjects in Groups 1 to 4 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 
(i.e., 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 (e.g., medication) 
The action(s) taken by the subject to treat and/or manage any solicited reactions will be 
classified in the CRB using the following list (all applicable items should be checked): 
• None 
• Medication 
• Health care provider contact 
• Hospitalized 
 
Subjects will be contacted by telephone 8 days after vaccination to remind them to record all 
safety information in the diary card. 
If the timing of the telephone call should fall on a weekend or a holiday, the call should be made 
on the next business day. If contact is not made on the designated day, study 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 prelisted in the diary cards and CRB, together with the intensity scales. 
 
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Table 9.1: Solicited Injection Site Reactions: Terminology, Definitions, and Intensity Scales 
CRB term (MedDRA 
lowest level term 
[LLT]) 
Injection site pain 
Injection site erythema 
Injection site swelling  
Diary card term 
Pain 
Redness 
Swelling 
Definition 
Pain either present spontaneously or when the 
injection site is touched or injected limb is 
mobilized 
Presence of a redness including the approximate 
point of needle entry 
Swelling at or near the injection site 
Swelling or edema is caused by a fluid 
infiltration in tissue or cavity and, depending on 
the space available for the fluid to disperse, 
swelling may be either soft (typically) or firm 
(less typical) to touch and thus can be best 
described by looking at the size of the swelling 
Intensity scalea 
 
Grade 1: A type of adverse event that is usually 
transient and may require only minimal 
treatment or therapeutic intervention. The event 
does not generally interfere with usual activities 
of daily living. 
Grade 2: A type of adverse event that is usually 
alleviated with additional therapeutic 
intervention. The event interferes with usual 
activities of daily living, causing discomfort but 
poses no significant or permanent risk of harm to 
the research participant. 
Grade 3: A type of adverse event that interrupts 
usual activities of daily living, or significantly 
affects clinical status, or may require intensive 
therapeutic intervention. 
Grade 1: ≥ 25 to ≤ 50 mm 
Grade 2: ≥ 51 to ≤ 100 mm 
Grade 3: > 100 mm 
Grade 1: ≥ 25 to ≤ 50 mm 
Grade 2: ≥ 51 to ≤ 100 mm 
Grade 3: > 100 mm 
a For the subjective reaction of pain, subjects will record the intensity level (Grade 1, 2, or 3) in the diary card. For the measurable reactions of redness and swelling, they will record 
just the size of the reaction, and the classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis. 
 
 
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Table 9.2: Solicited Systemic Reactions: Terminology, Definitions, and Intensity Scales 
CRB term 
(MedDRA lowest 
level term [LLT]) 
Fever 
 
Headache 
Malaise 
Myalgia 
Diary card term 
Temperature 
Headache 
Feeling unwell 
Muscle aches and pains 
Definition 
Elevation of temperature to 
≥°38.0°C (≥ 100.4°F) 
Pain or discomfort in the head or 
scalp. Does not include migraine. 
General ill feeling. 
Malaise is a generalized feeling of 
discomfort, illness, or lack of well-
being that can be associated with a 
disease state. It can be accompanied 
by a sensation of exhaustion or 
inadequate energy to accomplish 
usual activities. 
Muscle aches and pains are 
common and can involve more than 
one muscle at the same time. 
Muscle pain can also involve the 
soft tissues that surround muscles. 
These structures, which are often 
referred to as connective tissues, 
include ligaments, tendons, and 
fascia (thick bands of tendons). 
Does not apply to muscle pain at the 
injection site which should be 
reported as injection site pain. 
Intensity scalea 
Grade 1: ≥ 38.0°C to ≤ 38.4°C, 
or ≥ 100.4°F to ≤ 101.1°F 
Grade 1: A type of adverse event 
that is usually transient and may 
require only minimal treatment or 
therapeutic intervention. The event 
does not generally interfere with 
usual activities of daily living. 
Grade 1: A type of adverse event 
that is usually transient and may 
require only minimal treatment or 
therapeutic intervention. The event 
does not generally interfere with 
usual activities of daily living. 
Grade 1: A type of adverse event 
that is usually transient and may 
require only minimal treatment or 
therapeutic intervention. The event 
does not generally interfere with 
usual activities of daily living. 
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Grade 2: ≥ 38.5°C to ≤ 38.9°C, 
or ≥ 101.2°F to ≤ 102.0°F 
Grade 2: A type of adverse event 
that is usually alleviated with 
additional therapeutic intervention. 
The event interferes with usual 
activities of daily living, causing 
discomfort but poses no significant 
or permanent risk of harm to the 
research participant. 
Grade 2: A type of adverse event 
that is usually alleviated with 
additional therapeutic intervention. 
The event interferes with usual 
activities of daily living, causing 
discomfort but poses no significant 
or permanent risk of harm to the 
research participant. 
Grade 2: A type of adverse event 
that is usually alleviated with 
additional therapeutic intervention. 
The event interferes with usual 
activities of daily living, causing 
discomfort but poses no significant 
or permanent risk of harm to the 
research participant. 
 
Grade 3: ≥ 39.0°C 
or ≥ 102.1°F 
Grade 3: A type of adverse event 
that interrupts usual activities of 
daily living, or significantly affects 
clinical status, or may require 
intensive therapeutic intervention. 
Grade 3: A type of adverse event 
that interrupts usual activities of 
daily living, or significantly affects 
clinical status, or may require 
intensive therapeutic intervention. 
Grade 3: A type of adverse event 
that interrupts usual activities of 
daily living, or significantly affects 
clinical status, or may require 
intensive therapeutic intervention. 
a  For all reactions but fever, subjects will record the intensity level (Grade 1, 2, or 3) in the diary card. For fever, they will record the body temperature, and the classification as 
Grade 1, 2, or 3 will be assigned at the time of the statistical analysis based on the unit used to measure the temperature and the intensity scale. 
 
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Important notes for the accurate assessment of temperature: 
Subjects 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 oral. 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, subjects will be instructed to record any other medical 
events that may occur during the 30-day period after vaccination. Space will be provided in the 
diary card for this purpose.  
Information on SAEs will be collected and assessed throughout the study, from inclusion until 
30 days after vaccination. Any SAE occurring at any time during the study will be reported by the 
Investigator in the CRB according to the completion instructions provided by the Sponsor; this 
includes checking the “Serious” box on the AE CRF and completing the appropriate Safety 
Complementary Information CRFs. All information concerning the SAE is to be reported either as 
part of the initial reporting or during follow-up reporting if relevant information became available 
later (e.g., outcome, medical history, results of investigations, copy of hospitalization reports). 
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 AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of 
daily living. 
• Grade 2: A type of AE that is usually alleviated with additional therapeutic intervention. 
The event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the research participant.  
                                                 
a  The stop date of all related AEs will be actively solicited. For other events, the investigator will provide the stop 
date when it becomes available. AEs for which no stop date was obtained during the course of the study will be 
considered as ongoing at the end of the study. 
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• Grade 3: A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
• Whether the AE was related to the investigational product (for unsolicited systemic AEs) 
The Investigator will assess the causal relationship between the AE and the investigational 
product as either “Not related” or “Related”, as described in Section 9.3.2.3.5. 
• Action taken for each AE (e.g., medication) 
The action(s) taken by the subject 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) (19) (20) 
• Kawasaki disease (21) (22) (23) 
• Guillain-Barré syndrome (24) 
• Idiopathic thrombocytopenic purpura (25) (26) 
These events have been listed as AESIs based on the feedback received from the European Union 
regulators for other studies (conducted in younger age groups). No safety concerns relating to 
these AESIs have been identified with the use of MenACYW conjugate vaccine in completed 
clinical trials. Because of their medical importance and to ensure expedited communication to the 
Sponsor, these AESIs are to be considered and collected as SAEs and reported to the Sponsor 
according to the procedure described in Section 10. Further instructions on the data collection for 
these events and the relevant definitions will be provided in the Operating Guidelines. 
9.3.2.3.5 
Assessment of Causality  
The Investigator will assess the causal relationship between each unsolicited systemic AE and 
the product administered as either not related or related, based on the following definitions: 
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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. 
Adverse events likely to be related to the product, whether serious or not, that persist at the end of 
the study will be followed up by the Investigator until their complete disappearance or the 
stabilization of the subject’s condition. The Investigator will inform the Sponsor of the date of 
final disappearance of the event or the date of “chronicity” establishment. 
9.3.3 
Efficacy 
No clinical efficacy data will be obtained in the study. 
10 Reporting of Serious Adverse Events  
To comply with current regulations on SAE reporting to health authorities, the Investigator must 
document all SAEs regardless of causal relationship and notify the Sponsor and the Clinical 
Research Associate (CRA) within the notification timelines stated in the following sections. The 
Investigator will give access and provide the Sponsor and the CRA with all necessary information 
to allow the Sponsor to conduct a detailed analysis of the safety of the investigational products. It 
is the responsibility of the Investigator to request all necessary documentation (e.g., medical 
records, discharge summary, autopsy report) 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 
Serious adverse events occurring during a subject’s participation in the study or experiment must 
be reported within 24 hours to the Sponsor’s GPV Department and to the CRA. Every SAE must 
be reported, even if the Investigator considers that it is not related to the vaccine. The Investigator 
(licensed physician [MD or DO]) must validate the information entered on the AE CRF by 
completing the investigator validation form. 
The Investigator must indicate on the AE CRF that the event was serious and must complete the 
relevant SAE section of this form as well as the appropriate Safety Complementary Information 
CRFs. An e-mail alert will automatically be sent by the EDC system to the GPV mailbox, the 
CRA and the MTLs with relevant SAE information details. 
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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 & Triage – Case Management 
Global Pharmacovigilance Department  
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 RMOs as described in 
Section 5.3.  
10.2 Follow-up Reporting by the Investigator 
The AE CRF completed initially must be updated within 24 hours after the Investigator has 
become aware of any new relevant information concerning the SAE (e.g., 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 (e.g., 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, other products (e.g., a benefit vaccine), or to the experiment must also be 
reported as soon as possible. In such a case, the reporting procedure to be followed is identical to 
that described in Section 10.1. 
10.4 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. 
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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 local 
regulatory requirements. Reporting to health authorities will be according to the Sponsor’s 
standard operating procedures. 
The Sponsor’s RMOs will notify the Investigators in writing of the occurrence of any reportable 
SAEs. The Investigators/Sponsor will be responsible for informing the IRB(s) that reviewed the 
study protocol. 
11 Data Collection and Management 
11.1 Data Collection and CRF 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 prelisted 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. Subjects will also be provided with rulers for measuring the size of 
injection site reactions, and with standard digital thermometers for measuring daily temperatures. 
To ensure consistency of reporting, the study sites will instruct subjects on how to correctly use 
these tools.  
At specified intervals, the Investigator or an authorized designee will interview the subjects to 
collect the information recorded in the diary card, and will attempt to clarify anything that is 
incomplete or unclear. All clinical study information gathered by the study site will be reported 
electronically by the Investigator or authorized designee using a web-based CRB. (Any 
information that was not documented in the diary card will first be captured in the source 
document and then reported electronically.) The CRB has been designed specifically for this 
study under the responsibility of the Sponsor, using a validated Electronic Records / Electronic 
Signature-compliant platform (21 CFR Part 11). 
To ensure the correct and consistent completion of the CRBs, the Sponsor or authorized 
representative will provide all necessary tools, instructions, and training to all site staff involved 
in data entry prior to study start. Additional instructional documents such as training manuals and 
completion instructions will be provided to assist with data entry during the course of the study. 
Upon completion of training, each user requiring access to the EDC system will be issued a 
unique username and password. In the event of a change in study personnel, each newly assigned 
individual will receive a unique username and password; the username and password of a 
previous user may not be reissued. If any study personnel leave the study, the Investigator is 
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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 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 and Pregnancy Data 
During the study, SAE data (reported on the AE and Safety Complementary Information CRFs) 
and pregnancy data (reported by the Investigator on ePregnancy Forms) will be integrated into the 
Sponsor’s centralized GPV database upon receipt of these forms and after a duplicate check. Each 
case will be assigned a case identification number. Each case will be assessed by the case 
management platform or its delegate before being reported to the relevant authorities as 
necessary. The assessment of related cases will be done in collaboration with the Global Safety 
Officer and the RMO(s). Follow-up information concerning a completed case will be entered into 
the GPV database, and a new version of the case will be created. 
The information from the GPV database cases will be reconciled with that in the clinical database. 
Management of Clinical and Laboratory Data 
Clinical data, defined as all data reported in the CRB, and laboratory data will be handled by the 
Sponsor’s Clinical Data Management (CDM) platform or authorized representative. 
During the study, clinical data reported in the CRBs will be integrated into the clinical database 
under the responsibility of the Sanofi Pasteur CDM platform. Data monitoring at the sites and 
quality control in the form of computerized logic and/or consistency checks will be systematically 
applied to detect errors or omissions. In addition, data reviews may be performed several times by 
the Sponsor’s staff in the course of the study. Any questions pertaining to the reported clinical 
data will be submitted to the Investigator for resolution using the EDC system. Each step of this 
process will be monitored through the implementation of individual passwords to maintain 
appropriate database access and to ensure database integrity. 
The validation of the immunogenicity data will be performed at the laboratory level following the 
laboratory’s procedures. Information from the laboratory will be checked for consistency before 
integration into the clinical data warehouse. 
After integration of all corrections in the complete set of data, and after the SAE information 
available from CDM and the GPV Department has been reconciled, the database will be released for 
statistical analysis. 
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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 in a blinded manner. Periodic safety data review will be performed by the Sponsor’s 
Safety Management Team. 
12 Statistical Methods and Determination of Sample Size 
12.1 Statistical Methods 
Clinical data will be analyzed under the responsibility of the Biostatistics Platform of the Sponsor. 
A statistical analysis plan (SAP) will be written and peer reviewed before any statistical analyses 
are conducted. 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. 
Summaries of baseline demographic characteristics of the study subjects will be presented. The 
number of subjects enrolled and their age at enrollment, sex, race, and ethnic origin will be 
summarized for each group, as well as the number and description of protocol deviations. 
Categorical variables will be summarized and presented by frequency counts, percentages and 
95% confidence intervals (CIs). Continuous variables will be summarized and presented with 
means, standard deviations, and 95% CIs. 
The 95% CIs of point estimates will be calculated using the normal approximation for quantitative 
data and the exact binomial distribution (Clopper-Pearson method) for percentages. For GMTs, 
95% CIs of point estimates will be calculated using the normal approximation assuming they are 
log-normally distributed. 
12.1.1 Hypothesis and Statistical Methods for the Primary Objective 
Thirty days after the administration of MenACYW conjugate vaccine, the sufficiency of the 
vaccine seroresponse as assessed by the percentages of subjects who achieve an hSBA vaccine 
seroresponse* for meningococcal serogroups A, C, W, and Y, in Group 1 will be tested. 
Vaccine seroresponse will be considered sufficient if the lower limit of the 1-sided 97.5% CI for 
the percentage of subjects with an hSBA vaccine seroresponse against serogroups A, C, W and Y 
is greater than 40%.  
This is equivalent to testing H0: p ≤ 0.40 against H1: p > 0.40, where p is the observed proportion 
of subjects with hSBA vaccine seroresponse against serogroups A, C, W and Y. The 1-sided 
97.5% CI for the single proportion will be calculated using the exact method (Clopper-Pearson 
method). 
*hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
• For a subject with a pre-vaccination titer < 1:8, the post-vaccination titer must be ≥ 1:16. 
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• For a subject with a pre-vaccination titer ≥ 1:8, the post-vaccination titer must be at least 
4-fold greater than the pre-vaccination titer. 
12.1.2 Hypotheses and Statistical Methods for Secondary Objectives 
12.1.2.1 Secondary Objective 1 
Thirty days after the administration of MenACYW vaccine, the sufficiency of the vaccine 
seroresponse, as assessed by the percentages of subjects who achieve an hSBA vaccine 
seroresponse* for meningococcal serogroups A, C, W, and Y, in Group 2 will be tested. 
Vaccine seroresponse will be considered sufficient if the lower limit of the 1-sided 97.5% CI for 
the percentage of subjects with an hSBA vaccine seroresponse against serogroups A, C, W and Y 
is greater than 40%. 
This is equivalent to testing H0: p ≤ 0.40 against H1: p > 0.40, where p is the observed proportion 
of subjects with hSBA vaccine seroresponse against serogroups A, C, W and Y. The 1 sided 
97.5% CI for the single proportion will be calculated using the exact method (Clopper-Pearson 
method). 
*hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: 
• For a subject with a pre-vaccination titer < 1:8, the post-vaccination titer must be ≥ 1:16. 
• For a subject with a pre-vaccination titer ≥ 1:8, the post-vaccination titer must be at least 
4-fold greater than the pre-vaccination titer. 
12.1.2.2 Secondary Objective 2 
No hypotheses will be tested.  
The proportions of subjects in a planned nonrandom subset (approximately 60 subjects from 
Group 1 and approximately 60 subjects from Group 2) with vaccine seroresponse for 
meningococcal serogroups A, C, W, and Y at 6 (window, 5–7) days following vaccination will be 
determined; 95% CIs of point estimates will be calculated assuming proportions follow a binomial 
distribution using the Exact method. 
12.1.2.3 Secondary Objective 3 
No hypotheses will be tested. 
For GMTs, the 95% CIs of point estimates will be calculated using the normal approximation 
assuming antibody titers/concentrations are log normally distributed. For proportions, 95% CIs of 
point estimates will be calculated assuming proportions follow a binomial distribution using the 
Exact method. 
Categorical variables will be summarized and presented by frequency counts, proportion 
percentages, and CIs. The 95% CIs of point estimates will be calculated using the normal 
approximation for quantitative data and the exact binomial distribution (Clopper-Pearson method) 
for percentages.  
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RCDC figures and kinetic curves will be provided for the antibody titers against meningococcal 
serogroups contained in MenACYW conjugate vaccine. 
Descriptive analyses on A, C, W, and Y serogroups will include: 
• hSBA and rSBA GMTs and corresponding 95% CIs 
• hSBA and rSBA titer distribution and RCDCs 
• Percentages of subjects with hSBA titer ≥ 1:4 and ≥ 1:8 and corresponding 95% CIs 
• Percentages of subjects with rSBA titer ≥ 1:8 and ≥ 1:128 and corresponding 95% CIs 
12.1.3 Statistical Methods for Observational Objectives 
Immunogenicity 
All analyses will be descriptive; no hypotheses will be tested.  
For GMTs and geometric mean concentrations (GMCs), 95% CIs of point estimates will be 
calculated using the normal approximation assuming antibody titers/concentrations are log 
normally distributed. For proportions, 95% CIs of point estimates will be calculated assuming 
proportions follow a binomial distribution using the Exact method. 
Descriptive analyses on A, C, W, and Y serogroups will include: 
• hSBA and rSBA GMTs and corresponding 95% CIs 
• hSBA and rSBA titer distribution and RCDCs 
• Percentages of subjects with hSBA titer ≥ 1:4 and ≥ 1:8 and corresponding 95% CIs 
• Percentages of subjects with rSBA titer ≥ 1:8 and ≥ 1:128 and corresponding 95% CIs 
• Proportion with at least a 4-fold increase in hSBA and rSBA antibody titer compared to 
baseline (Group 1 and Group 2 during Stage I and Group 3 and Group 4 during Stage II) 
• An hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as a post-
vaccination titer ≥ 1:16 for subjects with pre-vaccination titer < 1:8, or a post-vaccination 
titer  ≥ 4 times the pre-vaccination titer for subjects with a pre-vaccination titer ≥ 1:8. 
• An rSBA vaccine seroresponse is defined as a post-vaccination titer ≥ 1:32 for subjects with 
pre-vaccination rSBA titer <1:8, or a post-vaccination titer ≥ 4 times the pre-vaccination titer 
for subjects with pre-vaccination rSBA titer ≥ 1:8. 
• Ratio of the GMT post-vaccination/GMT pre-vaccination and the associated 95% CI of the 
ratio (at Day 30 for Group 1 and Group 2 and at Day 6 in a subset of Group 1 and Group 2 
[during Stage I], and at Day 30 for Group 3 and Group 4 [during Stage II]). 
Descriptive analyses on anti-tetanus antibody concentrations will include: 
• Geometric mean concentrations at Day 0 (all groups), 2 years after enrollment (Groups 3 and 
4), and 30 (window, + 14) days after the administration of a single dose of MenACYW 
conjugate vaccine in Study MEQ00066 (Groups 1–4) 
• Proportion of subjects achieving seroprotective antibody levels ≥ 0.01 IU (international units) 
/mL, ≥ 0.1 IU/mL, and ≥ 1.0 IU/mL to tetanus toxoid 30 (window, + 14) days after the 
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administration of a single dose of MenACYW conjugate vaccine in Study MEQ00066 
(Groups 1–4)  
• RCDCs and kinetic curves 
Safety 
All analyses will be descriptive; no hypotheses will be tested.  
Safety results will be described for subjects revaccinated with MenACYW conjugate vaccine 
(i.e., Groups 1–4). The main parameters for the safety endpoints will be described by 95% CIs 
(based on the Clopper-Pearson method). 
The frequency and percentage of subjects who had solicited injection site and systemic reactions 
and their 95% CIs will be provided. These events will be tabulated by type of reactions and 
intensity for each study group. These events will also be summarized by other categories specified 
in the endpoints (e.g., time of onset, number of days of occurrence, action taken). 
Unsolicited AEs will be collected, coded, and summarized by MedDRA system organ class and 
PT. For each unsolicited AE, the number of subjects with at least one instance of that event will 
be reported. Unsolicited AEs will also be tabulated by intensity and relatedness of study vaccine 
and by other categories specified in the endpoints. 
Immediate reactions, SAEs, and any event that leads to subject withdrawal from the study will be 
tabulated separately. 
12.2 Analysis Sets 
12.2.1 Stage I Analysis Sets 
12.2.1.1 Full Analysis Sets 
The Stage I Day 30 Full Analysis Set (FAS1) is defined as subjects in Groups 1 and 2 who 
received the study vaccine and have a valid serology result for at least 1 serogroup from a blood 
sample provided 30 (window, +14) days post-vaccination. 
The Stage I Day 6 FAS (FAS2) is defined as the subset of Group 1 and 2 subjects who received 
the study vaccine and have a valid serology result for at least 1 serogroup from a blood sample 
provided 6 (window, 5–7) days post-vaccination. 
The Stage I FAS for persistence (FAS3) includes subjects in Groups 1, 2, 3, 4, 5 and 6 who have a 
valid serology result for at least 1 serogroup from a pre-vaccination blood sample (3-year or 6–7-
year antibody persistence). 
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12.2.1.2 Per-Protocol Analysis Sets 
12.2.1.2.1 Day 30 Per-Protocol Analysis Set  
Groups 1 and 2 
The Stage I Day 30 Per-Protocol Analysis Set (PPAS1) is a subset of Stage I Day 30 FAS (FAS1). 
Subjects with at least 1 of the following relevant protocol deviations will be excluded from the 
PPAS1: 
• Subject did not meet all protocol-specified inclusion criteria or met at least 1 of the 
protocol-specified exclusion criteria 
• Subject did not receive MenACYW conjugate vaccine according to randomization 
• Preparation and/or administration of vaccine was not done as per-protocol 
• Subject did not receive vaccine in the proper time window 
• Subject did not provide a post-dose serology sample in the pre-specified time window at 
30 (window, + 14) days post-vaccination 
• Subject received a protocol-prohibited therapy/medication/vaccine that might impact 
antibody response to the study vaccine 
• Subjects received study vaccine deemed unacceptable for use (e.g., because of a temperature 
excursion). 
• Subject’s post-vaccination serology sample did not produce a valid test result for any antigen 
(i.e., results for all antigens are missing) 
• Any other deviation identified during conduct of the study and judged by the clinical team 
during data review as having a potential impact on the assessment of immunogenicity 
12.2.1.2.2 Day 6 Per-Protocol Analysis Set 
Groups 1 and 2 
The Day 6 PPAS (PPAS2) is a subset of Day 6 FAS (FAS2). Subjects with at least 1 of the 
following relevant protocol deviations will be excluded from the Day 6 PPAS: 
• Subject did not meet all protocol-specified inclusion criteria or met at least 1 of the 
protocol-specified exclusion criteria 
• Subject did not receive MenACYW conjugate vaccine according to randomization 
• Preparation and/or administration of vaccine was not done as per-protocol 
• Subject did not receive vaccine in the proper time window 
• Subject did not provide a post-dose serology sample in the pre-specified time window at 
6 (window, 5 to 7) days post-vaccination  
• Subject received a protocol-prohibited therapy/medication/vaccine that might impact 
antibody response to the study vaccine 
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• Subjects received study vaccine deemed unacceptable for use (e.g., because of a temperature 
excursion). 
• Subject’s post-vaccination serology sample did not produce a valid test result for any antigen 
(i.e., results for all antigens are missing) 
• Any other deviation identified during conduct of the study and judged by the clinical team 
during data review as having a potential impact on the assessment of immunogenicity 
12.2.1.3 Safety Analysis Set 
Groups 1 and 2  
The Stage I Safety Analysis Set (SafAS1) is defined as those subjects who have received the 
study vaccine and have any safety data available. Safety will be analyzed according to the vaccine 
actually received by the subject.   
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.2 Stage II Analysis Sets 
Groups 3 and 4 
12.2.2.1 Full Analysis Sets 
The Stage II Day 30 FAS (FAS4) is defined as subjects in Groups 3 and 4 who received the study 
vaccine and have a valid serology result for at least 1 serogroup from a blood sample provided 
30 (window, +14) days post-vaccination.  
The Stage II FAS for persistence (FAS5) includes subjects in Groups 3 and 4 who have a valid 
serology result for at least 1 serogroup from a pre-vaccination blood sample (5-year antibody 
persistence). 
12.2.2.2 Day 30 Per-Protocol Analysis Set 
The Stage II Day 30 PPAS (PPAS3) is a subset of the Stage II Day 30 FAS (FAS4). Subjects with 
at least 1 of the following relevant protocol deviations will be excluded from the Stage II Day 30 
PPAS: 
• Subject did not meet all protocol-specified inclusion criteria or met at least 1 of the 
protocol-specified exclusion criteria 
• Subject did not receive MenACYW conjugate vaccine according to randomization 
• Preparation and/or administration of vaccine was not done as per-protocol 
• Subject did not receive vaccine in the proper time window 
• Subject did not provide a post-dose serology sample in the pre-specified time window at 
30 (window, + 14) days post-vaccination 
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• Subject received a protocol-prohibited therapy/medication/vaccine that might impact 
antibody response to the study vaccine 
• Subjects received study vaccine deemed unacceptable for use (e.g., because of a temperature 
excursion). 
• Subject’s post-vaccination serology sample did not produce a valid test result for any antigen 
(i.e., results for all antigens are missing) 
• Any other deviation identified during conduct of the study and judged by the clinical team 
during data review as having a potential impact on the assessment of immunogenicity 
12.2.2.3 Safety Analysis Set 
The Stage II Safety Analysis Set (SafAS2) is defined as those subjects who have received the 
study vaccine and have any safety data available. Safety will be analyzed according to the vaccine 
actually received by the subject.   
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.3 Populations Used in Analyses 
12.2.3.1 Stage I 
The primary immunogenicity analyses will be performed on the Stage I Day 30 PPAS (PPAS1) 
and will be confirmed on the Stage I Day 30 FAS (FAS1). In the FAS1, subjects will be analyzed 
by the vaccine group to which they were randomized.  
The secondary immunogenicity analyses (Day 6 subset) will be performed on the Day 6 PPAS 
(PPAS2) and Day 6 FAS (FAS2). 
The secondary antibody persistence analyses will be performed on the FAS3. 
The safety analysis will be performed on the Stage I Safety Analysis Set (SafAS1). Subjects will 
be analyzed according to the vaccine they actually received. 
12.2.3.2 Stage II 
Immunogenicity analyses will be performed on Stage II Day 30 PPAS (PPAS3) and confirmed on 
the Stage II Day 30 FAS (FAS4). 
The secondary antibody persistence analyses will be performed on FAS5.  
The safety analysis will be performed on the Stage II Safety Analysis Set (SafAS2). Subjects will 
be analyzed according to the vaccine they actually received. 
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12.3 Handling of Missing Data and Outliers 
12.3.1 Immunogenicity 
Missing data will not be imputed. No search for outliers will be performed. 
For the computations, LLOQ and upper limit of quantification (ULOQ) will be managed as 
follows:  
• If a titer is < LLOQ, then LLOQ/2 will be used 
• If a titer is ≥ LLOQ and < ULOQ, then the titer itself will be used 
• If a titer is ≥ ULOQ, then ULOQ will be used 
The derived endpoint of fold-rise is computed as follows for extreme values, to minimize the 
numerator and maximize the denominator: 
• If the baseline computed value is < LLOQ and the post-baseline computed value is < LLOQ 
then the fold-rise is 1 
• If the baseline computed value is ≥ LLOQ and the post-baseline computed value is ≥ LLOQ 
then the fold-rise is post-baseline computed value/baseline computed value 
• If the baseline computed value is ≥ LLOQ and the post-baseline computed value is < LLOQ 
then the fold-rise is (LLOQ/2)/baseline computed value 
• If the baseline computed value is < LLOQ and the post-baseline computed value is ≥ LLOQ 
then the fold-rise is post-baseline computed value/LLOQ 
12.3.2 Safety 
No replacement will be done.  
12.3.3 Efficacy 
Not applicable. 
12.4 Interim/Preliminary Analysis 
Relevant analyses will be completed for subjects in Groups 1, 2, 3, 4, 5, and 6 after completion of 
Stage I. After collecting all planned data for Groups 1, 2, 3, 4, 5, and 6 after completion of 
Stage I, the study database will be cleaned and locked. All statistical analyses planned for these 
groups will be conducted, and a final study report will be written. 
After the post-revaccination safety and immunogenicity data for Group 3 and Group 4 are 
collected during Stage II, the database will be updated to include the newly collected data, which 
will be cleaned, and the database will be relocked. Analysis of the new data will be conducted and 
an addendum to the CSR will be written. 
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12.5 Determination of Sample Size and Power Calculation 
A total of 560 subjects are planned to be enrolled: 
• Group 1 (subjects who received Menomune vaccine in Study MET49) will receive a single 
dose of MenACYW conjugate vaccine at enrollment in Study MEQ00066: n=180 
• Group 2 (subjects who received MenACYW conjugate vaccine in Study MET49) will receive 
a single dose of MenACYW conjugate vaccine at enrollment in Study MEQ00066: n=180 
• Group 3 (subjects who received Menomune vaccine in Study MET49) will receive a single 
dose of MenACYW conjugate vaccine 2 years after enrollment in Study MEQ00066: n=40 
• Group 4 (subjects who received MenACYW conjugate vaccine in Study MET49) will receive 
a single dose of MenACYW conjugate vaccine 2 years after enrollment in Study MEQ00066: 
n =40 
• Group 5 (subjects who previously received Menomune vaccine in Study MET44): n=60 
• Group 6 (subjects who previously received MenACYW conjugate vaccine in Study MET44): 
n=60 
For the Primary Objective and Secondary Objective 1: For Group 1 and Group 2, a sample size 
of 120 achieves at least 90.0% power to detect that the lower bound of the one-sided 97.5% CI is 
greater than 0.40 (proportion under the null hypothesis) using a 1-sided exact test with a 
significance level (alpha) of 0.025. 
For all other groups (i.e., Groups 3–6), descriptive statistics will be calculated and presented in 
this study; hence, no sample size or study power was calculated for these groups. 
13 Ethical and Legal Issues and Investigator/Sponsor Responsibilities 
13.1 Ethical Conduct of the Study/Good Clinical Practice 
The conduct of this study will be consistent with the standards established by the Declaration of 
Helsinki and compliant with the ICH guidelines for GCP as well as with all local and/or national 
regulations and directives. 
13.2 Source Data and Source Documents 
“Source data” are the data contained in source documents. Source documents are original 
documents or certified copies, and include, but are not limited to, diary cards, medical and 
hospital records, screening logs, informed consent/assent forms, telephone contact logs, and 
worksheets. The purpose of study source documents is to document the existence of subjects and 
to substantiate the integrity of the study data collected. Investigators must maintain source 
documents so that they are accurate, complete, legible, and up to date. 
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For missing or discrepant data on a diary card, the study coordinator will obtain verbal clarification 
from the subject, enter the response into the “Investigator’s comment” page of the diary card, and 
transfer the information to the CRB. 
The subject pre-screening log should list all individuals contacted by the Investigators to 
participate in the study, regardless of the outcome. 
The Investigator must printa any electronic records on an ongoing basis, sign and date them 
immediately after creation, and keep the printouts on file as source documents that can be verified 
by the Sponsor or an inspector against the electronic records. Any subsequent changes of an 
electronic record require the record to be re-printed, dated (with an indication of the date of 
change), and signed. Such records must also be kept together with the original printed copy. 
Good Documentation Practice should be followed by the Investigator and the site staff managing 
source documents. 
13.3 Confidentiality of Data, Data Protection, and Access to Subject Records 
Prior to initiation of the study, the Investigator will sign a fully executed confidentiality 
agreement with Sanofi Pasteur. In the event a subject’s medical records are not at the 
investigational site, it is the responsibility of the Investigator to obtain those records if needed. 
All personal data collected related to subjects, Investigators, or any person involved in the study, 
which may be included in the Sponsor’s databases, shall be treated in compliance with all 
applicable laws and regulations including the General Data Protection Regulation. Data collected 
must be adequate, relevant and not excessive, in relation to the purposes for which they are 
collected. Each category of data must be properly justified and in line with the study objective. 
Each subject’s race and ethnicity will be collected in this study because these data are required by 
regulatory agencies (e.g., on the African American population for the Food and Drug 
Administration or on Japanese population for the Pharmaceuticals and Medical Devices Agency 
in Japan) (29). 
Subjects will be assigned a unique identifier by the Sponsor. Any subject records or datasets that 
are transferred to the Sponsor will contain the identifier only; subject names or any information 
which would make the subject identifiable will not be transferred. 
The subject must be informed that his/her personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to the 
subject. 
The subject must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate IRB 
members, and by inspectors from regulatory authorities. 
                                                 
a  Unless the electronic medical records are managed by validated computerized systems that are compliant with US 
21 CFR Part 11, in which case they are acceptable on their own. 
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When archiving or processing personal data pertaining to the Investigator and/or to the subjects, 
the Sponsor shall take all appropriate measures to safeguard and prevent access to this data by any 
unauthorized third party. 
13.4 Monitoring, Auditing, and Archiving 
13.4.1 Monitoring 
Before the start of the study (i.e., before the inclusion of the first subject in the first center), the 
Investigators and the Sponsor’s staff or a representative will meet at the site-initiation visit to 
discuss the study protocol and the detailed study procedures. Emphasis will be placed on inclusion 
and exclusion criteria, visit timing, safety procedures, informed consent procedures, SAE 
reporting procedures, CRB completion, and the handling of samples and products. The Sponsor’s 
staff or a representative will ensure and document that all material to be used during the study has 
been received at the site; and that the study investigator team and local Sponsor/delegate staff 
have been properly informed about the study, GCP and regulatory requirements, and the 
Sponsor’s procedures. Specific training sessions for the study investigator team and the CRAs on 
these topics may be performed as necessary and should be documented. 
The following instruction manuals will be provided: the CRF Completion Instructions for entering 
data into the CRB, and the Operating Guidelines for detailed study procedures such as product 
management and sample-handling procedures. 
After the start of the study, the Sponsor’s staff or a representative will be in regular contact with 
the investigational team through telephone calls and regular follow-up visits. The Investigator or 
delegate must be available for these visits and must allow the Sponsor/delegate staff direct access 
to subject medical files and CRBs. During these visits, the Sponsor/delegate staff will: 
• Evaluate the quality of the study progress (adherence to protocol and any study-specific 
guidelines, quality of data collection and document completion, signature of consent forms, 
occurrence of SAEs, sample and product management, cold-chain monitoring, archiving) 
• 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 
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13.4.2 Audits and Inspections 
A quality assurance audit may be performed at any time by the Sponsor’s Clinical Quality 
Assessment department 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 planned addendum to the final study report or  
• such longer period as required by applicable regulatory requirements 
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 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 
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recognition to the study group. In addition, Sanofi Pasteur shall be offered an association with all 
such publications, it being understood that Sanofi Pasteur is entitled to refuse the association. 
Sanofi Pasteur must have the opportunity to review all proposed abstracts, manuscripts, or 
presentations regarding this study at least 90 days prior to submission for publication/presentation. 
Any information identified by Sanofi Pasteur as confidential must be deleted prior to submission, 
it being understood that the results of this study are not to be considered confidential. 
Sanofi Pasteur’s review can be expedited to meet publication guidelines. 
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14 Reference List 
 
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Rosenstein NE, Perkins BA, Stephens DS, et al. The changing epidemiology of 
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Centers for Disease Control and Prevention. Meningococcal Vaccine Recommendations.  
[cited on 19 March 2019]. Available at: 
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Centers for Disease Control and Prevention. CDC Yellow Book 2018. Chapter 3: Infectious 
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Keyserling H, Papa T, Koranyi K, et al. Safety, immunogenicity, and immune memory of a 
novel meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid 
conjugate vaccine (MCV-4) in healthy adolescents. Arch Pediatr Adolesc Med. 
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Vu DM, Welsch JA, Zuno-Mitchell P, et al. Antibody persistence 3 years after 
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15 
Cohen AC, MacNeil JR, Harrison LH, et al. Effectiveness and duration of protection of one 
dose of a meningococcal conjugate vaccine. Pediatrics. 2017;139(2):e20162193. 
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Centers for Disease Control and Prevention. Update: Guillain-Barré syndrome among 
recipients of Menactra meningococcal conjugate vaccine--United States, June 2005-
September 2006. Morb Mortal Wkly Rep. 2006; 55(41):1120-4. 
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Velentgas P, Amato AA, Bohn RL, et al. Risk of Guillain-Barre syndrome after 
meningococcal conjugate vaccination. Pharmacoepidemiol Drug Saf. 2012;21(12):1350-8. 
18 
National Research Council. Diphtheria toxoid, tetanus toxoid, and acellular pertussis-
containing vaccines. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse effects of 
vaccines: evidence and causality. Washington (DC): The National Academies Press; 
2012:557-8. 
19 
Marcy SM, Kohl KS, Dagan R, et al. Fever as an adverse event following immunization: 
case definition and guidelines of data collection, analysis and presentation. Vaccine. 2004; 
22:551-556. 
20 
Bonhoeffer J, Menkes J, Gold M, et al. Generalized convulsive seizure as an adverse event 
following immunization: case definition and guidelines for data collection, analysis, and 
presentation. Vaccine. 2004;22:557-62. 
21 
Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term 
management of Kawasaki disease: a statement for health professionals from the Committee 
on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular 
Disease in the Young, American Heart Association. Pediatrics. 2004;114(6):1708-33. 
22 
Centers for Disease Control and Prevention. Kawasaki Syndrome Case Report. Atlanta: 
Department of Health & Human Services. [cited 03 December 2018]. Available from: 
http://www.cdc.gov/kawasaki/pdf/ks_case_report-fillable.pdf. 
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Phuong LK, Bonetto C, Buttery J, et al; Brighton Collaboration Kawasaki Disease Working 
Group. Kawasaki disease and immunisation: standardised case definition & guidelines for 
data collection, analysis. Vaccine. 2016;34(51):6582-9. 
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Sejvar JJ, Kohl KS, Gidudu J, et al. Guillain-Barré syndrome and Fisher syndrome: case 
definitions and guidelines for collection, analysis, and presentation of immunization safety 
data. Vaccine. 2011;29(3):599-612. 
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Wise RP, Bonhoeffer J, Beeler J, et al. Thrombocytopenia: case definition and guidelines 
for collection, analysis, and presentation of immunization safety data. 
Vaccine.2007;25(31):5717-24. 
26 
Chu YW, Korb J, Sakamoto M. Idiopathic thrombocytopenic purpura. Pediatr Rev. 
2000;21(3):95-104. 
27 
Bonett DG, Price RM. Adjusted Wald confidence interval for a difference of binomial 
proportions based on paired data. J Educ Behav Stat. 2012;37(4):479-88. 
28 
Committee for Proprietary Medicinal Products (CPMP). Points to consider on switching 
between superiority and non-inferiority. London: The European Agency for the Evaluation 
of Medicinal Products; 2000 Jul 27. [cited on 23 April 2019]. Available from: 
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between-superiority-non-inferiority_en.pdf 
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29 
Food and Drug Administration. Collection of Race and Ethnicity Data in Clinical Trials. 
Guidance for Industry and Food and Drug Administration Staff. [cited on 31 March 2019]. 
Available from: 
https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126396.pdf 
 
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15 Signature Page 
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Document Number
CLI_00070361
Version Number
3.0
Project Code
MenQuad TT
Arficact Name
Protocol Body
-
-
-
Approver Name
Date
(Universal Time)
Reason for Signature
Approval
-
-
 
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