Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix®, and When Administered Alone or Concomitantly With 9vHPV and Tdap-IPV Vaccines in Healthy Adolescents
Phase: PHASE3
Conditions: Meningococcal Immunisation, Healthy Volunteers
Sponsor: Sanofi Pasteur, a Sanofi Company

 
 
  
 
 
 
 
 
 
  
 
 
Title Page 
Protocol Title: 
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Versus 
Nimenrix®, and When Administered Alone or Concomitantly with 9vHPV and Tdap-IPV 
Vaccines in Healthy Adolescents  
Study Code: MEQ00071 
Protocol Version Number: 5.0 
Amendment Number: 1.0 
Compound: MenACYW Conjugate Vaccine 
Study Phase: Phase IIIb 
Short Title: 
Study on a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) 
Compared to a Meningococcal Reference Vaccine, and When Given Alone or Concomitantly with 
Two Other Vaccines in Healthy Adolescents 
Sponsor Name and Legal Registered Address: 
Sanofi Pasteur 
14 Espace Henry Vallée, 69007 Lyon, France 
Manufacturer: 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, USA 
Regulatory Agency Identifier Numbers: 
EudraCT: 2020-001665-37 
WHO UTN: U1111-1249-2973 
Approval Date: 19-May-2021 
Medical Monitor Name and Contact Information are Provided in the Operating Guidelines. 
The study centers, the Investigators at each center, and the Coordinating Investigators are listed in 
a separate document. 
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NCT04490018

 
 
 
  
 
 
 
 
 
 
  
 
 
Document History  
Previous 
Versions 
Date 
Comments 
1.0 
07 May 2020 
Internal version not submitted 
2.0 
29 May 2020 
Updated document with changes in version 2.0 of the Common 
Protocol Template (CPT) dated 13 May 2020 and released on 
19 May 2020 
3.0 
22 July 2020 
IEC/IRB-approved version. Updated in response to comments 
provided by the Health Authorities prior to study initiation 
4.0 
08 December 2020 
Updated document submitted to the IEC/IRB and the Health 
Authorities in Italy 
 
 
 
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Table of Contents 
List of Tables .................................................................................................................................... 7 
List of Figures .................................................................................................................................. 8 
1 
Protocol Summary ............................................................................................................. 9 
1.1 
Synopsis ............................................................................................................................ 9 
1.2 
Schema ............................................................................................................................ 14 
1.3 
Schedule of Activities (SoA) .......................................................................................... 16 
2 
Introduction ..................................................................................................................... 22 
2.1 
Study Rationale ............................................................................................................... 22 
2.2 
Background ..................................................................................................................... 22 
2.3 
Benefit/Risk Assessment ................................................................................................ 24 
2.3.1 
Risks from Study Participation ..................................................................................... 25 
2.3.2 
Benefits from Study Participation ................................................................................ 28 
2.3.3 
COVID-19 Risk Assessment ........................................................................................ 28 
2.3.4 
Overall Benefit-Risk Conclusion .................................................................................. 28 
3 
Objectives and Endpoints ............................................................................................... 28 
4 
Study Design .................................................................................................................... 33 
4.1 
Overall Design ................................................................................................................ 33 
4.2 
Scientific Rationale for Study Design ............................................................................. 35 
4.3 
Justification for Dose ...................................................................................................... 36 
4.4 
End of Study Definition .................................................................................................. 36 
5 
Study Population ............................................................................................................. 36 
5.1 
Inclusion Criteria ............................................................................................................ 37 
5.2 
Exclusion Criteria ........................................................................................................... 37 
5.3 
Lifestyle Considerations ................................................................................................. 39 
5.4 
Screen Failures ................................................................................................................ 39 
6 
Study Intervention ........................................................................................................... 39 
6.1 
Note: routine vaccines administered outside of study protocol are not considered 
as study interventions. Study Intervention Administered ............................................... 39 
6.2 
Preparation/Handling/Storage/Accountability ................................................................ 43 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................................ 43 
6.3.1 
Randomization and Allocation Procedures .................................................................. 43 
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6.3.2 
Blinding and Code-breaking Procedures ...................................................................... 44 
6.4 
Study Intervention Compliance ...................................................................................... 45 
6.5 
Concomitant Therapy ...................................................................................................... 45 
6.5.1 
Rescue Medicine ........................................................................................................... 47 
6.6 
Dose Modification .......................................................................................................... 47 
6.7 
Intervention After the End of the Study .......................................................................... 48 
7 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal .......................................................................................... 48 
7.1 
Discontinuation of Study Intervention ............................................................................ 48 
7.1.1 
Temporary Contraindications ....................................................................................... 48 
7.1.2 
Temporary Contraindications for Blood Sample .......................................................... 48 
7.1.3 
Definitive Contraindications ......................................................................................... 49 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................ 49 
7.3 
Lost to Follow-up ............................................................................................................ 50 
8 
Study Assessments and Procedures ............................................................................... 50 
8.1 
Efficacy and Immunogenicity Assessments ................................................................... 52 
8.1.1 
Efficacy Assessments ................................................................................................... 52 
8.1.2 
Immunogenicity Assessments ...................................................................................... 52 
8.2 
Safety Assessments ......................................................................................................... 54 
8.2.1 
Medical History ............................................................................................................ 54 
8.2.2 
Physical Examinations .................................................................................................. 54 
8.2.3 
Vital Signs .................................................................................................................... 55 
8.2.4 
Clinical Safety Laboratory Assessments ...................................................................... 55 
8.3 
Adverse Events and Serious Adverse Events ................................................................. 55 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information ......................... 55 
8.3.2 
Method of Detecting AEs and SAEs ............................................................................ 56 
8.3.3 
Follow-up of AEs and SAEs ........................................................................................ 57 
8.3.4 
Regulatory Reporting Requirements for SAEs ............................................................ 57 
8.3.5 
Pregnancy ..................................................................................................................... 57 
8.3.6 
Adverse Events of Special Interest ............................................................................... 58 
8.4 
Treatment of Overdose ................................................................................................... 58 
8.5 
Pharmacokinetics ............................................................................................................ 58 
8.6 
Pharmacodynamics ......................................................................................................... 58 
8.7 
Genetics ........................................................................................................................... 59 
8.8 
Biomarkers ...................................................................................................................... 59 
8.9 
Immunogenicity Assessments ......................................................................................... 59 
8.10 
Medical Resource Utilization and Health Economics .................................................... 59 
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9 
Statistical Considerations ............................................................................................... 59 
9.1 
Statistical Hypotheses ..................................................................................................... 59 
9.2 
Sample Size Determination ............................................................................................. 60 
9.3 
Populations for Analyses ................................................................................................ 61 
9.4 
Statistical Analyses ......................................................................................................... 64 
9.4.1 
General Considerations ................................................................................................. 64 
9.4.2 
Primary Hypotheses and Methods ................................................................................ 64 
9.4.3 
Secondary Hypotheses and Methods ............................................................................ 65 
9.4.4 
Observational Endpoints ............................................................................................... 65 
9.4.5 
Sensitivity analysis due to COVID-19 pandemic ......................................................... 65 
9.5 
Interim Analyses ............................................................................................................. 66 
9.6 
Data Monitoring Committee ........................................................................................... 66 
10 
Supporting Documentation and Operational Considerations .................................... 67 
10.1 
Appendix: Regulatory, Ethical, and Study Oversight Considerations ............................ 67 
10.2 
Regulatory and Ethical Considerations ........................................................................... 67 
10.2.1 
Financial Disclosure ..................................................................................................... 68 
10.2.2 
Informed Consent Process ............................................................................................ 68 
10.2.3 
Data Protection and Future Use of Stored Samples ..................................................... 69 
10.2.4 
Committees Structure ................................................................................................... 70 
10.2.5 
Dissemination of Clinical Study Data .......................................................................... 70 
10.2.6 
Data Quality Assurance ................................................................................................ 71 
10.2.7 
Source Documents ........................................................................................................ 71 
10.2.8 
Study and Site Start and Closure .................................................................................. 72 
10.2.9 
Publication Policy ......................................................................................................... 72 
10.3 
Appendix: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................ 73 
10.3.1 
Definition of AE ........................................................................................................... 73 
10.3.2 
Definition of SAE ......................................................................................................... 75 
10.3.3 
Recording and Follow-Up of AE and/or SAE .............................................................. 76 
10.3.4 
Reporting of SAEs ........................................................................................................ 78 
10.3.5 
Assessment of Intensity ................................................................................................ 79 
10.3.5.1 
Tables for Clinical Abnormalities .............................................................................. 79 
10.3.5.1.1 
Solicited AR Intensity Grading Scale ...................................................................... 79 
10.3.5.1.2 
Unsolicited AE Intensity Grading Scale .................................................................. 84 
10.4 
Appendix: Collection of Pregnancy Information ............................................................ 85 
10.4.1 
Contraception Guidance ............................................................................................... 87 
10.5 
Appendix: Risk-based Approach .................................................................................... 88 
10.6 
Appendix: Abbreviations ................................................................................................ 89 
11 
References ........................................................................................................................ 91 
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12 
Sponsor Signature Page .................................................................................................. 94 
 
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List of Tables 
Table 1.1: Schedule of activities for Group 1 and Group 2 ........................................................... 16 
Table 1.2: Schedule of activities for Group 3 ................................................................................ 19 
Table 2.1: Potential risks of clinical significance and risk management ...................................... 25 
Table 3.1: Objectives and endpoints ............................................................................................. 29 
Table 4.1: Overall design .............................................................................................................. 33 
Table 6.1: Identity of study intervention ....................................................................................... 40 
Table 8.1: Blood sampling volume (mL) per visit- Groups 1 and 2 ............................................. 51 
Table 8.2: Blood sampling volume (mL) per visit- Group 3 ......................................................... 52 
Table 9.1: Power of the study for the primary objective ............................................................... 60 
Table 10.1: Solicited injection site reactions: terminology, definitions, and intensity scales – 
Adolescents aged ≥ 10  to <17 years ............................................................................................. 80 
Table 10.2: Solicited systemic reactions: terminology, definitions, and intensity scales –
Adolescents aged ≥ 10 to < 17 years ............................................................................................. 82 
 
 
 
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List of Figures 
Figure 1.1 – Study design .............................................................................................................. 15 
 
 
 
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Groups 1 and 2, and on D01 and D31 
(+14 days) in Group 3: 
• 
Anti-tetanus and anti-diphtheria 
antibody concentrations  
• 
Anti-tetanus and anti-diphtheria 
antibody concentrations ratio  
• 
Anti-tetanus and anti-diphtheria 
antibody concentrations ≥ 0.1 
international units/milliliter (IU/mL) 
and ≥ 1.0 IU/mL 
• 
Anti-polio 1, 2, and 3 antibody titers 
• 
Anti-polio 1, 2, and 3 antibody titers 
ratio  
• 
Anti-polio 1, 2, and 3 antibody titers 
≥ 1:8  
• 
Anti-pertussis antibody concentration 
(pertussis toxoid [PT], filamentous 
hemagglutinin [FHA], pertactin 
[PRN], fimbriae types 2 and 3 [FIM])  
• 
Anti-pertussis antibody 
concentrations ratio (PT, FHA, PRN, 
FIM) 
• 
Anti-pertussis vaccine seroresponse 
(PT, FHA, PRN, FIM), defined as 
follows: 
• 
≥ 4 × baseline concentration, if 
the anti-pertussis antibody 
concentration at baseline (D01) 
is < 4 × lower limit of 
quantification (LLOQ)  
• 
or ≥ 2 × baseline concentration, 
if the anti-pertussis antibody 
concentration at baseline (D01) 
is ≥ 4 × LLOQ  
• Antibody titers against antigens contained 
in human papillomavirus (HPV) vaccine 
measured on D31 (+14 days) and D61 
(+14 days) in Groups 1 and 2, and on D01 
and D31 (+14 days) in Group 3: 
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• 
Anti-HPV antibody titers for each of 
the HPV types (types 6, 11, 16, 18, 
31, 33, 45, 52, and 58) 
• 
Anti-HPV antibody titer ratio for 
each of the HPV types 
• 
Vaccine seroconversion for each of 
the HPV types (6, 11, 16, 18, 31, 33, 
45, 52, and 58) by D31 (+14 days) 
after vaccination, with 
seroconversion defined as follows: 
• 
Changing serostatus from 
seronegative at baseline (D01) to 
seropositive by D31 (+14 days) 
after vaccination. A participant 
with a titer at or above the 
serostatus cut-off for a given 
HPV type is considered 
seropositive for that type. The 
serostatus cut-offs for HPV types 
6, 11, 16, 18, 31, 33, 45, 52, and 
58 are 30, 16, 20, 24, 10, 8, 8, 8, 
and 8 milli-Merck units 
(mMU)/mL, respectively 
Safety 
• To describe the safety profile in each 
group after each and any vaccination 
The safety profile will be evaluated for each 
vaccine within 30 days (+14 days) after each 
vaccination. The following endpoints will be 
used for the evaluation of safety: 
• Unsolicited systemic adverse events (AEs) 
reported in the 30 minutes after each 
vaccination 
• Solicited (pre-listed in the participant’s 
diary card and [electronic] Case Report 
Form [CRF]) injection site and systemic 
reactions starting any time from the day of 
vaccination through 7 days after each 
vaccination 
• Unsolicited (recorded in a diary card) non-
serious AEs reported up to 30 days after 
each vaccination 
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Disclosure Statement: This is a parallel group prevention study with 2 groups that are 
observer-blind (only the person administering the vaccine is unblinded), and 1 group that is 
open-label. 
Number of Participants: 
A total of 464 participants are expected to be randomized. 
Intervention Groups and Duration: 
Eligible participants will be randomized in a 3:3:2 ratio in the following study groups: 
• Group 1 (investigational group – sequential administration): MenACYW conjugate vaccine on 
Day (D) 01 and 9vHPV* + Tdap-IPV vaccines on D31: n=174 
• Group 2 (control group – sequential administration): Nimenrix® on D01 and 9vHPV* + 
Tdap-IPV vaccines on D31: n=174 
• Group 3 (investigational group – concomitant administration): MenACYW conjugate vaccine 
+ 9vHPV* + Tdap-IPV vaccines on D01: n=116 
*Note: This is the first dose of 9vHPV, of the 2-dose or 3-dose series according to the national 
recommendations and age of the participant. These additional vaccinations for the completion of 
9vHPV schedule will take place outside of the objectives and scope of this study and thus will not 
be described in this protocol. 
All injections will be given via intramuscular route. The duration of study participation for each 
participant will be approximately 30 to 60 days. 
Data Monitoring Committee: No 
1.2 
Schema 
The study design of MEQ00071 study is presented in Figure 1.1. 
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Figure 1.1 – Study design 
 
 
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1.3 
Schedule of Activities (SoA) 
Visits procedures are detailed in the Operating Guidelines. 
The schedule of activities for Group 1 and Group 2 are given in Table 1.1 and for Group 3 are 
given in Table 1.2. 
Table 1.1: Schedule of activities for Group 1 and Group 2 
Phase IIIb Study, 3 Visits, 2 Vaccination Visits, 2 Telephone Calls, 3 Vaccine Injections, 
3 Blood Collections, 60 Days Duration Per Participant 
Visit/Contact 
Collection of 
information 
in the CRF  
Visit 1 
TC 1 
Visit 2 
TC2 
Visit 3 
Study timelines (days) 
 
Day 01 
Day 09 
(Visit 
1 +  
8 days) 
Day 31 
(Visit 1 + 
30 days) 
Day 39 
(Visit 2 + 
8 days) 
Day 61 (Visit 2 
+ 30 days) 
Time windows (days) 
 
 
+2 
days 
+14 days 
+2 days 
+14 days 
Visit procedures: 
 
 
 
 
 
 
ICF and AF 
X 
X 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
Collection of 
demographic data 
X 
X 
 
 
 
 
Urine pregnancy test (if 
applicable) 
 
X 
 
X 
 
 
Collection of medical 
history 
X 
X 
 
 
 
 
Physical examination 
(including temperature)* 
 
X 
 
X 
 
X 
Contact IRT system for 
participant number 
allocation and vaccine 
dose randomization 
X 
X 
 
 
 
 
Review of temporary 
contraindications for 
blood sampling† 
 
X 
 
X 
 
X 
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Visit/Contact 
Collection of 
information 
in the CRF  
Visit 1 
TC 1 
Visit 2 
TC2 
Visit 3 
Study timelines (days) 
 
Day 01 
Day 09 
(Visit 
1 +  
8 days) 
Day 31 
(Visit 1 + 
30 days) 
Day 39 
(Visit 2 + 
8 days) 
Day 61 (Visit 2 
+ 30 days) 
Time windows (days) 
 
 
+2 
days 
+14 days 
+2 days 
+14 days 
Visit procedures: 
 
 
 
 
 
 
Blood sampling 
 
BL01AA 
or 
BL01AR ¥ 
(5 mL)‡ 
 
BL02AA 
or 
BL02AR ¥ 
(8 mL)‡ 
 
BL03AA 
(8 mL) 
Review warnings and 
precautions to 
vaccination 
 
X 
 
X 
 
 
Review of 
contraindications to 
subsequent vaccination 
 
 
 
X 
 
 
Vaccination with 
MenACYW conjugate 
vaccine or Nimenrix® 
(IM in deltoid muscle) 
 
X 
 
 
 
 
Vaccination with 
9vHPV and Tdap-IPV 
vaccines (IM in deltoid 
muscle of contralateral 
arm, with the 2 
injections separated by 
minimum 2.5 cm) 
 
 
 
X 
 
 
Immediate surveillance 
(30 minutes) 
X 
X 
 
X 
 
 
Diary card provided 
 
DC1 
 
DC2 
 
 
Telephone call 
 
 
X§ 
 
X§ 
 
Diary card reviewed and 
collected 
 
 
 
DC1 
 
DC2 
Collection of solicited 
injection site and 
systemic reactions 
X 
X** 
 
X**†† 
 
X†† 
Collection of unsolicited 
non-serious AEs 
X 
Day of vaccination to 30 days after vaccination 
Collection of SAEs, 
including AESI‡‡ 
X 
To be reported at any time during the study 
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Visit/Contact 
Collection of 
information 
in the CRF  
Visit 1 
TC 1 
Visit 2 
TC2 
Visit 3 
Study timelines (days) 
 
Day 01 
Day 09 
(Visit 
1 +  
8 days) 
Day 31 
(Visit 1 + 
30 days) 
Day 39 
(Visit 2 + 
8 days) 
Day 61 (Visit 2 
+ 30 days) 
Time windows (days) 
 
 
+2 
days 
+14 days 
+2 days 
+14 days 
Visit procedures: 
 
 
 
 
 
 
Collection of reportable 
concomitant medications 
X 
X 
 
X 
 
X 
Collection of pregnancies 
X 
To be reported at any time during the study 
End of Active Phase 
participation record 
X 
 
 
 
 
X 
Abbreviations: AE: adverse event; AESI: adverse events of special interest; AF: Assent Form; BL: blood sampling; 
CRF: Case Report Form; DC: diary card; ICF: Informed Consent Form; IM: intramuscular; IRT: interactive response 
technology; SAE: serious adverse event; TC: telephone call 
* Physical examination should be performed as per standard of care including, but not limited to, a general 
examination of the main body systems of interest (ie, heart, lung, skin, neurologic, muscular-skeletal, lymphatic 
system, etc). Temperature to be measured by oral (preferred route), rectal, or axillary route using a digital 
thermometer before vaccination and daily during the 7 days after vaccination and recorded in the diary card. If a 
routine examination had been performed within the last week by the Investigator, a sub-Investigator, or a licensed 
nurse practitioner, it does not need to be repeated unless there were some changes in health status, in which case it 
may be limited to the affected area. 
† Should a participant receive oral or injectable antibiotic therapy within 3 days prior to any blood draw, the 
Investigator will postpone that blood draw until it has been 3 days since the participant last received oral or injectable 
antibiotic therapy. Postponement must still be within the timeframe for blood draw. If postponement would result in 
the sample collection falling outside of this timeframe, the blood sample should be collected without postponement, 
and it should be appropriately documented that the sample was taken less than 3 days after stopping antibiotic 
treatment. 
¥ Blood sample corresponding to the rSBA subset of participants. 
‡ Blood sample at Day 01 and Day 31 will be drawn before administration of the vaccines. 
§ This call is made 8 days to 10 days after the respective vaccinations. If Day 09 (+2 days) or Day 39 (+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 participant experienced any SAE (including any AESI) not yet reported, and will 
remind the participant’s parent/legally acceptable representative to continue using the diary card, bring the diary card 
to the study center at the next visit, and confirm the date and time of the next visit. 
** Solicited injection site and systemic reactions will be recorded from the day of vaccination through 7 days after 
each vaccination. 
†† Solicited injection site and systemic reactions will be recorded during the review and collection of DC1 and DC2 
at Day 31 (+14 days) and Day 61 (+14 days).  
‡‡ AESI will be collected throughout the study as SAEs to ensure that the events are communicated to the Sponsor in 
an expedited manner and followed up until the end of the follow-up period or resolution, as per the assigned causal 
relationship. 
 
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Table 1.2: Schedule of activities for Group 3 
Phase IIIb Study, 2-3 Visits, 1 Vaccination Visit, 0-1 Telephone Call, 3 Vaccine Injections, 2-
3 Blood Collections, 30 Days Duration Per Participant 
Visit/Contact 
Collection of 
information in the 
CRF 
Visit 1 
Visit 2* 
TC 1† 
Visit 3 
Study timelines (days) 
 
Day 01 
Day 07 
(Visit 1 + 
6 days) 
Day 
09 
(Visit 
1 +  
8 
days) 
Day 31 (Visit 
1 + 30 days) 
Time windows (days) 
 
 
+2 days 
+2 
days 
+14 days 
Visit procedures: 
 
 
 
 
 
ICF and AF 
X 
X 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
Collection of demographic data 
X 
X 
 
 
 
Urine pregnancy test (if applicable) 
 
X 
 
 
 
Collection of medical history 
X 
X 
 
 
 
Physical examination (including 
temperature)‡ 
 
X 
 
 
X 
Contact IRT system for participant 
number allocation and vaccine 
dose randomization 
X 
X 
 
 
 
Review of temporary 
contraindications for blood 
sampling§ 
 
X 
X 
 
X 
Blood sampling 
 
BL01BB 
or 
BL01BR ¥ 
(8 mL)** 
BL02D7 
(5 mL) 
 
BL03BB 
or BL03BR ¥ 
(8 mL) 
Vaccination with MenACYW 
conjugate vaccine (IM in deltoid 
muscle) 
 
X 
 
 
 
Vaccination with 9vHPV and 
Tdap-IPV vaccines (IM in 
deltoid muscle of contralateral 
arm, with the 2 injections 
separated by minimum 2.5 cm) 
 
X 
 
 
 
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Visit/Contact 
Collection of 
information in the 
CRF 
Visit 1 
Visit 2* 
TC 1† 
Visit 3 
Study timelines (days) 
 
Day 01 
Day 07 
(Visit 1 + 
6 days) 
Day 
09 
(Visit 
1 +  
8 
days) 
Day 31 (Visit 
1 + 30 days) 
Time windows (days) 
 
 
+2 days 
+2 
days 
+14 days 
Visit procedures: 
 
 
 
 
 
Immediate surveillance 
(30 minutes) 
X 
X 
 
 
 
Diary card provided 
 
DC1 
 
 
 
Telephone call 
 
 
 
X†† 
 
Diary card reviewed and collected 
 
 
 
 
DC1 
Collection of solicited injection site 
and systemic reactions 
X 
X‡‡ 
 
 
X§§ 
Collection of unsolicited non-
serious AEs 
X 
Day of vaccination to 30 days after vaccination 
Collection of SAEs, including 
AESI***  
X 
To be reported at any time during the study 
Collection of reportable 
concomitant medications 
X 
X 
X 
 
X 
Collection of pregnancies 
X 
To be reported at any time during the study 
End of Active Phase participation 
record 
X 
 
 
 
X 
Abbreviations: AE: adverse event; AESI: adverse events of special interest; AF: Assent Form; BL: blood sampling; 
CRF: Case Report Form; DC: diary card; ICF: Informed Consent Form; IM: intramuscular; IRT: interactive response 
technology; SAE: serious adverse event; TC: telephone call 
* Visit at Day 07 (+2 days) is applicable only for a subset of participants, N=60. This subset of participants will have 
3 blood samplings. All other participants in Group 3 will have only 2 study visits and 2 blood samplings.  
† For a subset of participants (N=60) who have Day 07 (+2 days) visit, TC1 discussions can occur during Day 07 visit 
and TC1 at Day 09 (+2 days) is therefore optional. 
‡ Physical examination should be performed as per standard of care including, but not limited to, a general 
examination of the main body systems of interest (ie, heart, lung, skin, neurologic, muscular-skeletal, lymphatic 
system, etc). Temperature to be measured by oral (preferred route), rectal, or axillary route using a digital 
thermometer before vaccination and daily during the 7 days after vaccination and recorded in the diary card. If a 
routine examination had been performed within the last week by the Investigator, a sub-Investigator, or a licensed 
nurse practitioner, it does not need to be repeated unless there were some changes in health status, in which case it 
may be limited to the affected area. 
§ Should a participant receive oral or injectable antibiotic therapy within 3 days prior to any blood draw, the 
Investigator will postpone that blood draw until it has been 3 days since the participant last received oral or injectable 
antibiotic therapy. Postponement must still be within the timeframe for blood draw. If postponement would result in 
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the sample collection falling outside of this timeframe, the blood sample should be collected without postponement, 
and it should be appropriately documented that the sample was taken less than 3 days after stopping antibiotic 
treatment. 
¥ Blood sample corresponding to the rSBA subset of participants. 
** Blood sample at Day 01 will be drawn before administration of the vaccines. 
†† This call is made 8 days to 10 days after the vaccinations and is optional for the subset of participants (N=60) who 
have TC1 discussions during the Day 07 visit. For the remaining participants who have TC1 at Day 09 (+2 days), if 
this day 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 participant experienced any SAE (including any AESI) not yet 
reported, and will remind the participant’s parent / legally acceptable representative to continue using the diary card, 
bring the diary card to the study center at the next visit, and confirm the date and time of the next visit.  
‡‡ Solicited injection site and systemic reactions will be recorded from the day of vaccination through 7 days after 
vaccination 
§§ Solicited injection site and systemic reactions will be recorded during the review and collection of DC1 at Day 31 
(+14 days). 
*** AESI will be collected throughout the study as SAEs to ensure that the events are communicated to the Sponsor 
in an expedited manner and followed up until the end of the follow-up period or resolution, as per the assigned causal 
relationship 
 
 
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2 
Introduction 
2.1 
Study Rationale 
The purpose of MEQ00071 study will be to compare a quadrivalent meningococcal conjugate 
vaccine (MenACYW conjugate vaccine) versus a licensed quadrivalent meningococcal 
polysaccharide (Groups A, C, W-135, Y) conjugate vaccine (Nimenrix®) in the adolescent 
population. Nimenrix® is a standard of care in several countries and no data of Nimenrix® versus 
MenACYW conjugate vaccine has been generated in the adolescent population to date. 
Until now, co-administration data of MenACYW conjugate vaccine have been generated with 
other vaccines, ie, 4vHPV (4-valent human papilloma virus) vaccine and Tdap (tetanus, 
diphtheria, and acellular pertussis) vaccine. In some countries, other vaccines used for adolescents 
are 9vHPV (9-valent human papilloma virus) vaccine and Tdap-IPV vaccine. This study will also 
generate co-administration data of MenACYW conjugate vaccine with these 2 other adolescent 
vaccines. 
2.2 
Background 
Invasive meningococcal disease (IMD) is a serious illness caused by the bacterium Neisseria 
meningitidis (N. meningitidis), a Gram-negative diplococcus found exclusively in humans. It is 
associated with high morbidity and mortality. Worldwide, most cases of IMD are caused by 
serogroups A, B, C, Y, and W (1-3). Some age groups are disproportionately affected by IMD, 
with major peaks of IMD incidence occurring in infants and in adolescents and young adults. 
The epidemiology of N. meningitidis can be described as complex, unpredictable, geographically 
variable, and changing over time. IMD occurs worldwide in both endemic and epidemic forms 
with seasonal variation. 
In Europe, the European Center for Disease Prevention and Control (ECDC) annually publishes 
an epidemiological report on IMD, based on data retrieved from the European Surveillance 
System (TESSy) which is used to collect, analyze, and disseminate data on communicable 
diseases. The last report has been published in April 2019, based on 2017 data. As per this report, 
in 2017, the overall notification rate of IMD in European Union (EU)/European Economic Area 
(EEA) countries was 0.6 per 100 000 population, similar to the notification rate for previous 
years. Four countries (France, Germany, Spain, and the United Kingdom) accounted for 58% of 
all confirmed cases. In Italy, the notification rate of IMD was 0.3 per 100 000 population, while in 
Spain it was 0.6 per 100 000 population (4). 
In Europe the incidence rate of IMD has remained stable over the last 5 to 10 years, with the 
highest peak occurring in the population less than 4 years of age and a smaller peak in the 15 to 
24-years age group. Overall, the highest incidence rate in Europe is caused by serogroup B, 
followed by serogroups W and C (4). 
The incidence of IMD in Italy reported by the Istituto Superiore di Sanità showed a slight increase 
from 2008 to 2016 in the general population (0.30 to 0.38 per 100 000) and among young children 
below 4 years of age (1.64 to 1.83 per 100 000) (5). In 2017, age-specific serogroup distribution 
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showed a higher incidence of serogroup B in infants and highest incidence of serogroup Y in the 5 
to 9-years age group, 15 to 24-years age group, and > 65 years age group (6). 
The incidence of IMD in Spain showed nearly similar rate from 2013 to 2017 (0.3 to 0.6 per 
100 000) in the general population (4). In 1999 and 2000, the incidence of IMD was 1.53 and 1.75 
per 100 000, respectively, leading to the inclusion of MenC conjugate vaccine in the infant 
vaccination schedule in 2000 (7). 
The incidence of IMD in Singapore from 2001 to 2018 was 0.1 to 0.3 per 100 000 population (8). 
Meningococcal carriage is low in infants but increases during childhood and peaks in 12 to 
19-years age group (9). Vaccination of adolescents not only provides direct protection against 
IMD, but also reduces carriage, thus maintaining a herd effect shown to be important even in 
other age groups (10-12). Therefore, adolescent vaccination against N. meningitidis is already 
recommended in several countries worldwide (13). 
In Europe, increased incidence of IMD due to serogroup C in the late 1990s, and availability of 
meningococcal serogroup C conjugate vaccine (MenC), have led many countries to introduce 
MenC vaccination for toddlers (± infants) in the 2000’s (14). By 2016, MenC was integrated into 
the national routine childhood immunization programs of 15 EU/EEA countries (4). Therefore, as 
of today, many European adolescents have been primed with monovalent MenC before 2 years of 
age. This is not the case in Singapore where meningococcal vaccination is not part of routine 
vaccination recommended for children and adolescents, hence, adolescents in Singapore are 
MenC naïve (8). 
Bordetella pertussis and human papilloma virus (HPV) are also important disease-causing 
pathogens, with a high risk of transmission in adolescents and young adults. Periodic resurgences 
of pertussis were recorded every 3 to 5 years even in industrialized countries with high 
immunization rates, with increased incidence in adolescents and adults (15). 
The HPV is a group of viruses, of which more than 100 types have been described. About 40 of 
them can infect the genitals. At least 14 HPV types classified as ‘high risk’ can cause cervical 
cancer in women and are associated with other anogenital cancers and head and neck cancers in 
both men and women. 
Immunizations against diphtheria, tetanus, pertussis, and polio (as a booster dose) and against 
HPV (primarily in females, but also in males, as 2- or 3-dose schedules according to age) are also 
recommended by the World Health Organization (WHO) during adolescence (16) and most 
countries worldwide have implemented their use in vaccination programs. 
However, adherence to current recommendations and vaccination schedules among adolescents is 
problematic (17), especially for the multi-dose schedules needed for HPV vaccination (18). 
Therefore, vaccine co-administration resulting in a reduced number of clinic visits may improve 
the implementation and achievable coverage of adolescent vaccination programs. 
The goal for MenACYW conjugate vaccine is to provide broad protection against IMD caused by 
serogroups A, C, W, and Y. Initial licensure in EU (planned Q1 2021) and other countries will be 
in individuals from 12 months of age, adolescents, and adults, including those 56 years of age and 
older. MenACYW conjugate vaccine is licensed in the US since April 2020 for individuals 
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24 month of age and older. Further, clinical studies are ongoing to support an extension of the 
licensure in individuals from 6 weeks of age and older. 
Data regarding co-administration with other vaccines are available for 4vHPV and Tdap in 
meningococcal vaccine naïve adolescents (19), but not available to date with 9vHPV and 
Tdap-IPV. 
This study (MEQ00071) will compare the immunogenicity and describe the safety of MenACYW 
conjugate vaccine versus Nimenrix®, and when administered alone or concomitantly with 9vHPV 
and Tdap-IPV vaccines in a healthy adolescent population who are MenC naïve or primed before 
2 years of age. 
MenACYW conjugate vaccine has been given to over 7000 participants (infants, toddlers, 
children, adolescents, and adults > 56 years of age) in completed Phase II and Phase III studies. In 
these studies, MenACYW conjugate vaccine was found to be well tolerated and did not reveal any 
apparent safety concerns. The relevant Phase II (MET50) and Phase III (MET43 and MET56) 
studies that concern the adolescents and adult populations (10 to 55 years of age) are discussed in 
the Investigator’s Brochure Section 5. 
2.3 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks, reasonably expected 
adverse events (AEs), the potential risks, and uncertainties of MenACYW conjugate vaccine may 
be found in the Investigator’s Brochure.
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2.3.2 
Benefits from Study Participation 
MenACYW conjugate vaccine is undergoing active clinical investigation. Based on the data from 
previous studies, evaluation of the immunogenicity profile of MenACYW conjugate vaccine in 
different age groups shows that most participants developed seroprotective levels of antibodies after 
vaccination. The safety evaluation indicates that the vaccine is well tolerated, and no safety issues 
have been detected to date.  
Participants who receive Nimenrix® will likely be protected against meningococcal disease caused 
by N. meningitidis serogroups A, C, W, and Y. 
Since all participants will receive the adolescent dose of Tdap-IPV, they will likely gain 
immunological protection against tetanus, diphtheria, acellular pertussis (whooping cough), and 
poliomyelitis. 
Participants who complete the 2- or 3-dose series of 9vHPV vaccine will likely gain 
immunological protection against genital cancers, precancers, and (genital) warts caused by 
human papillomavirus (types 6/11/16/18/31/33/45/52/58). 
As with any vaccine, MenACYW conjugate vaccine, Nimenrix®, 9vHPV, and Tdap-IPV vaccines 
may not protect 100% of individuals against the diseases they are designed to prevent. 
2.3.3 
COVID-19 Risk Assessment 
MenACYW conjugate vaccine, Nimenrix®, 9vHPV, and Tdap-IPV vaccines would not cause 
immune suppression. Therefore, the risk that a participant in this study will contract COVID-19 
solely due to the administration of the study vaccine will be similar to the risk that a person not 
participating in this study will contract COVID-19. 
However, the risk of exposure to infected people cannot be completely excluded as the participants 
may need to expose to public area (eg, commute to the site and at the site). 
Risk Mitigation:  
• Not start the study until the local confinement measures or other safety restrictions linked to 
the Covid-19 pandemic are lifted by the local Authorities. 
• Continued risk assessment by the Investigator and Sponsor before deciding to start the study.  
• Reduce the public exposure while ambulatory when possible. 
2.3.4 
Overall Benefit-Risk Conclusion 
Considering the measures taken to minimize risk to participants enrolled in this study, the 
potential risks that may result from study participation are balanced by the anticipated benefits 
that may be afforded to participants. 
3 
Objectives and Endpoints 
The study objectives and the corresponding endpoints are described in Table 3.1. 
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Objectives 
Endpoints 
 
 
 
of Groups 1 and 2 according to MenC 
primed status assessed before vaccination 
(D01) and at D31 (+14 days) 
The specific endpoints will be similar to those 
defined for the first observational objective. 
• To describe the antibody response against 
antigens of 9vHPV and Tdap-IPV vaccines, 
before and 1 month following vaccination 
• Antibody titers or concentrations against 
antigens contained in Tdap-IPV measured on 
D31 (+14 days) and D61 (+14 days) in 
Groups 1 and 2, and on D01 and D31 
(+14 days) in Group 3: 
• 
Anti-tetanus and anti-diphtheria 
antibody concentrations  
• 
Anti-tetanus and anti-diphtheria 
antibody concentrations ratio  
• 
Anti-tetanus and anti-diphtheria 
antibody concentrations ≥ 0.1 
international units/milliliter (IU/mL) 
and ≥ 1.0 IU/mL 
• 
Anti-polio 1, 2, and 3 antibody titers 
• 
Anti-polio 1, 2, and 3 antibody titers 
ratio 
• 
Anti-polio 1, 2, and 3 antibody titers 
≥ 1:8 
• 
Anti-pertussis antibody concentration 
(pertussis toxoid [PT], filamentous 
hemagglutinin [FHA], pertactin 
[PRN], fimbriae types 2 and 3 [FIM])  
• 
Anti-pertussis antibody concentrations 
ratio (PT, FHA, PRN, FIM) 
• 
Anti-pertussis vaccine seroresponse 
(PT, FHA, PRN, FIM), defined as 
follows: 
• ≥ 4 × baseline concentration, if the 
anti-pertussis antibody concentration 
at baseline (D01) is < 4 × lower limit 
of quantification (LLOQ)  
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Objectives 
Endpoints 
• or ≥ 2 × baseline concentration, if the 
anti-pertussis antibody concentration 
at baseline (D01) is ≥ 4 × LLOQ 
• Antibody titers against antigens contained in 
HPV vaccine measured on D31 (+14 days) 
and D61 (+14 days) in Groups 1 and 2, and 
on D01 and D31 (+14 days) in Group 3: 
• 
Anti-HPV antibody titers for each of 
the HPV types (types 6, 11, 16, 18, 
31, 33, 45, 52, and 58) 
• 
Anti-HPV antibody titer ratio for each 
of the HPV types 
• 
Vaccine seroconversion for each of 
the HPV types (6, 11, 16, 18, 31, 33, 
45, 52, and 58) by D31 (+14 days) 
after vaccination, with seroconversion 
defined as follows: 
• Changing serostatus from 
seronegative at baseline (D01) to 
seropositive by D31 (+14 days) after 
vaccination. A participant with a titer 
at or above the serostatus cut-off for a 
given HPV type is considered 
seropositive for that type. The 
serostatus cut-offs for HPV types 6, 
11, 16, 18, 31, 33, 45, 52, and 58 are 
30, 16, 20, 24, 10, 8, 8, 8, and 8 milli-
Merck units (mMU)/mL, respectively 
Safety 
• To describe the safety profile in each group 
after each and any vaccination 
The safety profile will be evaluated for each 
vaccine within 30 days (+14 days) after each 
vaccination. The following endpoints will be 
used for the evaluation of safety: 
• Unsolicited systemic AEs reported in the 
30 minutes after each vaccination 
• Solicited (pre-listed in the participant’s diary 
card and [electronic] Case Report Form 
[CRF]) injection site and systemic reactions 
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4.2 
Scientific Rationale for Study Design 
The primary objective of this study is to demonstrate the non-inferiority of the seroprotection rate 
(using hSBA titer ≥ 1:8) to meningococcal serogroups A, C, W, and Y following the 
administration of a single dose of MenACYW conjugate vaccine (Group 1) compared to a single 
dose of Nimenrix® (Group 2). An hSBA titer ≥ 1:8 is a well-recognized surrogate of protection 
against IMD caused by serogroups A, C, W, and Y. Seroprotection is preferred over seroresponse 
by the EMA. 
In this study, we will be comparing the immunogenicity of MenACYW conjugate vaccine versus 
Nimenrix® in the adolescent population. To date, comparison data of MenACYW conjugate 
vaccine versus Nimenrix® has only been generated in toddlers. Nimenrix® is the standard of care 
in several countries, hence, it will be used as the active comparator in this study to generate data 
in adolescents. Both, toddlers and adolescents are the age groups that are targeted by national 
immunization program in Europe and other regions. 
Other vaccines which will be co-administered in this study along with MenACYW conjugate 
vaccine include 9vHPV (first dose of the 2-dose or 3-dose series according to the National 
recommendations and age of the participant) and Tdap-IPV. The 9vHPV has been recently 
licensed in Europe and is becoming the standard of care. Generating co-administration data of 
MenACYW conjugate vaccine with 9vHPV and Tdap-IPV may help obtain high vaccine coverage 
rates. 
In other studies, included in the MenACYW conjugate vaccine Common Technical Dossier for 
initial licensure, titers were measured by hSBA for the primary endpoint. The same assay will 
therefore be used in this study for the comparison of MenACYW conjugate vaccine to Nimenrix®. 
Titers measured by rSBA will also be described in a subset of the first 50 participants from each 
group. 
According to the country and vaccination strategies, adolescents are either the only age group 
targeted for meningococcal vaccination (and therefore are meningococcal vaccination naïve 
before that age) or have been primed before 2 years of age (mainly with MenC as MenACYW 
vaccines have only been implemented more recently). Many European countries have MenC 
recommendations for infants/toddlers since the 2000’s, hence, an important part of the current 
adolescent population in Europe are MenC primed. Therefore, this study plans to enroll both 
MenC naïve and MenC primed adolescents. Currently available data generated for MenACYW 
conjugate vaccine is only in meningococcal vaccine naïve adolescents or in adolescents primed 
with quadrivalent meningococcal conjugate vaccine at 10 years or above. The aim of this study is 
to generate data in the ‘real life’ situation with adolescents who are MenC primed before 2 years 
of age and unprimed adolescents. 
This study will be conducted in European countries (Spain, Italy and Hungary) and Asian 
countries (Singapore, potential other countries to be determined). In Italy’s and Spain’s national 
vaccination plan for infants, MenC vaccination was introduced in 2005 and 2000, respectively 
(31-33). Thus, in Italy and Spain, an important part of the adolescent population will be MenC 
primed (MenC CRM or MenC-TT conjugate vaccines). In Singapore, adolescents will be MenC 
naïve. Nimenrix®, 9vHPV, and Tdap-IPV vaccines are available in all these countries. 
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An additional blood sample will be taken at D07 in a subset of the first 60 participants in Group 3 
for evaluation of antibody kinetics. Kinetics will be described in order to have a better knowledge 
on the immune response in the week following vaccination. This could be of interest for travelers 
and adolescents studying abroad who are being vaccinated only a few days before departure. 
Since the vaccines for the study groups have different appearances, this study will be partially 
observer-blind. This means that Groups 1 and 2 will be observer-blind (ie, everyone in the study 
other than the staff member who will administer the vaccine will be blinded) and Group 3 will be 
open-label. This open-label design for Group 3 is due to the different vaccination schedule for this 
group than for Groups 1 and 2. The primary objective of this study will include Groups 1 and 2 
(both groups being observer-blind), while Group 3 (open-label) will be a part of secondary and 
observational objectives. 
4.3 
Justification for Dose 
All participants will receive a single dose of either MenACYW conjugate vaccine or Nimenrix® 
as per the current/intended indication in this age group for quadrivalent meningococcal conjugate 
vaccines. 
One dose of Tdap-IPV vaccine is indicated for active booster immunization for the prevention of 
tetanus, diphtheria, acellular pertussis (whooping cough), and poliomyelitis. 
Depending on National recommendations and age of the participant, the schedule for 9vHPV 
vaccination can be 2 or 3 doses. The first dose will be administered during this study. All 
participants should then receive a second dose (and third dose) of 9vHPV vaccine several months 
after the first dose. These vaccinations for the completion of 9vHPV schedule will take place 
outside of the objectives and scope of this study and thus will not be described in this protocol. 
4.4 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed the last visit 
planned in the SoA. 
The end of the study is defined as the date of the last visit of the last participant in the study. 
However, for periodic safety reports, the study is considered completed when the clinical study 
report is finalized. 
5 
Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
There is no screening period nor screening criteria other than the inclusion and exclusion criteria. 
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5.1 
Inclusion Criteria 
Participants are eligible for the study only if all of the following criteria are met: 
I01: Aged 10 to 17 years on the day of inclusiona 
I02: Meningococcal serogroup C conjugate vaccine (MenC) naïve participants or participants 
having received monovalent MenC priming in infancy (< 2 years of age)b 
I03: Assent form has been signed and dated by the participant as per local regulation, and 
Informed Consent Form has been signed and dated by the parent/legally acceptable representative 
and by the participant if she/he turns 18 years old during the study 
I04: Participant and parent/legally acceptable representative are able to attend all scheduled visits 
and to comply with all study procedures 
I05: Covered by health insurance, if required by local regulations 
5.2 
Exclusion Criteria 
Participants are not eligible for the study if any of the following criteria are met: 
E01: Participant 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 until at least 4 
weeks after last vaccination. To be considered of non-childbearing potential, a female must be 
pre-menarchec 
E02: Previous vaccination against meningococcal disease with either the study vaccine or another 
vaccine (ie, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, W, 
or Y; or meningococcal B serogroup-containing vaccine), except licensed monovalent MenC 
vaccination received before 2 years of age 
E03: Participation at the time of study enrollment (or in the 4 weeks preceding the first study 
vaccination) or planned participation during the present study period in another clinical study 
investigating a vaccine, drug, medical device, or medical procedure 
E04: Receipt of any vaccine in the 4 weeks preceding any study vaccination or planned receipt of 
any vaccine in the 4 weeks following any study vaccination except for influenza vaccination, 
which may be received at least 2 weeks before study vaccines. This exception includes 
monovalent pandemic influenza vaccines and multivalent influenza vaccines 
                                                 
 
 
a  “10 to 17 years” means from the day of the 10th birthday to the day before the 18th birthday 
b  Irrespective of the number of doses of MenC received in infancy 
c  Pre-menarche females will declare by themselves that they have not yet started menstruation. If a young female 
participant reaches menarche during the study, then she is to be considered as a female of childbearing potential 
from that time forward 
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E05: History of vaccination with any tetanus, diphtheria, pertussis, or inactivated polio virus 
vaccine within the previous 3 years 
E06: Previous human papilloma virus (HPV) vaccination 
E07: Receipt of immune globulins, blood or blood-derived products in the past 3 months 
E08: 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) 
E09: History of meningococcal infection, confirmed either clinically, serologically, or 
microbiologically 
E10: Known history of diphtheria, tetanus, pertussis, poliomyelitis, and/or HPV infection or 
disease. 
E11: Known systemic hypersensitivity to any of the vaccine components, or history of a life-
threatening reaction to the vaccines used in the study or to a vaccine containing any of the same 
substancesa 
E12: Personal history of Guillain-Barré syndrome 
E13: 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 
E14: Personal history of new or past encephalopathy, progressive or unstable neurological 
disorder, or unstable epilepsy 
E15: Verbal report of thrombocytopenia, contraindicating intramuscular vaccination 
E16: Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating intramuscular vaccination 
E17: Deprived of freedom by an administrative or court order, or in an emergency setting, or 
hospitalized involuntarily 
E18: Current alcohol abuse or drug addiction 
E19: Chronic illnessb that, in the opinion of the Investigator, is at a stage where it may interfere 
with study conduct or completion 
E20: Moderate or severe acute illness/infection (according to Investigator’s judgment) on the day 
of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participant 
                                                 
 
 
a  The components of MenACYW conjugate vaccine are listed under Section 6.1 of this protocol and in the 
Investigator’s Brochure Section 3. The components of Nimenrix®, 9vHPV, and Tdap-IPV are listed under 
Section 6.1 of this protocol 
b  Chronic illness may include, but is not limited to cardiac disorders, congenital heart disease, chronic lung disease, 
renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases 
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should not be included in the study until the condition has resolved or the febrile event has 
subsided 
E21: Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw 
E22: 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 (ie, parent, 
spouse, natural or adopted child) of the Investigator or employee with direct involvement in the 
proposed study 
E23: Participant at high risk for meningococcal infection during the study (specifically but not 
limited to participants with persistent complement deficiency, with anatomic or functional 
asplenia, or participants traveling to countries with high endemic or epidemic disease) 
If the participant has a primary physician who is not the Investigator, the site may contact this 
physician with the participant’s/parent’s/legally acceptable representative’s consent to inform 
him/her of the participant’s participation in the study. In addition, the site may ask this primary 
physician to verify exclusion criteria relating to previous therapies, such as receipt of blood 
products or previous vaccines. 
5.3 
Lifestyle Considerations 
No other restrictions than the ones listed in the exclusion criteria or in the contraindications for 
subsequent vaccinations are required. 
5.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study intervention. Screening information is recorded in 
the source documents. 
Individuals who do not meet the criteria for participation in this study (screen failure) can be 
rescreened when the condition excluding them from participation is resolved (eg, fever, antibiotics 
received within 72 hours, etc). 
6 
Study Intervention 
Study intervention is defined as any investigational intervention, marketed product, placebo, or 
medical device intended to be administered to a study participant according to the study protocol. 
6.1 
Note: routine vaccines administered outside of study protocol are not 
considered as study interventions. Study Intervention Administered 
Study interventions are described in Table 6.1. 
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Table 6.1: Identity of study intervention 
Intervention 
Name 
MenACYW 
conjugate 
vaccine 
Meningococcal 
Polysaccharide 
(Serogroups A, 
C, Y, and W) 
Tetanus Toxoid 
Conjugate 
Vaccine (Sanofi 
Pasteur Inc., 
Swiftwater, PA, 
USA) 
Nimenrix®: 
Meningococcal 
group A, C, W-135, 
and Y conjugate 
vaccine (Pfizer 
Limited, Sandwich, 
United Kingdom) 
9vHPV 
(Gardasil® 9): 
Human 
Papillomavirus 9-
valent Vaccine 
(Recombinant, 
adsorbed) (Merck 
Sharp & Dohme 
Limited, 
Kenilworth, NJ, 
USA) 
Tdap-IPV 
(Repevax®/Triaxis® 
Polio/Adacel® 
Polio): 
Tetanus Toxoid, 
Reduced Diphtheria 
Toxoid and 
Acellular Pertussis 
Vaccine Adsorbed 
Combined with 
Inactivated 
Poliomyelitis 
Vaccine (Sanofi 
Pasteur Limited, 
Toronto, Ontario, 
Canada) 
Use 
Experimental 
Active comparator 
Co-administered 
vaccine 
 Co-administered 
vaccine 
IMP and NIMP 
IMP 
IMP 
IMP 
IMP 
Type  
Vaccine 
Vaccine 
Vaccine 
Vaccine 
Dose 
Formulation 
Liquid solution  
Powder and solvent 
for solution for 
injection  
Suspension for 
injection 
Suspension for 
injection 
Unit Dose 
Strength 
Meningococcal 
capsular 
polysaccharides: 
• 
Serogroup A 
10 µg 
• 
Serogroup C 
10 µg 
• 
Serogroup Y 
10 µg 
• 
Serogroup 
W 10 µg 
• N. meningitidis 
group A 
polysaccharide
* 5 µg 
• N. meningitidis 
group C 
polysaccharide
* 5 µg 
• N. meningitidis 
group W-135 
polysaccharide
* 5 µg 
• 30 µg of 
HPV 6 L1 
protein 
• 40 µg of 
HPV 11 L1 
protein 
• 60 µg of 
HPV 16 L1 
protein 
• 40 µg of 
HPV 18 L1 
protein 
• Tetanus toxoid 
5 Lf 
• Diphtheria 
toxoid 2 Lf 
• Acellular 
pertussis:  
• 
PT 2.5 µg 
• 
FHA 5 µg  
• 
PRN 3 µg  
• 
FIM 5 µg  
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Tetanus toxoid 
protein carrier 
approximately 
55 µg* 
*Tetanus toxoid 
protein quantity is 
approximate and 
dependent on the 
polysaccharide-
to-protein ratio 
for the conjugates 
used in each 
formulation 
• N. meningitidis 
group Y 
polysaccharide
* 5 µg 
*Conjugated to 
tetanus toxoid protein 
carrier 44 µg 
 
• 20 µg of 
HPV 31 L1 
protein 
• 20 µg of 
HPV 33 L1 
protein 
• 20 µg of 
HPV 45 L1 
protein 
• 20 µg of 
HPV 52 L1 
protein 
• 20 µg of 
HPV 58 L1 
protein 
L1 protein in the 
form of virus-like 
particles produced 
in yeast cells 
(Saccharomyces 
cerevisiae CANA
DE 3C-5 [Strain 
1895]) by 
recombinant DNA 
technology. 
Adsorbed on 
amorphous 
aluminum 
hydroxyphosphate 
sulphate adjuvant 
(0.5 mg 
aluminum). 
• 
Inactivated 
Poliomyelitis 
Vaccine  
• 
Type 1 
(Mahoney) 
40 D-
antigen 
units*  
• 
Type 2 
(MEF-1) 8 
D-antigen 
units*  
• 
Type 3 
(Saukett) 
32 D-
antigen 
units*  
 
* Or the equivalent 
antigen quantity, 
determined by 
suitable 
immunochemical 
method  
• 
Aluminum 
phosphate 
(adjuvant) 
1.5 mg (0.33 mg 
aluminum) 
 
Excipients/ 
Diluent 
Sodium acetate 
buffered saline 
Sucrose, 
trometamol, 
sodium chloride, 
and water for 
injections 
Sodium chloride, 
L-histidine, 
polysorbate 80, 
sodium borate, 
and water for 
injections 
• 
2-
phenoxyethanol 
0.6% v/v  
• 
Polysorbate 80 
< 5 µg 
(< 10 ppm) 
• 
Also contains 
traces of water 
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for injection q.s. 
0.5 mL  
Manufacturing 
Process Residuals 
Bovine serum 
albumin, 
formaldehyde, 
glutaraldehyde, 
polymyxin B, 
neomycin, and 
streptomycin are 
present in trace 
amounts. 
Dosage Level 
0.5 mL per dose 
0.5 mL per dose 
0.5 mL per dose 
0.5 mL per dose 
Number of 
Doses/Dosing 
Interval 
1 dose  
1 dose 
1 dose 
1 dose 
Route of 
Administration 
Intramuscular 
injection 
Intramuscular 
injection  
Intramuscular 
injection  
Intramuscular 
injection  
Site of 
Administration 
Deltoid muscle  
Deltoid muscle  
Deltoid muscle  
Deltoid muscle  
Sourcing 
Provided by 
Sponsor 
Provided by the 
Sponsor  
Provided by the 
Sponsor  
Provided by the 
Sponsor  
Packaging and 
Labeling 
The study interventions, MenACYW conjugate vaccine (single-dose vial), 
Nimenrix®, and other products will be supplied with investigational labeling and 
packaging according to national regulations. Each single dose of study interventions 
will be identified by a unique number on the detachable label and on the outer 
carton label. The detachable label is for the sites to attach to the source documents. 
See the Operating Guidelines for additional label detail. 
Current/Former 
Name or Alias 
NA 
NA 
NA 
NA 
Batch Number 
C1100201 
C1100426 
C1099228 
C1100891 
DNA: deoxyribo nucleic acid; FHA: filamentous hemagglutinin; FIM: fimbriae types 2 and 3; IMP: investigational 
medicinal product; Lf: limits of flocculation; NA: not applicable; NIMP: non-investigational medicinal product; ppm: 
part per million; PRN: pertactin; PT: pertussis toxoid; q.s.: quantity sufficient; v/v: volume/volume 
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6.2 
Preparation/Handling/Storage/Accountability 
MenACYW conjugate vaccine is supplied in single-dose (0.5 mL) vials. Nimenrix® is supplied as 
a white powder or cake in a single dose glass vial and a clear and colorless solvent in a pre-filled 
syringe. The other products (9vHPV vaccine and Tdap-IPV vaccine) are supplied as a suspension 
in a pre-filled syringe. 
All study interventions will be administered intramuscularly in the deltoid muscle of arm. Also 
see Nimenrix®, 9vHPV, Tdap-IPV vaccine package inserts for more details on administration.  
In all 3 groups, 9vHPV and Tdap-IPV vaccines will be administered in the contralateral arm (ie, 
arm opposite to the one where MenACYW conjugate vaccine or Nimenrix® is given) with the 
9vHPV and Tdap-IPV vaccine injections separated by minimum 2.5 cm distance. 
The site of injection for each vaccine should be prepared with a suitable antiseptic. After 
administration of the vaccine, the used syringe and needle will be disposed of in accordance with 
currently established guidelines.  
Prior to administration, all study products must be inspected visually for cracks, broken seals, 
correct label content, and extraneous particulate matter and/or discoloration, whenever solution 
and container permit. If any of these conditions exist, the vaccine must not be administered. A 
replacement dose is to be used, and the event is to be reported to the Sponsor. The rubber stopper 
should not be removed from any of the vaccine vials. 
Detailed guidance and information are provided in the Operating Guidelines. 
• The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention. 
• Only participants enrolled in the study may receive study intervention and only authorized site 
staff may supply or administer study intervention. All study interventions must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the Investigator and 
authorized site staff. 
• The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
• Further guidance and information for the final disposition of unused study interventions are 
provided in the Operating Guidelines. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Randomization and Allocation Procedures 
On the day of enrollment, participants who meet the inclusion/exclusion criteria, and who sign the 
Assent Form (AF) and whose parents/legally acceptable representatives sign the Informed 
Consent Form (ICF) will be randomly assigned to Groups 1, 2, or 3 in a 3:3:2 ratio. 
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The site staff will connect to the interactive response technology (IRT) system, enter the 
identification and security information, and confirm a minimal amount of data in response to IRT 
system prompts. The IRT system will then provide at least the participant number and vaccine 
group assignment. The IRT will also state whether the participant has been assigned to the D07 
blood draw subset (first 60 participants of Group 3 only), and whether the participant will be in 
the rSBA testing subset (first 50 participants of each group). The full detailed procedures for 
group allocation are described in the Operating Guidelines. If the participant is not eligible to 
participate in the study, then the information will only be recorded on the participant recruitment 
log. 
Participant numbers that are assigned by the IRT system will consist of a 12-digit string (a 3-digit 
country identifier, a 4-digit study center identifier, and a 5-digit participant identifier). For 
example: 
Participant 380000100005 is the fifth participant enrolled in Center Number 1 in Italy (380 being 
the Italy country code). 
Participant 724001100006 is the sixth participant enrolled in Center Number 11 in Spain (724 
being the Spain country code). 
Participant 702000800004 is the fourth participant enrolled in Center Number 8 in Singapore (702 
being the Singapore country code). 
Participant numbers should not be reassigned for any reason. The randomization codes will be 
kept securely in the IRT system. 
6.3.2 
Blinding and Code-breaking Procedures 
The study will be performed in a partially observer-blind fashion: 
In Groups 1 and 2 
• Investigators and study staff who conduct the safety assessment, participants, parents/legally 
acceptable representatives, the Sponsor, and laboratory personnel performing the serology 
testing will be kept blinded to the vaccine received 
• 
Only the study staff who prepare and administer the vaccine and are not involved with the 
safety evaluation will know which vaccine is administered 
In Group 3 
• Everyone involved in the study (ie, Investigator, study staff, the Sponsor, participants, 
parents/legally acceptable representatives) will know which vaccine is administered. This 
open-label design for Group 3 is due to the different vaccination schedule for this group than 
for Groups 1 and 2. 
The code may be broken in the event of an AE only when the identification of the vaccine 
received could influence the treatment of the participant. Code-breaking should be limited to the 
participant experiencing the AE. 
The blind can be broken by the Investigator or a delegate through the IRT system, as explained in 
the code-breaking procedures described in the Operating Guidelines. Once the emergency has 
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been addressed by the site, the Investigator or a delegate must notify the Sanofi Pasteur 
Responsible Medical Officer if a participant’s code was broken. All contact attempts with the 
Sponsor prior to unblinding are to be documented in the source documents, and the code-breaking 
Case Report Form (CRF) is to be completed. 
The Independent Ethics Committees (IEC)/Institutional Review Boards (IRB) must be notified of 
the code-breaking, in accordance with local regulations. All documentation pertaining to the event 
must be retained in the site’s study records and, in the Sanofi Pasteur files. Any intentional or 
unintentional code-breaking must be reported, documented, and explained, and the name of the 
person who requested it must be provided to the Sponsor. 
A request for the code to be broken may also be made: 
• by the Global Pharmacovigilance (GPV) Department through an internal system for reporting 
to Health Authorities in the case of an unexpected SAE considered causally related, as 
described in International Council for Harmonisation (ICH) E2Aa. In this case, the code will 
be broken only for the participant in question. The information resulting from code-breaking 
(ie, the participant’s vaccine or group assignment) will not be communicated to either the 
Investigator or the immediate team working on the study, except for the GPV representative. 
 
The code-breaking procedures are described in the Operating Guidelines. 
6.4 
Study Intervention Compliance 
The following measures will ensure that the study intervention is administered  as planned (see 
Table 6.1), and that any noncompliance is documented so that it can be accounted for in the data 
analyses: 
• All vaccinations will be administered by qualified and trained study personnel 
• The person in charge of study intervention management at the site will maintain accountability 
records of study intervention delivery to the study site, study intervention inventory at the site, 
dose given to each participant, and unused or wasted doses 
6.5 
Concomitant Therapy 
At the time of enrollment, ongoing medications and other therapies (eg, 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 CRF of ongoing concomitant medication will be limited to specific 
categories of medication of interest beginning on the day of first vaccination. This may include 
medications of interest that were started prior to the day of vaccination. 
                                                 
 
 
a All unexpected and related SAEs submitted to European Union and Asian competent authorities must be unblinded. 
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Reportable medications (Category 1, 2, and 3) will be collected in the source document from the 
day of first vaccination to the end of the studya and in the CRF as per the instructions given below 
for each category. 
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 
(eg, antipyretics, analgesics, and non-steroidal anti-inflammatory drugs [NSAIDs], systemic 
steroids/corticosteroids [therapy duration less than 2 weeks], and other immune-modulators) 
Category 1 medication do not define the Per-Protocol Analysis Set (PPAS). 
Note: Topical steroids (inhaled, optic, ophthalmic, nasal, etc.) should not be captured or 
reported. 
• Category 1 medications will be reported in the CRF from the day of each vaccination to the 
end of the solicited and unsolicited follow-up period after each vaccination.  
• Category 2: medications impacting or that may have an impact on the immune response and 
used to define the PPAS; for example: 
• 
Flu vaccines administered within 14 days pre or post each trial vaccination, including the 
day of the study vaccination visit 
• 
Any vaccine (including COVID-19 vaccine) other than study vaccines (vaccines not 
described in the Protocol) within the 28 days (4 weeks) preceding or after the trial 
vaccination, including the day of the study vaccination visit 
• 
Immune globulins, blood or blood-derived products: used in the 3 months preceding the 
first blood draw and up to the last blood draw 
• 
Immunosuppressive therapy such as immune-suppressors, immune-modulators with 
immunosuppressive properties, long-term systemic corticosteroids therapy (prednisone or 
equivalent for more than 2 consecutive weeks) used in the past 3 months preceding the 
study vaccination and up to the last blood draw, anti-cancer chemotherapy, anti-
proliferative drugs such as deoxyribonucleic acid (DNA) synthesis inhibitors, or radiation 
therapy: used in the 6 months preceding the first study vaccination, and up to the last 
blood draw 
Category 2 medications will be reported in the CRF during the study period and up to the last 
blood draw. 
• Category 3: systemic (oral or injectable) antibiotics received within 72 hours preceding each 
visit for blood draw related to IMP assessment (meningococcal vaccines) and used to define 
                                                 
 
 
a  Participant’s parents/legally acceptable representatives will be required to document all medications received in 
the diary cards. The sites will focus on only recording the medications belonging to the 3 categories in the other 
source documents. 
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the PPAS, as they may interfere with bioassays used for antibody testing when taken before a 
blood draw 
Category 3 medications will be reported in the CRF for the period of 3 days (72 hours) before 
each blood draw. 
Note: Topical antibiotics (Inhaled, optic, ophthalmic, nasal, etc.) should not be captured or 
reported. 
The information reported in the CRF for each reported medication will be limited to: 
• Trade name 
• Rationale for the origin of prescription: Whether it was a prophylactica medication? 
Prophylactic medications will be recorded in the Action Taken section of the AE collection 
tables. 
• Medication category (1, 2, or 3) 
• Start and stop dates 
 
Dosage and administration route, homeopathic medication, 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. 
If the participant has received medications other than those listed in Categories 1, 2, and 3, the 
detailed information will be collected in the source documents only. 
Medications given 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 
received belongs to one of the pre-listed categories. Medications will not be coded. 
6.5.1 
Rescue Medicine 
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. 
6.6 
Dose Modification 
Not applicable. 
                                                 
 
 
a  Medication prescribed for preventing AE occurrence (e.g. paracetamol to reduce the risk of fever) 
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6.7 
Intervention After the End of the Study 
Depending on the age of the participant at the time of first dose administration during this study, 
and according to national recommendation, all participants should receive a second dose (and 
third dose) of 9vHPV vaccine several months after the first dose. These additional vaccinations 
for the completion of 9vHPV schedule will take place outside of the objectives and scope of this 
study and thus will not be described in this protocol. Also, these additional 9vHPV vaccinations 
will not be provided by the Sponsor. 
7 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal 
7.1 
Discontinuation of Study Intervention 
7.1.1 
Temporary Contraindications 
Should a participant experience one of the conditions listed below, the Investigator will postpone 
further vaccination until the condition is resolved. Postponement must still be within the 
timeframe for vaccination indicated in the SoA. 
• Febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) or moderate or severe acute 
illness/infection on the day of vaccination, according to Investigator’s judgment. 
• Receipt of any vaccine (other than the study vaccines) in the 4 weeks preceding any study 
vaccination or planned receipt of any vaccine in the 4 weeks following any study 
vaccination except for influenza vaccination, which may be received at least 2 weeks 
before study vaccines. This exception includes monovalent pandemic influenza vaccines 
and multivalent influenza vaccines. 
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months. 
• 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). 
7.1.2 
Temporary Contraindications for Blood Sample 
Should a participant receive oral or injectable antibiotic therapy within 3 days (72 hours) prior to a 
blood draw, the Investigator will postpone that blood draw until it has been 3 days since the 
participant last received oral or injectable antibiotic therapy. Postponement must still be within the 
timeframe for blood draw. If postponement would result in the sample collection falling outside of 
the appropriate timeframe, the blood sample should be collected without postponement, and it 
should be documented appropriately that the sample was taken less than 3 days after stopping 
antibiotic treatment. 
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7.1.3 
Definitive Contraindications 
Participants will permanently discontinue (definitive discontinuation) study intervention for the 
reasons listed below. These participants must not receive any additional dose of study intervention 
but should continue to be followed for safety and immunogenicity. Additional unscheduled visits 
may be performed for safety reasons and information will be reported in the source documents. 
Should a participant experience 1 of the conditions listed below, the Investigator will discontinue 
vaccination: 
DCI01: 
Pregnancy, as indicated by a positive urine test 
In the event of a local or national immunization program with a pandemic influenza 
vaccine,COVID-19 vaccine or any other vaccine as needed, participants who receive the vaccine 
mentioned above at any time during the study will not be withdrawn from the study. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
• Participants and their parents/legally acceptable representatives will be informed that they 
have the right to withdraw their child from the study at any time. 
• A participant may withdraw from the study at any time at his/her own request, or at the 
request of the participant’s parent/legally acceptable representative, or may be withdrawn at 
any time at the discretion of the Investigator for safety, behavioral, compliance, or 
administrative reasons without the permission of the participant or their parent/legally 
acceptable representative. This is expected to be uncommon. 
• The reason for withdrawal should be clearly documented in the source documents and in the 
CRF: AE, Lost to Follow-up, Protocol Deviation, or Withdrawal by participant or 
parent/legally acceptable representative. 
• The withdrawn participants will be permanently discontinued both from the study intervention 
and from the study at that time. 
• If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws consent, he/she may request destruction of any samples taken and 
not tested, and the Investigator must document this in the site study records. 
• Withdrawn participants may be replaced. 
Follow-up of Discontinuations 
For participants who have prematurely terminated the study, the site should attempt to contact 
them and complete all scheduled safety follow-ups, except if they specified that they do not want 
to be contacted again and it is documented in the source document. 
For participants where the reason for early termination is lost to follow-up, the site will not 
attempt to obtain further safety information. See Section 7.3 for definition of “lost to follow-up”. 
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7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the site for a required study 
visit or cannot be contacted as planned in the SoA: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the Investigator or designee must make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods), or at least to determine his/her health status while fully respecting his/her rights. 
These contact attempts should be documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 10.1. 
8 
Study Assessments and Procedures 
• Study procedures and their timing are summarized in the SoA. Protocol waivers or exemptions 
are not allowed. 
• Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention. 
• Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
• There is no screening period nor screening criteria for this study other than the inclusion and 
exclusion criteria (see Section 5). The initial evaluations will include collection of medical 
history, recent or ongoing treatments, physical examination as per standard of care (see 
Section 8.2.2), and urinary pregnancy test (for female participant sexually active and that have 
reached puberty) will be performed for all groups at Visit 1 and also at Visit 2 (Groups 1 and 
2) to check that all the inclusion and exclusion criteria are fulfilled before enrolment of the 
participant and the vaccine(s) administration. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Blood samples will be collected as described in the SoA table (Section 1.3). 
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Physical examination should be performed as per standard of care including, but not limited to, a 
general examination of the main body systems of interest (ie, heart, lung, skin, neurologic, 
muscular-skeletal, lymphatic system, etc). Temperature to be measured by oral (preferred route), 
rectal, or axillary route using a digital thermometer before vaccination and daily during the 7 days 
after vaccination and recorded in the diary card. If a routine examination had been performed 
within the last week by the Investigator, a sub-Investigator, or a licensed nurse practitioner, it does 
not need to be repeated unless there were some changes in health status, in which case it may be 
limited to the affected area. 
8.2.3 
Vital Signs 
Pre-vaccination temperature will be systematically collected by the Investigator on the source 
document by oral (preferred route), rectal, or axillary route using a digital thermometer. Tympanic 
scan, infrared skin scan, and temporal artery scan thermometers must not be used. 
8.2.4 
Clinical Safety Laboratory Assessments 
A urine human chorionic gonadotropin pregnancy test will be performed in sexually active female 
participants of childbearing potential before each vaccination visit. 
8.3 
Adverse Events and Serious Adverse Events 
The definitions of an AE, SAE, and the different categories of AEs can be found in 
Appendix 10.3. 
AEs will be reported by the participants/parents/legally acceptable representatives to the 
Investigator, then by the Investigator to the Sponsor. 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study (see Section 7). 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
Immediate Post-vaccination Observation Period 
Participants will be kept under observation for 30 minutes after each vaccination to ensure their 
safety. The post-vaccination observation should be documented in the source document. 
Reactogenicity 
Solicited injection site reactions will be collected from D01 to D08 after each vaccination. 
Solicited systemic reactions will be collected from D01 to D08 after each vaccination.  
The solicited injection site reactions and systemic reactions that are pre-listed in the diary cards 
and CRF, together with the intensity scales, are presented in Appendix 10.3.5.1.1. 
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Unsolicited Non-serious Adverse Events 
Unsolicited non-serious AEs will be collected from D01 to D31 after each vaccination. 
The intensity grading scale for unsolicited non-serious AEs are presented in Appendix 10.3.5.1.2. 
Adverse Events of Special Interest  
AESI will be collected throughout the study. 
See Section 8.3.6 for the list of AESI. 
Serious Adverse Events 
Information on SAEs will be collected and assessed throughout the study, from D01 (first 
vaccination) until 30 days after the last vaccination. However, before the first study intervention 
administration, only SAEs related to study procedures are to be collected (eg, SAE related to the 
blood sampling before the vaccination). 
Medical occurrences that begin before the start of study intervention but after obtaining informed 
consent will not be recorded on the AE section of the CRF. 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 10.3. The Investigator will 
submit any updated SAE data to the Sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the Investigator must promptly notify the 
Sponsor. 
8.3.2 
Method of Detecting AEs and SAEs 
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. These 
diary cards will include pre-listed terms and intensity scales as well as areas for free text to 
capture additional safety information or other relevant details. Participants/parents/legally 
acceptable representatives will also be provided with rulers for measuring the size of injection site 
reactions, and with standard digital thermometers for measuring daily temperatures. To ensure 
consistency of reporting, the study sites will instruct participants/parents/legally acceptable 
representatives on how to correctly use these tools. 
At specified intervals, the Investigator or an authorized designee will interview the 
participants/parents/legally acceptable representatives to collect the information recorded in the 
diary card and will attempt to clarify anything that is incomplete or unclear. All clinical study 
information gathered by the study site will be reported electronically by the Investigator or 
authorized designee using a web-based CRF. Any information that was not documented in the 
diary card will first be captured in the source document and then reported electronically. 
The method of recording, evaluating, and assessing causal relationship of AE and SAE and the 
procedures for completing and transmitting SAE reports are provided in Appendix 10.3. 
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Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
Unless a participant or parent/legally acceptable representative refuses further contact, each 
participant 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 participant’s participation in the study) if either of the following is true: 
• The AE is considered by the Investigator to be related to the study intervention administered 
• The AE caused the discontinuation of the participant from the study or from vaccination 
The Investigator will inform the Sponsor of the date of final disappearance of the event or the date 
of “chronicity” establishment. 
8.3.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting 
to the regulatory authority, IEC/IRB, and Investigators. 
• For all studies except those investigating medical devices, Investigator safety reports must be 
prepared for suspected unexpected serious adverse reactions according to local regulatory 
requirements and Sponsor policy and forwarded to Investigators as necessary. 
• An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then 
file it and will notify the IEC/IRB, if appropriate according to local requirements. 
8.3.5 
Pregnancy 
Pregnancy and/or the absence of the use of effective contraceptive methods are exclusion criteria 
for enrollment in this study, but a participant could potentially become pregnant during her 
participation. 
• Details of all pregnancies in female participants will be collected after the start of study 
intervention and until delivery, by the Investigator, and recorded in the Pregnancy CRF. Any 
data collected after CRF lock will be transmitted to the pharmacovigilance department on the 
paper form. 
• If a pregnancy is reported, the Investigator should inform the Sponsor within 1 month of 
learning of the pregnancy and should follow the procedures outlined in Appendix 10.4. 
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• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
Adverse Events of Special Interest 
An AESI is defined as an event for which ongoing monitoring and rapid communication by the 
Investigator to the Sponsor must be done. The following AEs will be captured as AESI throughout 
the study: 
• Generalized seizures (febrile and non-febrile) (34) 
• Kawasaki disease (35-37) 
• Guillain-Barré syndrome (38) 
• Idiopathic thrombocytopenic purpura (39) 
These events have been listed as AESI based on the feedback received from the EU regulators for 
the MenACYW conjugate vaccine. 
No safety concerns relating to these AESI have been identified with the use of MenACYW 
conjugate vaccine in the completed clinical studies. Due to their medical importance and to ensure 
expedited communication to the Sponsor, these AESI are to be considered and collected as SAEs 
and reported to the Sponsor according to the procedure described in Appendix 10.3.4. Further 
instructions on the data collection for these events and the relevant definitions will be provided in 
the Operating Guidelines. 
 
8.4 
Treatment of Overdose 
Since the study intervention is administered by a health care professional, it is unlikely that 
overdose by injection occurs. 
However, in the event of an overdose, the Investigator should: 
• Contact the Medical Monitor immediately 
• Closely monitor the participant for any AE/SAE 
• Document the quantity of the excess of the overdose in the source documents 
8.5 
Pharmacokinetics 
Pharmacokinetics parameters are not evaluated in this study. 
8.6 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
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8.7 
Genetics 
Genetics are not evaluated in this study. 
8.8 
Biomarkers 
No other biomarkers than those described in the immunogenicity assessments section 
(Section 8.1.2) are evaluated in this study. 
8.9 
Immunogenicity Assessments 
See Section 8.1.2. 
8.10 Medical Resource Utilization and Health Economics 
Medical Resource Utilization and Health Economics parameters are not evaluated in this study. 
9 
Statistical Considerations 
Clinical data will be analyzed under the responsibility of the Biostatistics Platform of the Sponsor. 
A Statistical Analysis Plan (SAP) will be written and peer-reviewed before any analyses. In 
accordance with the protocol, the SAP will describe all analyses to be performed by the Sponsor 
and all the conventions to be taken. 
9.1 
Statistical Hypotheses 
Primary Objective 
A non-inferiority approach will be used to compare post-vaccination (ie, 30 days after the 
vaccination) seroprotection rates of MenACYW conjugate vaccine (Group 1) to that of Nimenrix® 
(Group 2). 
The primary objective is to demonstrate that 30 days after the administration of MenACYW 
conjugate vaccine or Nimenrix®, the percentage of participants who achieve an hSBA titer 
≥ 1:8 for meningococcal serogroups A, C, W, Y in participants who received MenACYW 
conjugate vaccine (Group 1) is non-inferior to the corresponding percentage in participants who 
received Nimenrix® (Group 2). 
Details on statistical methods are provided in Section 9.4. 
 
Secondary and Observational Objectives 
No hypotheses will be tested. The analyses will be descriptive. 
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9.2 
Sample Size Determination 
Approximately 464 participants are expected to be enrolled. 
 
For the Primary Objective 
With 174 enrolled participants in Group 1 and Group 2 each, the study will have a > 90% power 
(Farrington and Manning formula) to declare the non-inferiority of Group 1 versus Group 2 based 
on A, C, W, and Y hSBA antibody titers ≥ 1:8 (difference in the percentage of seroprotected 
participants in the 2 groups) after a single dose of MenACYW conjugate vaccine or Nimenrix®, 
assuming: 
• A 10% dropout rate from the PPAS (155 participants evaluable per Group 1 and Group 2) 
• A 1-sided alpha level of 2.5% 
• A non-inferiority margin of 10% (percentage difference) 
See Table 9.1 below for power of the study for primary objective. 
 
Table 9.1: Power of the study for the primary objective 
Antigen 
Estimated percentage of 
hSBA titer ≥ 1:8  
MenACYW* 
Non-inferiority 
margin† 
Power 
A 
93.5% 
10% 
90.7% 
C 
98.5% 
10% 
> 99.9% 
Y 
97.2% 
10% 
99.3% 
W 
99.1% 
10% 
> 99.9% 
Overall 
 
 
≥ 90% 
Since the hypothesis needs to be met for all serogroups, no alpha adjustment for multiple comparisons is necessary in 
these calculations. 
* Percentages of participants with an hSBA titer ≥ 1:8 are based on the MET50 MenACYW (Group 1) post-dose 
result. The power is calculated with the assumption that the estimates from Group 1 equal that of Group 2 
corresponding to the estimated percentages in Group 2 described above. 
† A non-inferiority margin of 10% has been widely used in previous studies evaluating the same antigens and in a 
competitor’s study of the same type. Also, considering the level of the reference rate taken in Group 2, it is reasonable 
to use 10%. 
 
For the Secondary and Observational Objectives 
The sample size has been arbitrarily set to 116 participants in Group 3, as well as the sample size 
of the subsets, as these data are not intended to be used for any hypothesis testing. No formal 
sample size calculations were performed. 
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In case of unexpected situations or any study hold resulting in an unexpected number of 
unevaluable participants, total sample size may be increased to replace withdrawn, or unevaluable 
participants. 
9.3 
Populations for Analyses 
The following populations are defined: 
Population 
Description 
Safety Analysis Set 
(SafAS) 
Participants who have received at least one dose of the study 
vaccinesa and have any safety data available. 
Three SafAS will be defined. 
Overall SafAS for any dose: 
Participants who have received at least one dose of the study 
vaccinesb and have any safety data available. 
SafAS for vaccination at Visit 1 (SafAS1): 
Participants who have received at least one dose of the study 
vaccinesa at Visit 1 (all groups) and have any safety data 
available. 
SafAS for vaccination at Visit 2 (SafAS2): 
Participants who have received at least one dose of the study 
vaccinesa at Visit 2 (Group 1 and 2) and have any safety data 
available. 
For each SafAS, all participants will have their safety analyzed 
according to the study vaccine they actually received. 
Safety data recorded for a vaccine received out of the protocol 
design will be excluded from the analysis (and listed separately). 
Full analysis set (FAS) 
Two FAS will be defined: one for hSBA measurement and one 
for rSBA measurement. 
hSBA FAS: 
                                                 
 
 
a For which safety data are scheduled to be collected. 
b For which safety data are scheduled to be collected. 
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Population 
Description 
Subset of randomized participants who received at least one dose 
of the study vaccines and had a valid post-vaccination serology 
result.  
rSBA FAS: 
Subset of randomized participants who received at least one dose 
of the study vaccines and had a valid post-vaccination serology 
rSBA result. 
Participants will be analyzed according to the intervention to 
which they were randomized. 
Per-protocol analysis sets 
(PPAS) 
Subset of hSBA FAS and rSBA FAS. 
Three PPAS will be defined: two for meningococcal vaccines 
(hSBA PPASM and rSBA PPASM) and one for concomitant 
vaccines (PPASC). 
hSBA and rSBA PPASM: 
Participants presenting with at least 1 of the following relevant 
protocol deviations will be excluded from the hSBA and rSBA 
PPASM: 
• Participant did not meet all protocol-specified inclusion 
criteria or met at least 1 of the protocol-specified exclusion 
criteria 
• Participant did not receive the meningococcal vaccine 
• Participant received a vaccine other than the one that he/she 
was randomized to receive 
• Preparation and/or administration of vaccine was not done as 
per-protocol 
• Participant did not provide a post-dose serology sample in the 
proper time window or a post-dose serology sample was not 
drawn: 
• Blood sampling 2 (BL02AA or BL02AR) in Group 1 and 2: 
• Visit 2: Visit 1 + 30 days [+14 days]  
• Blood sampling 3 (BL03BB or BL03BR) in Group 3: 
• Visit 3: Visit 1 + 30 days [+14 days] 
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Population 
Description 
• Participant received a protocol-prohibited therapy/medication 
/vaccine (Category 2 or Category 3) 
• Participant had other protocol violations that affected the 
participant’s immune response, as determined by the clinical 
team before locking the database 
In addition, to the reasons listed above, participant will also be 
excluded from the hSBA PPASM if: 
• Participant serology samples did not produce a valid test result 
(ie, hSBA result for all meningococcal antigens are missing) 
And from rSBA PPASM if: 
• Participant serology samples did not produce a valid test result 
(ie, rSBA result for all meningococcal antigens are missing) 
PPASC: 
Participants presenting with at least 1 of the following relevant 
protocol deviations will be excluded from the PPASC: 
• Participant did not meet all protocol-specified inclusion 
criteria or met at least 1 of the protocol-specified exclusion 
criteria 
• Participant did not complete the vaccination schedule 
• Participant received a vaccine other than the one that he/she 
was randomized to receive 
• Preparation and/or administration of vaccine was not done as 
per-protocol 
• Participants did not receive the vaccine in the proper time 
window: 
• Visit 2: Visit 1 + 30 days [+14 days] (Group 1 and 2) 
• Participant did not provide a post-dose serology sample in the 
proper time window or a post-dose serology sample was not 
drawn: 
• Blood sampling 3 (BL03AA) in Group 1 and 2: 
• Visit 3: Visit 2 + 30 days [+14 days] 
• Blood sampling 3 (BL03BB or BL03BR) in Group 3: 
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Population 
Description 
• Visit 3: Visit 1 + 30 days [+14 days] 
• Participant received a protocol-prohibited therapy/medication 
/vaccine (Category 2 or Category 3) 
• Participants with their serology samples that did not produce a 
valid test result (ie, results for all antigens contained in 
9vHPV and Tdap-IPV vaccines are missing) 
• Participant had other protocol violations that affected the 
participant’s immune response, as determined by the clinical 
team before locking the database 
In the event of a local or national immunization program (eg, with 
a pandemic influenza vaccine or COVID-19 vaccine), participants 
who receive 1 or more doses of pandemic influenza vaccine or 
COVID-19 vaccine at any time during the study will not be 
withdrawn from the study. 
If the participant receives the COVID-19 vaccine within this 
period of 28 days pre or post IMP vaccination (including the day 
of the study visit for IMP vaccine), she/he will be excluded from 
the PPAS population but will not be excluded from the study. 
9.4 
Statistical Analyses 
The SAP will be finalized prior to database lock and it will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of all the endpoints including primary, secondary, and observational 
endpoints. 
9.4.1 
General Considerations 
Immunogenicity analyses will be performed on the appropriate PPAS and FAS. Safety analysis 
will be performed on the SafAS. 
9.4.2 
Primary Hypotheses and Methods 
For primary endpoint, refer to Section 3.  
The primary objective will be met if the following null hypothesis is rejected for each of the 4 
serogroup A, C, W, Y: 
𝐻𝐻0: 𝑝𝑝MenACYW −𝑝𝑝𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁≤−0.1  
𝐻𝐻1: 𝑝𝑝MenACYW −𝑝𝑝𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁> −0.1  
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where p(MenACYW) and p(Nimenrix) are the percentages of participants who achieve an hSBA titer 
≥ 1:8 in the MenACYW conjugate vaccine group and the comparator group (Nimenrix®), 
respectively. 
The 95% confidence interval (CI) of the difference in proportion will be computed using the 
Wilson Score method without continuity correction (Newcombe method) (40). 
If the lower limit of the 2-sided 95% CI of the difference between the 2 percentages is > -0.1, the 
non-inferiority will be demonstrated. 
Non-inferiority will be demonstrated if all 4 individual null hypotheses (4 serogroups) are 
rejected. 
 
9.4.3 
Secondary Hypotheses and Methods 
Immunogenicity 
For secondary immunogenicity endpoints, refer to Section 3. 
The statistical analysis for secondary objectives will be descriptive. 
In general, categorical variables will be summarized and presented by frequency counts, 
percentages, and CIs. The 95% CIs of percentages will be calculated using the exact binomial 
distribution (Clopper-Pearson method). For geometric mean titer and geometric mean 
concentration, 95% CIs of point estimates will be calculated using a normal approximation 
assuming they are log-normally distributed. 
Safety 
For secondary safety endpoints, refer to Section 3. 
Safety results will be described for participants in all study groups. The main parameters for the 
safety endpoints will be described by frequency counts and 95% CIs (based on the Clopper-
Pearson method). 
9.4.4 
Observational Endpoints 
For observational endpoints, refer to Section 3. 
The statistical analysis for observational objectives will be descriptive and will be carried out 
similar to the secondary immunogenicity analysis described in Section 9.4.3. More details about 
statistical analyses of observational objectives will be given in the SAP. 
9.4.5 
Sensitivity analysis due to COVID-19 pandemic 
The impact of COVID-19 pandemic situation on study conduction will be summarized through 
impact on visit procedures, study completion and major/critical protocol deviations due to 
COVID-19. The participants impacted by COVID-19 pandemic situation will be defined as the 
participants with at least one major/critical protocol deviation due to COVID-19 or who did not 
complete the study due to COVID-19. If more than 10% of participants are impacted as per this 
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definition, the main immunogenicity and safety endpoints will also be summarized in these 
participants to assess the impact of COVID-19 situation on the study outcome. 
9.5 
Interim Analyses 
This study will not include an early safety data review. However, participant safety will be 
continuously monitored by the Sponsor’s internal safety review committee which includes safety 
signal detection at any time during the study. 
No analyses are planned to be performed prior to the formal completion of the study. 
9.6 
Data Monitoring Committee 
Not applicable. 
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10 Supporting Documentation and Operational Considerations 
10.1 Appendix: Regulatory, Ethical, and Study Oversight Considerations 
Note: The term “participant” is used throughout this protocol. However, the term “participant” 
will be used in the CRF in order to comply with the Clinical Data Interchange Standards 
Consortium requirements. 
10.2 Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
• 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines 
• 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
• 
Applicable laws and regulations (eg, data protection law as General Data Protection 
Regulation [GDPR]) 
• The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant documents 
(eg, advertisements) must be submitted to an IEC/IRB by the Investigator or the Sponsor 
(according to local regulations) and reviewed and approved by the IEC/IRB before the study is 
initiated 
• Any amendments to the protocol will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants 
• The Investigator  will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IEC/IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IEC/IRB. 
• 
Determining whether an incidental finding (as per Sanofi policy) should be returned to a 
participant and, if it meets the appropriate criteria, to ensure the finding is returned (an 
incidental finding is a previously undiagnosed medical condition that is discovered 
unintentionally and is unrelated to the aims of the study for which the tests are being 
performed). The following should be considered when determining the return of an 
incidental finding: 
• The return of such information to the study participant (and/or his/her designated 
healthcare professional, if so designated by the participant) is consistent with all 
applicable national, state, or regional laws and regulations in the country where the 
study is being conducted, and 
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• The finding reveals a substantial risk of a serious health condition or has 
reproductive importance, AND has analytical validity, AND has clinical validity. 
• The participant in a clinical study has the right to opt out of being notified by the 
Investigator of such incidental findings. In the event that the participant has opted out 
of being notified and the finding has consequences for other individuals, eg, the 
finding relates to a communicable disease, Investigators should seek independent 
ethical advice before determining next steps. 
• In case the participant has decided to opt out, the Investigator must record in the 
site medical files that she/he does not want to know about such findings. 
• 
Notifying the IEC/IRB of SAEs or other significant safety findings as required by 
IEC/IRB procedures. 
• Providing oversight of the conduct of the study at the site and adherence to requirements of 21 
CFR, ICH guidelines, the IEC/IRB, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations. 
10.2.1 Financial Disclosure 
Information related to financial disclosure is described in the Investigator’s contract. 
10.2.2 Informed Consent Process 
• The Investigator or his/her representative will explain the nature of the study to the participant 
and his/her parent/legally acceptable representative and answer all questions regarding the 
study. 
• Participants and their parents/legally acceptable representatives must be informed that their 
participation is voluntary. Participants and their parents/legally acceptable representatives will 
be required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
requirements, where applicable, and the IEC/IRB or study center. 
• As this study is conducted in adolescent participants, a separate AF has to be signed by the 
participants (as per local regulation). The AF is in addition to, not in place of an ICF that is 
signed by the parent/legally acceptable representative (and by an independent witness if 
required) and by the participant if he/she turns18 years old during the study. 
• The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF and AF. 
• The actual ICF and AF used at each center may differ, depending on local regulations and 
IEC/IRB requirements. However, all versions must contain the standard information found in 
the sample ICF and AF provided by the Sponsor. Any change to the content of the ICF and AF 
must be approved by the Sponsor and the IEC/IRB prior to the form being used. 
• If new information becomes available that may be relevant to the participant’s or 
parent’s/legally acceptable representative’s willingness to continue participation in the study, 
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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 and via a revised AF or an addendum to 
the original AF. 
• Participants and their parents/legally acceptable representatives must be re-consented to the 
most current version of the ICF and AF during their participation in the study. 
• A copy of the ICF and AF must be provided to the participants and their parents/legally 
acceptable representatives. 
• A participant who is rescreened is not required to sign another AF and his/her parent/legally 
acceptable representative is not required to sign another ICF. 
• The ICF will contain a specific section that addresses the use of remaining mandatory samples 
for optional exploratory research. The Investigator or authorized designee will explain to each 
participant and their parent/legally acceptable representative the objectives of the exploratory 
research. Participants and their parents/legally acceptable representatives will be told that they 
are free to refuse to participate and may withdraw their consent at any time and for any reason 
during the storage period. 
 
Recruitment Procedures 
As this is a multi-center study with recruitment procedures differing between sites, the procedures 
will be described in a separate “Recruitment and Consent Process Form” in each site. In such a 
case, the form will be archived on-site. 
10.2.3 Data Protection and Future Use of Stored Samples 
• All personal data collected related to participants, Investigators, or any person involved in the 
study, which may be included in the Sponsor’s databases, shall be treated in compliance with 
all applicable laws and regulations including the GDPR. 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. 
• Participants’ race and ethnicity will be collected in this study because these characteristics 
may influence the immune response to the vaccines. 
• Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant name or 
any information which would make the participant identifiable will not be transferred to the 
Sponsor. 
• The participant 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 participant as described in the informed consent. 
• The participant 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 IEC/IRB members, and by inspectors from regulatory authorities. 
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• When archiving or processing personal data pertaining to the Investigator and/or to the 
participants, the Sponsor shall take all appropriate measures to safeguard and prevent access to 
this data by any unauthorized third party. 
• Participant data will be used for this study and in support of the whole drug development 
program for the Investigational Product, including negotiations with payers and publication of 
results. 
• Any unused part of the serum samples (blood samples) will be securely stored at the Sanofi 
Pasteur serology laboratory (GCI) for up to 25 years after the end of the study. These samples 
are being retained in long-term storage to support answers to regulatory questions related to 
the product’s licensure and the potential revalidation of the study results. 
The other biological samples collected to qualify the participant for inclusion in the study or to 
monitor his/her health are dedicated for immediate use. In case they are not completely used 
up, they will be destroyed at the latest at the end of the study or after the time requested by 
local law. 
In addition, parents/legally acceptable representatives will be asked to indicate in the ICF 
whether they will permit the future use of any unused stored serum samples for other tests. If 
they refuse permission, the samples will not be used for any testing other than that directly 
related to this study. If they agree to this use, they will not be paid for giving permission. 
Anonymity of samples will be ensured. The aim of any possible future research is unknown 
today and may not be related to this particular study. It may be to improve the knowledge of 
vaccines or infectious diseases, or to improve existing tests or develop new tests to assess 
vaccines. Human genetic tests will never be performed on these samples without specific 
individual informed consent. 
10.2.4 Committees Structure 
This study will not include an early safety data review. However, participant safety will be 
continuously monitored by the Sponsor’s internal safety review committee which includes safety 
signal detection at any time during the study. 
10.2.5 Dissemination of Clinical Study Data 
Sanofi shares information about clinical trials and results on publically accessible websites, based 
on company commitments, international and local legal and regulatory requirements, and other 
clinical trial disclosure commitments established by pharmaceutical industry associations. These 
websites include clinicaltrials.gov, EU clinicaltrialregister (eu.ctr), and sanofi.com, as well as 
some national registries. 
In addition, results from clinical trials in individuals are required to be submitted to peer-reviewed 
journals following internal company review for accuracy, fair balance, and intellectual property. 
For those journals that request sharing of the analyzable data sets that are reported in the 
publication, interested researchers are directed to submit their request to 
clinicalstudydatarequest.com. 
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Individual participant data and supporting clinical documents are available for request at 
clinicalstudydatarequest.com. While making information available we continue to protect the 
privacy of participants in our clinical trials. Details on data sharing criteria and process for 
requesting access can be found at this web address: clinicalstudydatarequest.com. 
10.2.6 Data Quality Assurance 
• All participant data relating to the study will be recorded on electronic CRF unless transmitted 
to the Sponsor or designee electronically (eg, laboratory data). The Investigator is responsible 
for verifying that data entries are accurate and correct by physically or electronically signing 
the CRF. 
• The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
• The Investigator must permit study-related monitoring, audits, IEC/IRB review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), 
methods, responsibilities and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring) are provided in the Monitoring 
Plan. 
• The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals (eg, Contract 
Research Organizations). 
• Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
• Records and documents, including signed ICFs and AFs, pertaining to the conduct of this 
study must be retained by the Investigator for 25 years after the signature of the final study 
report unless local regulations or institutional policies require a longer retention period. No 
records may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor. 
10.2.7 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, ICFs/AFs, telephone contact logs, and worksheets. 
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• Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 
• Data entered in the CRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
Detailed guidance and information are provided in the Operating Guidelines. 
10.2.8 Study and Site Start and Closure 
Details on which clinical supplies are provided by the Sponsor or the site are described in the 
Operating Guidelines. 
The study start date is considered as the date of the first visit planned in the SoA of the first 
participant. The study end date is considered as the date of the last visit of the last participant. 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been either destroyed or returned to the Sponsor, all samples are shipped to the appropriate 
laboratories, the center study-site has all the documents necessary for archiving and a study-site 
closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IEC/IRB or 
local Health Authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study intervention development 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any Contract Research Organization 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.2.9 Publication Policy 
Information related to publication policy is described in the Investigator’s contract. 
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Table 10.1: Solicited injection site reactions: terminology, definitions, and intensity scales – Adolescents aged ≥ 10  to <17 years 
CRF term 
(MedDRA 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 
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Intensity scale* 
CRF: 
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. 
Diary card: 
Grade 1: No interference with usual 
activities 
Grade 2: Some interference with usual 
activities 
Grade 3: Significant; prevents usual 
activities 
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 
LLT: lowest level term; MedDRA: Medical Dictionary for Regulatory Activities. 
* For the subjective reaction of pain, participants or parents/legally acceptable representatives will record the intensity level (Grade 1, 2, or 3) in the diary card. For the measurable 
reactions of redness and swelling, they will record just the size of the reaction, and the classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis. 
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Table 10.2: Solicited systemic reactions: terminology, definitions, and intensity scales –Adolescents aged ≥ 10 to < 17 years 
CRF term (MedDRA 
LLT) 
Fever 
Headache 
Malaise 
Myalgia 
Diary card term 
Temperature 
Headache 
Feeling unwell 
Muscle aches and pains 
Definition 
Elevation of temperature to 
≥°38.0°C (≥ 100.4°F) 
Pain or discomfort in the head or 
scalp. Does not include migraine. 
General ill feeling. 
Malaise is a generalized feeling of 
discomfort, illness, or lack of well-
being that can be associated with a 
disease state. It can be accompanied 
by a sensation of exhaustion or 
inadequate energy to accomplish 
usual activities. 
Muscle aches and pains are 
common and can involve more than 
one muscle at the same time. 
Muscle pain can also involve the 
soft tissues that surround muscles. 
These structures, which are often 
referred to as connective tissues, 
include ligaments, tendons, and 
fascia (thick bands of tendons). 
Does not apply to muscle pain at 
the injection site which should be 
reported as injection site pain. 
Intensity scale* 
Grade 1: ≥ 38.0°C to ≤ 38.4°C, 
or ≥ 100.4°F to ≤ 101.1°F 
CRF: 
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. 
CRF: 
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. 
CRF: 
Grade 1: A type of adverse event 
that is usually transient and may 
require only minimal treatment or 
therapeutic intervention. The event 
does not generally interfere with 
usual activities of daily living. 
 
Grade 2: ≥ 38.5°C to ≤ 38.9°C, 
or ≥ 101.2°F to ≤ 102.0°F 
Grade 2: A type of adverse event 
that is usually alleviated with 
additional therapeutic intervention. 
The event interferes with usual 
activities of daily living, causing 
discomfort but poses no significant 
or permanent risk of harm to the 
research participant. 
Grade 2: A type of adverse event 
that is usually alleviated with 
additional therapeutic intervention. 
The event interferes with usual 
activities of daily living, causing 
discomfort but poses no significant 
or permanent risk of harm to the 
research participant. 
Grade 2: A type of adverse event 
that is usually alleviated with 
additional therapeutic intervention. 
The event interferes with usual 
activities of daily living, causing 
discomfort but poses no significant 
or permanent risk of harm to the 
research participant. 
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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. 
Diary card: 
Grade 1: No interference with usual 
activities 
Grade 2: Some interference with 
usual activities 
Grade 3: Significant; prevents usual 
activities 
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. 
Diary card: 
Grade 1: No interference with usual 
activities 
Grade 2: Some interference with 
usual activities 
Grade 3: Significant; prevents usual 
activities 
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. 
Diary card: 
Grade 1: No interference with usual 
activities 
Grade 2: Some interference with 
usual activities 
Grade 3: Significant; prevents usual 
activities 
LLT: lowest level term; MedDRA: Medical Dictionary for Regulatory Activities 
* For all reactions but fever, participants or parents/legally acceptable representatives will record the intensity level (Grade 1, 2, or 3) in the diary card. For fever, they will record the 
body temperature, and the classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis based on the unit used to measure the temperature and the intensity 
scale. 
 
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Important Notes for the Accurate Assessment of Temperature: 
Participants or parents/legally acceptable representatives 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 CRF. The 
preferred route for this study is oral. 
10.3.5.1.2 Unsolicited AE Intensity Grading Scale 
For measurable unsolicited AEs that are part of the list of solicited reactions, the corresponding 
scale for solicited reactions will be used (see Section 10.3.5.1.1). 
All other unsolicited AEs will be classified according to the following intensity scale: 
• Grade 1 
• 
CRF: 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. 
• 
Diary card: No interference with usual activities. 
• Grade 2 
• 
CRF: 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. 
• 
Diary card: Some interference with usual activities. 
• Grade 3 
• 
CRF: A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
• 
Diary card: Significant; prevents usual activities. 
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10.4 Appendix: Collection of Pregnancy Information 
DEFINITIONS: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Women in the Following Categories Are Not Considered WOCBP 
• Premenarchal 
• Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), Investigator discretion should be 
applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the participant’s medical 
records, medical examination, or medical history interview. 
• Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
• 
A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, confirmation with more than one FSH measurement is 
required. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
COLLECTION OF PREGNANCY INFORMATION 
Female Participants Who Become Pregnant 
• The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information together with the 
contraceptive method if any will be recorded on the appropriate form and submitted to the 
Sponsor within 1 month of learning of a participant's pregnancy. 
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• The participant will be followed to determine the outcome of the pregnancy. The Investigator 
will collect follow-up information on the participant and the neonate and the information will 
be forwarded to the Sponsor. Generally, follow-up will not be required for longer than 
8 weeks beyond the estimated delivery date but will be in accordance with local regulations. 
Any termination of pregnancy will be reported, regardless of fetal status (presence or absence 
of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
• A spontaneous abortion (occurring at < 22 weeks gestational age) or still birth (occurring at 
> 22 weeks gestational age) is always considered to be an SAE and will be reported as such. 
• Any post-study pregnancy related SAE considered reasonably related to the study intervention 
by the Investigator will be reported to the Sponsor as described in Section 8.3.4. While the 
Investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
• In case of pregnancy during the primary series and if at least 1 dose of the study vaccine has 
been administered, the participant will not be discontinued from the study, but no further 
vaccination will be administered until after delivery (if applicable and still within the study 
vaccination window). However, the participant will be followed for safety assessment (and 
may be followed for immunogenicity assessment, if applicable). 
 
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10.4.1 
Contraception Guidance 
• 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
• 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year when used 
consistently and correctly. 
• Implantable progestogen-only hormone contraception associated with inhibition of ovulationb 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) b 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole sexual partner of 
the woman of childbearing potential and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used. 
• 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly. 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationc 
− oral 
− intravaginal 
− transdermal 
− injectable 
• Progestogen-only hormone contraception associated with inhibition of ovulationc 
− oral 
− injectable 
• Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant. 
• Effective Methodsd That Are Not Considered Highly Effective Failure rate of ≥ 1% per year when used 
consistently and correctly. 
• Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of 
action 
• Male or female condom with or without spermicide 
• Cervical cap, diaphragm, or sponge with spermicide 
• A combination of male condom with either cervical cap, diaphragm, or sponge with spermicide (double-
barrier methods)c 
a) Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b) Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c) Male condoms must be used in addition to hormonal contraception. 
d) Considered effective, but not highly effective - failure rate of ≥1% per year. Periodic abstinence (calendar, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhea method (LAM) are not acceptable methods of contraception.  
e) Male condom and female condom should not be used together (due to risk of failure from friction). 
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10.5 Appendix: Risk-based Approach 
ICH E6-R2 guideline for GCP is introducing the « risk-based approach » concept which permits 
to focus efforts on what is critical for a study and most specifically on Critical Data and Critical 
Processes. Critical data and processes are defined for the study with associated risks in the Study 
Risk Management Plan. 
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10.6 Appendix: Abbreviations 
4vHPV 
4-valent human papilloma virus 
9vHPV 
9-valent human papilloma virus 
AE 
 
adverse events 
AESI  
adverse events of special interest 
AR 
 
adverse reaction 
CI 
 
confidence interval 
CO2 
 
carbon dioxide 
CRF  
Case Report Form 
D 
 
day 
DNA  
deoxyribonucleic acid 
ECDC  
European Center for Disease Prevention and Control 
EEA  
European Economic Area 
EMA  
European Medicines Agency 
EU 
 
European Union  
FAS 
 
Full Analysis Set 
FHA  
filamentous hemagglutinin 
FIM 
 
fimbriae types 2 and 3 
FSH 
 
follicle stimulating hormone 
GCI 
 
Global Clinical Immunology 
GCP  
Good Clinical Practice 
GPV  
Global Pharmacovigilance 
HPV  
human papillomavirus 
HRT  
hormonal replacement therapy 
hSBA  
serum bactericidal assay using human complement  
ICF 
 
Informed Consent Form 
ICH 
 
International Council for Harmonisation 
IEC 
 
Independent Ethics Committee 
IMD  
invasive meningococcal disease 
IMP 
 
investigational medicinal product 
IRB 
 
Institutional Review Board 
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IRT 
 
interactive response technology 
IU 
 
international units 
LLOQ  
lower limit of quantification 
LLT 
 
lowest level term 
MedDRA 
Medical Dictionary for Regulatory Activities 
MenC  
meningococcal serogroup C conjugate vaccine 
NIMP  
non-investigational medicinal product 
PPAS  
Per-Protocol Analysis Sets 
PPASC 
Per-Protocol Analysis Set for concomitant vaccines 
PPASM 
Per-Protocol Analysis Set for meningococcal vaccines 
PRN  
pertactin 
PT 
 
pertussis toxoid 
RMO  
Responsible Medical Officer 
rSBA  
serum bactericidal assay using baby rabbit complement 
SAE  
serious adverse events 
SafAS  
Safety Analysis Set 
SAP 
 
Statistical Analysis Plan 
SoA 
 
Schedule of Activities 
SmPC   
summary of product characteristics 
TBD  
to be determined 
Tdap  
tetanus, diphtheria, and acellular pertussis 
Tdap-IPV 
tetanus, diphtheria, and acellular pertussis - inactivated polio vaccine [adsorbed, 
reduced antigen(s) content]  
VLP  
virus-like particle 
WHO  
World Health Organization 
WOCBP 
Woman of Childbearing Potential 
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11 References 
1. 
Borrow R, Alarcon P, Carlos J, Caugant DA, Christensen H, Debbag R, et al. The Global 
Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease 
and the importance of herd protection. Expert Rev Vaccines. 2017;16(4):313-28. 
2. 
Harrison OB, Claus H, Jiang Y, Bennett JS, Bratcher HB, Jolley KA, et al. Description and 
nomenclature of Neisseria meningitidis capsule locus. Emerg Infect Dis. 2013;19(4):566-73. 
3. 
Pollard AJ. Global epidemiology of meningococcal disease and vaccine efficacy. Pediatr 
Infect Dis J. 2004;23(12 Suppl):S274-9. 
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European Centre for Disease Prevention and Control. Invasive meningococcal disease. In: 
ECDC. Annual epidemiological report for 2017. Stockholm 2019 [Available from: 
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meningococcal-disease.pdf. Accessed on 10 Jul 2020. 
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Sanità ISD. Dati di sorveglianza delle malattie batteriche invasive aggiornati al 3 aprile 
2017  [Available from: http://old.iss.it/binary/mabi/cont/Report_MBI_20170403_finale.pdf. 
Accessed on 31 Mar 2020. 
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Sanita ISD. Sorveglianza delle malattie batteriche invasive in Italia. 2018  [Available 
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European Centre for Disease Prevention and Control. Surveillance network for invasive 
Neisseria meningitidis in Europe 1999 -2000. 2007 [Available from: 
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veillance_network_for_Invasive_Neisseria_Meningitidis.pdf. Accessed on 16 Jul 2020. 
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Communicable disease surveillance in Singapore 2018 [Internet]. 2018. Available from: 
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singapore-2018. Accessed on 24 Apr 2020. 
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Christensen H, May M, Bowen L, Hickman M, Trotter CL. Meningococcal carriage by 
age: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(12):853-61. 
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Bijlsma MW, Brouwer MC, Spanjaard L, van de Beek D, van der Ende A. A decade of 
herd protection after introduction of meningococcal serogroup C conjugate vaccination. Clin 
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Burman C, Serra L, Nuttens C, Presa J, Balmer P, York L. Meningococcal disease in 
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Trotter CL, Maiden MC. Meningococcal vaccines and herd immunity: lessons learned 
from serogroup C conjugate vaccination programs. Expert Rev Vaccines. 2009;8(7):851-61. 
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World Health Organization. WHO vaccine-preventable diseases: monitoring system. 2019 
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=EURO&sc%5Bc%5D%5B%5D=IRL&sc%5Bd%5D=&sc%5Bv%5D%5B%5D=MENACWY-
135+CONJ&sc%5BOK%5D=OK. Accessed on 22 Mar 2020. 
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14. 
Trotter CL, Ramsay ME. Vaccination against meningococcal disease in Europe: review 
and recommendations for the use of conjugate vaccines. FEMS Microbiol Rev. 2007;31(1):101-7. 
15. 
Esposito S, Principi N, European Society of Clinical M, Infectious Diseases Vaccine Study 
G. Immunization against pertussis in adolescents and adults. Clin Microbiol Infect. 2016;22 Suppl 
5:S89-S95. 
16. 
World Health Organization. WHO vaccine-preventable diseases: monitoring system. 2019 
global summary.  [Available from: 
https://apps.who.int/immunization_monitoring/globalsummary/countries. Accessed on 31 Mar 
2020. 
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Bernstein HH, Bocchini JA, Jr., Committee On Infectious D. The Need to Optimize 
Adolescent Immunization. Pediatrics. 2017;139(3). 
18. 
Gallagher KE, Kadokura E, Eckert LO, Miyake S, Mounier-Jack S, Aldea M, et al. Factors 
influencing completion of multi-dose vaccine schedules in adolescents: a systematic review. BMC 
Public Health. 2016;16:172. 
19. 
Chang LJ, Hedrick J, Christensen S, Pan J, Jordanov E, Dhingra MS. A Phase II, 
randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate 
vaccine, MenACYW-TT, in healthy adolescents in the United States. Vaccine. 2020;38(19):3560-
9. 
20. 
Velentgas P, Amato AA, Bohn RL, Chan KA, Cochrane T, Funch DP, et al. Risk of 
Guillain-Barre syndrome after meningococcal conjugate vaccination. Pharmacoepidemiol Drug 
Saf. 2012;21(12):1350-8. 
21. 
Yih WK, Weintraub E, Kulldorff M. No risk of Guillain-Barre syndrome found after 
meningococcal conjugate vaccination in two large cohort studies. Pharmacoepidemiol Drug Saf. 
2012;21(12):1359-60. 
22. 
Update: Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate 
vaccine--United States, June 2005-September 2006. MMWR Morb Mortal Wkly Rep. 
2006;55(41):1120-4. 
23. 
Medicine Io. Diphtheria toxoid, tetanus toxoid, and acellular pertussis-containing vaccines. 
In: Stratton K, Ford A, Rusch E, Clayton EW, editors. Adverse Effects of Vaccines: Evidence and 
Causality. Washington, DC: The National Academies Press; 2012. p. 557-8. 
24. 
Tseng HF, Sy LS, Ackerson BK, Hechter RC, Tartof SY, Haag M, et al. Safety of 
Quadrivalent Meningococcal Conjugate Vaccine in 11- to 21-Year-Olds. Pediatrics. 2017;139(1). 
25. 
Nimenrix: Summary of Product Characteristics [Internet]. Available from: 
https://www.ema.europa.eu/en/documents/product-information/nimenrix-epar-product-
information_en.pdf. 
26. 
Centers for Disease Control and Prevention. Syncope after vaccination--United States, 
January 2005-July 2007. MMWR Morb Mortal Wkly Rep. 2008;57(17):457-60. 
27. 
Gardasil 9 Summary of Product Characteristics (SmPC).2020 Accessed on 05 May 2021. 
Available from: https://www.ema.europa.eu/en/documents/product-information/gardasil-9-epar-
product-information_en.pdf. 
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